Asthmatic Bronchial Epithelial Cells (BEC) do not undergo apoptosis in response to Rhinovirus (RV) infection and this is associated with increased viral replication.

Extracellular vesicles in airway homeostasis and pathophysiology

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

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

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

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

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

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

ADAM33, alpha smooth muscle actin and collagen expression in human embryonic lung in vivo and in culture.

Interleukin-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction.

Brain Tumor-Derived Extracellular Vesicles as Carriers of Disease Markers: Molecular Chaperones and MicroRNAs

Primary and metastatic brain tumors are usually serious conditions with poor prognosis, which reveal the urgent need of developing rapid diagnostic tools and efficacious treatments. To achieve these objectives, progress must be made in the understanding of brain tumor biology, for example, how they resist natural defenses and therapeutic intervention. One resistance mechanism involves extracellular vesicles that are released by tumors to meet target cells nearby or distant via circulation and reprogram them by introducing their cargo. This consists of different molecules among which are microRNAs (miRNAs) and molecular chaperones, the focus of this article. miRNAs modify target cells in the…

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

Hsp60 is actively secreted by human tumor cells

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

Modulation of MMP-2 activity in human lung fibroblasts by sigarette smoke: role in the maintenance of the inflamed state in COPD.

Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit

Background/Aim: Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture. Materials and Methods: Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE). Res…

Effect of IL-13Ralpha2 Receptor levels on the biological activity of IL-13 variant R110Q.

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three-Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

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

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

Cigarette smoke promotes inflammasome‐independent activation of caspase‐1 and ‐4 leading to gasdermin D cleavage in human macrophages

Mechanisms and consequences of gasdermin D (GSDMD) activation in cigarette smoke (CS)-associated inflammation and lung disease are unknown. GSDMD is a downstream effector of caspase-1, -8, and -4. Upon cleavage, GSDMD generates pores into cell membranes. Different degrees of GSDMD activation are associated with a range of physiological outputs ranging from cell hyperactivation to pyroptosis. We have previously reported that in human monocyte-derived macrophages CS extract (CSE) inhibits the NLRP3 inflammasome and shifts the response to lipopolysaccharide (LPS) towards the TLR4-TRIF axis leading to activation of caspase-8, which, in turn, activates caspase-1. In the present work, we investig…

Polmunary epithelial barrier formation on biodegradable poly-L-lactic-acid (PLLA) membrane

Aims: Investigation of epithelial barrier formation using PLLA membranes for application in bioengineering. Background: The development of functional and biocompatible substitutes for damaged tissue or organs is a major challenge in biomedical engineering. The epithelial barrier plays a central role in tissue homeostasis and immunity preventing damage and contamination of the interstitial tissues. Different in vitro models of the lung and intestinal epithelial barriers have been well characterized, however these tend to use non-biodegradable and/or poorly biocompatible scaffolds. Therefore, there is a need for better supports for epithelial cells for future applications in tissue engineerin…

Neutrophil apoptosis in COPD.

Laboratory Technologies and Methodologies

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

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

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

EXTRACELLULAR RELEASE OF HSP60 FROM TUMOR CELLS

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

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

Molecular Chaperones and Thyroid Cancer

Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identifying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of t…

Effect of IL-13Rα2 receptor levels on the biological activity of IL-13 variant R110Q.

CD40 ligation induces stress-mediated apoptosis in bronchial epithelial cells

Role of chronic exposure to cigarette smoke on endoglin/CD105 expression in airway epithelium

Dysregulation of airway epithelium function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD and is associated to tissue damage and disease severity. CD105 is a component of the receptor complex of TGF-β, a pleiotropic cytokine involved in cellular proliferation, differentiation and migration. CD105 regulates the expression of different components of the extracellular matrix suggesting a role of CD105 in cellular transmigration and remodeling processes. The aim of the present study was to investigate the expression of endoglin/CD105 in airway epithelium of COPD patients and its involvement in tissue remodeling and COPD progression. We evaluated the …

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

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

Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses

Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers,…

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

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

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

The temporal expression of ciliated bronchial epithelium (CBE) 1 in embryonic lungs.

Exosome Involvment in Hsp60 secretion by tumor cells.

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

<i>Objectives:</i> 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. <i>Methods and Results:</i> 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…

STUDYING EMBRYONIC LUNG DEVELOPMENT BY TISSUE ENGINEERING.

