Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A Short Report

HSPs demonstrate a strong association with gamma-delta (γδ) T cells. Most of the studies regarding interactions between the parameters were conducted in the 1990s. Despite promising results, the concept of targeting γδ T cells by HSPs seems to be a forgotten direction due to potent non-peptidic phosphoantigens rather than HSPs have been found to be the essential stimulatory components for human γδ cells. Currently, with greater knowledge of lymphocyte diversity, and more accurate diagnostic methods, we decided to study the correlation once again in the neoplastic condition. Twenty-one children with newly diagnosed acute lymphoblastic leukaemia (ALL) were enrolled on the study. Serum HSP90 c…

Cardiac progenitor cells and the development of the human heart

The balance of HSPs expression during pregnancy: the role of placenta

Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis

In this work we analysed, by immunohistochemistry, a series of brain tumors to detect the levels and cellular distribution of Hsp60 and Hsp70. We found that Hsp60 levels were significantly higher than those of Hsp70 in neuroepithelial tumors, while levels of both molecules were not significantly different from each other in meningeal neoplasms. In particular, Hsp60 immunopositivity was present mainly at the cytoplasmic level, while Hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells. The levels of these molecules in healthy control cells were always very low. Finally, Hsp60 and Hsp70 levels did not correlate with the different types (WHO grade) of neopla…

HSP90 and eNOS partially co-localize and change cellular localization in relation to different ECM components in 2D and 3D cultures of adult rat cardiomyocytes.

Background information. Cultivation techniques promoting three-dimensional organization of mammalian cells are of increasing interest, since they confer key functionalities of the native ECM (extracellular matrix) with a power for regenerative medicine applications. Since ECM compliance influences a number of cell functions, Matrigel-based gels have become attractive tools, because of the ease with which their mechanical properties can be controlled. In the present study, we took advantage of the chemical and mechanical tunability of commonly used cell culture substrates, and co-cultures to evaluate, on both two- and three-dimensional cultivated adult rat cardiomyocytes, the impact of ECM c…

Trattamento simultaneo di metastasi epatiche e spleniche da carcinoma colo-rettale

MOESM7 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 7. Figure S6. Histogram representing the distance and the frequency of macroH2A1.2-binding regions from transcriptional starting site (TSS), genome-wide.

Hsp60 and AChR cross-reactivity in myasthenia gravis: An update.

NURBS Modelling in Virtual Reality

Simulation of the Behaviour of a New Semitrailer with Structural Load-Carrying Platform in Composite Material

Hsp27 and Hsp60 in human submandibular salivary gland: Quantitative patterns in healthy and cancerous tissues with potential implications for differential diagnosis and carcinogenesis

Tumors of the submandibular salivary gland (SMG) are uncommon but sufficiently frequent for the physician to consider them in routine examinations and for the pathologist to be prepared to differentiate them from other tissue abnormalities. However, scarcity of specimens makes training difficult, a situation compounded by the lack of accepted universal diagnostic guidelines. Furthermore, there is little information on the chaperone system (CS) of the gland, despite the increasing evidence of its participation in carcinogenesis as a biomarker for diagnosis and patient follow up, and in the mechanisms by which the tumor cells thrive. We are investigating this aspect of various tumors, and her…

New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity.

In recent years, human mesenchymal stem cells (MSC) have been extensively studied. Their key characteristics of long-term self-renewal and a capacity to differentiate into diverse mature tissues favour their use in regenerative medicine applications. Stem cells can be found in embryonic and extra-embryonic tissues as well as in adult organs. Several reports indicate that cells of Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells, expressing markers of bone marrow mesenchymal stem cells (BM-MSC), and giving rise to different cellular types of both connective and nervous tissues. Wharton's jelly mesenchymal stem cells (WJ-MSC) express …

A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model

Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone's structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major…

Anatomia della malasanità e prospettive di cura

Synchronous colorectal carcinoma

Expression of heat shock proteins in bladder cancers

Approccio Metodico alla Riprogettazione di un Semirimorchio

Economic competition leads to continuous development of new products and processes, but it is opposed by the decrease of speed of characteristics improvement and by the consequent tendency of the market to saturation. Redesign assumes in this context a particular remark because it cans allowing the acceleration of process of performances increase. This objective needs a methodical and structured approach that can leading, even, to the modification of product concept. In this work it has been studied the possibility of reducing the mass of a road semitrailer, by intervening on its structural elements. Some solutions, characterized by new topology and/or materials, have been examined and a st…

The Role of the Heme Oxygenase System in the Metabolic Syndrome

Molecular chaperones and the heat shock response play a major role in the maintenance of cellular homeostasis under various pathological conditions. In particular, their role is to regulate protein conformation, protect proteins from misfolding and aggregation, and maintain signalling and organellarnetworks. Among variousheat shock proteins, Hsp32 also known as heme oxygenase-1 (HO-1), has demonstrated an important role in metabolic syndrome. In particular, the HO system seems to play a major role in the complex pathophysiological cascade involved in insulin resistance mechanisms, and adipocyte functions as measured by the release of important adipokynes. The aim of the present review is to…

Oxidative stress markers at birth: Analyses of a neonatal population

In order to further understand neonatal stress and, thus, control it efficaciously, there is a need for more information on the manifestations of stress at the molecular level in the newborn, with particular regard to oxidants, and anti-oxidant and anti-stress mechanisms, including mitochondrial heat shock protein-chaperones such as Hsp60. We investigated patterns of anti-oxidants, biomarkers of oxidative stress, and Hsp60 levels in sera from newborns and found significant associations between glutathione (GSH) levels and gestational age, delivery modality, and lipid hydroperoxydes (LOOH) level. LOOH levels and spontaneous (vaginal) delivery were independently associated with increased GSH …

Simulation of fatigue delamination growth in composites with different mode mixities

Oxidative stress upregulates eNOS and myeloperoxidase (MPO) immunoexpression in hydrogen peroxide (H2O2) exposed HUVEC cells.

Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy

The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1,…

ROLE OF CHAPERONES IN HEALTHY BOWEL AND IBD.

The chaperoning system is the wole complement of chaperones, co-chaperones and chaperone cofactors of the body that preserves cell and tissue homeostasis. Its structural and/or functional defects can cause pathologic conditions, nemed chaperonopathies. Large bowel homeostasis includes a healthy status of the mucosal tissues and the microbiota. An alteration of one of them may determine, in turn, modifications of the other. Molecular chaperones of bacteria and human origin have been implicated in inflammatory bowel disease (IBD). In IBD chaperone levels usually increase and their cellular and subcellular loclization change. This is considered a physiological stress-response of mucosal cells …

Extracellular vesicles in airway homeostasis and pathophysiology

The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, inclu…

CCL5(RANTES) inhibits TGFbeta1 induced collagen production in human bronchial epithelial cells by action of Smad protein

Airway epithelial cells modulate bronchial remodelling in COPD and asthma. TGF-β1 up-regulation was observed in the bronchial epithelial cells of asthmatics and COPD patients. TGF-β is involved in airways remodelling mainly acting via the Smad pathway. Increased CCL5 was also observed in bronchi of patients with severe COPD. We investigated the effects of TGF-β1 on collagen type I, Smad 3-4 and 7 expression and the effects of CCL5 on TGF-β1-induced collagen production in human bronchial epithelial cells (16HBE).Cells were treated with 10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5 for 0,3 and 24 hours.TGF-b1 increased Smad3,Smad4 and collagen type I(p=0.0472, p=0.043…

Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts

Abstract Background Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD.…

Clinical anatomy of central cenous catheterization guided

Evalutaion of HSP60, Procaspase-3 and P53 expression after oxydative stress in NCI-H292 cells.

Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy.

Hsp60 in eukaryotes is considered typically a mitochondrial chaperone (also called Cpn60) but in the last few years it has become clear that it also occurs in the cytosol, the cell surface, the extracellular space, and in the peripheral blood. Studies with prokaryotic models have shown that Hsp60 plays a role in assisting nascent polypeptides to reach a native conformation, and that it interacts with Hsp10 (which also resides in the mitochondria and is also named Cpn10). In addition to its role in polypeptide folding in association with Hsp10, other functions and interacting molecules have been identified for Hsp60 in the last several years. Some of these newly identified functions are asso…

Contrast-enhanced versus baseline ultrasonography in the characterization of benign focal hepatic lesions

The many lives of Hsp10: From Early Pregnancy Factor to Potential Antitumoral Agent. New Proteomic Data and a Review of the Literature Focusing on Its Immunologic Properties

Human recombinant vasostatin-1 may interfere with cell-extracellular matrix interaction

Anatomy and Physiology of the Peripheral and Central Auditory System

The auditory system is responsible for the hearing sense and it consists of the peripheral auditory system (outer, middle and inner ear) and of the central auditory system (vestibular and cochlear nuclei, auditory and vestibular pathways and vestibular and auditory cortices). The outer ear comprises the auricle and the auditory canal and its function is to guide air pressure waves to the middle ear. The middle ear consists of the tympanic membrane, connected to the inner ear by three ossicles (malleus, incus and stapes), which vibrations allow the transmission of originally airborne sound waves to the perilymph of the inner ear. The middle ear provides a pressure gain as well as enhanced qu…

Hsp60 and Hsp10 as antitumour molecular agent.

Hsp60 and Hsp10 as antitumour molecular agents

The molecular chaperones Hsp60 and Hsp10 are, according to recent reports, involved in cancer development and progression. We, for instance, have found that their expression varies with distinctive patterns in different malignancies: they are overexpressed in colorectal, exocervical and prostate carcinogenesis, and colorectal cancer progression, but they are downregulated during bronchial carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used as therapeutic agents, for example in rheumatoid arthritis. In view of these findings we want now to call attention to the potential of Hsp60 and Hsp10 in cancer therapy.

Mutual Antagonism between Circadian Protein Period 2 and Hepatitis C Virus Replication in Hepatocytes

BackgroundHepatitis C virus (HCV) infects approximately 3% of the world population and is the leading cause of liver disease, impacting hepatocyte metabolism, depending on virus genotype. Hepatic metabolic functions show rhythmic fluctuations with 24-h periodicity (circadian), driven by molecular clockworks ticking through translational-transcriptional feedback loops, operated by a set of genes, called clock genes, encoding circadian proteins. Disruption of biologic clocks is implicated in a variety of disorders including fatty liver disease, obesity and diabetes. The relation between HCV replication and the circadian clock is unknown.MethodsWe investigated the relationship between HCV core…

Lay-up optimization for the hull of a racing sailing yacht

Abstract Deformability and buckling load of yacht hulls with fiber reinforced plastic sandwich structure depend on the stack sequence of the skins. In this work an optimization of fiber directions of the laminae for a racing yacht is proposed. This procedure has been divided into three parts (i.e. material characterization, surface model definition, lay-up optimization). First of all a set of unidirectional specimens has been realized, by using the same fibers and matrix (carbon/epoxy) used for the hull as well as the same procedure and workers, in order to characterize the material according to American Society for Testing and Materials (ASTM) Standard D3039, employing strain gage techniqu…

Recombinant human vasostatin-1 in adult rat myocardiocytes: interactions with Heat Shock Protein 90, endothelial nitric oxide synthase expression and extracellular matrix components

Towards a fully integrated CAD system in virtual reality environment

Chaperonology: A novel research field for experimental medicine in the XXI century.

Syncronous colorectal carcinoma.

Hsp60 levels in the skeletal muscle are fibre-type specific and increase after endurance training

HEART MOBILE LEARNING

The widespread diffusion of mobile technologies in today’s society and the technological developments of recent years offers new opportunities for learning providing innovative techniques and tools in education. In this paper, we will introduce HeARt, an augmented reality mobile Learning system to support university medical students in their learning activities during an anatomy laboratory. Students usually use, in their daily anatomy laboratory, a physical human heart model to investigate and learn about heart anatomy. Even though these models are perfect education tools to observe details and touch "with hands" all the heart sections, they need a supplementary encyclopaedia to learn all h…

Hsp60 quantification in human gastric mucosa shows differences between pathologies with various degrees of proliferation and malignancy grade

Background: Stomach diseases are an important sector of gastroenterology, including proliferative benign

Extracellular Vesicle-Mediated Cell–Cell Communication in the Nervous System: Focus on Neurological Diseases

Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear…

Three-dimensional geometrical models of the liver.

In this work we used a virtual approach to study the human liver by three-dimensional geometrical models. We built the models through computer aided geometric modelling techniques starting from pictures taken during both real dissections and diagnostic medical imaging. The results show in a complete modular synthesis and with a schematic iconology the structural organization of this organ in a logic sequence of layers and topographic and spatial relationship among its components. This approach represents an amazing support to clinical anatomy for teaching and research.

Expression of Heat Shock Protein in bladder cancers.

Expression of Heat Shock Protein in bladder cancers.

No effects of low-intensity endurance exercise on muscle necrosis in the diaphragm of mdx mice

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle weakness. We have previously shown that low-intensity endurance training prevented muscle damage (Frinchi et al, Int J Sports Med 2014). Since the effects of low-intensity endurance training on the the diaphragm in the mdx mouse model are unknown, in the same animals we investigated Cx39 protein levels (Western blotting) in homogenates of the diaphragm before and after training. Mdx and wild-type (WT) mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 days/week for 6 weeks at progress…

Malpighi, la Iatromeccanica e la Nuova Medicina Sperimentale

Cancer as a “Mitochondriopathy”.

Mitochondria are subcellular organelles, whose well-known function is to produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). Alterations in respiratory activity and mtDNA appear to be a general feature of malignant cells. The presence of mtDNA mutations has been reported in various cancer cells, and the abundance of mtDNA damage is consistent with the intrinsic susceptibility to constitutive oxidative stress. Research about the functional aspects of mtDNA mutations in cancer development and therapeutic response is likely to be fruitful and to have significant clinical and prognostic impact. Although many studies to date have been focused on the identification an…

3D cultures as an in vitro model to study human vasostatin-1 effects

Hsp60 Friend and Foe of the Nervous System

Hsp60 belongs to the subgroup of molecular chaperones named chaperonins and, typically, resides and functions in the mitochondria but it is also present in extramitochondrial sites. It chaperones client peptides as they fold to achieve the native conformation and also displays anti-stress roles by helping stress-damaged proteins regain a functional shape. Thus, Hsp60 is central to the integrity and functionality of mitochondria and energy production. All cells in the nervous system depend on Hsp60 so when the chaperonin malfunctions the consequences on nervous tissues are usually devastating, causing diverse diseases. These are the Hsp60 chaperonopathies, which can be genetic or acquired wi…

TLR4 and NOD1 increase in stable COPD of increasing severity. Relationship with tissutal bacterial load

Background: The immune host response related to bacterial and viral infections in the airways and lung of COPD patients is unclear. Objectives: To investigate the expression of anti-bacterial and anti-viral antigens in bronchial biopsies and lung parenchyma of stable COPD patients in relation to bacterial load. Methods: Immunohistochemical (IHC) and qRT-PCR-expression of TLR2-3-4-7-8-9, NOD1, NOD2, MYD88, TRIF, TIRAP, pIRAK1, IRAK4, IRF3, pIRF3, IRF7, pIRF7, RIG1, MDA5, LGP2, MAVS, STING, DAI, IFNα and IFNβ was measured in bronchial mucosa in patients with mild/moderate (n=16), severe/very severe (n=18) stable COPD, control smokers (n=12) and control non-smokers (n=12). Selected relevant an…

HSP10,HSP70 AND HSP90 IMMUNOHISTOCHEMICAL LEVELS CHANGE IN ULCERATIVE COLITIS AFTER THERAPY

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones:…

Extracellular release of HSP60 from tumor cells occurs via various secretory pathways

HSP60 and HSP10 downregulation predicts bronchial epithelial carcingenesis.

Immunohistochemistry of Human Hsp60 in Health and Disease: From Autoimmunity to Cancer

Hsp60 (also called Cpn60) is a chaperonin with essential functions for cell physiology and survival. Additionally, its involvement in the pathogenesis of a variety of diseases (e.g., some autoimmune disorders and cancer) is becoming evident with new research. For example, the distribution and levels of Hsp60 in cells and tissues have been found altered in many pathologic conditions, and the significance of these alterations is being investigated in a number of laboratories. The aim of this ongoing research is to determine the meaning of these Hsp60 alterations with regard to pathogenetic mechanisms, diagnosis, classification of lesions, and assessing prognosis and response to treatment. Hsp…

Molecular chaperones in tumors of salivary glands.

The salivary glands are key components of the mouth and play a central role in its physiology. Their importance may be appreciated considering their number, occurrence in pairs, and distribution in the mouth: two parotids, two submandibular, two sublingual, and many other small ones scattered throughout the mouth. They produce saliva, without which ingestion of non-liquid nutrients and speech would be practically impossible. Nevertheless, the physiology and pathology of salivary glands are poorly understood. For instance, tumors of salivary glands occur, and their incidence is on the rise, but their etiology and pathogenesis are virtually unknown, although some risk factors have been identi…

Hsp60 is actively secreted by human tumor cells

Background Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings S…

Molecular Approaches to Target Heat Shock Proteins for Cancer Treatment

HSP90 was the first molecular target to inhibit the interaction of this heat shock protein (HSP) with client proteins in cancer cells and tissues. The HSP90 inhibition was attempted to liberate from this chaperone the oncogenic fusion proteins, mutated and activated serine/threonine protein kinases, tyrosine kinases, as well as transcription factors with oncogenic activity, in this manner, the free proteins could be recognized by the proteasome system to be degraded. We should remember here that many HSP family members are overexpressed in different kinds of cancer tissues, these molecules act as chaperones of tumorigenesis. In cancer patients, the first generation of HSP90 inhibitors showe…

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

This review will analyze growing evidence suggesting a convergence between two major areas of research: Alzheimer’s disease (AD) and chaperonopathies. While AD is a widely recognized medical, public health, and social problem, the chaperonopathies have not yet been acknowledged as a related burden of similar magnitude. However, recent evidence collectively indicates that such possibility exists in that AD, or at least some forms of it, may indeed be a chaperonopathy. The importance of considering this possibility cannot be overemphasized since it provides a novel point of view to examine AD and potentially suggests new therapeutic avenues. In this review, we focus on the mitochondrial chape…

Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet.

Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3–33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt–villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%;P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%;P&l…

Expression of Orphanin FQ in Mature Mucous Tissue

High-resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD

<b><i>Background:</i></b> The literature shows conflicting results when high-resolution computed tomography (HRCT) scores of emphysema were correlated with different indices of airflow obstruction. <b><i>Objectives:</i></b> We correlated HRCT scores of emphysema with different indices of airflow obstruction. <b><i>Methods:</i></b> We performed HRCT of the chest in 59 patients, all smokers or ex-smokers, with stable chronic obstructive pulmonary disease of different severity [GOLD stages I–IV; mean age ± SD 67.8 ± 7.3 years; pack/years 51.0 ± 34.6; percent predicted forced expiratory volume in 1 s (FEV<sub>1</su…

Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of t…

Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.

BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …

The discovery of stapes

Giovanni Filippo Ingrassia revisited and redefined some of Galeno's reports, and was recognized as one of the leading Italian Physicians of the 16th century. Ingrassia principally studied the skull, and gave very important contributions to otorhinolaryngology, including the discovery of the stapes. He also isolated the inferior nasal concha from the maxillary bone, described the frontal sinus, the pterygopalatine fossa and several foramina of the skull. Ingrassia firstly attributed a sensorial function to the middle ear bones, which he called fifth particular function. He also added some details to the description of the VIII cranial nerve, which introduces the concept of bone conducting so…

Impact of Chaperonopathies in Protein Homeostasis and Beyond

Chaperones have functions other than those classically attributed to them pertaining to protein homeostasis. These “other” non-canonical functions are the focus of chapter 8. The close interaction of the chaperoning and the immune systems and the impact of their malfunctioning on aging and cancer are highlighted. Conversely, the impact of ageing and cancer on the two systems is also underscored. The connections between stress, protein damage (including chaperones), protein misfolding, protein aggregation and precipitation, and tissue degeneration, are analyzed, indicating that all these processes are aggravated by a decline in chaperoning potential with aging (chaperonopathies of the aged) …

COVID-19 and molecular mimicry: The Columbus’ egg?

Highlights • Recently, this Journal published a report about Guillain-Barré syndrome associated with COVID-19 infection. • Guillain-Barré syndrome can be due to molecular mimicry phenomena. • Molecular mimicry had already been described in another SARS. • It could explain the autoimmune signs and symptoms that some patients affected by SARS-CoV-2 can experience.

NOVEL ANTAGONISTS FOR AN Hsp60-BASED ANTICANCER CHAPERONOTHERAPY

The Heat shock proteins (Hsps) are nowadays considered the most important cell chaperones, which result overexpressed in response to a number of cell stress stimuli.In tumor cells, when Hsp60 accumulates in the cytosol, without mitochondrial release, it exerts an anti-apoptotic effect, by inhibiting pro-caspase-3 (pC3) activation. In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and pC3 and to design novel antagonists able to specifically block this interaction. The analysis of virtual screening results highlights the 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines of type 1 and the N-{5-[1H-imidazo…

COMPUTER MODEL OF ARTERIAL BIO-MECHANICS.EVALUATION OF RUPTURED ABDOMINAL AORTIC ANEURYSM WALL THROUGH FINITE ELEMENT ANALYSIS

Other Types of Chaperonopathies

A mechanism causing a chaperonopathy that is introduced in this chapter consists of the absence of a chaperone from the place where it is needed (i.e., chaperonopathies by misplacement). Also in this chapter are discussed the unfolded-protein response (UPR), chaperone-mediated autophagy (CMA), and illustrative examples of chaperonopathies by mistake, or collaborationism. In these conditions, one or more chaperones, apparently normal in structure, perform functions that favor disease rather than the contrary, hence the name of chaperonopathy by mistake or collaborationism (a molecule that ought to protect the cell and the organism promotes pathogenesis instead). Many examples of chaperonopat…

Virtual bronchoscopy and preoperative assessment of airways stenosis

Evaluation of hsp60, procaspase-3 and p53 expression after oxydative stress in H292 cells

Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis.

Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host’s antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.

