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, including inflammatory ones. How nanovesicles produced by EMTU and MML may affect the airway integrity, leading to the onset of asthma and COPD, as well as their putative use in therapy will be discussed here

Extracellular vesicles derived from gut microbiota in inflammatory bowel disease and colorectal cancer

The human gut microbiome encompasses inter alia, the myriad bacterial species that create the optimal host-micro-organism balance essential for normal metabolic and immune function. Various lines of evidence suggest that dys-regulation of the microbiota-host interaction is linked to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Extracellular vesicles (EVs), found in virtually all body fluids and produced by both eukaryotic cells and bacteria are involved in cell-cell communication and crosstalk mechanisms, such as the immune response, barrier function and intestinal flora. This review highlights advancements in knowledge of the functional role that EVs may have in IBD and CRC, and discusses the possible use of EVs derived from intestinal microbiota in therapeutic strategies for treating these conditions

EXTRACELLULAR VESCICLES DERIVED FROM GUT MICROBIOTA IN INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER

The human gut microbiome encompasses inter alia, the myriad bacterial species that create the optimal host-microrganism balance essential for normal metabolic and immune function. Various lineas of evidence suggest that dysregulation of the microbiota-host interaction is linked to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Extracellular vescicles (EVs), found in virtually all body fluids and produced by both eukaryotic cells and bacteria are involved in cell-cell communication and crosstalk mechanism, such as the immune resèponse, barrier function and intestinal flora. This review highlligts advancements in knbowledge of the functional role that Evs may have in IBD and CRC, and discusses the possible use of EVs derived from intestinal microbiota in therapeutic strategies for treating these conditions

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 with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed thatHsp60Fclassically a mitochondrial proteinFwas abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease

Prognostic role of aldosterone in patients with acute coronary syndrome: short and medium term follow-up.

AIMS: Different studies have shown a correlation between aldosterone, atherosclerosis and ischemia in the past decade. Evidence exists for the relationship between high levels of aldosterone and augmented risk of cardiovascular diseases, such as hypertension, cardiac failure, coronary artery disease and stroke. The objective of this study was to determine the prognostic role of aldosterone in patients with myocardial infarction. METHODS:The study population included 96 consecutive patients admitted to our department for ST-elevated and non-ST-elevated myocardial infarction from June 2009 to March 2012. Plasma aldosterone levels were measured at admission to hospital in all patients. A 2-year prospective follow-up was performed, and fatal events and non-fatal events, such as reinfarction, congestive heart failure and arrhythmias, were recorded. RESULTS:Aldosterone levels at admission were associated with incidence of congestive heart failure (P\u200a=\u200a0.02), ventricular arrhythmias (P\u200a=\u200a0.01) and all complications (P\u200a=\u200a0.003) after 1-month follow-up. Moreover, high aldosterone levels gave important information in the medium term (24\u200a\ub1\u200a6 months). Specifically, aldosterone was a predictive variable of reinfarction (P\u200a<\u200a0.0001), congestive heart failure (P\u200a<\u200a0.0001) and adverse events (P\u200a=\u200a0.0002). The logistic regression analysis confirmed these results and showed that aldosterone may be predictive of adverse events at medium-term follow-up (odds ratio 1.1, 95% confidence interval 1.03-1.15, P\u200a=\u200a0.02). CONCLUSION:These data show a strong and significant correlation between plasma aldosterone levels at admission for myocardial infarction and fatal and nonfatal adverse events. Aldosterone appears to be a main marker of adverse clinical outcome, in accordance with the literature. These data suggest the need to identify whether antialdosteronic drug treatment, applied acutely in patients with aldosterone elevation, can influence favorably the prognosis of patients with myocardial infarction

Morphological alterations and stress protein variations in lung biopsies obtained from autopsies of covid-19 subjects

Molecular chaperones, many of which are heat shock proteins, play a role in cell stress response and regulate the immune system in various ways, such as in inflammatory/autoimmune reactions. It would be interesting to study the involvement of these molecules in the damage done to COVID-19-infected lungs. In our study, we performed a histological analysis and an immunomorphological evaluation on lung samples from subjects who succumbed to COVID-19 and subjects who died from other causes. We also assessed Hsp60 and Hsp90 distribution in lung samples to determine their location and post-translational modifications. We found histological alterations that could be considered pathognomonic for COVID-19-related lung disease. Hsp60 and Hsp90 immunopositivity was significantly higher in the COVID-19 group compared to the controls, and immunolocalization was in the plasma membrane of the endothelial cells in COVID-19 subjects. The colocalization ratios for Hsp60/3-nitrotyrosine and Hsp60/acetylate-lisine were significantly increased in the COVID-19 group compared to the control group, similar to the colocalization ratio for Hsp90/acetylate-lisine. The histological and immunohistochemical findings led us to hypothesize that Hsp60 and Hsp90 might have a role in the onset of the thromboembolic phenomena that lead to death in a limited number of subjects affected by COVID-19. Further studies on a larger number of samples obtained from autopsies would allow to confirm these data as well as discover new biomarkers useful in the battle against this disease

The challenging riddle about the janus‐type role of hsp60 and related extracellular vesicles and miRNAs in carcinogenesis and the promises of its solution

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasmacell membrane, and extracellular vesicles (EVs). Consequently, non‐canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi‐faceted role of this chaperonin in human cancers, showing the contribution of intra‐ and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA‐mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti‐cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro‐ or anti‐tumor

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 identi-fying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9μM concentration of nandrolone and return to the basal level a 15.6μM dose of nandrolone. Nandrolone-induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a-hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6μM dose of nandrolone induced a down-regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects

A BRIEF GUIDE TO THE ANATOMICAL DISSECTION OF THE STOMACH

The purpose of this article is to write a short guide on the macroscopic anatomy of the stomach, describing its structures, its relationships within the abdominal cavity and the dissection methods used during the internship performed by a group of students from the University of Palermo, Palermo, Italy, at the University of Malta, Msida, Malta, during the summer of 2018. Indeed,, they had the opportunity to spend a period of two weeks at the department of Anatomy in the Maltese University for studying and practining on some corpses, with the aim of improving their anatomical knowledge