Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy?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

2021

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…

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

2013

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 card…

2007

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

2005

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

2010

Hsp27 and Hsp60 in human submandibular salivary gland: Quantitative patterns in healthy and cancerous tissues with potential implications for differe…

2021

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.

2010

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

2014

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…

The Role of the Heme Oxygenase System in the Metabolic Syndrome

2014

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

2015

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 …

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

2019

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.

2015

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

2021

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…

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

2007

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.…

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

2008

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

2006

Anatomy and Physiology of the Peripheral and Central Auditory System

2019

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 agents

2007

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

2013

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

2001

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…

HEART MOBILE LEARNING

2018

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

2021

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

2019

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.

2006

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.

Hsp60 Friend and Foe of the Nervous System

2019

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

2016

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

2011

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:…

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

2017

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.

2020

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

2010

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

2015

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

2015

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.

2013

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…

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

2012

<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?"

2017

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.

2006

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

2013

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

2013

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?

2020

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.

Other Types of Chaperonopathies

2013

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…

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

2020

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

2006

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…

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

2015

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 …

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

2015

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…

2013

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

2016

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

2021

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…

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

2015

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

2015

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…

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

2021

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

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

2003

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

2016

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

2015

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).

2016

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

2011

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?

2009

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 Differ…

2023

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…

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

2012

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…

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

2010

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…

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

2017

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

2008

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, …

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

2021

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…

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.

2016

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 Insu…

2022

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

2007

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

2007

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

2009

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?

2005

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…

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

2019

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.

2014

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

2021

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…

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

2012

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 Progr…

2016

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…

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

2020

2-Methoxyestradiol is one of the natural 17&beta

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

2008

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…

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

2019

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

2020

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

2012

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

2016

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…

Overview and Book Plan

2013

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

2017

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…

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

2010

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.

2010

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

2017

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 po…

2009

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

2002

&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…

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

2015

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

1999

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…

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

2005

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

2018

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…

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

2023

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?

2020

Mature teratoma of the uterine corpus with thyroid differentiation

2000

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:,

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

2015

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

2017

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 pre…

2014

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…

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

2003

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

2020

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) adenocarcino…

2003

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…

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

2011

Lymphatic vessels of the dura mater: a new discovery?

2015

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.

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

2013

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.

2006

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

2010

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

2015

&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…

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

2021

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?

2020

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

2013

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

2018

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?

2006

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

2005

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

2023

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…

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

2013

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…

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

2009

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…

Research of cardiomyocyte precursors in adult rat heart

2006

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.

2017

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…

SPECIAL ISSUE: The clinical relevance of exosomes in cancer

2021

Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for diff…

2019

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 H…

2011

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

2019

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

1999

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 …

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

2020

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 R…

2012

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

2010

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.

2013

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.

2018

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…

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

2021

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

2014

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.

2018

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

2016

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…

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

2012

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

2007

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…

The Chaperonopathies: Classification, Mechanisms, Structural Features

2013

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

2014

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

2022

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

2009

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…

A genetic algorithm for combined topology and shape optimisations

2003

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

2019

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 Concentrati…

2014

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…

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

2019

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

2020

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

2016

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

2014

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

2017

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.

2009

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.

2008

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…

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

2007

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

2005

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

2013

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.

2014

[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

2001

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

2006

On the Choice of the Extracellular Vesicles for Therapeutic Purposes

2019

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…

Chaperones: General Characteristics and Classifications

2013

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 Marke…

2009

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…

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

2021

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

2001

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

2015

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.

2010

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…

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

2017

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

2019

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…

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

2022

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…

Zebrafish as a Model for the Study of Chaperonopathies

2016

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…

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

2020

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…

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

2019

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…

2023

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…

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

2021

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

2014

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 n…

2008

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

2008

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.

2007

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 geometrical models of the inguinal region. Towards a new stereology.

2003

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.

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

2003

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.

2022

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…

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

2023

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…

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

2015

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

2017

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…

Distribution of mitochondrial chaperonins in lung cells

2011

Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?

2010

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 …

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

2015

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

2018

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

2021

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…

HSP60 activity on human bronchial epithelial cells

2017

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.

2022

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…

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

2016

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

2020

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…

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

2011

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…

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

2015

// 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 re…

2017

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…

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

2020

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.

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

2012

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 …

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the …

2013

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

2021

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.

2020

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

2007

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 …

Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection: effect of ACE-2 expression on tumor cells or molecul…

2021

Lactobacillus casei and Bifidobacterium lactis supplementation reduces tissue damage of intestinal mucosa and liver after 2,4,6-trinitrobenzenesulfon…

2014

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?

2004

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…

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

2015

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

2021

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…