Numerical analysis of composite plates with multiple delaminations subjected to uniaxial buckling load

Abstract In this paper the buckling and post-buckling behaviour of unidirectional and cross-ply composite laminated plates with multiple delaminations has been studied. Finite elements analyses have been performed, using a linear buckling model, based on the solution of the eigenvalues problem, and a non-linear one, based on an incremental-iterative method. With non-linear method large displacements have been taken into account and also contact constraints between sublaminates have been added to avoid their interpenetration. It has been found that both delamination length and position and stacking sequence of the plies influence the critical load of the plate; furthermore, linear and non-li…

Clinical anatomic, immunomorphologic and molecular anatomic data suggest interplay of thyroidal molecules, autoantibodies and Hsp60 in Hashimoto’s disease

Hsp60 is, typically, a mitochondrial protein, but it also occurs in the cytosol, vesicles, and plasma membrane, and in the intercellular space and biological fluids, e.g., blood. Changes in the levels and distribution of Hsp60 are linked to several pathologies, including cancer and chronic inflammatory and autoimmune disorders. What is the histopathological pattern of Hsp60 in the thyroid of Hashimoto’s patients? Are there indications of a pathogenic role of Hsp60 that may make Hashimoto’s thyroiditis a chaperonopathy? Experiments reported here provide information regarding those questions. We found by various immunomorphological techniques increased levels of Hsp60 in the thyroid from HT p…

Hsp27 and Hsp70 in chronic obstructive pulmonary disease: certainties vs doubts

Dear Editor, We read with great interest the work by Cui et al. (2015) in which they measured the levels of Hsp70 and Hsp27 in plasma and lymphocytes obtained from coal workers (CW) affected by chronic obstructive pulmonary disease (COPD) alone or associated with pneumoconiosis (CWP). They found that Hsp70 levels were higher in plasma of COPD subjects affected by CWP compared to COPD subjects without CWP and to controls. There was no difference in Hsp70 levels between COPD without CWP and controls. Hsp70 levels in lymphocytes did not show differences among the three groups. The authors found lower levels of Hsp27 in plasma from patients when comparing controls to both COPD with and without …

ANALISI TRIDIMENSIONALE DI BUCKLING DI PIASTRE IN COMPOSITO CON DELAMINAZIONI MULTIPLE: APPLICAZIONE AI LAMINATI ANGLE-PLY

GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet

Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to dietary nutrients, which acts through a specific receptor, the GLP-2 receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving also the intestinal adaptation to high fat diet (HFD). In consideration of the well-known relationship between chronic HFD and impaired glucose metabolism, in the present study we examined if the blocking of the GLP-2 signaling by chronic treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional consequences in the regulation of glucose metabolism in HFD-fed mice. Compared with animals fed standard diet (STD), mice at the 10th week of HFD showed hy…

Presence of Oxytocin, Vasopressin and Atrial Natriuretic Peptide and Their Modification in Rat Hypothalamic Paraventricular Nucleus During Resistance Training

Summary Many studies have demonstrated the physiological effects of oxytocin (OT), atrial natriuretic peptide (ANP) and vasopressin (VP) in the homoeostasis of body fluids during physical exercise. However, a little information is available about the related immunohistochemical changes in hypothalamic magnocellular neurosecretory system during and after the training. The aim of the present work was to study the immunohistochemical changes in OT, ANP and VP levels in the hypothalamic paraventricular nucleus during and after resistance exercise protocol. Three groups of Wistar rats were trained by a rung ladder protocol for 15, 30 and 45 days, respectively; a fourth group was left to rest for…

Chaperone patterns in vernal keratoconjunctivitis are distinctive of cell and Hsp type and are modified by inflammatory stimuli

Background Vernal keratoconjunctivitis (VKC) is a severe ocular allergy with pathogenic mechanism poorly understood and no efficacious treatment. The aims of the study were to determine quantities and distribution of Hsp chaperones in the conjunctiva of VKC patients and assess their levels in conjunctival epithelial and fibroblast cultures exposed to inflammatory stimuli. Methods Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, Hsp105, and Hsp110 were determined in conjunctiva biopsies from nine patients and nine healthy age-matched normal subjects, using immunomorphology and qPCR. Conjunctival epithelial cells and fibroblasts were cultured and stimulated with IL-1β, histamine, IL-4, TNF-α, or UV-…

Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease

Abstract In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response…

BENIGN GASTRIC POLYPS AND HELICOBACTER PYLORI INFECTION.

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.

Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

AbstractAmphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also ass…

Is CD1a involved in antitumour immune responses during carcinogenesis?

Editorial for the Special Issue “Extracellular Chaperones and Related miRNA as Diagnostic Tools of Chronic Diseases”

Molecular chaperones are a family of proteins that are highly conserved during phylogenesis [...]

STRESS, CHAPERONI MOLECOLARI E MALATTIE INFIAMMATORIE CRONICHE DELL'INTESTINO

This brief article is focused on HSP60, a very important molecular chaperon for cell surviving, involved in the pathogenesis of several degenerative, autoimmune, and neoplastic disorders. Recent reports confer unravelling role in IBD pathogenesis. involvement of HSP60 in CD and UC development has been recently confirmed. in fact HSP60 levels increase in mucosal epithelium and also in lamina propria of affected subjects.

Human chaperonin disease-causing mutations: study with a prokaryotic model.

MOESM2 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 2. Figure S1. Representative images of wild-type and macroH2A1.2 transgenic (Tg) mice adipose tissue (VAT) sections immunostained for macroH2A1.2 (red). Nuclei were counterstained with Hoechst (blue), while perilipin was immunostained to define adipose cell membranes (green). macroH2A1.2 expression was detected only in the VAT of Tg animals but not in wild-type animals (white arrows).

Presence of atrial natriuretic factor in normal and hyperplastic human prostate and its relationship with oxytocin localisation

In this work, we showed the presence of atrial natriuretic factor (ANF) in human prostate and compared its localisation in normal and hyperplastic conditions. ANF was localised in epithelial and stromal cells, being increased in hyperplasia, mainly in the stromal component. Moreover, we compared ANF and oxytocin positivity in the same glands, focusing on the possible relationship between the paracrine effects of these two hormones.

Influence of endogenous glucagon-like peptide-2 on lipid disorders in mice fed a high-fat diet

Aim: The purpose of the present study was to investigate the influence of endogenous glucagon-like peptide-2 (GLP-2) on lipid profile in mice fed a standard diet (STD) or a high-fat diet (HFD). Materials and methods: HFD- and age-matched STD mice were injected once a day with GLP-2 (3-33), a GLP-2 receptor (GLP-2R) antagonist, or vehicle for 4 weeks. Results: HFD mice displayed increased intrahepatic lipid concentration and hepatic steatosis and higher plasma concentrations of cholesterol, LDL, AST, and ALT than STD mice. No difference was observed in lipid fecal elimination. In STD mice, the chronic treatment with GLP-2 (3-33) did not affect any parameter, while in HFD mice, it enhanced pl…

Insulin resistance as common molecular denominator linking obesity to Alzheimer’s disease

Alzheimer’s disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ 40 /Aβ 42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments…

Editorial (Thematic Issue: Current and Perspective Therapeutic Strategies for Alzheimer's Disease).

Effect of HSP60 on fibrillogenesis of A-beta amyloid peptide

Alzheimer Hsp60 Aggregation

Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction

Heat shock proteins (Hsps) are produced in response to various stressors, including ischemia-reperfusion, and they can exit cells and reach the blood. In this pilot study, we determined serum levels of Hsp60 and heme-oxygenase-1 (HO-1; also named Hsp32) in subjects with acute myocardial infarction (AMI) to assess their clinical significance and potential prognostic value. We also performed a bioinformatics analysis of the 2 molecules in search of structural clues on the mechanism of their release from cells. We studied 40 patients consecutively admitted for AMI (male:female patient ratio = 20:20, mean age: 64 ± 13 years) and 40 matched controls. A blood sample was drawn for biochemical anal…

Cardiac Stem Cell Research: An Elephant in the Room?

Heart disease is the leading cause of death in the industrialized world, and stem cell therapy seems to be a promising treatment for injured cardiac tissue. To reach this goal, the scientific community needs to find a good source of stem cells that can be used to obtain new myocardium in a very period range of time. Since there are many ethical and technical problems with using embryonic stem cells as a source of cells with cardiogenic potential, many laboratories have attempted to isolate potential cardiac stem cells from several tissues. The best candidates seem to be cardiac "progenitor" and/or "stem" cells, which can be isolated from subendocardial biopsies from the same patient or from…

Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy

Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried…

The evolutionary course of vertebrate foot, from fish to man

Oxidative stress apoptosis in carcinogenesis: molecular players and interactions.

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactiv…

ANALISI NUMERICO-SPERIMENTALE DI SANDWICH IN COMPOSITO CON CORE CORRUGATO

Giovanni Filippo Ingrassia: A five-hundred year-long lesson.

Giovanni Filippo Ingrassia was born five centuries ago in Regalbuto, a small town in the center of Sicily. After his medical course in Padua, under the guidance of Vesalius and Fallopius, he gained international fame as a physician and was recruited as a Professor of human anatomy in Naples and later in Palermo. He is remembered as "the new Galen" or "the Sicilian Hippocrates." He contributed to the knowledge of human anatomy through the description of single bones rather than the whole skeleton. In particular, he was the first to describe the "stapes," the "lesser wings of the sphenoid" and various other structures in the head (probably the pharyngotympanic tube) as well as in the reproduc…

HSP60 and HASP10 overexpression in metastatic colon cancer

Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy

Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (P…

VirDe: A new virtual reality design approach

Virtual reality (VR), even if it does not represent any more a novel technology, is one of the most powerful tool to help designers during the development of new projects. This is proved by very numerous research activities related to this field. In this research, we have studied a new way to approach the development of a product. We present the ongoing development of a system, called VirDe, acronym of virtual design, which can allow the designers to perform the whole design process, from the modelling phase to the finite element method (FEM) simulation analysis, in a virtual reality environment. This new method allows remarkable time and money saving in the overall product design process, …

NUTRACEUTICALS IMPROVE EXPERIMENTAL COLITIS: PLACE OF CATECHINS IN THE 2,4,6-TRINITROBENZENE SULFONIC ACID MODEL RATS

Background: Nutraceuticals provide added health benefits for inflammatory bowel disese (IBD) and Epigallocatechin-3-galate (EGCG), a green tea catechin, has been shown to possess such anti-inflammatory and anti-oxidant effects. Aim: To evaluate the molecular modulation of Reactive Oxygen Species (ROS), Tumor Necrosis Factor-alpha (TNF_alpha), nuclear factor Kappa Beta (NF-Kbeta), Interleukin 6 (IL-6) by EGCG on experimental colitis. Matherial and Methods: Thirthy five male sprague-dawley rats were randomly divided into 4 groups: Normal control group (n=5), EGCG group (n=9), TNBS group (n=9), and TNBS + EGCG group (n=12). For both TNBS and EGCG treated groups, 1 mg/Kg EGCG was administered d…

Laboratory Technologies and Methodologies

Extracellular heat shock proteins in cancer: From early diagnosis to new therapeutic approach

In cancer, human cells lose the ability to properly control the series of events that occur constantly during cell growth and division, including protein expression, stability, and dynamics. Heat shock proteins (Hsps) are key molecules in these events, constitutively expressed at high levels and could furthermore be induced by the response to cancer-induced stress. In tumor cells, Hsps have been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis; in some cases, they can be overexpressed and dysregulated, representing important cancer hallmarks. In the past few years, it has been demonstrated that Hsps can be released by tumor cells through s…

Serological, immunomorphological and bioinformatics analyses suggest Hsp60 is involved in Hashimoto’s thyroiditis pathogenesis.

EXTRACELLULAR RELEASE OF HSP60 FROM TUMOR CELLS

A multipronged approach to unveil the emerging role of Hsp60 in chronic obstructive pulmonary disease

Inflammation is a major component of chronic obstructive pulmonary disease (COPD) and its cause and mechanisms are still incompletely understood. For example, the role of heat shock proteins (Hsps), many of which are molecular chaperones, has not been explored in detail in COPD, despite the fact that these molecules are known to participate in inflammation in other diseases. It has been shown that extracellular Hsps can signal certain types of T cells, macrophages, dendritic cells, and neutrophils and, thereby, elicit inflammation and immunity. However, these phenomena have not been investigated in COPD despite: a) the increasing awareness of Hsp participation in inflammation and immunity; …

Study of the effects of Pleurotuseryngii var. eryngii on heat shock proteins and cytokines levels in a mouse model of colon carcinoma

Medicinal mushrooms are wonderful source of nutraceuticals with a wide range of benefit for human health. The current anti-cancer therapy is not always target specific and often is associated with complications for patients. Therefore new effective and less toxic therapeutic approaches are needed. Heat shock proteins (Hsps) are highly expressed in a variety of cancer types contributing to tumor cell propagation. Here, we treated C26 colon cancer cells with a cold-water extracts of an edible mushrooms Pleurotuseryngii var. eryngii (Pleuery). Hsp90, 70, 60 and 27 levels were measured by western blotting and immunofluorescence analysis. Moreover, we evaluated Pleueryanti cancer effect in an an…

NUTRITION, OXIDATIVE STRESS AND INTESTINAL DYSBIOSIS: INFLUENCE OF DIET ON GUT MICROBIOTA IN INFLAMMATORY BOWEL DISEASES.

Background: Microbiota refers to the population of microorganisms (bacteria, viruses and fungi) that inhabit the entire gastrointestinal tract, more particularly the colon whose role is to maintain the integrity of the intestinal mucosa and control the proliferation of pathogenic bacteria. Alteration in the composition of the gut microbiota is called dysbiosis. Dysbiosis redisposes to inflammatory bowel diseases such as ulcerative colitis, Crohn disease and indeterminate colitis. Methods: The purpose of this literature review is to elucidate the influence of diet on the composition of the gastrointestinal microbiota in the healthy gut and the role of diet in the development of dysbiosis. Co…

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic ac…

Simulation of Fatigue Delamination Growth in Composites with Different Mode Mixtures

A numerical model, obtained by implementing a cyclic damage model in the framework of an interface element, is here proposed to reproduce the crack growth in laminated composites subjected to cyclically repeated loads. This model, which differs from the few studies in the literature on the topic, applies not only to single fracture modes but also to mixed modes, and to constant or variable crack growth rates. The applied load (in terms of force or displacement) is assumed to oscillate between a minimum and a maximum constant value. The Paris curve can be reproduced with accuracy once some parameters in the numerical model are tuned with experiments. These parameters are preliminarily found…

Experimental Tests of Fatigue Induced Delamination in Gfrp and Cfrp Laminates

This work deals with the experimental analysis of the delamination phenomena in various composite materials under different loading conditions. Quasi-static and fatigue tests are performed on specimens made of glass-fibre reinforced plastic (GFRP) and carbon-fibre reinforced plastic (CFRP). In particular, under both quasi-static and fatigue loading, single fracture modes I and II (using standard DCB and ENF test configurations) and mixed modes I+II (using the MMB test configuration) with several mode mixtures, have been analysed. Further experiments of delamination growth with mode mixture that varies with the crack length, will be performed.

Increased nitrotyrosine plasma levels in relation to systemic markers of inflammation and myeloperoxidase in chronic heart failure

The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO …

HSP60 expression during carcinogenesis: a molecular “Proteus” of carcinogenesis?

Sir, I read with much interest the comprehensive review by Ciocca and Calderwood (2005) in which they analyze the diagnostic, prognostic, predictive, and treatment values of a number of Hsps in oncology. Concerning the implications of Hsps in cancer diagnosis in particular, they report that since “Hsps are overexpressed in a wide range of malignant cells and tissues … Hsp detection is not useful in diagnostic immunopathology.” Nevertheless, “Hsp expression levels can help indicate the presence of abnormal changes during the process of carcinogenesis.” The authors support this remark by reference to several papers by our group (Cappello et al 2002–2003, 2003a, 2003b, 2003c) in which we demon…

Oxidative Stress Upregulates eNOS and Myeloperoxidase (MPO) immunoexpression in hydrogen peroxide (H202) exposed HUVEC cells

Direct Simulation of Electronic Transport through Deformed Single and Multiwall Carbon Nanotubes. NANOMEC-06 Materials Science and Materials Mechanics at the Nanoscale,

&lt;p&gt;Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD&lt;/p&gt;

Background Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. Methods We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB4, MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. Results AATD-AT patient…

Modulation of MMP-2 and MMP-9 in Churg-Strauss syndrome respiratory mucosa: potential monitoring parameters.

Churg-Strauss (CSS) syndrome is rare and of unknown etiology. It is associated with vasculitis, blood eosinophilia and granulomatosis, and affects multiple organs and systems at various stages of the disease. Specific diagnostic and monitoring tests are not yet available. This study aims to assess the changes in MMP-2 and MMP-9 along with the histopathological alterations in two cases of CSS, as possible potential diagnostic and monitoring criteria. Two adult male patients were diagnosed with CSS in the otorhinolaryngology clinic in the University of Palermo, based on multiple clinical and histopathologic criteria. Biopsies of respiratory mucosa were taken after the consent of the patients…

Molecular profile study of extracellular vesicles for the identification of useful small “hit” in cancer diagnosis

Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognosis, monito…

Curve and Surface Fitting via Optimisation Technique

The Odyssey of Hsp60 from Tumor Cells to Other Destinations Includes Plasma Membrane-Associated Stages and Golgi and Exosomal Protein-Trafficking Modalities

BACKGROUND: In a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here. PRINCIPAL FINDINGS: We found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevent…

DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progression

Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…

Clinical Anatomy and information technology.

Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD.

Background In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. Objectives To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Methods Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NA…

PRENATAL DEVELOPMENT OF TEMPORO-MANDIBULAR JOINTS: STATE OF ART

The aim of this work is to analyze the state of the art of temporo-mandibular joint (MJ) to understand the varoius stage of the development of the same during embryogenesis. Various theories have been analyzed, such as the formation of apoptotic or the important role of growth factors, or the Valencia et studies in which are analyzed to numerous articular diseases in various stage of development. By the aforementioned studies show that many factors, of a different nature, are to be involved in the prenatal developlment of this important joint.

The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model

2-Methoxyestradiol is one of the natural 17&beta

Morphological features of the idiopathic dilated cardiomyopathy.

Evaluation od hsp60, pro-caspase-3 and p53 expression after oxidative stress in NCI-H292 cells

Effects of curvature of the Carbon Nanotubes and Carbon Nanotube/matrix bonding on Nanocomposite stiffness

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Expos…

A mouse model of alcoholic liver disease reveals protection by Lactobacillus fermentum

The knowledge and treatment of alcoholic liver disease is still plagued with gaps mostly due to the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp-chaperones involvement, and response to treatment. The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum for 4, 8 and 12 weeks and applying a battery of techniques (histology, immunohistochemistry, Western blotting, real-time PCR, immunoprecipitation, 3-nitrotyrosine labeling) to assess liver pathology and Hsp60, iNOS gene expression and protein levels, and Hsp60 post-translational modifications. Stea…

Hsp60 in embryonic and adult submandibular salivary gland: quantitative distribution patterns in normal tissue and comparison with benign and malignant tumors

Introduction: Heat Shock Protein 60 (Hsp60) is a member of the chaperoning system that assists protein folding inside mitochondria and plays other roles beyond these organelles. It is implicated in the carcinogenic processes in various types of cancer. In human salivary glands, Hsp60 has not yet been measured or mapped in detail and its role in gland development and functioning is virtually unknown. Consequently, its potential as biomarker for gland diseases, including malignancies cannot be assessed. The S-100 protein, a known marker for schwannomas, has been found also in myoepithelial-cell carcinomas of the salivary glands. Here, we present our initial findings on the anatomic-histologic…

Heat shock proteins in embryonic and adult submandibular salivary glands in healthy and tumorigenic tissues

Hsp60 secretion and migration from cancer cells: a proposal for a multistage pathway

CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome.

AIMS: CD1a is a molecule belonging to the highly conserved group of CD1 proteins. Its expression in dendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently, the development of a successful antitumour response. The aim was to investigate the presence of CD1a+ cells in both primary tumours and lymph nodes (LN) of a series of 35 invasive ductal carcinomas by both immunohistochemistry and reverse transcription-polymerase chain reaction. METHODS AND RESULTS: CD1a antigen was more expressed in N0 than N1 breast cancer (P < 0.0001) in both primary lesions and LN metastases and correlated positively and significantly with oestrogen (ER) (P =…

Exosome levels in human body fluids: A tumor marker by themselves?

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discrimin…

Synchronous liver metastases from colorectal carcinoma

Overview and Book Plan

This chapter provides an introduction to the biology and pathology of molecular chaperones, many of which are heat-shock proteins, involved in protein homeostasis and other unrelated functions. When chaperones are defective structurally and/or functionally they may cause disease. These diseases in which chaperones play an etiologic-pathogenic role are the chaperonopathies. The chapter also gives a clinical-pathological overview of chaperonopathies and guidelines for their identification and diagnosis. It briefly describes how to detect and characterize a chaperonopathy in a patient. Chaperones can be useful biomarkers for disease diagnosis and monitoring, including evaluation of prognosis a…

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in NCI-H292 cancer cells

Abstract Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole) 2 (H 2 O) 2 ](ClO 4 ) 2 , CubipyOXA , a copper-containing compound with cytotoxic properties. We treated cells with various doses of the compound and measured cell viability; apoptosis indicators; and le…

Immunophenotypical characterization of a case of pulmonary metastatic biphasic synovial sarcoma: anatomoclinical aspects and short review of literature

Role of mitochondrial chaperones in cancer development

Exosome Involvment in Hsp60 secretion by tumor cells.

Cell- extracellular matrix interaction: a putative non-conventional target of vasostatin-1

MIXED FINITE ELEMENT-TIGHT BINDING TECHNIQUE FOR STUDYING THE ELECTROMECHANICAL BEHAVIOR OF SINGLE AND MULTIWALL CARBON NANOTUBES

MDMA Administration and Heat Shock Proteins Response: Foreseeing a Molecular Link

Molecular and cellular mechanisms of MDMA-induced toxicity have been extensively studied in a number of experimental models. Nevertheless, only few studies investigated the involvement of HSPs ("molecular chaperones") in MDMA organs toxicity. In the present minireview we highlight this subject analysing the results of these studies conducted especially on brain tissue. Despite of it seems obvious that HSPs overexpression is a protective reaction against MDMA treatment, the molecular mechanisms for exerting their action are far to be undiscovered. At the same time, we need of comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after acute and chronic…

Taravana: documentation of bubbles by computerized tomography.

Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking broken symmetries in molecular biology, mood disorders and personalistic emergentism

Abstract In this paper we present a mechanistic model that integrates subneuronal structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain. We also argue that subtle changes in the composition of the membrane’s fatty acids may lead to down-stream effects causing dysregulation of the membrane, cytoskeleton and their interface. Such exquisite sensitivity to minor changes is known to occur in physical systems undergoing phase transitions, the simplest and most studied of them is the so-called Ising model, which exhibits a phase transition at a finite temperature between an ordered and disorde…

A comparative analysis of the products of GROEL-1 gene fromChlamydia trachomatisserovar D and the HSP60 var1 transcript fromHomo sapienssuggests a possible autoimmune response

Summary Chlamydia trachomatis serovar D produces large quantities of HSP60-1 during infections, which accumulate inside the host cell inducing autoimmunity. We compare the aminoacid sequences of the human HSP60 with the bacterial counterpart to better elucidate how CTHSP60 may simulate HSP60 from human origin during infection and may induce an autoimmune response. As a result of the comparison we suggest several possible epitopes of the CTHSP60, which may induce autoimmunity.

