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 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

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

Antitumoral activity of curcumin: an adjuvant therapeutic strategy

Curcumin, an active substance contained in an Indian spice called turmeric or curcuma, is well known for its anti-inflammatory and antioxidant properties. In recent times, it was taken into account and studied as an antitumoral molecule, by relying on its interference on several biological mechanisms, such as the inhibition of inflammatory mediators, the enhancement of detoxifying enzymes’ action and processes of cell growth and proliferation

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

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