Exosomal Hsp60 in human colon cancer

IL-13 receptor α 2: A regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts

Background IL-13 and IL-4 share many functional properties as a result of their use of a common receptor complex comprising IL-13 receptor α 1 (IL-13Rα1) and IL-4 receptor α (IL-4Rα). The nonsignaling receptor IL-13 receptor α 2 (IL-13Rα2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13. Objective We sought to examine the inhibitory effects of soluble and membrane-bound IL-13Rα2 on IL-13– and IL-4–mediated effects. Methods Primary human fibroblasts were grown from endobronchial biopsy specimens obtained from volunteers. Upregulation of IL-13Rα2 mRNA was measured by means of RT-PCR, and the level of surface expression was measured by means of F…

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

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

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

Lymphatic vessels of the dura mater: a new discovery?

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

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

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

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

Asthmatic epithelial cells are more sensitive to smoke-induced apoptosis: differential role of antioxidants.

Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients

AbstractCigarette smoke is a risk factor for COPD and lung cancer. In cancer, epigenetic modifications affect the expression of Enhancer of Zester Homolog 2 (EZH2), and silenced disabled homolog 2 interacting protein gene (DAB2IP) (onco-suppressor gene) by Histone H3 tri-methylation in lysine 27 (H3K27me3). In“ex vivo”studies, we assessed EZH2, H3K27me3 and DAB2IP immunoreactivity in bronchial epithelial cells from COPD patients (smokers, ex-smokers), Smoker and control subjects. In“in vitro” experiments we studied the effect of cigarette smoke extract (CSE) on EZH2/H3K27me3/DAB2IP expression, apoptosis, invasiveness, and vimentin expression in 16HBE, primary cells, and lung cancer cell lin…

Chronological expression of Ciliated Bronchial Epithelium 1 during pulmonary development

Ciliated Bronchial Epithelium (CBE) 1 is a novel gene, which is expressed in ciliated cells. As cilia are important during embryogenesis, the present authors characterised the murine homologue of CBE1 (Cbe1) and compared its temporal expression during murine and human lung development. Cbe1 cDNA was cloned and characterised using sequencing, standard PCR and Western blotting. Mouse and human embryonic/fetal lungs (HELs) were harvested for mRNA analysis and protein localisation in vivo and in vitro using RT-PCR and immunohistochemistry. The Cbe1 amino acid sequence was >75% identical with CBE1 and its alternative splicing and tissue distribution were highly conserved. Pulmonary expression of…

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

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

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

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

Corrigendum to “Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis” [Dig. Liver Dis. 44 (2012) 334–342]

ADULT STEM CELLS: THE REAL ROOT INTO THE EMBRYO?

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

Trafficking and secretion patterns of Hsp60 in tumor cells.

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

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

Augmented Reality Gamification for Human Anatomy

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

Role of chronic exposure to cigarette smoke on Oct-4/CD146 imbalance in human bronchial epithelial cells

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

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

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

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

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

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

Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.

Aims: Substantial evidence indicates that 5-HT2C receptors are involved in the control of neuronal network excitability and in seizure pathophysiology. Here, we have addressed the relatively unexplored relationship between temporal lobe epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs. Methods: In this study, we investigated this issue using a model of partial complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology, immunohistochemistry, and western blotting techniques. Results: The 5-HT2C agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p), but not RO60-0…

Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors

BackgroundEpidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke.ObjectivesSince primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death.MethodsPBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by fl…

5-Fluororacile-loaded matrix tablets for locoregional delivery: effects on a three-dimensional culture model of primary oral squamous cell carcinoma

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

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

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

Poorly differentiated synovial sarcoma: A case report

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

Medium-term Culture of Normal Human Oral Mucosa: A Novel Three-dimensional Model to Study the Effectiveness of Drugs Administration

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an arti…

TISSUE ENGINEERING FOR THE DEVELOPMENT OF THREE-DIMENSIONAL INVITRO MODELS OF HUMAN MUCOSAE

Traditional two-dimensional (2D) cell cultures only partially reflect the morpho-molecular pattern of human cells in tissues, and they are also unable to fully mimic the complexity of the in vivo microenvironment. Cell development in in vivo systems differs significantly from classical 2D cell culture models, especially with regard to the morphology, growth kinetics, gene expression and the degree of differentiation. Tissue engineering allows the reproduction of tissues by cell seeding on biocompatible scaffolds, to form a homogenous ...