Expression of 60-kD Heat Shock Protein Increases during Carcinogenesis in the Uterine Exocervix

&lt;i&gt;Objectives:&lt;/i&gt; The aim of the present study was to determine the presence and expression of the 60-kD heat shock protein (HSP60) in the dysplasia-carcinoma sequence in the uterine exocervix and to evaluate its diagnostic and prognostic significance. &lt;i&gt;Methods and Results:&lt;/i&gt; We performed Western blot and immunohistochemical analyses on biopsies from 40 cases, consisting of 10 normal exocervical biopsies, 10 low-grade squamous intraepithelial lesions (L-SIL), 10 high-grade squamous intraepithelial lesions (H-SIL) and 10 cancerous exocervices (G2 grade). The immunohistochemical results were quantified by computer-assisted image analysis. Western blot analysis sho…

Composti curcumin-like come agenti neuro-protettori. Interazione con HSP60

La Malattia di Alzheimer rappresenta una sfida fondamentale del XXI secolo per la salute pubblica. Le terapie attualmente utilizzate per la cura dell’Alzheimer si basano sugli aspetti sintomatici della patologia [1]. Un importante ruolo nella malattia è rivestito dalle Heat shock proteins (HSPs), proteine che presiedono al controllo del ripiegamento proteico [2]. Recentemente, è stato dimostrato che HSP60 media la traslocazione del Precursore della Proteina Amiloide (APP) e del Peptide Beta Amiloide (Aβ) nei mitocondri, portando alla perdita della funzionalità dell’organulo [3]. Nel campo degli approcci delle terapie potenziali, la curcumina sta emergendo come lead compound per lo sviluppo …

Exosomal Hsp60 in human colon cancer

Comparative analysis of Hsp10 and Hsp90 in large bowel healthy mucosa and adenocarcinomas

Heat shock proteins (Hsps) are an important class of molecules with various functions. Their classic role is to assist other proteins in folding and re-folding and, when proteins are defective or irreversibly misfolded, to drive their degradation. For this reason, some Hsps are also named molecular chaperones. During evolution, this class of proteins has also acquired extrachaperoning roles such as participation in immune system regulation, cell differentiation, programmed cell death and carcinogenesis. Hsp10 is a partner of Hsp60 in the Hsp60/10 folding machine, but numerous scientific studies have shown that Hsp10 may also play other roles. In fact, Hsp10 seems to have an immunomodulatory…

On the Elastic Behavior of a Cross-Ply Composite Pin-Joint with Clearance Fits

The effect of pin/hole clearance fits on the elastic membranal behavior of a cross-ply fiber glass-reinforced epoxy laminate plate loaded in tension through a pin is examined by a finite element nonlinear contact analysis. No a priori assumption is made on the distribution of the contact pressure on the surface of the hole. Friction effects are not included. The numerical results correlate well with Hertzian theory of contact. It is demonstrated that clearance increases the peak compressive stress in the plate up to a factor of 3000% with respect to the perfect-fit case. Clearance also shifts the location of the peak tensile stress towards the pin/hole contact arc and decreases its magnitu…

Expression of CD1a by Barrett’s metaplasia epithelial cells

COULD THE ENDOSCOPIC RESECTION OF A LARGE RECTAL LEIOMYOMA BE AN EFFETCIVE AND SAFE TECHNIQUE?

Summary. Rectal leiomyomas are a rare conditions, with low reported incidence in literature and constitute about 0.1% of rectal tumours; in fact rectal leiomyomas occur in approximately 1 out of 2000-3000 rectal tumors. We report on a patient with a 3 cm semi-pedunculated colonic leiomyoma, which was successfully removed by endoscopic polypectomy after normal saline-epinephrine submucosal injection. When we encounter a tumor during a colonoscopic examination, we usually evaluate the tumor carefully and perform an endoscopic resection when we judge it is appropriate. When a symptomatic smooth muscle tumors smaller than 2 cm are incidentally found on colonoscopy, surgical resection is unneces…

Carcinosarcoma of monoclonal origin arising in a dermoid cyst of ovary: a case report.

Abstract Background Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated. Case presentation A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC). The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio. Positive staining for vimentin, alpha smooth muscle actin and CD1…

Ascending aorta phenotypic and genotypic changes in bicuspid aortic valve disease

Bicuspid aortic valve (BAV) with left-right (L-R), right-non coronary (R-NC) and left-non coronary (L-NC) cusp fusion represents distinct pathological entities and the rate of aortic enlargement varies according to the pattern of cusps fusion (1). Here, we investigated the histological features of aneurysms associated to different BAV phenotypes and we looked for specific microRNAs (miRNA) as biomarkers of medial degeneration severity. Aortic specimens and blood were obtained from BAV patients treated surgically for the repair of thoracic aortic aneurysm and were divided into two groups: low grade medial degeneration (LGMD, n=10); high grade medial degeneration (HGMD, n=10). A control group…

La tracheostomia in urgenza

Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS

Many neurodegenerative disorders are characterized by the abnormal aggregation of misfolded proteins that form amyloid deposits which possess prion-like behavior such as self-replication, intercellular transmission, and consequent induction of native forms of the same protein in surrounding cells. The distribution of the accumulated proteins and their correlated toxicity seem to be involved in the progression of nervous system degeneration. Molecular chaperones are known to maintain proteostasis, contribute to protein refolding to protect their function, and eliminate fatally misfolded proteins, prohibiting harmful effects. However, chaperone network efficiency declines during aging, prompt…

Is molecular mimicry the culprit in the autoimmune haemolytic anaemia affecting patients with COVID‐19?

Bovine seminal vesicles ANP, Oxytocin, immunohistochemical expression.

Mature teratoma of the uterine corpus with thyroid differentiation

A case of a clinically silent mature teratoma of the uterine corpus is reported. A 55-year-old woman presented with multiple uterine leiomyomas. The discovery was incidental, because the patient was asymptomatic. Macroscopically, a colloid-hemorrhagic-looking nodule was present. Histologic and immunohistochemical studies showed that this tumor was a small thyroid mass. Key words:,

CD1a expression in Barrett’s oesophagus: new role for an old molecule against metaplastic progression

O101 : Histone variant macroH2A1 orchestrates escape from hepatocyte senescence during ageing and cancer

Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration

AbstractTumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stroma…

Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to predict clinical outcomes in pancreatic ductal adenocarcinoma patients.

Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. Methods mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients a…

Multi-chaperone – interactors network (mtcin) in mitochondria: role in neoplasm development and methodology of analysis.

ISOLATION AND CHARACTERIZATION OF CD276+/HLA-E+ HUMAN SUB-ENDOCARDIAL MESENCHYMAL STROMAL CELLS FROM CHRONIC HEART FAILURE PATIENTS: ANALYSIS OF DIFFERENTIATION CAPACITY AND IMMUNOMODULATORY MARKERS EXPRESSION.

NUTRITION IN IBD PATIENTS

Inflammatory Bowel Disease (IBD) is a chronic disorder characterized by a relapsing-remitting course, which alternates between active and quiescent states, ultimately impairing a patients' quality of life.The two main types of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). CD Shows a transmural granulomatous inflammation that can involve any segment of the intestine affecting all layers of the intestinal wall, while UC is limited to the mucosa and superficial submucosa of the colon. In physiological conditions the gut is costantly exposed to various antigens, commensal microflora and pathogens and the inflammatory response is finely balanced. Anyhow i some individuals with geneti…

Ten kilodalton heat shock protein (HSP10) is overexpressed during carcinogenesis of large bowel and uterine exocervix

In the present study, we evaluated the presence and the level of expression of HSP10 in two carcinogenetic models: the 'adenoma-carcinoma sequence' of large bowel and the 'dysplasia-carcinoma sequence' of uterine exocervix. We found HSP10 was overexpressed during the carcinogenesis of both organs. In particular, HSP10 was overexpressed early in large bowel carcinogenesis, while the expression of this protein in exocervical carcinogenesis gradually increased from normal through dysplastic to neoplastic tissues. The quantitative analysis of immunohistochemistry and the Western blotting confirmed these results. Our previous observations showed overexpression of HSP60 in the same carcinogenetic…

The Role of Molecular Chaperones in Virus Infection and Implications for Understanding and Treating COVID-19

The COVID-19 pandemic made imperative the search for means to end it, which requires a knowledge of the mechanisms underpinning the multiplication and spread of its cause, the coronavirus SARS-CoV-2. Many viruses use members of the hosts’ chaperoning system to infect the target cells, replicate, and spread, and here we present illustrative examples. Unfortunately, the role of chaperones in the SARS-CoV-2 cycle is still poorly understood. In this review, we examine the interactions of various coronaviruses during their infectious cycle with chaperones in search of information useful for future research on SARS-CoV-2. We also call attention to the possible role of molecular mimicry in the dev…

Biological aggressiveness evaluation in prostate carcinomas: immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear rel…

ATRIAL NATRIURETIC FACTOR,BUT NOT OXYTOCIN, PRESENCE IN ATHEROSCLEROTIC PLAQUES OF HUMAN COMMON CAROTID

Evaluation of neuropeptide Y expression during acetaldehyde withdrawal in rats. Focus on hippocampus and nucleus accumbens

Stress-related neuropeptides are involved in setting up alcohol addiction. Ethanol is able to acutely induce CRH and ACTH release, while cronically a dampered response of the hypothalamus -pituitary- adrenal (HPA) axis has been observed. Also neuropeptide Y (NPY) has been shown to modulate ethanol consumption, and its central expression seems inversely correlated to ethanol intake. Recent in vivo and in vitro evidence have highlighted the key role of acetaldehyde (ACD), ethanol first metabolite, as a mediator of the central effects of ethanol, even as modulator of the neuropeptidergic transmission in the rat brain. The aim of this study was to investigate NPY immunoreactivity following a 4-…

Distinctive patterns of Hsp60 levels and localization in human colon mucosa.

Lymphatic vessels of the dura mater: a new discovery?

Aspelund et al. discover the presence of a lymphatic vessel network in the dura mater of the mouse brain and show that these dural lymphatic vessels are important for the clearance of macromolecules from the brain.

Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit.

During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in…

Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 w…

Hsp60 and Hsp10 overexpression in metastatic colon cancer.

Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems

Aging entails progressive deterioration of molecules and supramolecular structures, including Hsp chaperones and their complexes, paralleled by functional decline. Recent research has changed our views on Hsp chaperones. They work inside and outside cells in many locations, alone or forming teams, interacting with cells, receptors, and molecules that are not chaperones, in roles that are not typically attributed to chaperones, such as protein folding. Hsp chaperones form a physiological system with a variety of functions and interactions with other systems, for example, the immune system. We propose that chaperone malfunctioning due to structural damage or gene dysregulation during aging ha…

Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in pat…

STANDARD PANCREATICODUODENECTOMY VERSUS PYLORUS-PRESERVING PANCREATICO-DUODENECTOMY

Molecular mimicry in the post-COVID-19 signs and symptoms of neurovegetative disorders?

Many individuals who have severe forms of COVID-19 experience a suite of neurovegetative signs and symptoms (eg, tachycardia) after their recovery, suggesting that the imbalance of the sympathetic-parasympathetic activity of the autonomic nervous system1 could continue for many weeks or months after respiratory symptoms stop. Moreover, a reduction of the parasympathetic tone could have a role in restricting the cholinergic anti-inflammatory pathway, thus favouring hyperinflammation and cytokine storm in the most severe phases of the disease. As reported by Guglielmo Lucchese in The Lancet Microbe,2 SARS-CoV-2 can damage the nervous system via an indirect mechanism, resulting in a high preva…

Is COVID-19 a proteiform disease inducing also molecular mimicry phenomena?

Chaperonopathies and chaperonotherapy. Hsp60 as therapeutic target in cancer: potential benefits and risks.

In this minireview we focus on Hsp60 as a target for anticancer therapy. We discuss the new concepts of chaperonopathies and chaperonotherapy and present information on Hsp60 localization in the cell membrane of human tumor cells. We describe novel mechanisms for Hsp60 reaching the extracellular environment that involve membrane-associated stages, as well as data on anti-Hsp60 antibodies found in human sera, both in normal subjects and patients affected by autoimmune diseases. Finally, we discuss possible therapeutic applications of anti-Hsp60 antibodies in cancer treatment, evaluating also side effects on non-tumor cells. In conclusion, the way for investigating Hsp60-targeted anti-tumor t…

Molecular chaperones expression levels and localization in non-tumoral and tumoral thyroid tissues

Papillary thyroid carcinoma (PTC) is the most frequently occurring subtype of thyroid cancer. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normality and pathology. Recent data indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment(1). Heat Shock Protein (HSPs) are often overexpressed during carcinogenesis and different studies shown that they can be released by tumors cells and that the mechanism of release is mediated by EXs pathway. In this project we performed an immunomorphological study to investigate Hsp60, 90,70,27 levels expression profile…

HSP60 expression during carcinogenesis: where is the pilot?

Carbon Nanotube-Reinforced Nanocomposites.

ANP and CD34 expression in human dilated cardiomiopathies: a new insight

Multiobjective optimisation in industrial design

Immunopositivity of heat shock protein 60 as a biomarker of bronchial carcinogenesis

Air Pollution: Role of Extracellular Vesicles-Derived Non-Coding RNAs in Environmental Stress Response

Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRN…

Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated wi…

Probiotics, prebiotics and symbiotics in inflammatory bowel diseases: state-of-the-art and new insights

Inflammatory bowel disease (IBD) consists of two distinct clinical forms, ulcerative colitis (UC) and Crohn's disease (CD), with unknown aetiology, which nevertheless are considered to share almost identical pathophysiological backgrounds. Up to date, a full coherent mechanistic explanation for IBD is still lacking, but people start to realize that the pathogenesis of IBD involves four fundamental components: the environment, gut microbiota, the immune system and the genome. As a consequence, IBD development might be due to an altered immune response and a disrupted mechanism of host tolerance to the non-pathogenic resident microbiota, leading to an elevated inflammatory response. Consideri…

CARCINOSARCOMA ARISING IN A DERMOID CYST OF OVARY: A CASE REPORT

BACKGROUND: Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated. CASE PRESENTATION: A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC). The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio. Positive staining for vimentin, alpha smooth muscle actin and CD10, as w…

Chlamydia trachomatis Infection and Anti-Hsp60 Immunity: The Two Sides of the Coin

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on detai…

ADULT STEM CELLS: THE REAL ROOT INTO THE EMBRYO?

During embryonic development, a pool of cells may become a reserve of undifferentiated cells, the embryo-stolen adult stem cells (ESASC). ESASC may be responsible for adult tissue homeostasis, as well as disease development. Transdifferentiation is a sort of reprogramming of ESASC from one germ layer-derived tissue towards another. Transdifferentiation has been described to take place from mesoderm to ectodermal- or endodermal-derived tissues and viceversa but not from ectodermal- to endodermal-derived tissues. We hypothesise that two different populations of ESASC could exist, the first ecto/mesoblast-committed and the second endo/mesoblast-committed. If confirmed, this hypothesis could le…

Hsp10 beyond mitochondria: novel locations predict as yet undescribed roles

A novel copper compound, CuNV110, induces apoptosis in tumor cells by dissociation of the Hsp60- pro-caspase 3 complex

The biological activity of CuNV1110, a novel copper chemical compound, has been recently studied on cancer cells and it has been showed that it reduces the cell viability, in a dose and time dependent manner, and induces cell apoptosis. In this study we evaluated the possible mechanisms by which CuNV1110 induces cell apoptosis. In particular we looked at its effects on Hsp60 levels and caspase 3 activation. We used an in vitro model of a pulmonary mucoepidermoid carcinoma (NCI-H292 cells). We found that CuNV1110 reduces the cell viability and induces cell apoptosis in a dose/time dependent manner. Then, we found that Hsp60 levels decrease with the increasing concentrations of CuNV110; by co…

Research of cardiomyocyte precursors in adult rat heart

Recent reports supported the existence of stem cells in adult hearts. However, phenotype and localization of these cells have not been completely described and it is unknown if cardiac regenerative potential differs from one subject to another. The aims of our work were to identify different populations of cardiac stem cells by the analysis of specific markers and to evaluate the expression variability of these markers in 12 adult rat hearts. The expression of CD9, taube nuss and nanog suggests the presence of stem cells from the earliest stages of embryogenesis in adult myocardium. Their different expression could be associated to the degree of stem cell differentiation. CD34 and c-Kit ant…

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…

Effects of interfacial adhesion between phases on the stiffness of carbon nanotube reinforced nanocomposite with polymer matrix

Does the orthodontic treatment induces dental pulp cellular death? Caspase-3 and-9, HSP60 and TUNEL expression

Objective: To evaluate the hypothesis of human dental pulp cell death during orthodontic treatement (O.T) and the degree of apoptosis through the expression level of the proteins Caspase-3,-9, TUNEL and HSP60. Materials and methods: Human dental Pulp were coming from both male and female patients (N=20; age 10-14years). The technique used was the Straight Wire, which involves Nickel-Titanium or Steel archwires. The increase of pressure applied on teeth was gradual. Some patients were subjected to a premolar extraction after 3 months treatment, and others after 6 months. Samples were Bouin-fixed, paraffin-embedded and afterwards processed for immunohistochemistry using anti-caspase-3,-9 anti…

Zebrafish as a Model for the Study of Chaperonopathies.

There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during developmen…

CD1a expression in primary breast cancer and lymph nodes: correlation with clinicopathological parameters.

The pathogenetic role of the chaperonin Hsp60 in chronic obstructive pulmonary disease: new data and perspectives

Trafficking and secretion patterns of Hsp60 in tumor cells.

SPECIAL ISSUE: The clinical relevance of exosomes in cancer

CuNV1110 induces dissociation of the Hsp60-pro-caspase 3 complex and activation of apoptosis in tumor cells

Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for differential diagnosis and points to a role in carcinogenesis

Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular ca…

Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein.

Abstract Background There is increasing evidence for the role of High Risk (HR) Human PapillomaVirus (HPV) in the pathogenesis of Oral Squamous Cell Carcinoma (OSCC). The E6 and E7 oncogenes from HR HPVs are responsible for the deregulation of p53 and pRB proteins involved in cell cycle and apoptotic pathways. In cell lines experiments, the HPV E7 protein seems to be able to enhance Hypoxia Inducible Factor-1 alpha (HIF-1α) activity, normally involved in the response to hypoxia and able to enhance angiogenesis. Results We studied tumor specimens from 62 OSCC; a higher prevalence of tumors in TNM stage II and also in pT2 class between OSCC infected positive HPV16 DNA than non-infected ones w…

Augmented Reality Gamification for Human Anatomy

This paper focuses on the use of Augmented Reality technologies in relation to the introduction of game design elements to support university medical students in their learning activities during a human anatomy laboratory. In particular, the solution we propose will provide educational contents visually connected to the physical organ, giving also the opportunity to handle a 3D physical model that is a perfect reproduction of a real human organ.

Defective apoptosis as potential mechanism in the tumorogenesis of myelolipoma

Apoptosis is considered an important mechanism of selective deletion that occurs during hematopoiesis. Myelolipoma is a rare benign tumor composed of adipose tissue and hematopoietic cells. The pathogenesis of this benign tumor is still unclear. Analysing the structural levels and apoptosis of normal human bone marrow (NHBM) and human myelolipoma (HM), the apoptotic events resulted abundantly present in NHBM compared to HM, which showed a small number of apoptotic cells. By contrast, Fas expression was strongly present both in NHBM and HM. These findings suggest that an altered function of Fas in myelolipoma is not able to trigger the apoptotic machinery. In conclusion, we hypothesize that …

EVALUATION OF HSP60, PROCASPASE-3 AND p53 EXPRESSION AFTER OXYDATIVE STRESS IN NCI-H292 CELLS

COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy!

The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community&amp;rsquo;s efforts, there is an increasing body of published studies describing the virus&amp;rsquo; biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death ha…

The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic Role of Anti-Chaperonin Immunity in Myasthenia Gravis.

Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this s…

Defective apoptosis and tumorigenesis: role of p53 mutation and Fas/FasL system dysregulation

The transcription factor p53 and the cytokine receptor FasL are two of the most famous regulators of cell life, and their alterations can cause a large number of pathologies, including cancer. In this review, we focused on how they can determine defective apoptosis, one of the causes of tumorigenesis and tumor progression. The importance of this knowledge lies in the new perspectives that gene therapy can offer to cure cancer.

Potential therapeutic effects of natural heme oxygenase-1 inducers in cardiovascular diseases.

Significance: Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of α-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defenses and modulate the cellular redox state. Such effects may have wide-ranging consequences for cellular growth and differentiation. Critical Issues: The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chem…

Nandrolone decanoate interferes on testosterone biosynthesis and alters blood-testis barrier.

Nandrolone decanoate (ND) is a synthetic testosterone analogue considered one of the most commonly abused anabolic androgenic steroids by adolescents and athletes. ND is alleged to promote an increase in muscle mass and improves both physical appearance and sporting performance, but ND abuse is often associated with serious adverse effects, interfering with the endocrine system and the reproductive system. In a previous study, we demonstrated that ND treatment of Leydig cells interferes with the biosynthesis of testosterone in a dose increase-dependent fashion (1). As a consequence of the results obtained in vitro, in this study an animal model was utilized to better understand the side eff…

Post-translational modifications of hsp60 and its extracellular release via exosomes are induced by the histone deacetylase inhibitor (HDACi) SAHA in the mucoepidermoid tumor H292 cells.

The chaperonin Hsp60 has multiple functions, among which that of supporting the growth of some type of tumours (1). HDACi (histone-deacetylase inhibitors) are drugs that regulate gene expression via modulation of epigenetic mechanisms, and induce tumor-cell death (2). Here, we show that in the tumor cells H292 the HDACi SAHA decreases the intracellular level of Hps60 and promotes its extracellular trafficking by exosomal vesicles. SAHA caused a time- and dose-dependent decrease in cell viability with a G/2M cell-cycle arrest at 24 h and cell death at 48 h. These effects were accompanied by production of reactive oxygen species and mitochondrial membrane-potential dissipation. The marked dec…

Extracellular vesicles in cancer pros and cons: The importance of the evidence-based medicine

In this paper we want to introduce a hot topic for clinical and translational research in oncology and all the related medical fields: the "exosomology", i.e., the science that looks at exosomes as nanovesicular tools for theranostics. Exosomes are extracellular vesicles (EVs) of nanometric sizes actively secreted by normal and, above all, tumor cells. Among the EVs, exosomes are surely the most investigated and with the most promising results, mainly for what concerns their potential as representing the future of the so-called "liquid biopsy". Unfortunately, the huge and increasing amount of data coming from preclinical studies was not followed by an adequate number of clinical investigati…

Heat Shock Protein 70 Serum Levels Differ Significantly in Patients with Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Members of the heat shock protein 70 (HSP70) family play an important role in assisting protein folding, preventing protein aggregation and transport of proteins across membranes under physiological conditions. Following environmental (i.e., irradiation, chemotherapy), physiological (i.e., cell growth, differentiation), and pathophysiological (i.e., inflammation, tumorigenesis) stress, the synthesis of heat shock proteins (HSPs) is highly up-regulated, whereas protein synthesis in general is reduced. In contrast to normal cells, many tumor entities including hepatocellular carcinoma (HCC) overexpress HSP70, the major-stress-inducible member of the HSP70 family, present it on their cell surf…

Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological Findings.

Background. The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods. This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these …

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the ba…

Modifications of the vasopressin and ANP in the rat hypothalamic supraoptic nucleus during and after the physical exercise.

Morphological features of the idiopathic dilated cardiomyopathy

Aumentare la sicurezza passiva

Inhibition of Hsp60 expression by doxorubicin and replicative senescence instauration in mucoepidermoid carcinoma cells

Human dental pulp cell apoptosis: immunohistochemical study after applying orthodontic traction.

The aim of this study was to compare human dental pulp stress and programmed cell death after 3 and 6 months of orthodontic treatments by assessing the degree of apoptosis and related proteins. Human dental pulps were collected from twenty young patients orthodontically treated by Straight Wire technique. Samples were fixed, paraffin-embedded and processed for histology and immunohistochemistry using anti-heat shock protein 60 kDa (Hsp60), -caspase 3, -caspase 9, and -PCNA antibodies, as well as TUNEL reactions. Moreover, we performed immunoprecipitation for Hsp60 and caspase 3, and for Hsp60 and caspase 9, from paraffin extracted tissues. Increased levels of both caspases and Hsp60 occurre…

CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome

Aims: CD1a is a molecule belonging to the highlyconserved group of CD1 proteins. Its expression indendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently,the development of a successful antitumour response.The aim was to investigate the presence of CD1a+ cellsin both primary tumours and lymph nodes (LN) ofa series of 35 invasive ductal carcinomas by bothimmunohistochemistry and reverse transcription-poly-merase chain reaction.Methods and results: CD1a antigen was more expressedin N0 than N1 breast cancer (P < 0.0001) in bothprimary lesions and LN metastases and correlatedpositively and significantly with oestrogen (ER) (P =0.0025) and…

Synchronous adenomatous polyps and colorectal carcinoma

The Chaperonopathies: Classification, Mechanisms, Structural Features

The classification of chaperonopathies is presented in this chapter. Like many other diseases, chaperonopathies can be genetic or acquired, primary or secondary, structural and/or functional, and qualitative and/or quantitative. In addition, considering pathogenic mechanism, chaperonopathies can be by defect, excess, or mistake. In the latter, a chaperone is normal but favors disease, a situation that occurs, for instance, in various types of cancers. Structural chaperonopathies are characterized by a change in the molecule of a chaperone due to mutation (genetic chaperonopathy) or due to aberrant post-translational modification (acquired chaperonopathy). In both cases, the impact of the st…

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms.Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed.The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pa…

The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90

Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s)…

Immunohistochemical and Biomolecular Identification of Orphanin FQ, eNOS, Atrial natriuretic Factor and Oxytocin in Rat Seminal Vesicles

In previous studies performed on rodents, we detected the presence of adreno-cholinergic and peptidergic innervation in seminal vesicles and other organs of the male genital system, such as prostate and ductus deferens, in which we also investigated the expression of NOS and NADPH-diaphorase. During the present project we focused our attention on the expression of some peptides involved in local control of smooth muscle relaxation, contractility, vasodilatation and control of blood flow in rat seminal vesicles. We investigated, through immunohistochemistry and RT-PCR, the presence of four peptides: orphanin, eNOS, ANF and oxytocin. Immunohistochemistry was used to detect the presence of the…

CD1a and antitumour immune response: expression of CD1a by metaplastic epithelial cells

Epithelial overexpression of Interleukin-8 in bronchial biopsies from patients with COPD

Virtual bronchoscopy in the pre-operative assessment of peripheral airway stenosis

An uncommon case of pneumothorax

The effects of oxidative stress on neoplastic cell survival.

Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems.

Aging entails progressive deterioration of molecules and supramolecular structures, including Hsp chaperones and their complexes, paralleled by functional decline. Recent research has changed our views on Hsp chaperones. They work inside and outside cells in many locations, alone or forming teams, interacting with cells, receptors, and molecules that are not chaperones, in roles that are not typically attributed to chaperones, such as protein folding. Hsp chaperones form a physiological system with a variety of functions and interactions with other systems, for example, the immune system. We propose that chaperone malfunctioning due to structural damage or gene dysregulation during aging ha…

A genetic algorithm for combined topology and shape optimisations

A method to find optimal topology and shape of structures is presented. With the first the optimal distribution of an assigned mass is found using an approach based on homogenisation theory, that seeks in which elements of a meshed domain it is present mass; with the second the discontinuous boundaries are smoothed. The problem of the optimal topology search has an ON/OFF nature and has suggested the employment of genetic algorithms. Thus in this paper a genetic algorithm has been developed, which uses as design variables, in the topology optimisation, the relative densities (with respect to effective material density) 0 or 1 of each element of the structure and, in the shape one, the coord…

Depleted uranium induces human carcinogenesis involving the immune and chaperoning systems: Realities and working hypotheses

Abstract Cancer is caused by a combination of factors, genetic, epigenetics and environmental. Among the latter, environmental pollutants absorbed by contact, inhalation, or ingestion are major proven or suspected culprits. Depleted uranium (DU) is one of them directly pertinent to the military and civilians working in militarized areas. It is considered a weak carcinogen but its implication in cancer development in exposed individuals is supported by various data. Since not all subjects exposed to DU develop cancer, it is likely that DU-dependent carcinogenesis requires cofactors, such as genetic predisposition and deficiencies of the chaperoning and immune systems. It is of the essence to…

Human Hsp60 with Its Mitochondrial Import Signal Occurs in Solution as Heptamers and Tetradecamers Remarkably Stable over a Wide Range of Concentrations

It has been established that Hsp60 can accumulate in the cytosol in various pathological conditions, including cancer and chronic inflammatory diseases. Part or all of the cytosolic Hsp60 could be naive, namely, bear the mitochondrial import signal (MIS), but neither the structure nor the in solution oligomeric organization of this cytosolic molecule has still been elucidated. Here we present a detailed study of the structure and self-organization of naive cytosolic Hsp60 in solution. Results were obtained by different biophysical methods (light and X ray scattering, single molecule spectroscopy and hydrodynamics) that all together allowed us to assay a wide range of concentrations of Hsp60…

L’implementazione del processo di redesign

Immunohistochemical expression of orphanin FQ, atrial natriuretic peptide and oxytocin in normal human seminal vesicles

Ethanol-Mediated Stress Promotes Autophagic Survival and Aggressiveness of Colon Cancer Cells via Activation of Nrf2/HO-1 Pathway

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetyl…

Heat Shock Protein in embryonic and adult submandibular salivary glands in healthy and tumorigenic tissues

Heat Shock Proteins (HSPs) role in development and function of human salivary glands have not yet been measured or mapped in detail, in particular, HSP60 role is unknown. They can be potential biomarkers for glandular diseases and malignancies. We present our initial findings on HSP10, HSP27, HSP60, HSP70 and HSP90 distribution in human submandibular salivary glands (SMG) at various stages of development and tumorigenesis.

Lack of Dystrophin Affects Bronchial Epithelium inmdxMice

Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower…

Prevention of TNBS-induced colitis by probiotic supplement in mice

Expression of Heat Shock Proteins Hsp10, Hsp27, Hsp60, Hsp70 and Hsp90 in urothelial carcinoma of urinary bladder

CD1A expression in Barrett’s oesophagus: new role for an old molecule against the metaplastic progression

FOCAL ACTIVE COLITIS AS A PREDICTOR OF INFLAMMATORY BOWEL DISEASE: RESULTS FROM A SINGLE-CENTER EXPERIENCE.

The term focal active colitis (FAC) is conventionally used to describe the presence of isolated cryptitis, characterized by an inflammatory infiltrate consisting of intraepithelial neutrophils and/or neutrophils invading the lumen of the criptae, with no other microscopic alteration of the colonic mucosa and, in particular, without the presence of signs of chronic inflammation. To date, only four studies, including one conducted in a pediatric population, have been performed to evaluate the clinical significance of this disease. The aim of this retrospective study on prospectively-collected data is to evaluate the clinical implications of the focal active colitis, since there still remains …

Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure.

Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 mic…

Spatial and temporal dynamics of innervation during the development of fetal human pancreas.

The delineation of pancreatic nerve innervations during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the…

Hsp60 response in experimental and human temporal lobe epilepsy due to hyppocampal sclerosis

Hsp60 is widely distributed in the brain, and its alteration has been involved in different neurological disorders. Epilepsy is considered one of the most common neurological disorders and typically involves the hippocampal formation. Compelling evidence describes a role of mitochondria, oxidative stress and both innate and adaptive immunity during epileptogenesis in temporal lobe epilepsy due to hyppocampal sclerosis (TLE-HS). Here, we investigate the Hsp60 involvement in experimental and human epilepsy. Firstly, expression and distribution of Hsp60 in epileptic hippocampi of a rat model of temporal lobe epilepsy (TLE), based on the phenomenon of maximal dentate gyrus activation (MDA), usi…

A new design approach to the use of composite materials for heavy transport vehicles

In order to keep or to reach a high level of competitiveness and performance of a product, it is necessary to explore all the possible solutions that allow the best compromise between costs and project requirements. By this point of view the study of alternative designs and/or materials to use, is an important aspect that can identify a new concept or way of thinking about a product. This paper presents how to make use of composite materials in the field of heavy vehicles transportation. A new semitrailer in composite material has been designed, using a methodical redesign approach and an optimisation process. The main innovation in this project is, besides the use of the Glass Fibre Reinfo…

CD1a immunopositivity could help to address prognosis of intestinal-type Barrett's metaplasia

Hsp60, a Novel Target for Antitumor Therapy: Structure-Function Features and Prospective Drugs Design

Heat shock protein 60 kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60's function, especially in prokaryotes, fundamental issues still remain unexplored, including the definition of its role in cancer. Key questions still unanswered pertain to the differences in structure-function features that might exist between the well-studied prokaryotic GroEL and the largely unexplored eukaryotic Hsp60 proteins. In this article we discuss these …

Association between COX-2 rs 6681231 genotype and interleukin-6 in periodontal connective tissue. A pilot study.

[Objectives] The aim of this pilot study was to investigate associations between IL-6 and COX-2 expression in gingival biopsies and both clinical diagnosis and genotypes in the IL-6 and COX-2 genes. [Design] A case-control study included 41 gingival biopsies obtained from Caucasian patients grouped according to clinical diagnosis of gingival health (n = 10), gingivitis (n = 15) or chronic periodontitis (n = 16). Immunohistochemistry analyses were performed to determine COX-2 expression in lamina propria, IL-6 expression in lamina propria and gingival epithelium and level of inflammatory cell infiltrate. Individual DNA was extracted and genotyped by real-time PCR for IL6 SNPs rs 2069827 and …

Poorly differentiated synovial sarcoma: A case report

Poorly differentiated synovial sarcoma is a rare soft tissue tumor. We studied a case arising in the pleural cavity of a young subject, characterised by the presence of spindle cell, small cell, and large epithelioid cell areas. We performed stains for mucosubstances and analysed the expression of cytokeratins 5/6, 7, 8, 18, 19, CEA, CD34, Ber-Ep4 and calretinin to characterize the phenotype of this neoplasm. We furthermore assessed immunohistochemically the presence of p53, Bcl-2, Bax and caspase 3, four apoptotic markers, to evaluate a relationship between apoptotic activity and the behaviour of this tumor. Our findings showed a strong presence of calretinin, p53 and Bcl-2 in all three ar…

CD1A expression in Barrett's oesophagus: new role for an old molecule against metaplastic progression

On the Choice of the Extracellular Vesicles for Therapeutic Purposes

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of diseas…

BENIGN GASTRIC POLYPS AND HELICOBACTER PYLORI

Effects of mild aerobic exercise training on the diaphragm in mdx mice

Mild endurance exercise training positively affects limb skeletal muscle in the mdx mice model of Duchenne Muscular Dystrophy (DMD). However, few and controversial data are available on the effects of mild exercise training on the diaphragm of mdx mice. The diaphragm was examined in mdx and wild type mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline and after 30 and 45 days of training (5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonin Hsp60 were measured at the same time points in gastrocnemius, quadriceps and diaphragm in each experimental group. A…

Chaperones: General Characteristics and Classifications

This chapter presents the classification of chaperones, their molecular properties among which that of forming functional complexes involving various molecules, and their distribution inside and outside the cell. The chaperone genes in the human genome are listed and briefly described, focusing on the small heat-shock proteins (sHsp), Hsp60, Hsp70, and Hsp90, and mentioning all others known. The chapter also introduces the concept of chaperoning system, i.e., the physiological system of an organism which is composed of all its chaperones, co-chaperones, and chaperone co-factors.

Evidence of Heavy Methylation in the Galectin 3 Promoter in Early Stages of Prostate Adenocarcinoma: Development and Validation of a Methylated Marker for Early Diagnosis of Prostate Cancer

Galectins, soluble intracellular and extracellular β-galactoside–binding proteins, are known to be involved in the progression and metastasis of various cancers, including prostate adenocarcinoma, but the detailed mechanism of their biological roles remains elusive. In the prostate cancer cell lines PC-3 and DU-145, galectin 3 (gal3) is present at normal levels, whereas in LNCaP, its expression is silenced. In LNCaP, the gal3 promoter was heavily methylated, whereas PC-3 or DU-145 cells showed negligible or no methylation in the gal3 promoter indicating a negative correlation between gal3 promoter methylation and its expression. On immunohistochemical analysis of normal and tumor prostate t…

Presence of ANP in internal carotid artery (ICA) with and without atherosclerotic lesions

Mutual antagonism between clock protein Period2 and hepatitis C virus replication in hepatocytes.

Background: Hepatitis C virus (HCV) infects approximately 3% of the world population and is the leading cause of liver disease, impacting hepatocyte metabolism, depending on virus genotype. Hepatic metabolic functions show rhythmic fluctuations with 24-h periodicity (circadian), driven by molecular clockworks ticking through translational-transcriptional feedback loops, operated by a set of genes, called clock genes, encoding circadian proteins. Disruption of biologic clocks is implicated in a variety of disorders including fatty liver disease, obesity and diabetes. The relation between HCV replication and the circadian clock is unknown. Methods: We investigated the relationship between HCV…

Three-dimensional computer models in a case of Azygos lobe discovered during adenocarcinoma surgery

The neurochaperonopathies: Anomalies of the chaperone system with pathogenic effects in neurodegenerative and neuromuscular disorders

The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic …

Study of axillary lymph node asymmetry in a female population

We analysed a large series of axillary lymph nodes, with and without metastases following radical mastectomy for breast cancer. We found left/right asymmetry in numbers of lymph nodes, and also asymmetry of lymph node dimensions, which could have been the caused by tumoral antigenic stimulation. The distribution of hyperplastic node patterns differed significantly.

Biological properties of extracellular vesicles and their physiological functions

The authors wish to thank Dr R Simpson and Dr D Taylor for critical reading of the manuscript and acknowledge the Horizon 2020 European Cooperation in Science and Technology programme and its support of our European Network on Microvesicles and Exosomes in Health & Disease (ME-HaD; BM1202 www.cost.eu/COST_Actions/bmbs/Actions/BM1202). In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive invest…

Hsp60 and Hsp10 increase in colon mucosa of Crohn's disease and ulcerative colitis.

The purpose of this work was to determine in colon mucosa of Crohn’s disease (CD) and ulcerative colitis (UC) in relapse: a) the levels of the chaperonins Hsp60 and Hsp10; b) the quantity of inflammatory cells; and c) if the levels of chaperonins parallel those of inflammation cells. Twenty cases of CD and UC and twenty normal controls (NC) were studied using immunohistochemistry, Western blotting and immunofluorescence. Immunohistochemically, Hsp60 and Hsp10 were increased in both inflammatory bowel diseases (IBD) compared to NC. These results were confirmed by Western blotting. Hsp60 and Hsp10 occurred in the cytoplasm of epithelial cells in CD and UC but not in NC. Hsp60 and Hsp10 co-loc…

Un nuovo strumento per lo studio dei risultati di analisi FEM

Quantitative analysis of the impact of a human pathogenic mutation on the CCT5 chaperonin subunit using a proxy archaeal ortholog

The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions. This study quantifies the loss of structural stability in the hexadecamer due to the pathogenic mutation, using differential scanning calorim…

Hsp60 Friend and Foe of the Nervous System

Hsp60 belongs to the subgroup of molecular chaperones named chaperonins and, typically, resides and functions in the mitochondria but it is also present in extramitochondrial sites. It chaperones client peptides as they fold to achieve the native conformation and also displays anti-stress roles by helping stress-damaged proteins regain a functional shape. Thus, Hsp60 is central to the integrity and functionality of mitochondria and energy production. All cells in the nervous system depend on Hsp60 so when the chaperonin malfunctions the consequences on nervous tissues are usually devastating, causing diverse diseases. These are the Hsp60 chaperonopathies, which can be genetic or acquired wi…

TERAPIA INFILTRATIVA INTRA-ARTICOLARE ASSOCIATA A MESALAZINA E PROBIOTICI NEL TRATTAMENTO DELL'ARTRITE NEL PAZIENTE CON MALATTIA INFIAMMATORIA CRONICA INTESTINALE (IBD)

L'artrite secondaria a malattia infiammatoria cronica intestinale può essere presente parecchi anni prima della diagnosi oppure manifestarsi come una vera complicanza.

Muscle Histopathological Abnormalities in a Patient With a CCT5 Mutation Predicted to Affect the Apical Domain of the Chaperonin Subunit.

Recognition of diseases associated with mutations of the chaperone system genes, e.g., chaperonopathies, is on the rise. Hereditary and clinical aspects are established, but the impact of the mutation on the chaperone molecule and the mechanisms underpinning the tissue abnormalities are not. Here, histological features of skeletal muscle from a patient with a severe, early onset, distal motor neuropathy, carrying a mutation on the CCT5 subunit (MUT) were examined in comparison with normal muscle (CTR). The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. CCT5 was diversely present in the sarcolem…

MacroH2A1 isoforms as markers of steatosis and hepatolcellular carcinoma

Expression of CD1a by Barrett’s metaplasia epithelial cells.

Zebrafish as a Model for the Study of Chaperonopathies

There is considerable information on the clinical manifestations and mode of inheritance for many genetic chaperonopathies but little is known on the molecular mechanisms underlying the cell and tissue abnormalities that characterize them. This scarcity of knowledge is mostly due to the lack of appropriate animal models that mimic closely the human molecular, cellular, and histological characteristics. In this article we introduce zebrafish as a suitable model to study molecular and cellular mechanisms pertaining to human chaperonopathies. Genetic chaperonopathies manifest themselves from very early in life so it is necessary to examine the impact of mutant chaperone genes during developmen…

Hsp60 from cancer cells can reach near and distant targets: A proposal for a multistage pathway

Cancer cells have means to influence other cells in their vicinity and distant, and in this signal-delivering mechanisms the chaperonin Hsp60 plays a role, which is currently being recognized as potentially crucial for the growth and dissemination of at least certain types of tumors. In order to arrive at its destination, Hsp60, a typical resident of mitochondria in normal and tumor cells, leaves the organelle and reaches the blood. In the latter, Hsp60 can travel and arrive at targets situated far away from its origin. The details of the route followed by Hsp60 and their molecular mechanisms have not yet been fully elucidated. We investigated Hsp60 levels and secretion in normal and tumor …

Sex-based differences after a single bout of exercise on PGC1α isoforms in skeletal muscle: A pilot study

To date, there are limited and incomplete data on possible sex-based differences in fiber-types of skeletal muscle and their response to physical exercise. Adult healthy male and female mice completed a single bout of endurance exercise to examine the sex-based differences of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), heat shock protein 60 (Hsp60), interleukin 6 (IL-6) expression, as well as the Myosin Heavy Chain (MHC) fiber-type distribution in soleus and extensor digitorum longus (EDL) muscles. Our results showed for the first time that in male soleus, a muscle rich of type IIa fibers, endurance exercise activates specifically genes involved in mito…

DISPOSITIVO PARAINCASTRO POSTERIORE AD ELEVATO ASSORBIMENTO ENERGETICO

European Week of Sport: innovative initiative of European Commission that inspires children to be active

BAC KGROU ND: Estimates indicate that more than one third of European adults are inactive, despite the known benefits of physical activity. In 2015 the European Commission launched the European Week of Sport (EWoS), to encourage people to engage in sport and physical activity. The aim of this study was to evaluate if participation in the EWoS could motivate children to participate in physical activity in future. METHOD S: A total of 10,892 children (aged 6-14), from 6 EU cities (Palermo, Italy; Ankara, Turkey; Lousada, Portugal; Gardabaer, Iceland; Rijeka, Croatia; Albacete, Spain), were enrolled in sport activities (running sport event, extra hours of physical activity, seminars on physica…

Structural and Dynamic Disturbances Revealed by Molecular Dynamics Simulations Predict the Impact on Function of CCT5 Chaperonin Mutations Associated with Rare Severe Distal Neuropathies

Mutations in genes encoding molecular chaperones, for instance the genes encoding the subunits of the chaperonin CCT (chaperonin containing TCP-1, also known as TRiC), are associated with rare neurodegenerative disorders. Using a classical molecular dynamics approach, we investigated the occurrence of conformational changes and differences in physicochemical properties of the CCT5 mutations His147Arg and Leu224Val associated with a sensory and a motor distal neuropathy, respectively. The apical domain of both variants was substantially but differently affected by the mutations, although these were in other domains. The distribution of hydrogen bonds and electrostatic potentials on the surfa…

Two isoelectric variants of HSP10 are down-regulated by cigarette smoke exposure in airway cells: A Proteomic study

Cigarette smoke exposure affects expression and extracellular activity levels of gelatinase A and B in airway epithelial cells

The complex interplay between vitamin D deficiency and diabetes

It has been recently highlighted the link between vitamin D and metabolic and immunological pro- cesses, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and through the activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. In this setting, vita- min D has also been reported to influence glucose regulation via effects on insulin secretion and action. Vitamin D deficiency is strongly associated with obesity mostly due to the storage of vitamin D in adipose tissue because of its lipophilic properties. The dec…

Editorial Commentary on “The role of periodontal microorganisms in the pathogenesis of myocardial infarction. From PCR techniques to microbiome sequencing”

Extracellular Vesicles as Shuttles of Tumor Biomarkers and Anti-Tumor Drugs

Extracellular vesicles (EV) include vesicles released by either normal or tumor cells. EV may exceed the nanometric scale (microvesicles), or to be within the nanoscale, also called exosomes. Thus, it appears that only exosomes and larger vesicles may have the size for potential applications in nanomedicine, in either disease diagnosis or therapy. This is of particular interest for research in cancer, also because the vast majority of existing data on EV are coming from pre-clinical and clinical oncology. We know that the microenvironmental features of cancer may favor cell-to-cell paracrine communication through EV, but EV have been purified, characterized, and quantified from plasma of tu…

Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers

The presence of multipotent cells in several adult and embryo-related tissues opened new paths for their use in regenerative medicine. Extraembryonic tissues such as umbilical cord are considered a promising source of stem cells, potentially useful in therapy. The characterization of cells from the umbilical cord matrix (Wharton''s Jelly) and amniotic membrane revealed the presence of a population of mesenchymal-like cells, sharing a set of core-markers expressed by "mesenchymal stem cells". Several reports enlightened the differentiation capabilities of these cells, even if at times the lack of an extensive characterization of surface markers and immune co-stimulators expression revealed h…

Multiwalled carbon nanotube reinforced polymer composites

Due to their high stiffness and strength, as well as their electrical conductivity, carbon nanotubes are under intense investigation as fillers in polymer matrix composites. The nature of the carbon nanotube/polymer bonding and the curvature of the carbon nanotubes within the polymer have arisen as particular factors in the efficacy of the carbon nanotubes to actually provide any enhanced stiffness or strength to the composite. Here the effects of carbon nanotube curvature and interface interaction with the matrix on the composite stiffness are investigated using micromechanical analysis. In particular, the effects of poor bonding and thus poor shear lag load transfer to the carbon nanotube…

Atrial natriuretic peptide and CD34 overexpression in human idiopathic dilated cardiomyopathies.