Study of axillary lymph node asymmetry in a female population

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

Modulation of MMP-2 activity in human lung fibroblasts by cigarette smoke: role in maintenance of the inflamed state in copd

Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes

Development of biocompatible and functional scaffolds for tissue engineering is a major challenge, especially for development of polarised epithelia that are critical structures in tissue homeostasis. Different in vitro models of the lung epithelial barrier have been characterized using non-degradable polyethylene terephthalate membranes which limits their uses for tissue engineering. Although poly-L-lactic acid (PLLA) membranes are biodegradable, those prepared via conventional Diffusion Induced Phase Separation (DIPS) lack open-porous geometry and show limited permeability compromising their use for epithelial barrier studies. Here we used PLLA membranes prepared via a modification of the…

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

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

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

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

Three-Dimensional Bioprinting for Cartilage Tissue Engineering: Insights into Naturally-Derived Bioinks from Land and Marine Sources

In regenerative medicine and tissue engineering, the possibility to: (I) customize the shape and size of scaffolds, (II) develop highly mimicked tissues with a precise digital control, (III) manufacture complex structures and (IV) reduce the wastes related to the production process, are the main advantages of additive manufacturing technologies such as three-dimensional (3D) bioprinting. Specifically, this technique, which uses suitable hydrogel-based bioinks, enriched with cells and/or growth factors, has received significant consideration, especially in cartilage tissue engineering (CTE). In this field of interest, it may allow mimicking the complex native zonal hyaline cartilage organiza…

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

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

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

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

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

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

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

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

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

HSP60 activity on human bronchial epithelial cells

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

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…

EXPOSURE OF BRONCHIAL EPITHELIAL CELLS TO CIGARETTE SMOKE EXTRATS (CSE) INDUCES CASPASE-3-INDEPENDENT APOPTOSIS

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

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

Epithelial-Mesenchimal communication in response to rhinovirus infection of primary bronchial epithelial cells.

Airway epithelial dysfunction and mesenchymal transition in chronic obstructive pulmonary disease: Role of Oct-4

Abstract The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airway epithelial function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD. Oct4 is a transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 and CD105/Endoglin are adhesion molecules involved in cell proliferation, differentiation, epithelial-mesenchymal-transition and tissue remodeling. Bronchial biopsy specimens (BBs) were obtained from 7 healthy controls (HC) and 10 COPD and subjected to paraffin embedding; BBs from HC were also used for epithelial cell expansion and pHBEC/ALI (air-liquid inter…

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…

Geldanamycin and its derivatives as Hsp90 inhibitors

The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and…

Biological evaluation of PLLA membranes, with different pore diameters, to stimulate cell adhesion and growth in vitro

Polymeric membranes prepared via DIPS (Diffusion Induced Phase Separation) are widely studied and utilized as scaffolds for the regeneration of tissue. In this work, poly (L)-lactide membrane are prepared through a DIPS protocol starting from a ternary solution made of polymer, dioxane (solvent) and water (non-solvent). A three-dimensional, porous and mechanically stable membrane is desirable for ingrowth of human bronchial epithelial cells. Polymeric membranes prepared via DIPS (Diffusion Induced Phase Separation) are widely studied and utilized as scaffolds for the regeneration of tissue. In this work, poly (L)-lactide membrane are prepared through a DIPS protocol starting from a ternary …

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

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

Asthmatic Bronchial Epithelium Is More Susceptible to Oxidant-Induced Apoptosis

Abnormal apoptotic mechanisms are associated with disease pathogenesis. Because the asthmatic bronchial epithelium is characteristically damaged with loss of columnar epithelial cells, we postulated that this is due to unscheduled apoptosis. Using an antibody directed toward the caspase cleavage product of poly(ADP-ribose) polymerase, immunohistochemistry applied to endobronchial biopsies showed higher levels of staining in the bronchial epithelium of subjects with asthma as compared with normal control subjects (% epithelial staining [median (range) = 10.5 (1.4-24.5) versus 0.4 (0.0-9.7)]; P < 0.001). Because we were unable to determine whether this difference was due to ongoing inflammati…

Role of immunohistochemical expression of PCNA and p53 in prostate carcinoma

Circulating exosomal Hsp60 as a new marker of colon cancer.

Differential effects of IL-13 on morphogenesis and MUC5AC expression in human embryonic lung explants – a role for IL-13R&#945;2?

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

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

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

Studying embrionic lung development by tissue engineering.

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Neutrophilic airway inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD) and correlates with disease severity. The mechanisms that determine the extent of neutrophilia could involve increased influx or prolonged survival of neutrophils. The aim of the study was to assess whether neutrophil pro-survival mechanisms are increased in the airways of subjects with COPD owing to the presence of anti-apoptotic factors in the bronchial lining fluid. Induced sputum samples were collected from 20 subjects with stable COPD, 14 healthy smokers and 14 healthy controls. Quantification of apoptotic neutrophils was based on typical morphological cell changes. Anti-apoptotic, p…

Exposure of bronchial epithelial cells to Cigarette Smoke Extracts (CSE) induces caspase-independent apoptosis.

Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.

Cigarette smoke alters primary human bronchial epithelial cell (PBEC) differentiation atAir-Liquid Interface (ALI): role of Oct-4, CD146 and CD105

The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airway epithelial cell function related to cigarette smoke (CS) exposure plays an important role in the pathophysiology of COPD. Oct-4 is the crucial POU domain transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 and CD105 are adhesion molecule involved in cellular proliferation, differentiation, epithelial-mesenchymal transition and tissue remodelling. Bronchial biopsy specimens (BBs) were obtained from 9 healthy controls (C) and 9 COPD. ALI cultures of PBEC from C were exposed to CS extract (CSE) for 7, 14, 21 days. Oct-4, CD105 and CD146 expr…

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

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

ADAM 33 in Embryonic Airways.

Epithelial-Mesenchimal communication in response to rhinovirus infection of primary bronchial epithelial cells.

Bronchial epithelial cells from smokers have a deficient innate immune response to infection with rhinovirus.

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

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

IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts.

Epithelial-Mesenchymal communication following Rhinovirus infection of asthmatic bronchial epithelial cells.

Cigarette smoke alters primary human bronchial epithelial cell (PBEC) differentiation at air-liquid interface (ALI) and induces expression of CD105 and CD146

Dys-regulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD. CD105, a component of TGF-β complex, and CD146, an epithelial-mesenchymal transition inducer, are adhesion molecules involved in cellular proliferation, differentiation, transmigration and tissue remodelling. After validation of an ex vivo ALI culture of PBEC, we assessed the effect of long-term cigarette smoke extract (CSE) exposure on epithelium regeneration and differentiation. Endobronchial biopsy specimens (EBBs) were obtained from 8 controls (C) and 9 COPD. ALI cultures from EBBs of C were exposed to CSE for 7, 14, 21 days. Transepithelial Elect…

Inflammatory mediators release from asthmatic & non-asthmatic bronchial epithelial cells following infection with rhinovirus (RV)

Role of chronic exsposure to cigarette smoke on endoglin/CD105 expression in airway epithelium.

Dysregulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD and is associated to tissue damage and disease severity. CD105 is a component of the receptor complex of TGF-β, a pleiotropic cytokine involved in cellular proliferation, differentiation and migration. CD105 regulates the expression of different components of the extracellular matrix suggesting a role of CD105 in cellular transmigration and remodeling processes. The aim of the present study was to investigate the expression of endoglin/CD105 in airway epithelium of COPD patients and its involvement in tissue remodeling and progression of COPD. We evalua…

New Insights into Asthma Pathogenesis

CD40 ligation influences stress-mediated apoptosis in bronchial epithelial cells

Medium-term culture of embryonic lungs: a novel three-dimensional model

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

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

Modulation of MMP-2 activity in human lung fibroblasts by cigarette smoke: role in the manteinance of the inflamed state in COPD

Cigarette smoke alters the EZH2/DAB2IP expression in bronchial epithelial cells. A risk factor for lung cancer in COPD patients

Cigarette smoke is an environmental risk factor for COPD and Lung cancer, leading causes of morbidity and mortality worldwide. In cancer, enhancer of zeste homolog 2 (EZH2) silenced disabled homolog 2 interacting protein gene (DAB2IP) (tumor-suppressor gene) bytri-methylation of lysine 27 on histone H3 (H3K27me3). We studied EZH2 and DAB2IP expression in airway epithelial cells from COPD patients and their potential involvement in the progression of COPD toward lung cancer. We assessed EZH2 and DAB2IPimmunoreactivity in bronchial epithelial cells from surgical specimens of COPD patients and healthy control subjects (HC) by immunohistochemistry. Bronchial epithelial cell line (16HBE), primar…

Stem Cell Populations and Regenerative Potential in Chronic Inflammatory Lung Diseases

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

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

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

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

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

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

Exposure of bronchial epithelial cells to Cigarette Smoke Extract (CSE) induces caspase-indipendent apoptosis.

Establishment of a novel three-dimensional in vitro model to study the alterations of the epithelial-mesenchymal trophic unit (emtu) in asthma

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

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

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

Studying embryonic lung development by tissue engineering: a novel three-dimensional model

Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit

Background/Aim: Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture. Materials and Methods: Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE). Res…