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause characterized by ventricular chamber enlargement with impaired contractile function. In familial forms of IDCM, mutations of genes coding for cytoskeletal proteins related to force transmission, such as dystrophin, cardiac actin, desmin, and delta-sarcoglycan, have been identified. Here, we report the data of a retrospective investigation carried out to evaluate the expression of atrial natriuretic peptide (ANP), CD34, troponin T and nestin in the myocardium of patients affected with IDCM. Formalin-fixed and paraffin-embedded consecutive tissue sections from the ventricular wall of 10 human normal hear…

Three-dimensional computer models in a case of azygos lobe discovered durino adenocarcinoma surgery.

Three-dimensional geometrical models of the inguinal region. Towards a new stereology.

In this work we studied the inguinal-abdominal region and the inguinal canal using three-dimensional geometrical models. We built the models through computer aided geometric modeling techniques on the basis of observations during real dissections, operations and diagnostic medical imaging. The obtained models show in a complete modular synthesis and with a schematic iconology the structural organization of the anatomical districts in a logic sequence of layers and topographic and spatial relationships among its components. The models represent an amazing support to anatomy and clinical anatomy for teaching and research purposes on organogenesis, surgery and diagnosis.

MOESM3 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 3. Figure S2. Increased glucose clearance because of enhanced insulin sensitivity in the muscle, liver and adipose tissue. Mice fed a chow diet were injected with insulin (INS, 0.75 U kg − 1) 15 min before being killed, after which phosphorylation status of AKT (Ser473) was determined by western blot. Representative immunoblots are shown in the skeletal muscle, liver and adipose tissue. Immunoblots were quantified by densitometry and normalized against total protein levels of AKT. *P

60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis

The aim of the present study was to evaluate the expression of the heat shock protein 60 (HSP60), a mitochondrial matrix-associated protein belonging to the chaperonin family, in colorectal adenomas and cancers, comparing them to normal colonic tissues and hyperplastic polyps. We performed both immunohistochemistry and Western blot analysis for HSP60. Immunohistochemistry resulted positive in all tubular adenomas and infiltrating adenocarcinomas. By contrast, normal tissues and hyperplastic polyps were negative. Quantitative analysis showed that tubular adenomas with different levels of dysplasia did not present statistical differences concerning HSP60 positivity. In addition, carcinomas al…

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. METHODS: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and sp…

ANP immunolocalization in internal carotid artery wall of subjects with and without atherosclerotic lesions

C-12 Clinical And anatomical features of facial nerve in the surgery of parotid gland: our recent experience.

From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview

The microbiome research field has rapidly evolved over the last few decades, becoming a major topic of scientific and public interest. The gut microbiota (GM) is the microbial population living in the gut. The GM has many functions, such as maintaining gut homeostasis and host health, providing defense against enteric pathogens, and involvement in immune system development. Several studies have shown that GM is implicated in dysbiosis and is presumed to contribute to neurodegeneration. This review focuses mainly on describing the connection between the intestinal microbiome alterations (dysbiosis) and the onset of neurodegenerative diseases to explore the mechanisms that link the GM to nerv…

DNA sequence and comparative analysis of homologous HSP60 genes of Chlamydia trachomatis serovar D and Homo Sapiens

DATA FITTING WITH NURBS SURFACES BY A REAL-CODED GENETIC ALGORITHM

Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery

BACKGROUND: Heat shock protein 60 (Hsp60) is a chaperonin involved in tumorigenesis, but its participation in tumor development and progression is not well understood and its value as a tumor biomarker has not been fully elucidated. In the current study, the authors presented evidence supporting the theory that Hsp60 has potential as a biomarker as well as a therapeutic target in patients with large bowel cancer. METHODS: The authors studied a population of 97 subjects, including patients and controls. Immunomorphology, Western blot analysis, and quantitative real-time polymerase chain reaction were performed on tissue specimens. Exosomes were isolated from blood and characterized by electr…

Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

Abstract The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography–mass spectrometry. Western blot analysis and quantitative real‐time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression leve…

ANP and CD34 Expression in Human Dilated Cardiomiophaties: a new insight.

Role of Adrenomedullin in LSP-mediated lung injury

Distribution of mitochondrial chaperonins in lung cells

Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?

Abstract Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources …

AMYLOIDOSIS AND INFLAMMATORY BOWEL DISEASE: FACT OR MITH?

Inflammatory Bowel Disease (IBD), which includes both Crohn's Disease (CD) and Ulcerative Colitis (UC), is a chronic idiopathic inflammatory disorder affecting the gastrointestinal tract. Extraintestinal manifestations (EIM) are common in patients with IBD, and occur in 6-47% of patients with CD or UC. EIM can involve organs other than the gastrointestinal tract such as skin, eyes, joints, biliary tract and kidneis. Renal and urinary involvement particularly occurs in 4-23% of patients with IBD. Among the renal complications of IBD, seconfary amyloidosis (AA-type, AAA) is a rare but serious complication. renal amyloidosis has been proven to be the most common lethal manifestation of IBD-ass…

Pro-and anti-fibrotic molecule balance in the bronchial mucosa of stable COPD patients

Background: The mechanisms of inducing fibrotic events and remodeling in the airways of COPD are incompletely studied. Objectives: To investigate the expression of cytokines involved in the pro- and anti-fibrotic events in stable COPD. Methods: Expression of CTGF, TGFβ1-2-3, TGFβRI, TGFβRII, LTBP-1, TRAP-1, BAMBI, PP2Cα, Smad2-3-6-7, pSmad2, pSmad3, pro-collagen-I and collagen-I was measured in the bronchial mucosa using immunohistochemistry and RT-qPCR. Results: TGFβ1 was increased in the epithelium and TGFβ3 in the submucosa of healthy smokers and mild/moderate COPD compared to healthy non-smokers. In all smokers and patients with COPD TGFβ3+ cells in the submucosa correlated significantl…

Hsp60 in Skeletal Muscle Fiber Biogenesis and Homeostasis: From Physical Exercise to Skeletal Muscle Pathology

Hsp60 is a molecular chaperone classically described as a mitochondrial protein with multiple roles in health and disease, participating to the maintenance of protein homeostasis. It is well known that skeletal muscle is a complex tissue, rich in proteins, that is, subjected to continuous rearrangements, and this homeostasis is affected by many different types of stimuli and stresses. The regular exercise induces specific histological and biochemical adaptations in skeletal muscle fibers, such as hypertrophy and an increase of mitochondria activity and oxidative capacity. The current literature is lacking in information regarding Hsp60 involvement in skeletal muscle fiber biogenesis and reg…

Molecular chaperones and mirnas in epilepsy: Pathogenic implications and therapeutic prospects

Epilepsy is a pathologic condition with high prevalence and devastating consequences for the patient and its entourage. Means for accurate diagnosis of type, patient monitoring for predicting seizures and follow up, and efficacious treatment are desperately needed. To improve this adverse outcome, miRNAs and the chaperone system (CS) are promising targets to understand pathogenic mechanisms and for developing theranostics applications. miRNAs implicated in conditions known or suspected to favor seizures such as neuroinflammation, to promote epileptic tolerance and neuronal survival, to regulate seizures, and others showing variations in expression levels related to seizures are promising ca…

Curcumin-Like Compounds as Neuroprotective Agents: Interactions with HSP60 and Amyloid Beta Peptide

Alzheimer’s Disease (AD) represents a fundamental challenge for public health in the 21st century. Current AD therapies largely focus on symptomatic aspects of the clinical pathology, but they have yet to demonstrate any major impact on the disease progression [1]. The most important role of the research aimed at fighting the AD is the development of neuro-protective agents, able to interfere with the protein aggregation process whose clinical signature is represented by the plaques deposition. An important role in AD’s framework could be played by Heat shock proteins (HSPs), highly regulated proteins that mediate the proteins proper folding and promote recovery of their native conformation…

HSP60 and HSP10 as diagnostic and prognostic tools in the management of exocervical carcinoma [3]

HSP60 activity on human bronchial epithelial cells

HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1–4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (…

Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia.

Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome&mdash;a conditioned medium released by heat shock protein 60 (Hsp60)&mdash;overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an Hsp60-overexpressing plasmid. The secretion is used to treat na&iuml;ve C2C12 cell lines. Physiactisome activates the expression of PGC-1&alpha; isoform 1, which is di…

Exosomal HSP60 levels and related miRNAs in brain tumors

In cancer, Extracellular Vesicles (EVs), such as exosomes, contribute to tumor progression by regulating local and systemic parameters. Since exosomes are released into body fluids, they may be used in nanomedicine as a valuable source of diagnostic biomarkers. The prognosis of brain tumors is poor even after surgical resection followed by post-operatory chemo- and radio-therapies and it is cogent to find innovative treatments. The discovery that molecular chaperones can be determinant factors in tumorigenesis and the increasing understanding of exosomes, particularly in what refers to their release by tumor cells and contents, including chaperones and miRNA, provide elements to develop nov…

Hsp60 expression in skeletal muscle increase after endurance training

Downregulation of IL-27 bronchial epithelial expression by heat-shock protein-60

Background Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved Molecular chaperone. Hsp60 plays an important role in protein folding, inflammation, and tissue repair. We previously reported increased levels of HSP60 in COPD patients, suggesting a role for HSP60 in the inflammatory response in COPD. This study is aimed to evaluate the HSP60 immunomodulatory activity and Th1/Tc1 cytokines (IL-27/INFγ) production in Human Bronchial Epithelial cells line (16HBE). Methods 16HBE were plated in 6 wells plate with Dulbecco’s modified Minimum Essential Medium (DMEM) and exposed to various concentrations of HSP60 protein (1 ng/mL, 100 ng/mL and 1 µg/mL) for 8 and 24 hours. Induction of H…

Assessment of the interaction of Portland cement-based materials with blood and tissue fluids using an animal model

Portland cement used in the construction industry improves its properties when wet. Since most dental materials are used in a moist environment, Portland cement has been developed for use in dentistry. The first generation material is mineral trioxide aggregate (MTA), used in surgical procedures, thus in contact with blood. The aim of this study was to compare the setting of MTA in vitro and in vivo in contact with blood by subcutaneous implantation in rats. The tissue reaction to the material was also investigated. ProRoot MTA (Dentsply) was implanted in the subcutaneous tissues of Sprague-Dawley rats in opposite flanks and left in situ for 3 months. Furthermore the material was also store…

Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance

Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possi…

No effect of low-intensity endurance exercise on muscle necrosis in the diaphragm of mdx mice.

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle weakness. We have previously shown that low-intensity endurance training prevented muscle damage (Frinchi et al, Int J Sports Med 2014). Since the effects of low-intensity endurance training on the the diaphragm in the mdx mouse model are unknown, in the same animals we investigated C x39 protein levels (Western blotting) in homogenates of the diaphragm before and after training. Mdx and wild-type (WT) mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 days/week for 6 weeks at progres…

STUDIO DELLE PROPRIETÀ MECCANICHE ED ELETTRONICHE DI NANOTUBI IN CARBONIO E DI MATERIALI COMPOSITI DERIVABILI MEDIANTE UN NUOVO APPROCCIO NUMERICO MISTO ELEMENTI FINITI – TIGHT BINDING

Perinatal and Wharton's jelly-derived mesenchymal stem cells in cartilage regenerative medicine and tissue engineering strategies

Stem cells can be found in embryonic and extraembryonic tissues as well as in adult organs. In particular, research in the last few years has delineated the key features of perinatal stem cells derived from fetus-associated tissues. These cells show multiple differentiation potential, can be easily expanded ex vivo, and raise no ethical concerns as regards their use. Several reports indicate that cells isolated from Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells that express markers shared by other mesenchymal stem cells (MSC) and give rise to different mature cell types belonging to all three germ layers. Moreover, WJ-MSC display…

Effect of conjugated linoleic acid on testosterone synthesis

HSP60 and HSP10 overexpression in metastastic colon cancer

The histone deacetylase inhibitor SAHA induces HSP60 nitration and its extracellular release by exosomal vesicles in human lung-derived carcinoma cells

// Claudia Campanella 1, 2, * , Antonella D'Anneo 3, * , Antonella Marino Gammazza 1, 2, * , Celeste Caruso Bavisotto 1, 2 , Rosario Barone 1, 2 , Sonia Emanuele 4 , Filippa Lo Cascio 1 , Emanuele Mocciaro 1 , Stefano Fais 5 , Everly Conway De Macario 6 , Alberto J.L. Macario 2, 6 , Francesco Cappello 1, 2 , Marianna Lauricella 4 1 Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy “Emerico Luna”, University of Palermo, Palermo, Italy 2 Euro-Mediterranean Institute of Science and Technology, Palermo, Italy 3 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, Palermo, Ita…

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence.

Hsp60 is a pro-carcinogenic chaperonin in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not known whether or not doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of this protein. We used the human lung mucoepidermoid cell line NCI-H292 and different doses of doxorubicin to measure cell viability, cell cycle progression, cell senescence indicators, Hsp60 levels and its post-translational modifications as well as the release of the chaperonin into the extracellular environment. Cell viability was reduced in relation to doxorubicin dose and this was paralleled by the appearance of cell senescence markers. Con…

A novel isolation technique and extended characte-rization of mesenchymal stem cells from human umbilical cord matrix: disclosing new potentials for regenerative medicine applications.

The Post-Lockdown Era: What Is Next in Italy?

The current outbreak of the COVID-19 infection, which started in December 2019 in Wuhan (China), was declared a pandemic by the World Health Organization (WHO) on the 11th of March, 2020.

MOESM6 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 6. Figure S5. Representative images of liver (left panels) and heart (right panels) sections immunostained for macroH2A1.1 or for macroH2A1.2 (green). Both isoforms appear to be highly expressed in hepatocytes, whereas there a strong reduction in expression pattern of macroH2A1.2 is observed in mouse heart tissue. Nuclei were counterstained with DAPI.

Simulation of the Stress–strain Behavior of Single and Multiwall Carbon Nanotubes-reinforced Polymer Composites

Oxidative stress induces myeloperoxidase expression by HUVEC and chronic heart failure endocardial endothelial cells. Active contribution of endothelium to an inflammatory heart disease.

The molecular anatomy of human Hsp60 and its effects on Amyloid-β peptide

Heat Shock Protein 60 (HSP60) is ubiquitous and highly conserved, being present in eukaryotes and prokaryotes, including pathogens. This chaperonin is typically considered a mitochondrial protein but it is also found in other intracellular sites, extracellularly and in circulation. HSP60 is an indispensable component of the Chaperoning System and plays a key role in protein quality control, preventing off-pathway folding events and refolding misfolded proteins. This makes HSP60 a putative therapeutic agent for neurodegenerative diseases associated with aggregation of misfolded proteins, for example, Alzheimer’s Disease. We produced and purified recombinant human HSP60 and investigated the e…

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study

Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naive) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins …

Role of videoassisted thoracoscopy procedure in the diagnosis and treatment of malignant pleural mesothelioma

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Kast, Richard E. et al.

SARS-CoV-2 in patients with cancer: possible role of mimicry of human molecules by viral proteins and the resulting anti-cancer immunity

AbstractA few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against t…

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells.

The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial&#8722;mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of…

A continuum damage model to simulate failure in composite plates under uniaxial compression

Experimental investigations and numerical simulations are performed in order to numerically predict the buckling behaviour of thin composite laminated specimens. Experiments are aimed at two objectives: the first is to completely characterize the carbon/epoxy material under simple loading configurations, the second is to test this material in buckling and post-buckling situations. The data collected with the first campaign of experiments are used to obtain the strength parameters required to define a damage model based on the failure theory by Tsai-Wu. This model is implemented in a Finite Element (FE) code and numerical simulations of buckling are executed for unidirectional and cross-ply …

Contrast-enhanced versus baseline ultrasonography in the characterization of benign focal lesions.

Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection: effect of ACE-2 expression on tumor cells or molecular mimicry phenomena? Two not mutually exclusive hypotheses

Experimental study of peripheral nerve rigeneration

Lactobacillus casei and Bifidobacterium lactis supplementation reduces tissue damage of intestinal mucosa and liver after 2,4,6-trinitrobenzenesulfonic acid treatment in mice

Probiotics (PB) are living microorganisms that act as a commensal population in normal intestines and confer numerous beneficial effects on the host. The introduction of probiotics in the treatment of inflammatory bowel disease (IBD) prolongs remission. The aim of this study was to investigate the intestinal and hepatic effects of PB supplementation in an experimental IBD model in mice induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the first step of the experimental procedure, CD-1 male mice, 5 to 6 weeks old, were randomly divided into 3 groups and inoculated intrarectally with, respectively, saline, alcohol, or TNBS to assess the experimental IBD model. In the second step, mice…

Is CD1a involved in antitumour immune responses during carcinogenesis?

Sir, I read with interest the article of Coventry and Morton (2003) that investigated DC infiltration within breast cancers and the association with survival. Interestingly, they found that more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, but this failed to reach statistical significance at the P=0.05 level. In our opinion, the role of CD1 family molecules in antitumour immune responses, and in particular of CD1a, should be more debated, since its expression was recently described not only in monocyte-derived dendritic cells, but also in nonmesenchymal cytotypes, that is, epithelial cells (Ulanova et al, 2000). We recen…

MOESM4 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 4. Figure S3. MacroH2A1.1 and macroH2A1.2 expression in 3T3-L1 pre-adipocytes and adipocytes. 3T3-L1 pre-adipocytes with lentiviral-mediates stable expression of GFP, macroH2A1.1-GFP and macroH2A1.2-GFP were induced to differentiate into mature adipocytes as in Fig. 6. At the 1st, 5th and 15th day of differentiation, histones were extracted and processed for immunoblotting with anti-macroH2A1.1, macroH2A1.2 and anti-H3-specific antibodies. Representative blots are shown, together with MW ladder.

In vitro and in vivo detection of end-products of MPO-driven oxidative and nitrosative stress in human endocardial endothelial cells from patients affected by chronic heart failure

Virtual broncoscopy in the preoperative assessment of airways stenosis

Heat shock proteins and ulcerative colitis: The start of a new era?

Effects of Conjugated Linoleic Acid Associated With Endurance Exercise on Muscle Fibres and Peroxisome Proliferator-Activated Receptor γ Coactivator 1 α Isoforms

Conjugated linoleic acid (CLA) has been reported to improve muscle hypertrophy, steroidogenesis, physical activity, and endurance capacity in mice, although the molecular mechanisms of its actions are not completely understood. The aim of the present study was to identify whether CLA alters the expression of any of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) isoforms, and to evaluate the possible existence of fibre-type-specific hypertrophy in the gastrocnemius and plantaris muscles. Mice were randomly assigned to one of four groups: placebo sedentary, CLA sedentary, placebo trained, or CLA trained. The CLA groups were gavaged with 35 μl per day of Tonalin® FFA 8…

EUROMEDITERRANEAN BIOMEDICAL JOURNAL: THE RENEWED MANUSCRIPT LAYOUT AND WEB RENDERING FORESHADOW FURTHER JOURNAL IMPROVEMENT

In January 2006, a new journal, Capsula Eburnea, was born into the Italian scientific publishing scene with the initial goal of creating, at the same time, “an open scientific forum and a blog”, based on the premise that “in medicine, nothing should be considered stable, immutable or unsusceptible to critical review at any time, by any scientist”. The Editorial Team progressively sought to improve the quality of the manuscripts published, introducing the requirement for all articles to be written in English, and changed the Journal’s name to EuroMediterranean Biomedical Journal in 2012. Over the last five years, approximately 125 articles by young doctors (including original articles, revie…

Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer

Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlatio…

Effects of chromogranin a-derived peptides on hsp90 expression in co-cultures of adult rat cardiac myocytes and fibroblasts

Probiotics Can Cure Oral Aphthous-Like Ulcers in Inflammatory Bowel Disease Patients: A Review of the Literature and a Working Hypothesis

Dysbiosis has been associated with the onset of several chronic autoimmune or inflammatory pathologies (e.g., inflammatory bowel diseases—IBD), because of its primary role in the establishment of a chronic inflammatory process leading to tissue damage. Inflammatory bowel diseases can even involve areas far away from the gut, such as the extraintestinal manifestations involving the oral cavity with the onset of aphthous-like ulcers (ALU). Studies carried out on animal models have shown that intestinal dysbiosis may be related to the development of autoimmune diseases, even if the mechanisms involved are not yet well known. The aim of this paper is to verify the hypothesis that in inflammator…

Immunopositivity for histone macroH2A1 isoforms marks steatosisassociated hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to ou…

Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells.

The concept of a stem cell subpopulation as understood from normal epithelial tissue or bone marrow function has been extended to our understanding of cancer tissue and is now the target of treatment efforts specifically directed to this subpopulation. In glioblastoma, as well as in other cancers, increased expression of aldehyde dehydrogenase (ALDH) has been found localized within a minority sub-population of tumor cells which demonstrate stem cell properties. A separate body of research associated increased expression of heat-shock protein-90 (HSP90) with stem cell attributes. We present here results from our initial immunohistochemistry study of human glioblastoma biopsy tissue where bot…

Role of immunohistochemical expression of PCNA and p53 in prostate carcinoma

Circulating exosomal Hsp60 as a new marker of colon cancer.

Hsp60 and Hsp10 in Ageing

HSP and molecular chaperones, both referred to in this chapter as chaperones, are key players in development and senescence. With regard to senescence, several issues are critical: the role of normal chaperones in the process of ageing itself and in preventing and controlling age-associated diseases, the role of defective chaperones (chaperonopathies) in the onset and progression of senescence and in the etiology of old-age diseases, the interaction of chaperones with the immune system, and the potential of chaperones as therapeutic agents for counteracting the deleterious effects of ageing on molecules and cells and for treating proteinopathies of the elderly (chaperonotherapy). All these …

BRAF(V600E) mutation influences hypoxia-inducible factor-1alpha expression levels in papillary thyroid cancer

Abstract Hypoxia-inducible factor-1alpha is found frequently overexpressed in solid tumors cells, exerting an important role in angiogenesis, glucose metabolism, cell proliferation, survival and invasion. In thyroid carcinomas, hypoxia-inducible factor-1alpha expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1alpha induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1alpha synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously s…

CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma.

CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study…

3D buckling analysis of multidelaminated composite specimens

The behaviour of thin composite laminates (unidirectional, cross-ply and angle-ply) under compressive loads has been examined in cases where multiple delaminations are present. The problem is solved using the Finite Element Method (FEM) both with linear analyses, based on the eigenvalues research problem, and with nonlinear analyses, based on incremental-iterative procedures. In particular, the role of the delamination length, of the angle of the plies and of the stacking sequence on the critical load is investigated. Results are compared with those found in literature derived from experimental or numerical 2D analyses.

Abdominal aortic aneurysm wall rupture risk evaluation through computerized element analysis model and fuzzy-tosis decision method.

Thermo-Elasto-Hydrodynamic Analysis of a Crankshaft Journal Bearing

This paper summarizes the essential parts of a numerical analysis activity in which the application of the Thermo-Elasto-Hydro-Dynamic (TEHD) lubrication theory to a crankshaft journal bearing is examined. The study is carried out through numerical computations performed by a commercial flexible-multibody code which simulates the lubricated contact between elastic bodies in large displacement motion. A multibody model has been created and its thermal behaviour has been validated by comparison with experimental temperatures. The validated model is used to perform two comparative analyses between the TEHD modelling and the Elasto-Hydro-Dynamic (EHD) modelling for max torque and max power cond…

Hsp60 and hsp10 expression in advanced colorectal cancer

Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer

Lung cancer is one of the most common cancers worldwide, causing nearly one million deaths each year. Herein, we present the effect of 2-methoxyestradiol (2-ME), the endogenous metabolite of 17β-estradiol (E2), on non-small cell lung cancer (NSCLC) cells. We observed that 2-ME reduced the viability of lung adenocarcinoma in two-dimensional (2D) and three-dimensional (3D) spheroidal A549 cell culture models. Molecular modeling was carried out aiming to visualize amino acid residues within binding pockets of the acyl-protein thioesterases, namely 1 (APT1) and 2 (APT2), and thus to identify which ones were more likely involved in the interaction with 2-ME. Our findings suggest that 2-ME acts a…

THERMO-ELASTIC-HYDRODYNAMIC ANALYSIS OF A CRANKSHAFT JOURNAL BEARING

Cenni di campionamento e processazione del reperto istologico

Space medicine: use of ex vivo human respiratory mucosa in the survey of the effects of microgravity on the respiratory system

In the near future, the length and scope of space travel is set to increase significantly. The number of individuals who will have access to extra-terrestrial travels is also increasing. In view of the growing international interest towards manned long-term space exploration, possible effects of exposure to microgravity conditions affecting the respiratory system are subject of interest by major space agencies (NASA and ESA primarily). Our team has developed an advanced 3d tissue model of the human bronchial mucosa within a wide research project involving several universities and space agencies at international level. The model will be used to study the structural/functional alterations of …

Human HSP10 variants downregulation after cigarette smoke extract exposure in lung cells

The impact of cigarette-smoke stress (a form of oxidative stress) on human lung fibroblasts and epithelial cells, particularly its effect on Hsp10 expression, has not been characterized despite the fact that a role for mitochondrial chaperonins in the development of lung diseases, ranging from chronic obstructive pulmonary disease to bronchial carcinogenesis, has been suggested (1). We studied the effects of non-lethal doses of cigarette smoke extract (CSE) on the expression of Hsp10 in human lung fibroblasts (HFL-1 line) and epithelial cells (16HBE line). Proteomics was carried out using 2D-IPG, silver stain, western blotting, and mass-spectrometry; mRNA was measured by RT-PCR. Database se…

MEDIUM-TERM CULTURE OF THE NORMAL ORAL MUCOSA: A NOVEL THREE-DIMENSIONAL MODEL TO STUDY THE EFFECTIVENESS OF DRUGS ADMINISTRATION

Atrial natriuretic factor, but not oxytocin, is present in atherosclerotic plaques of human common carotid arteries

We performed a study on 25 common carotid arteries (CCA) affected by atherosclerotic plaques, comparing them to 25 normal CCA. We researched the presence and localisation of atrial natriuretic factor (ANF) and oxytocin (OX) by immunohistochemistry. We found ANF abundantly expressed in plaques, mainly localising in intima and subintima layers; by contrast normal vessels were scarcely positive or negative; finally, OX resulted negative or weakly positive in both atherosclerotic and normal vessels. Our results show for the first time ANF presence in atherosclerotic plaques of CCA and are in agreement with other studies, mainly performed in vitro, that hypothesise the involvement of this molecu…

Fibrosis markers and CRIM1 increase in chronic heart failure of increasing severity.

AbstractBackground: Fibrosis suppressors/activators in chronic heart failure (CHF) is a topic of investigation.Aim: To quantify serum levels of fibrosis regulators in CHF.Methods: ELISA tests were used to quantify fibrosis regulators, procollagen type-(PIP)I, (PIP)III, collagen-I, III, BMP1,2,3,7, SDF1α, CXCR4, fibulin 1,2,3, BMPER, CRIM1 and BAMBI in 66 CHF (NYHA class I, n = 9; II, n = 34; III n = 23), and in 14 controls.Results: In CHF, TGFβR2, PIPIII, SDF1α and CRIM1 were increased. PIPIII correlated with CRIM1.Conclusions: The BMPs inhibitor CRIM1 is increased and correlates with higher levels of serum PIPIII showing an imbalance in favor of pro-fibrotic mechanisms in CHF.

The eSports conundrum: is the sports sciences community ready to face them? A perspective

The reality of eSports is something much more complex than individual users playing video games. There are several characteristics that eSports have in common with traditional sports: from the spirit of competition to the structural composition of the teams, including the increase in performance with training and practice, up to the injuries and physical and psychological stress of the athlete. The number of scientific papers interested in this reality is still relatively low, although in recent years there has been a significant increase in this regard. Probably the lack of knowledge of the world of eSports by inexperts can represent an initial obstacle in the approach to this environment.…

Considerazioni circa i sistemi scheletrico ed articolare del piede

Corrigendum to “Hsp60 and AChR cross-reactivity in myasthenia gravis: An update.” [J. Neurol. Sci. 292 (2010) 117–118]

Corrigendum to “Hsp60 and AChR cross-reactivity in myasthenia gravis: An update.” [J. Neurol. Sci. 292 (2010) 117–118] Francesco Cappello ⁎, Antonella Marino Gammazza, Leila Zummo, Everly Conway de Macario, Alberto J.L. Macario a Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy b University of Maryland, IMET, 701 East Pratt Street, 21202, Baltimore, MD, USA

SUPERIOR MESENTERIC ARTERY SYNDROME: CLINICAL, ENDOSCOPICAL AND RADIOLOGICAL CORRELATIONS ACCORDING TO A SINGLE-CENTER EXPERIENCE

Background and aim: The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss, due to the compression of the third part of duodenum between the aorta and the SMA. Studies to determine the optimal methods of diagnosis and treatment are essential. This study aims to analyze the clinical presentation, the doagnosis and the management of this syndrome. Material and medthods: Over a 2-year (2013-2014), 8 cases of SMA syndrome (out of 2074 esophago-gastro-duodenoscopies, EGDS) were initially suspected through EGDS. Therefore, these patients performed computed tomography (CT) scan to confirm the diagnosis. Once the diagn…

INFLAMMATION IN IRRITABLE BOWEL SYNDROME: MYTH OR NEW TREATMENT TARGET?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms u…

ALCOHOLIC LIVER DISEASE: A MOUSE MODEL REVEALS PROTECTION BY LACTOBACILLUS FERMENTUM

Objectives Alcoholism is one of the most devastating diseases with high incidence, but knowledge of its pathology and treatment is still plagued with gaps mostly because of the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp (heat-shock protein)-chaperones involvement, and response to treatment. Methods The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum following a precise schedule over time and applying, at predetermined intervals, a battery of techniques (histology, immunohistochemistry, western blotting, real-time PCR, immunoprecipitation, …

ANATOMIC-CLINICAL CONSIDERATIONS NON RECURRENT LARYNGEAL NERVE COEXISTING TO RECURRENT NERVE:PERSONAL EXPERIENCE AND LITERATURE REVIEW

Human molecular chaperones share with SARS-CoV-2 antigenic epitopes potentially capable of eliciting autoimmunity against endothelial cells: possible role of molecular mimicry in COVID-19

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the cause of COVID-19 disease, has the potential to elicit autoimmunity because mimicry of human molecular chaperones by viral proteins. We compared viral proteins with human molecular chaperones, many of which are heat shock proteins, to determine if they share amino acid-sequence segments with immunogenic-antigenic potential, which can elicit cross-reactive antibodies and effector immune cells with the capacity to damage-destroy human cells by a mechanism of autoimmunity. We identified the chaperones that can putatively participate in molecular mimicry phenomena after SARS-CoV-2 infection, focusing on those for which endotheli…

Plantar pressure distribution analysis in normal weight young women and men with normal and claw feet: a cross-sectional study

We analyzed the plantar support in 72 normal-weight young voluntaries (46 women, 26 men), by a baropodometric platform. We considered subjects with claw foot (CFS) and subjects with normal foot (NFS). We found a significant reduction of total plantar support surface in the CFS (P < 0.0001 for women, P < 0.001 for men), due to the reduction of the forefoot and rear foot areas of both plantar imprints. Indeed, CFS of both sexes exhibited higher values of both plantar pressure and peak pressure, compared to the NFS. Moreover, the load per units of plantar surface increased in CFS compared to the NFS. In conclusion, the reduction of plantar support surfaces in CFS of both sexes was associated t…

Abdominal aortic aneurysm with congenital ectopic kidney and aberrant renal arteries

Morphological changes in the wall of anomalies of the extracranical internal carotid artery: histologic and anatomic features

Chaperonology: The Third Eye on Brain Gliomas

The European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial has validated as a current regimen for high-grade gliomas (HGG) a maximal safe surgical resection followed by radiotherapy with concurrent temozolamide. However, it is essential to balance maximal tumor resection with preservation of the patient&rsquo

Hsp60, amateur chaperone in amyloid-beta fibrillogenesis

BACKGROUND: Molecular chaperones are a very special class of proteins that play essential roles in many cellular processes like folding, targeting and transport of proteins. Moreover, recent evidence indicates that chaperones can act as potentially strong suppressor agents in Alzheimer's disease (AD). Indeed, in vitro experiments demonstrate that several chaperones are able to significantly slow down or suppress aggregation of Aβ peptide and in vivo studies reveal that treatment with specific chaperones or their overexpression can ameliorate some distinct pathological signs characterizing AD. METHODS: Here we investigate using a biophysical approach (fluorescence, circular dichroism (CD), t…

SENESCENCE-ASSOCIATED HSP60 EXPRESSION IN NORMAL HUMAN SKIN FIBROBLASTS

Morphological Alterations and Stress Protein Variations in Lung Biopsies Obtained from Autopsies of COVID-19 Subjects

Molecular chaperones, many of which are heat shock proteins, play a role in cell stress response and regulate the immune system in various ways, such as in inflammatory/autoimmune reactions. It would be interesting to study the involvement of these molecules in the damage done to COVID-19-infected lungs. In our study, we performed a histological analysis and an immunomorphological evaluation on lung samples from subjects who succumbed to COVID-19 and subjects who died from other causes. We also assessed Hsp60 and Hsp90 distribution in lung samples to determine their location and post-translational modifications. We found histological alterations that could be considered pathognomonic for CO…

Presence and interaction in tissues of atrial natriuretic peptide,oxytocin and vasopressin:new insights.

Atrial natriuretic peptide, oxytocin and vasopressin are three well known and widely studied molecules since many years. They have been fully characterised from a genetic and biomolecular point of view and a number of receptor-dependent functions have been recognised for them. Nevertheless, in the last years our group has conducted morphologic studies, using an immunohistochemical approach complemented by molecular biology techniques, and could show non-canonical localization and co-localization of these peptides in normal and pathologic tissues, that permitted us to postulate that they may be involved in a wider range of functions than usually assumed and not yet fully understood. In this …

Glutamatergic hypofunction in medication-free major depression: Secondary effects of affective diagnosis and relationship to peripheral glutaminase.

BackgroundThere is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations. MethodsIn this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n=29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n=20). We als…

Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases.

BACKGROUND. Patients with small papillary thyroid carcinoma (PTC) may have a high incidence of regional lymph-node (LN) metastases at presentation, and these are considered to be an independent risk factor for tumor recurrence. A mutated transketolase transcript (TKTL1) has been found up-regulated in different human malignancies, and strong TKTL1 protein expression has been associated with aggressiveness and poor patient survival in several epithelial cancers. METHODS. TKTL1 protein expression was analyzed in 256 consecutive cases of PTCs ≤1.5 cm by immunohistochemistry with a specific anti-TKTL1 antibody. RNA analysis was performed by real-time polymerase chain reaction (PCR) in all cases …

Effects of essential oils and selected compounds from Lamiaceae family as adjutants on the treatment of subjects with periodontitis and cardiovascular risk

Essential oils from different plant species were found to contain different compounds exhibiting anti-inflammatory effects with the potential to be a valid alternative to conventional chemotherapy that is limited in long-term use due to its serious side effects. Generally, the first mechanism by which an organism counteracts injurious stimuli is inflammation, which is considered a part of the innate immune system. Periodontitis is an infectious and inflammatory disease caused by a dysbiosis in the subgingival microbiome that triggers an exacerbated immune response of the host. The immune–inflammatory component leads to the destruction of gingival and alveolar bone tissue. The main anti-infl…

Atrial Natriuretic Factor Downregulation during Breast Cancer Progression

The articular system of the foot

Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated wi…

Effect of a pathogenic stressor on human HSP10.

Small airways in sedentary and endurance-trained dystrophic (mdx) mice.

The effects of mild endurance exercise training on the small airways in mdx mice are unknown. We compared epithelial thickness and turnover, apoptosis, and stress marker expression in small airways of mdx mice and wild-type (WT) controls, at rest and during exercise training. Mdx and WT mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx- EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 d/wk for 6 wk at progressively increasing speed (rpm from 16 to 24) and time (15 min to 1 h). Lungs were processed for light microscopy and periodic acid Schiff (PAS) staining. Hsp60 and PCNA were quantified by immunohistochemistry…

A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy

Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, Hsp60) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, CCT). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the CCT5 gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit b…

Nebulization of pharmacological solutions with an innovative medical device based on microvaporization

The currently available nebulization devices have a slow aerosol flow and produce vapor with large microdrops. Improved devices that achieve higher airflow and produce smaller microdrops are needed to improve the clinical care of patients. To address this critical need, we developed a novel system for the molecular vaporization of liquids. This device vaporizes an active pharma-cological substance dissolved in water, alcohol, or a mixture of water and alcohol using two energy sources at the same time: high-frequency ultrasound and thermal induction. Application of energy to a solution contained in the device's tank allows, within tens of seconds, for the vaporization of the solution itself,…

Senescence-associated HSP60 expression in Normal Human skin fibroblasts

Normal mammalian fibroblasts cultured in vitro undergo a limited number of divisions before entering a senescent phase in which they can be maintained for long periods but cannot be induced to divide. Senescent cells become unresponsive to growth-promoting signals and exhibit senescent cell morphology with flattened and enlarged cell shape. Several chaperones have a direct effect on cellular senescence. HSP60 has been largely studied in our laboratories and it has been associated with uncontrolled cell proliferation in tumor cells. Since senescence is firmly regulated during cell cycle progression, we wanted to investigate HSP60 protein level during cellular senescence. Our data show that H…

Cardiac stem cell-loaded poly-lactic acid and fibrinoin scaffolds as devices for cardiac muscle tissue regeneration

p53 and Ki-67 expression in renal cell carcinomas of pregnant women and their correlation with prognosis: a pilot study.

In the present study, we reported two cases of renal cell carcinoma (RCC) diagnosed in pregnant women (Pt) that were submitted to radical nephrectomy, in both cases within the fourth month. The patients, after 13 and 3 years, respectively, did not show evidence of recurrent disease. We performed an immunohistochemical study on RCC specimens in comparison to seven age-matched controls (Cl). The panel of antibodies included Ki-67, p53, bcl-2, ER, PgR, PCNA, and IGF-1. We describe a difference in the expression of p53 and Ki-67. Specifically, p53 was highly expressed in RCC of both Pt but scarcely present or absent in Cl; by contrast, Ki-67 was hardly expressed or negative in RCC of both Pt, b…

The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase

Abstract Background The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. The objective of the present study was to evaluate the presence and expression of HSP60 and HSP10 in a series of large bowel carcinomas and locoregional lymph nodes with and without metastases. Methods 82 Astler and Coller's stage C2 colorectal cancers, of which 48 well-differentiated and 34 poorly-differentiated, were selected along with 661 lymph nodes, including 372 with metastases and 289 with reactive hyperplasia only, from the same tumours. Primitive tumours and both metastatic and reactive lymph nodes were studied; specifically, three different compartment…

Chaperonin of Group I: Oligomeric spectrum and biochemical and biological implications

Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still inc…

Molecular mimicry may explain multi-organ damage in COVID-19

International audience

Increased expression of titin in mouse gastrocnemius muscle after an endurance-training program

Titin, a sarcomeric giant protein, plays crucial roles in muscle assembly, elasticity and stability. Little is known about titin adaptation to endurance exercise. We studied the effects of endurance training on titin expression in mouse gastrocnemius muscles (MGM). Sixty-three ten-week-old male Swiss mice were divided into seven groups. Four groups were composed of untrained control animals (C0, C15, C30, C45) instead the other three included mice trained for 15 (T15), 30 (T30) and 45 (T45) days by treadmill. The training protocol was mainly aerobic, characterized by moderate-intensity, rhythmic and continuous exercises. Titin expression was determined by immunohistochemistry on MGM section…

HSP-MOLECULAR CHAPERONES IN CANCER BIOGENESIS AND TUMOR THERAPY: AN OVERVIEW

Molecular chaperones, many of which are heat-shock proteins (HSPs), are an important class of molecules with various functions. Pathological conditions in which chaperones become etiological and/or pathogenic factors are called chaperonopathies, and are classified into by defect, by excess, and by "mistake". In the latter case, the chaperone is structurally and functionally normal but paqrtecipates in pathwais that favor diseases, aòlthough in some cases the chaperone may have post-translational modifications that may lead it to change its location and function and, thus, to become pathogenic. For example, HSP-chaperones are involved in acrcinogenesis in various ways, so that some forms of …

Could tubular interstitium be a source of adult epithelial stem cells?

Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma.

ABSTRACT Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine. Here we found that guadecitabine i…

ERYTHROPOIETIN FOR THE TREATMENT OF SUBARACHNOID HEMORRAGE: A FEASIBLE INGREDIENT FOR A SUCCESS MEDICAL RECIPE

Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebr…

Micromechanical modeling of carbon nanotube-reinforced nanocomposites

ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids

Objective: Metabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progression Methods: Through integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (N…

PROBIOTICI E TERAPIA CONVENZIONALE: NUOVE FRONTIERE NELLA GESTIONE DELLE MANIFESTAZIONI ARTICOLARI DELLE MALATTIE INFIAMMATORIE INTESTINALI (IBD)

Summary: This work reports a clinical trial performed at palermo University Hospital "paolo Giaccone". From January 2004 to December 2011, 79 patients were enrolled (40 men and 39 women). All patients suffered from Inflammatory Bowel Disease (IBD) and were subjected to orthopedic consultation at the institute of Orthopaedics, University Hospital of palermo, for arthropathy to IBD. The patients were divided into two groups (A and B) and dealt with different therapies for the resolution of the inflammatory picture of the colonic mucosa and the treatment of the extraintestinal articular manifestations. Group A was treated with drug therapy: Diclofenac (75 mg im/ day for 10 days9 and Mesalazine…

Modulation of mucin 2 and mucin 3 in colitis induced by iodoacetamide and enteropathogenic bacteria in rats

The iinate and acquired immune systems are both implicarted in the etiology of Inflammatory Bowel Disease (IBD) in addition to the genetic predisposition, the environmental factors and the intestinal flora covering the mucosa. A defect in the mucous covering will lead to an invasion of pathogens and stimulation of the immuune response with aberrations of mucin 2, the major mucin of the mucous layer. Aim: this study aims to assess the modulation of colonic MUC 2 and MUC 3 in a arat model of IBD induced by a combination of iodoacetamide and enteropatogenic E. Coli. Methods: 78 sprague-Dawley female rats were divided into 4 groups. Each group was subjeceted, on a basis, to a rectal injection o…

TRPA1 channel is a cardiac target of mIGF-1/SIRT1 signaling.

Cardiac overexpression of locally acting muscle-restricted (m)IGF-1 and the consequent downstream activation of NAD+-dependent protein deacetylase sirtuin 1 (SIRT1) trigger potent cardiac antioxidative and antihypertrophic effects. Transient receptor potential (TRP) cation channel A1 (TRPA1) belongs to the TRP ion channel family of molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce pain. Recently, it has been shown that TRPA1 activity influences blood pressure, but the significance of TRPA1 in the cardiovascular system remains elusive. In the present work, using genomic screening in mouse hearts, we found that TRPA1 is a target of mIGF-1/SIRT1 sign…

JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii without affecting tumor growth or cachexia.

In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The eff…

Oligomeric State and Holding Activity of Hsp60

Similar to its bacterial homolog GroEL, Hsp60 in oligomeric conformation is known to work as a folding machine, with the assistance of co-chaperonin Hsp10 and ATP. However, recent results have evidenced that Hsp60 can stabilize aggregation-prone molecules in the absence of Hsp10 and ATP by a different, “holding-like” mechanism. Here, we investigated the relationship between the oligomeric conformation of Hsp60 and its ability to inhibit fibrillization of the Ab40 peptide. The monomeric or tetradecameric form of the protein was isolated, and its effect on beta-amyloid aggregation was separately tested. The structural stability of the two forms of Hsp60 was also investigated using differentia…

ANP IMUUNOLOCALITATION IN INTERNAL CAROTID ARTERY WALL OF SUBJECTS WITH AN WITHOUT ATHEROSCLEROTIC LESIONS

CD1A AND ANTITUMOUR IMMUNE RESPONSE:EXPRESSION OF CD1A BY METAPLASTIC EPITHELIAL CELLS

HSP60 and HSP10 overespression in metastatic colon cancer

Anatomia clinica del sistema articolare del piede

From a semantic point of view the word “ankle” and “ankle region” are not synonyms as “ankle” identifies all the components of the ankle joint while “ankle region” identifies the ankle joint as well as every structures in the region, form the surface level to the skeletal one. The articular system of the foot is formed by thirthyfour synovial joints, seventeen of which have complementary curvilinear articular surface, the remaning seventeen having plane joints. The rounded surface joints are: the talonavicular joint (a spheroidal joint that is part of the transverse tarsal joint), the “anatomical” subtalar joint ( a saddle joint), five ellipsoid (or condylar) joints and ten, ankle and inter…

Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-cell Communication

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exoso…

Extracorporeal Shock Waves Increase Markers of Cellular Proliferation in Bronchial Epithelium and in Primary Bronchial Fibroblasts of COPD Patients

Chronic obstructive pulmonary disease (COPD) is due to structural changes and narrowing of small airways and parenchymal destruction (loss of the alveolar attachment as a result of pulmonary emphysema), which all lead to airflow limitation. Extracorporeal shock waves (ESW) increase cell proliferation and differentiation of connective tissue fibroblasts. To date no studies are available on ESW treatment of human bronchial fibroblasts and epithelial cells from COPD and control subjects. We obtained primary bronchial fibroblasts from bronchial biopsies of 3 patients with mild/moderate COPD and 3 control smokers with normal lung function. 16HBE cells were also studied. Cells were treated with a…

MODELLO NUMERICO PER LA CARATTERIZZAZIONE DI MATERIALI COMPOSITI A MATRICE POLIMERICA RINFORZATI DA NANOTUBI DI CARBONIO

Silibin hepatoprotection occur via NFKB signaling inhibition in murine nonalcholic fatty liver disease

An uncommon cause of pneumothorax

Numerical model for composite material with polymer matrix reinforced by carbon nanotubes

Due to the high stiffness and strength, as well as their ability to act as conductors, carbon nanotubes are under intense investigation as fillers in polymeric materials. The nature of the carbon nanotube/polymer bonding and the curvature of the carbon nanotubes within the polymer have arisen as particular factors in the efficacy of the carbon nanotubes to actually provide any enhanced stiffness or strength to the nanocomposite. Here the effects of carbon nanotube curvature and interface interaction with the matrix on the nanocomposite stiffness are investigated using nanomechanical analysis. In particular, the effects of poor bonding and thus poor shear lag load transfer to the carbon nano…

Effects of antioxidants on CSE-induced cell death in human asthmatic primary bronchial epithelial cells

The link between cigarette smoke (CS) and lung inflammation is quite strong, however relatively little is still known on the effects of CS on human bronchial epithelial cells survival during asthma. In this study we focused our attention on the apoptotic effects of CS on healthy (HC) and asthmatic (AS) primary bronchial epithelial cells (PBEC) and on the role of antioxidants to protect epithelial cells from CSE-induced apoptosis. Twenty subjects (10 HC and 10 AS) were recruited for this study and PBEC were obtained by bronchoscopy. PBEC were treated with oxidants (H2O), anti-oxidants (GSH and AA) and cigarette smoke extracts (CSE). Early apoptosis (EA) and necrosis were measured by flow cyt…

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is…

Chaperones in disease: quantitative changes in chronic obstructive pulmonary disease (COPD)

Causa rara di ostruzione delle vie aeree: linfoma tiroideo

ASSOCIATION BETWEEN HELYCOBACTER PYOLRI INFECTION AND PATHOLOGICAL ORAL MANIFESTATIONS

DATA FROM LITERATURE ARE CONTROVERSAL REGARDING THE PRESENCE OF bELICOBACTER PYLORI (HP) IN DENTAL PLAQUE AND ITS ASSOCIATION WITH GASTRIC INFECTION. oNE OF THE POSSIBLE MECHANISMS SUGGETSED FOR RE-INFECTION IS THE RECOLONIZATION WITH HP DENTAL PLAQUE. THE PURPOSE OF THIS REVIEW WAS TO DETERMINE WHETHER DENTAL PLAQUE, POOR ORAL HYGIENE, AND PERIODONTAL DISEASE WERE RISK FACTORS FOR HP INFECTION.

Human primary macrophages scavenge AuNPs and eliminate it through exosomes. A natural shuttling for nanomaterials.

Abstract The use of nanomaterials is increasing but the real risk associated with their use in humans has to be defined. In fact, nanomaterials tend to accumulate in organs over a long period of time and are slowly degraded or eliminated by the body. Exosomes are nanovesicles actively shuttle molecules, including chemical products and metals, through the body. Macrophages scavenge the body from both organic and inorganic substances, and they use to release high amounts of exosomes. We hypothesized that macrophages may have a role in eliminating nanomaterials through their exosomes. We treated human primary macrophages with 20 nm gold nanoparticles (AuNPs), analyzing the presence of AuNPs in…

Circulating Molecular Chaperones in Subjects with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Data from the Zabùt Aging Project

Molecular chaperones play essential roles in many processes such as cell differentiation, tissue homeostasis, and organ remodeling. Recent data indicate that chaperones can act as cytoprotectants for brain cells during the progression of neurodegenerative diseases, including Alzheimer’s disease (AD). However, very few data on the levels of chaperones in dementia, including its prodromal phases, have been reported. In this study, we used biological samples and epidemiological data collected during the Zabùt Aging Project (a prospective, community-based, cohort study of normal/pathological aging conducted in Sicily, Italy, with a follow-up of ten years) to determine if there is an association…

An uncomon case of pneumothorax

c-Kit positive cells isolated from Adult Rat Myocardium can organze them-selves into a tissue-like cell mass.

Hsp60 Protects against Amyloid β Oligomer Synaptic Toxicity via Modification of Toxic Oligomer Conformation

Alzheimer's disease (AD) is the leading cause of dementia worldwide. While the etiology of AD remains uncertain, neurotoxic effects of amyloid beta oligomers (Aβo) on synaptic function, a well-established early event in AD, is an attractive area for the development of novel strategies to modify or cease the disease's progression. In this work, we tested the protective action of the mitochondrial chaperone Hsp60 against Aβo neurotoxicity, by determining the direct effect of Hsp60 in changing Aβo toxic conformations and thus reducing their dysfunctional synaptic binding and consequent suppression of long-term potentiation. Our data suggest that Hsp60 has a direct impact on Aβo, resulting in a…

Effect of a pathogenetic stressor on human Hsp10.

Mild Aerobic Exercise Training Hardly Affects the Diaphragm ofmdxMice

In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and q…

Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics

Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis. Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization. This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HS…

Hsp10: Anatomic distribution, functions, and involvement in human disease

There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and sec…

ELECTROMECHANICAL PROPERTIES OF SINGLE AND MULTIWALL CARBON NANOTUBES UNDER MECHANICAL DEFORMATION

Role of Endogenous GLP-2 in the Intestinal Adaptation to a Chronic High Fat Diet

HSP60: A Story as Long as Life on the Earth

In this Chapter, we briefly recount a few salient aspects of our personal experience and ideas about one of the most important anti-stress proteins in all cells, i.e., HSP60 (HSPD1 in humans). We outline the progression of HSP60 from gene to protein and its voyages inside and outside the cell, mentioning its various roles in health and disease. We correlate scientific data obtained by different experimental approaches to personal visions about the existence of life on Earth, its perpetuation, and the future of the human-species evolution. We believe that Science should not only be the application of technologies to find an answer to an unsolved question but also a source of philosophical co…

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis

Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependabl…

NEW THERAPEUTIC PERSPECTIVES IN IRRITABLE BOWEL SYNDROME: TARGETING LOW-GRADE INFLAMMATION, IMMUNO-NEUROENDOCRINE AXIS, MOTILITY, SDECRETION AND BEYOND.

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune, dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiot…

Naïve Hsp60, similarly to GroEL, oligomerizes to build heptameric and tetradecameric structures.

CIGARETTE SMOKE EXPOSURE DOWNREGULATES TWO ISOELECTRIC VARIANTS OF HUMAN Hsp10 IN LUNG EPITHELIAL CELLS AND FIBROBLASTS: A PROTEOMIC STUDY.

Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surg…

CD1a: a novel biomarker for Barrett's metaplasia?

educational book. Alexandria: American Society for Clinical Oncology, 2001: 226–44. 49 Hussain M, Smith DC, Al-Sukhun S, et al. Preliminary results of HER-2/neu screening and treatment with trastuzumab (Herceptin) (T), paclitaxel (P), carboplatin (C) and gemcitabine (G) in patients with advanced urothelial cancer. Proc Am Soc Clin Oncol 2002; 21: 800a. 50 Al-Sukhun S, Hussain M. Current understanding of the biology of advanced bladder cancer. Cancer 2003; 97 (8 suppl): 2064–75. 51 Hussain SA, Ganesan R, Hiller L, et al. Pro-apoptotic genes BAX and CD40L are predictors of survival in transitional cell carcinoma of the bladder. Br J Cancer 2003; 88: 586–92. 52 Stein JP, Ginsberg DA, Grossfiel…

Virtual broncoscopy in the preoperative assessment of peripheral airways stenosis

A novel therapeutic approach to colorectal cancer in diabetes: role of metformin and rapamycin

International audience; The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been adopted. This study is a novel approach that aimed at assessing the effect of a combination therapy of metformin and rapamycin on the control or prevention of CRC in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells. They were equally divided into diabetics (induced by Streptozotocin) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via intra-peritoneal injections. Probiotics were added to the doub…

Endurance Exercise and Conjugated Linoleic Acid (CLA) Supplementation Up-Regulate CYP17A1 and Stimulate Testosterone Biosynthesis

A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone…

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus.

The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat sh…

Hsp60 as a Novel Target in IBD Management: A Prospect

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be …

Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

Contains fulltext : 155347.pdf (Publisher’s version ) (Closed access) BACKGROUND/OBJECTIVES: In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess. METHODS: Twelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60% energy from lard…

Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment.

Introduction: Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer. Many studies have fo…

Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

collaboration au projet H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD); International audience; Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding…

Clinical and anatomical features of facial nerve in the surgery of parotid gland: our recent experience

Heat shock proteins may have effects on cellular senescence and may lead to neoplastic transformation

IMMUNOLOCALIZATION STUDIES OF A NON-CONVENTIONAL RECEPTOR FOR VASOSTATIN-1 ON THREE-DIMENSIONAL PRIMARY CULTURES OF ADULT RAT MYOCARDIOCYTES

An interesting question of Pompe disease. A case report

Glycogenosis type II or Pompe disease is an inherited autosomal recessive disorder known in 3 different clinical forms (infantile, juvenile and adult). We report on a case diagnosed as a classic infantile form with the worst outcome of all 3 described, if we had followed and executed a correct and complete diagnostic pathway. A 7 months old female child was admitted for fever and dyspnoea. At chest auscultation weepings and weezings were found; on the cardiac apex a murmur due to mitralic failure was retrieved. The thorax X-ray showed a greatly increased heart shadow with a cardiothoracic index of 0.75. ECG showed high voltages and signs of bilateral ventricular hypertrophy. Cardiac ultraso…

HSP60 and HSP10 as diagnostic and prognostic tools in the management of exocervical carcinoma

Efficiency of transgenesis using sperm-mediated gene transfer: generation of hDAF transgenic pigs.

SINCE the beginning of this century, replacement of failing human organs with their animal counterparts has been an interesting topic of debate for writers and scientists. In the 1960s, prolonged survival after kidney transplantation from chimpanzee to human was obtained in the United States and Europe. Nevertheless, both the progressive improvement in surgical technique and in immunosuppressant therapy and the availability of cadaveric organs and living donation have reduced the interest in xenotransplantation. Because of the increasing requests for organs and the lack of donors to meet that need, xenotransplantation has become a reliable option again for temporary organ replacement (eg, o…

The Binding Mechanism of Epolactaene to Hsp60 Unveiled by in Silico Modelling

Molecular Dynamics (MD) simulations and DFT/MM calculations were performed in order to rationalize available experimental results and to provide structural details on the binding mechanism of Epolactaene (EPO) to the 60 KDa Heat Shock Protein (Hsp60). The available crystal structure of Hsp60 represents the last step of the chaperone folding cycle, while the Hsp60-EPO complex was obtained by using a homology model of Hsp60, in order to simulate a state related to the beginning of the folding cycle (Rs1). The results of MD simulations point out that EPO shows the highest binding affinity for the empty ATP binding site. The presence of ATP opens a channel that allows the entrance of both EPO d…

Cigarette smoke exposure downregulates two isoelectric variants of human HSP10 in airway epithelial cells: A Proteomic study

RMevioewlecular oncology focus - Is carcinogenesis a 'mitochondriopathy'?

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data f…

CD1a expression by Barrett's metaplasia of gastric type may help to predict its evolution towards cancer

As emerging in the recent literature, CD1a has been regarded as a molecule whose expression may reflect tumour evolution. The aim of the present work was to investigate the expression of CD1a in a series of Barrett's metaplasia (BM), gastric type (GTBM), with and without follow-up, in order to analyse whether its expression may help to diagnose this disease and to address the outcome. Indeed, GTBM may be confused sometimes with islets of ectopic gastric mucosa and its evolution towards dysplasia (Dy) or carcinoma (Ca) could not be foreseen. We showed a significant higher expression of CD1a in GTBM than in both Dy and Ca; nevertheless, the number of positive GTBM was significantly lower in t…

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were tre…

Integrazione di Tecnologie CAE in Ambienti VR

Applying virtual reality (VR) to numerical analyses (finite element –FE or fluid dynamics - CFD) produces considerable advantages, both for costs and for quality, in the mechanical engineering design process. Generally, during the stage of structural tests, after having carried out the CAD model, the designer runs FE and/or CFD analyses. Clearly, hardly ever, the obtained results are satisfactory during the first iteration, so that the designer, after having analysed the first data, needs to modify some parts of the model and to carry out a new analysis. Such re-analysis process is very improved and faster if it is carried out in a virtual reality environment; that because using the virtual…

Syncronous adenomatous polyps and colorectal carcinoma

Ruolo del peptide glucagone simile-2 nell'adattamento intestinale ad una dieta iperlipidica

L'hsp60 e l'hsp10 sono iperespresse durante la cancerogenesi prostatica

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) a…

Cell-extracellular matrix interaction: a putative non-conventional target of Vasostatin-1. A confocal analysis

CD1a and antitumour immune response

Primary immune response is based on the capacity of local professional antigen-presenting cells (whose prototype is represented by dendritic cells, DCs) to take up and present antigens to selected clones of T cells, but also to non-specific effector cells such as macrophages or natural killer cells. The four CD1 proteins, all of which share a limited homology to class I MHC proteins, are differently expressed in various cell types, of both mesenchymal and, as recently described, epithelial lineage. Regarding the role of CD1 molecules in the anti-tumour response, it has been reported that CD1+ dendritic cells are involved in the first steps of the primary immune response in a number of malig…

Bacterial-viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects.

Silvestro Ennio D&rsquo;Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefal&ugrave;, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) and Cassano delle Murge (BA), 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory respon…

HSP60 is a ubiquitous player in the physiological and pathogenic interactions between the chaperoning and the immune systems

HSP60 participates in many interactions between the system integrated by all chaperones and closely associated molecules (chaperoning system or CS) and the immune system (IS). These interactions occur constantly to maintain normal cell physiology but, occasionally, they are perturbed and become mediators of pathologic events that may lead to disease. This switch to pathology may be initiated by various factors, genetic or acquired, which cause qualitative and/or quantitative modifications of HSP60, or immune crossreactivity between the human and microbial chaperonin orthologs, or a break in the balance between the pro- and anti-inflammatory actions of the chaperonin. Thus, autoimmune and ch…

Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our a…

MOESM1 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 1.

Hsp60 Post-translational Modifications: Functional and Pathological Consequences.

Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The questio…

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of …

Apoptosis is not involved in the mechanism of myocardial dysfunction after resuscitation in a rat model of cardiac arrest and cardiopulmonary resuscitation.

OBJECTIVE To investigate the presence of apoptosis after the global myocardial ischemia of cardiopulmonary resuscitation and the regional myocardial ischemia after left anterior descending coronary artery occlusion and relate it to the severity of postresuscitation myocardial dysfunction. DESIGN Prospective animal study. SETTING University-affiliated animal research laboratory. SUBJECTS Male Sprague-Dawley rats. INTERVENTIONS Fifteen male Sprague-Dawley rats weighing 450-550 g were randomized to: (1) 8 mins of untreated cardiac arrest followed by 6 mins of cardiopulmonary resuscitation; (2)left anterior descending coronary artery occlusion for 45 mins followed by 4 hrs of reperfusion; and (…

DEVELOPMENTS OF A NUMERICAL METHOD TO SIMULATE FATIGUE DELAMONATION IN COMPOSITES

Finite element reanalysis in virtual reality environments

Development of software in the study of carotid artery in the neck.

The aim of this work was to develop and employ software for the study of the common carotid artery and its branches in the neck. We first constructed geometric models of anatomic components, for the building of knowledge bases to be used in automatic feature extraction techniques from images. Then, we developed a software system characterised by three-dimensional visualisation, image processing functions, knowledge base and a programming language to describe classification processing by means of fuzzy logic. The software system was used to perform automatic reconstruction of three-dimensional models of carotid arteries from contiguous CT scans of the neck. These findings suggest that such s…

Atrial natriuretic factor, but not oxytocin, is present in atherosclerotic plaques of human common carotid arteries: an immunohistochemical in vivo study.

The posterior talocalcaneal ligament: an MRI evaluation

Purpose Awideinter-individualvariabilityintermsofsize,orientationandinsertionisobservedregardingankleligaments. The aim of this study is to identify and describe the anatomical features of the posterior talocalcaneal ligament (PTCL) observed through the use of magnetic resonance imaging (MRI) of the ankle. Methods The study was retrospectively carried out on 893 ankle MRI’s exams. The exams have all been performed using a 1.5-T (T) MRI. The same scanning protocols and scan planes were carried out in all the exams. The first evaluated param- eter was the recognition of the PTCL. Subsequently, in all those cases where the ligament was present, its features such as insertion sites, length, and…

Pouchitis: A tridimensional view

The preferred surgical treatment of ulcerative colitis (UC) and familial adenomatous polyposis (FAP) is represented by proctocolectomy with ileal pouch-anal anastomosis (IPAA). However, patients with UYC who have undergone IPAA are prone to develop several complications, which include surgery related/mecchanical complications; inflammatory or infectious disoreders; dysplasia or neoplasia; and systemic or metabolic disorders. Pouchitis, which is defined as the acute and/or chronic inflammation of the ileal reservoir, represent the most common long-term adverese sequela after IPAA. Gut microbiota play a pivotal role in the initiation and disease progression of pouchitis. Pouchitis can be clas…

Hsp60 response in experimental and human temporal lobe epilepsy

The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper …

Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and practice.

AbstractFatty acid–binding proteins (FABPs) are lipid chaperones assisting in the trafficking of long-chain fatty acids with functions in various cell compartments, including oxidation, signaling, gene-transcription regulation, and storage. The various known FABP isoforms display distinctive tissue distribution, but some are active in more than one tissue. Quantitative and/or qualitative changes of FABPs are associated with pathological conditions. Increased circulating levels of FABPs are biomarkers of disorders such as obesity, insulin resistance, cardiovascular disease, and cancer. Deregulated expression and malfunction of FABPs can result from genetic alterations or posttranslational mo…

Bacterial&amp;ndash;viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

Silvestro Ennio D&amp;rsquo;Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefal&amp;ugrave;, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) and Cassano delle Murge (BA), 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammator…

CD1A IMMUNOPOSITIVITY COULD HELP TO DISTINGUISH BARRETT's METAPLASIA FROM HETEROTOPIC GASTRIC MUCOSA

Correction: Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.

[This corrects the article DOI: 10.1371/journal.pbio.2001951.].

Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their…

OPLA scaffold, collagen I, and horse serum induce a higher degree of myogenic differentiation of adult rat cardiac stem cells

In the last few years, a major goal of cardiac research has been to drive stem cell differentiation to replace damaged myocardium. Several research groups have attempted to differentiate potential cardiac stem cells (CSCs) using bi- or three-dimensional systems supplemented with growth factors or molecules acting as differentiating substances. We hypothesize that these systems failed to induce a complete differentiation because they lacked an architectural space. In the present study, we isolated a pool of small proliferating and fibroblast-like cells from adult rat myocardium. The phenotype of these cells was assessed and the characterized cells were cultured in a collagen I/OPLA scaffold …

The Microbiota Is Not an Organ: Introducing the Muco-Microbiotic Layer as a Novel Morphofunctional Structure

In this paper, we want to refute the notion that the microbiota should be considered an organ, given that an organ comprises tissue of similar or different embryological origin, while the microbiota is a pool of different microbial species originating individually from single replications and not from a common ancestral cellular element. Hence, we would like to propose a new morphological interpretation of its nature, based on the comprehensive context in which these microbes live: a muco-microbiotic layer of hollow organs, such as the airways and the bowel. The above concept should represent not only a new terminological annotation but also a more accurate portrayal of the physiology and p…

TGF-β Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD

Background: The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD. Methods: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis. Results: TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium…

Myocardial bridge pathology and preventable accidents during physical activity of healthy subjects: A case report and a literature review.

Myocardial bridging is a congenital coronary pathology described as a segment of coronary artery which courses through the myocardial wall under the muscle bridge. Although the prognosis of myocardial bridging is benign, sports medicine recognises myocardial bridging as a leading cause of sudden death among young basketball, football and soccer players. The authors report a case of a 42-year-old man who collapsed while playing football. He died notwithstanding prompt medical assistance and cardiopulmonary resuscitation. At autopsy, gross examination of the heart revealed the intramural course of the left anterior descending coronary artery to be 2 cm from its coronary ostial origin. Histol…

Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer

Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, …

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecularchaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60,the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotectivebut a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examplesof specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicatea pathogenic role for HSP60 but also its …

MOESM5 of Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Additional file 5. Figure S4. Gene expression in 3T3-L1 adipocytes. 3T3-L1 pre-adipocytes with lentiviral-mediates stable expression of GFP, macroH2A1.1-GFP and macroH2A1.2-GFP were induced to differentiate into mature adipocytes as in Fig. 6. At the 15th day of differentiation, RNA was extracted and processed for qPCR analyses with specific primers. Results were normalized to pre-differentiation gene levels. Values are represented as means (N = 3) ± S.E.M. *P

Stem Cell Populations and Regenerative Potential in Chronic Inflammatory Lung Diseases

Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modifications of airway mucosa that vary depending on the severity, duration and type of the disease. These morphological changes, that determine organ dysfunction, are not always reversible. Indeed, the cycle of injury and repair, influencing airway wall re- generation, may sometimes break off and an exacerbation of the pathology may occur. The mechanisms at the base of airway remodelling during inflammation have been widely studied and numerous evidences indicate that the molecular dialogue among the cells of the mucosa has an essential role in orchestrating cell differentiation and tissue repair.…

Histochemical Geography and Ultrastructural Remarks of the Urinary Tract in Some Mammals

Our investigations oriented towards the urinary tracts, particulary the bladder and ureter, were carried out by histochemical and ultrastructural studies by SEM and TEM observation. In this segment of urinary tract, by structural, ultrastructural and chemical analysis, have evinced variations related to different animal species (guinea pig, rabbit and rat). The bladder wall was considered from us for histochemical aspects related to hydrolytic lysosomial enzymes (Ac-Phase; Na-beta-Gase) and oxidative enzymes (SDH; Iso-DH; MADH) and ultrastructural aspect with TEM. The SEM observations showed the connection between morphovolumetric variations of uroepithelial cells and respiratory enzymatic …

Characterization of a novel three-dimensional outgrowth model of human bronchial mucosa

Recently it has been hypothesized that a reactivation of the epithelial-mesenchymal trophic unit (EMTU) of the respiratory mucosa, caused by extensive epithelial damage, may be responsible for the pathogenesis of asthma. However, most research on this subject so far has been limited by the unavailability of in vitro models correctly mimicking the three-dimensional architecture of the properly differentiated human bronchial mucosa. For this reason, we have developed a novel 3D outgrowth model, obtained from bronchial biopsies and composed of both human bronchial epithelial cells (goblet and columnar cells) and fibroblasts with their basement membrane. Here we present the preliminary data obt…

A Study on the Effects of Clearance and Interference Fits in a Pin-Loaded Cross-Ply FGRP Laminate

The elastic behavior of a cross-ply fiber glass-reinforced epoxy laminate loaded in tension through a pin fitted with clearance and interference is examined. A nonlinear contact analysis using the Finite Element Method and an experimental study by Speckle Interferometry are performed, showing fairly good correlation. An interesting comparison is performed between FEM results and Hertzian contact theory. Major conclusions are: (I) clearance causes high compressive stress in the bearing area, and does not influence the peak tensile stress; (2) interference has beneficial effects on the joint, as (a) it lowers the peak circumferential stress, and (b) it decreases the change of stress due to t…

Is chlamydial heat shock protein 60 a risk factor for oncogenesis?

Heat shock protein 60 (HSP60) plays an important role in the protein folding of prokaryotic and eukaryotic cells. Most of the papers published on chlamydial HSP60 concern its role in immune response during infection. In the last decade, exposure to Chlamydia trachomatis has been consistently associated with the development of cervical and ovarian cancer. Moreover, it has been suggested that chlamydial HSP60 may have an anti- apoptotic effect during persistent infection. We hypothesize that the accumulation of exogenous chlamydial HSP60 in the cytoplasm of actively replicating eukaryotic cells may interfere with the regulation of the apoptotic pathway. The concomitant expression of viral onc…

Sarcomatoid carcinoma of urinary bladder: Immunohistochemical study of an uncommon case

A case of sarcomatoid carcinoma of the bladder is reported herein. Immunohistochemical staining with human pancytokeratin antibody was negative, while vimentin staining was strongly positive, suggesting a diagnosis of sarcoma of the bladder. Further immunohistochemical analysis revealed positivity for AE1/AE3 cytokeratins, permitting a correct diagnosis of sarcomatoid carcinoma of the bladder. It can be difficult to distinguish between sarcomatoid carcinoma, undifferentiated carcinoma and sarcoma, particularly if the biopsy specimens are of small size. In rare cases, sarcomatoid tumors may express epithelial markers different from those revealed by human pancytokeratin staining. Copyright ©…

Exosomal Hsp60 levels and related miRNA in brain tumor cells

One of the many pathologic conditions still without a satisfactory solution is that of brain tumors. The prognosis is poor even after surgical resection followed by post-operatory chemo- and radio-therapie (1). It is, therefore, cogent to find innovative treatment tools. Three recent developments may provide elements to discover novel treatment strategies and means. These developments are: the discovery that molecular chaperones can be determinant factors in the process of tumorigenesis (2); the elucidation of the role of miRNAs in gene regulation and determination of protein functions, including molecular chaperones; in the various cell compartments (3);the increasing understanding and cha…

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

Hypoxia-inducible factor-1α is found frequently overexpressed in solid tumors cells, exerting an important role in angiogenesis, glucose metabolism, cell proliferation, survival and invasion. In thyroid carcinomas, hypoxia-inducible factor-1α expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1α induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1α synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously shown the role of BRAFV600…

Silybin enhances mitochondrial function and inhibits NFkB activation in murine nonalcoholic fatty liver disease

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Background Obesity has tremendous impact on the health systems. Its epigenetic bases are unclear. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Their role in adipose tissue plasticity is unknown. Results Here, we show evidence that macroH2A1.1 protein levels in the visceral adipose tissue of obese humans positively correlate with BMI, while macroH2A1.2 is nearly absent. We thus introduced a constitutive GFP-tagged transgene for macroH2A1.2 in mice, and we characterized their metabolic health upon being fed a standard chow diet or a hig…

Preoperative Considerations on the Thorax: Anatomy and Surgical Landmarks

The thoracic wall is the higher part of the thorax consisting of a musculoskeletal structure including the mediastinum, the pleuropulmonary cavities, viscera, lymphatic, vascular, and nervous structures. Its dimensions are influenced by age, gender, and life style including physical training. It changes constantly in shape and size according to respiration: Generally, males show an abdominal pattern while females have usually a thoracic respiration pattern. The anatomy of the chest differs between men and women, with considerable variations among different ages and races. The skin is thicker in male than in female. In the male thorax, hair is frequently present and the mammary glands are un…

Estrogens control inflammation in experimental colitis.

There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced…

On the Effect of Interference Fits in Composite Pin-Joints

The Finite Element Method is used to determine the effect of pin/hole interference fits on the elastic membranal behavior of an orthotropic plate loaded in tension through a pin. A complete contact analysis is performed to handle the nonlinear contact problem. The study encompasses two levels of interference fits, two degrees of anisotropy of the plate, and two load levels. Friction effects are not included. Experimental results from Digital Speckle Pattern Interferometry are also presented. It is shown that the stress changes in the plate vary linearly with load when no pin/plate separation occurs. It is also shown that interference fits can have beneficial effects on the static and fatig…

Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.

This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…

Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit.

During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in…

Hsp60 and human aging: Les liaisons dangereuses 

Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly…

Synovial sarcoma and malignant mesothelioma of the pleura: Review, differential diagnosis and possible role of apoptosis

Synovial sarcoma of the pleural cavity is exceptionally rare and may be confused, both clinically and histologically, with malignant mesothelioma, with subsequent inappropriate therapy. To address this dilemma, four biphasic synovial sarcomas (BSSs) and four biphasic malignant mesotheliomas (BMMs) were studied with a panel of mucin and immunohistochemical stains to determine if they would allow one to distinguish between the two. The BMMs were all pleural-based. The BSSs were extrapleural. The mucin and immunohistochemical stains were all performed on formalin-fixed, paraffin-embedded tissue using standard techniques, with appropriate positive and negative controls. Mucin present in BSS is,…

Effects of Conjugated Linoleic Acid Associated With Endurance Exercise on Muscle Fibres and Peroxisome Proliferator-Activated Receptor γ Coactivator 1 α Isoforms

Conjugated linoleic acid (CLA) has been reported to improve muscle hypertrophy, steroidogenesis, physical activity, and endurance capacity in mice, although the molecular mechanisms of its actions are not completely understood. The aim of the present study was to identify whether CLA alters the expression of any of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) isoforms, and to evaluate the possible existence of fibre-type-specific hypertrophy in the gastrocnemius and plantaris muscles. Mice were randomly assigned to one of four groups: placebo sedentary, CLA sedentary, placebo trained, or CLA trained. The CLA groups were gavaged with 35 μl per day of Tonalin® FFA 8…

BENEFICIAL EFFECT OF PROBIOTICS ADMINISTRATION IN INFLAMMATORY BOWEL DISEASE AND RELATED SPONDYLOARTHROPATHY: A PROSPECTIVE STUDY

Background: Therapeutic treatment for inflammatory bowel disease (IBD) may follow different approaches, systemic as well as local, especially when the target is the osteoarticular apparatus. Although some clinical trials have suggested benefits from probiotics administration in IBD, there is still a great deal of controversy on their use. The aim of this study was to further investigate the effects of probiotics in patients with IBD and related spondyloarthropathy. Material/Methods: Fifty-nine patients affected by IBD with extra-intestinal involvement where evaluated from 2006 to 2010. Twenty-eight patients received administration of a standard therapy with mesalazine and 31 where treated w…

Computer Model fo arterial bio-mechanics. Evaluation of Abdominal Aortic Aneurysm wall through Finite Element Analysis

Atrial natriuretic factor,but non oxytocin, presence in atherosclerotic plaques of human common carotid arteries

Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?

To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data sug…

2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90

Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytomet…

Chaperonin Hsp60 and Cancer Therapies

The heat shock protein 60 (Hsp60) is a chaperonin belonging to the chaperoning (chaperone) system that typically contributes to protein homeostasis inside mitochondria, but also plays various non-canonical roles unrelated to protein quality control beyond the organelle. Chaperonopathies are disorders in which chaperones play an etiologic-pathogenic role and contribute to the onset/progression of disease. Hsp60 chaperonopathies by mistake are diseases in which the chaperonin is apparently normal (as far as it can be determined with current methodologies) but it actively contributes to pathology, for example in certain types of cancer, and autoimmune and chronic inflammatory disorders. In cer…

A brief anatomo-surgical dissection guide to human mediastinal anatomy: results of the collaboration between the University of Palermo and the University of Malta.

In the summer of 2017, thanks to an agreement between the University of Malta and the University of Palermo, a group of students from the University of Palermo, who had already taken the anatomy exams and had a good knowledge of English, went for a 4 week period to the University of Malta to follow a dissection course . The students dissected skin, the sternum, the vessels, the nerves, analyzed the pericardium, the lungs and all the mediastinal organs. This work proves to be a small dissection guide for young medical students who want to learn the basics of dissection and the relevant topographical anatomy. The students were selected by the University of Palermo because of the good quality …

Other Genetic Chaperonopathies

In this chapter are presented chaperonopathies in which a genetic mechanism is involved but are different from those discussed in chapter 4. Thus, chaperonopathies due to gene dysregulation such as those observed in aged individuals and in some cases with neurodegenerative diseases (e.g., Alzheimer’s, Huntington’s, Parkinson’s, and other conditions), are presented. Likewise, examples of the impact of chaperone-gene polymorphisms on health and disease are given. The quantitative chaperonopathies attributable to gene dysregulation are discussed.

Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise

Simple Summary Skeletal muscle represents about 40% of the body mass in humans and it is a copious and plastic tissue, rich in proteins that are subject to continuous rearrangements. Physical exercise is considered a physiological stressor for different organs, in particular for skeletal muscle, and it is a factor able to stimulate the cellular remodeling processes related to the phenomenon of adaptation. All cells respond to various stress conditions by up-regulating the expression and/or activation of a group of proteins called heat shock proteins (HSPs). Although their expression is induced by several stimuli, they are commonly recognized as HSPs due to the first experiments showing thei…

Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 α1 expression

AbstractHeat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activa…

Role of endothelial cell stress in the pathogenesis of chronic heart failure.

Endothelial cells are key modulators of diverse physiological processes, and their impaired function is a cause of numerous cardiovascular diseases. Under physiologic condition, the reactive oxygen and nitrogen mediators in endothelia lead to the signal propagation of the initial stimulus, by forming molecules with a longer half-life like hydrogen peroxide. Hydrogen peroxide is the focus of growing attention in endothelial biology, and consequently the enzymes involved in its generation and clearance are viewed as novel mediators of great importance. In particular, among peroxidases, myeloperoxidase is recognized as a key enzyme, capable of impairing intracellular NO reservoirs as well as p…

High resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD.

BACKGROUND: The literature shows conflicting results when high-resolution computed tomography (HRCT) scores of emphysema were correlated with different indices of airflow obstruction. OBJECTIVES: We correlated HRCT scores of emphysema with different indices of airflow obstruction. METHODS: We performed HRCT of the chest in 59 patients, all smokers or ex-smokers, with stable chronic obstructive pulmonary disease of different severity [GOLD stages I-IV; mean age ± SD 67.8 ± 7.3 years; pack/years 51.0 ± 34.6; percent predicted forced expiratory volume in 1 s (FEV(1)% predicted) 52.3 ± 17.6; post-bronchodilator FEV(1)% predicted 56.5 ± 19.1; FEV(1)/forced vital capacity (FVC) ratio 50.8 ± 10.2;…

Effects of Pleurotus eryngii var. eryngii in "in vitro" and "in vivo" cancerogenetic models

Heat shock proteins (Hsps) are highly expressed in a variety of cancer types contributing to tumor cell propagation and protection against apoptosis [1]. The current anti-cancer therapy is not always target specific and often is associated with complications for patients, Therefore new effective, specific and less toxic therapeutic approaches are needed. Medicinal mushrooms have emerged as wonderful source of nutraceuticals, anti-oxidants, anticancer, prebiotic, anti-inflammatory, cardiovascular, anti-microbial, and anti-diabetic. The ongoing research projects are aimed to promote mushrooms as new generation ‘‘biotherapeutics’’[2]. The aim of this study was to evaluate whether the cold-wate…

Automatic induction of rules for computer-aided diagnosis in the multiple sclerosis by analysis of brain MR images

Hsp60/procaspase 3 complex formation in human cells: impact on apoptosis and carcinogenesis.

Isolation and Characterization of CD276+/HLA-E+ Human Subendocardial Mesenchymal Stem Cells from Chronic Heart Failure Patients: Analysis of Differentiative Potential and Immunomodulatory Markers Expression

Mesenchymal stem cells (MSCs) are virtually present in all postnatal organs as well as in perinatal tissues. MSCs can be differentiated toward several mature cytotypes and interestingly hold potentially relevant immunomodulatory features. Myocardial infarction results in severe tissue damage, cardiomyocyte loss, and eventually heart failure. Cellular cardiomyoplasty represents a promising approach for myocardial repair. Clinical trials using MSCs are underway for a number of heart diseases, even if their outcomes are hampered by low long-term improvements and the possible presence of complications related to cellular therapy administration. Therefore, elucidating the presence and role of MS…

Data mining-based statistical analysis of biological data uncovers hidden significance: clustering Hashimoto’s thyroiditis patients based on the response of their PBMC with IL-2 and IFN-γ secretion to stimulation with Hsp60

The pathogenesis of Hashimoto's thyroiditis includes autoimmunity involving thyroid antigens, autoantibodies, and possibly cytokines. It is unclear what role plays Hsp60, but our recent data indicate that it may contribute to pathogenesis as an autoantigen. Its role in the induction of cytokine production, pro- or anti-inflammatory, was not elucidated, except that we found that peripheral blood mononucleated cells (PBMC) from patients or from healthy controls did not respond with cytokine production upon stimulation by Hsp60 in vitro with patterns that would differentiate patients from controls with statistical significance. This "negative” outcome appeared when the data were pooled and ana…

Mitochondrial DNA mutations in cancer--from bench to bedside.

Mitochondria are cell organelles mostly known for their production of ATP through oxidative phosphorylation. As suggested over 70 years ago by O. Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA appear to be a common feature of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells. MtDNA mutation pattern may enhance the specificity of cancer diagnostics, detection and prediction of tumor growth rate and patients' outcome. Therefore it may be used as a molecular cancer bio-marker. Nevertheless recently published papers list a large number of mitochondrial DNA mutations in many different can…

Potential Health Benefits of Olive Oil and Plant Polyphenols

Beneficial effects of natural plant polyphenols on the human body have been evaluated in a number of scientific research projects. Bioactive polyphenols are natural compounds of various chemical structures. Their sources are mostly fruits, vegetables, nuts and seeds, roots, bark, leaves of different plants, herbs, whole grain products, processed foods (dark chocolate), as well as tea, coffee, and red wine. Polyphenols are believed to reduce morbidity and/or slow down the development of cardiovascular and neurodegenerative diseases as well as cancer. Biological activity of polyphenols is strongly related to their antioxidant properties. They tend to reduce the pool of reactive oxygen species…

Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.

BackgroundIt is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.Methods and resultsBronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between th…

Hsp60 molecular anatomy and role in colorectal cancer diagnosis and treatment

Quantitative changes in Hsp60 during the development of some tumors suggest that this chaperonin plays a role in carcinogenesis. A description of the specific role(s) of Hsp60 in tumor-cell growth and proliferation is still incomplete, but it is already evident that monitoring its levels and distribution in tissues and fluids has potential for diagnosis and staging, and for assessing prognosis and response to treatment. Although Hsp60 is considered an intramitochondrial protein, it has been demonstrated in the cytosol, cell membrane, vesicles, cell surface, extracellular space, and blood. The knowledge that Hsp60 occurs at all these locations opens new avenues for basic and applied research…

La tracheostomia in urgenza nel trattamento delle ostruzioni delle vie respiratorie

Structural and Hereditary Chaperonopathies: Mutation

This chapter deals with structural and hereditary chaperonopathies. The chaperonopathies caused by mutations in: sHsp, chaperonin genes (Hsp60 or Cpn60, and CCT subunits), Hsp40/DnaJ, Hsp70, sacsin, and dedicated chaperones (e.g., those involved in microtubule biogenesis, in maintenance of the respiratory chain inside the mitochondria, and others in various cell compartments and tissues), are described and discussed.

Heat shock protein 60 (Hsp60) modulation by the Histon Deacetylase Inhibitor (HDAC-i) SAHA in mucoepidermoid tumor H292 cells

hDAF expression in hearts of transgenic pigs obtained by sperm-mediated gene transfer.

TRANSPLANTATON has been the choice option to treat successfully an increasing number of acute and chronic human pathologies with declining morbidity and mortality. However, availability of organs from human donors is limited and dramatically inadequate with respect to patient requests. Xenotransplantation from large-sized mammals has thus been reconsidered as a tool to overcome the present unbalance between organ offers and requests. Pigs have been chosen because they can be easily and cheaply bred; they do not raise ethical questions—their use as alimentary resources is generally admitted; and they possess organs largely human compatible for size, anatomical organization, and physiology. N…

Characterization of c-kit positive cardiac stem cells subpopulations obtained from adult rat myocardium

Chaperonology: a novel research field for experimental medicine in XXI century.

Clinical Anatomy of Central Venous Catheterization Ultrasound-Guided

Small airways in in sedentary and endurance-trained dystrophic (mdx) mice

The effects of mild endurance exercise training on the small airways in mdx mice are unknown. We compared epithelial thickness and turnover, apoptosis, and stress marker expression in small airways of mdx mice and wild-type (WT) controls, at rest and during exercise training. Mdx and WT mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 d/wk for 6 wk at progressively increasing speed (rpm from 16 to 24) and time (15 min to 1 h). Lungs were processed for light microscopy and periodic acid Schiff (PAS) staining. Hsp60 and PCNA were quantified by immunohistochemistry.…

Senescence-associated HSP60 expression in normal human skin fibroblasts

Normal mammalian fibroblasts cultured in vitro undergo a limited number of divisions before entering a senescent phase in which they can be maintained for long periods but cannot be induced to divide. Senescent cells become unresponsive to growth-promoting signals and exhibit senescent cell morphology with flattened and enlarged cell shape. Several chaperones have a direct effect on cellular senescence. HSP60 has been largely studied in our laboratories and it has been associated with uncontrolled cell proliferation in tumor cells. Since senescence is firmly regulated during cell cycle progression, we wanted to investigate HSP60 protein level during cellular senescence. Our data show that H…

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease.

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of …

A brief anatomo-surgical dissection guide to the human neck: results of a collaboration between the University of Palermo and the University of Malta.

The aim of this work was to offer a guide to young students and medical doctors that want to learn the bases of neck dissection. In the summer of 2017 a group of students from the University of Palermo that had already passed the Human Anatomy exams took a 4 weeks dissection course at the University of Malta Medicine is a science that requires both a practical and theoretical approach, and the last one, unfortunately, often is not valued by our University. Studying Human Anatomy, which is the basis for a doctor's education, exclusively through books and atlases, is indeed partially lacking. For this reason a group of students from the University of Palermo have been selected, based on their…

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis.

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on …

Role of CD1A and HSP60 in the antitumoral response of oesophageal cancer

Oesophageal cancer (OC) is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Fur…

Benign gastric polyps and Helicobacter pilori infection

Primitive Neuroectodermal Tumor (PNET) of the kidney: a case report.

Abstract Background A case of Primitive Neuroectodermal Tumor (PNET) of the kidney in a 27-year-old woman is presented. Few cases are reported in the literature with a variable, nonspecific presentation and an aggressive behaviour. In our case, a radical nephrectomy with lymphadenectomy was performed and there was no residual or recurrent tumour at 24-month follow-up. Methods The surgical specimens were formalin-fixed and paraffin embedded. The sections were stained with routinary H&E. Immunohistochemistry was performed. Results The immunohistochemical evaluation revealed a diffuse CD99 positivity in the cytoplasm of the neoplastic cells. Pankeratin, cytokeratin AE1/AE3, vimentin, desmin, S…

Tree dimensional computer model in a case of azygos lobe discovered during adenocarcinoma surgery

Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine. Here we found that guadecitabine is an effe…

IDENTIFICATION OF C-KIT/CD105 AND ISL-1 CELLS IN HUMAN FETAL AND INFANT HEARTS

During embryogenesis, the mammalian heart develops from a primitive heart tube, which derives from two bilateral primary heart fields located in the lateral plate mesoderm. Later on in the development process, the atrioventricular (A-V) canal and the sinu-atrial segment, at the venous pole, and the conotruncus, at the arterial pole, are added to the heart tube just prior to tube looping. In 2001 Waldo and colleagues and Kelly and colleagues demonstrated the presence of a secondary or anterior heart field in the ventral pharyngeal mesoderm. This region contains a pool of NKX2.5 and GATA-4 positive precardiac cells which migrate to the arterial pole of the primary heart tube. Isl-1 is a marke…