Chronic brain damage in HIV-infected individuals under antiretroviral therapy is associated with viral reservoirs, sulfatide release, and compromised cell-to-cell communication.

HIV infection has become a chronic and manageable disease due to the effective use of antiretroviral therapies (ART); however, several chronic aging-related comorbidities, including cognitive impairment, remain a major public health issue. However, these mechanisms are unknown. Here, we identified that glial and myeloid viral reservoirs are associated with local myelin damage and the release of several myelin components, including the lipid sulfatide. Soluble sulfatide compromised gap junctional communication and calcium wave coordination, essential for proper cognition. We propose that soluble sulfatide could be a potential biomarker and contributor to white matter compromise observed in HIV-infected individuals even in the current ART era.

Interplay between the Chaperone System and Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus Pathogenesis: Is Molecular Mimicry the Missing Link between Those Two Factors?

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical manifestations are variable, making an early diagnosis challenging. Heat shock proteins (Hsps), belonging to the chaperone system, interact with the immune system, acting as pro-inflammatory factors, autoantigens, as well as immune tolerance promoters. Increased levels of some Hsps and the production of autoantibodies against them are correlated with SLE onset and progression. The production of these autoantibodies has been attributed to molecular mimicry, occurring upon viral and bacterial infections, since they are evolutionary highly conserved. Gut microbiota dysbiosis has been associated with the occurrence and severity of SLE. Numerous findings suggest that proteins and metabolites of commensal bacteria can mimic autoantigens, inducing autoimmunity, because of molecular mimicry. Here, we propose that shared epitopes between human Hsps and those of gut commensal bacteria cause the production of anti-Hsp autoantibodies that cross-react with human molecules, contributing to SLE pathogenesis. Thus, the involvement of the chaperone system, gut microbiota dysbiosis, and molecular mimicry in SLE ought to be coordinately studied.

Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.

Silk-Based Matrices and c-Kit-Positive Cardiac Progenitor Cells for a Cellularized Silk Fibroin Scaffold: Study of an in vivo Model.

The production of a cellularized silk fibroin scaffold is very difficult because it is actually impossible to differentiate cells into a well-organized cardiac tissue. Without vascularization, not only do cell masses fail to grow, but they may also exhibit an area of necrosis, indicating a lack of oxygen and nutrients. In the present study, we used the so-called tyrosine protein kinase kit (c-Kit)-positive cardiac progenitor cells (CPCs) to generate cardiac cellularized silk fibroin scaffolds, multipotent cells isolated from the adult heart to date that can show some degree of differentiation toward the cardiac phenotype. To test their ability to differentiate into the cardiac phenotype in vivo as well, CPC and collagen organoid-like masses were implanted into nude mice and their behavior observed. Since the 3-dimensional structure of cardiac tissue can be preserved by scaffolds, we prepared in parallel different silk fibroin scaffolds with 3 different geometries and tested their behavior in 3 different models of immunosuppressed animals. Unfortunately, CPC cellularized silk fibroin scaffolds cannot be used in vivo. CPCs implanted alone or in collagen type I gel were destroyed by CD3+ lymphocyte aggregates, whereas the porous and partially oriented scaffolds elicited a consistent foreign body response characterized by giant cells. Only the electrospun meshes were resistant to the foreign body reaction. In conclusion, c-Kit-positive CPCs, although expressing a good level of cardiac differentiation markers in vitro with or without fibroin meshes, are not suitable for an in vivo model of cardiac organoids because they are degraded by a T-cell-mediated immune response. Even scaffolds which may preserve the survival of these cells in vivo also induced a host response. However, among the tested scaffolds, the electrospun meshes (F-scaffold) induced a lower response compared to all the other tested structures.

Highlights in Pathophysiology of the Musculoskeletal System.

The intention of the present Special Issue is to focus on the latest research in the musculoskeletal system, with an emphasis on the molecular mechanisms underlying its pathophysiology, as well as innovative diagnostic tools and therapeutic perspectives [...].

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

To date, there are limited and incomplete data on possible sex-based differences in fiber-types of skeletal muscle and their response to physical exercise. Adult healthy male and female mice completed a single bout of endurance exercise to examine the sex-based differences of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), heat shock protein 60 (Hsp60), interleukin 6 (IL-6) expression, as well as the Myosin Heavy Chain (MHC) fiber-type distribution in soleus and extensor digitorum longus (EDL) muscles. Our results showed for the first time that in male soleus, a muscle rich of type IIa fibers, endurance exercise activates specifically genes involved in mitochondrial biogenesis such as PGC1 α1 isoform, Hsp60 and IL-6, whereas the expression of PGC1 α2 and α3 was significantly upregulated in EDL muscle, a fast-twitch skeletal muscle, independently from the gender. Moreover, we found that the acute response of different PGC1α isoforms was muscle and gender dependent. These findings add a new piece to the huge puzzle of muscle response to physical exercise. Given the importance of these genes in the physiological response of the muscle to exercise, we strongly believe that our data could support future research studies to personalize a specific and sex-based exercise training protocol.

Bayesian inference for discretely observed continuous time multi-state models.

Multi-state models are frequently applied to represent processes evolving through a discrete set of states. Important classes of multi-state models arise when transitions between states may depend on the time passed since entry into the current state or on the time elapsed from the start of the process. The former models are called semi-Markov while the latter are known as inhomogeneous Markov models. Inference for both the models presents computational difficulties when the process is only observed at discrete time points with no additional information about the state transitions. In fact, in both the cases, the likelihood function is not available in closed form. To obtain Bayesian inference under these two classes of models, we reconstruct the entire unobserved trajectories conditioned on the observed points via a Metropolis-Hastings algorithm. As proposal density we use that given by the nested Markov models whose conditioned trajectories can easily be drawn with the uniformization technique. The resulting inference is illustrated via simulation studies and the analysis of two benchmark datasets for multi-state models.

Cancer-Related Cachexia: The Vicious Circle between Inflammatory Cytokines, Skeletal Muscle, Lipid Metabolism and the Possible Role of Physical Training.

Cachexia is a multifactorial and multi-organ syndrome that is a major cause of morbidity and mortality in late-stage chronic diseases. The main clinical features of cancer-related cachexia are chronic inflammation, wasting of skeletal muscle and adipose tissue, insulin resistance, anorexia, and impaired myogenesis. A multimodal treatment has been suggested to approach the multifactorial genesis of cachexia. In this context, physical exercise has been found to have a general effect on maintaining homeostasis in a healthy life, involving multiple organs and their metabolism. The purpose of this review is to present the evidence for the relationship between inflammatory cytokines, skeletal muscle, and fat metabolism and the potential role of exercise training in breaking the vicious circle of this impaired tissue cross-talk. Due to the wide-ranging effects of exercise training, from the body to the behavior and cognition of the individual, it seems to be able to improve the quality of life in this syndrome. Therefore, studying the molecular effects of physical exercise could provide important information about the interactions between organs and the systemic mediators involved in the overall homeostasis of the body.

Heat Shock Proteins Alterations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease characterized by the attack of the immune system on the body's healthy joint lining and degeneration of articular structures. This disease involves an increased release of inflammatory mediators in the affected joint that sensitize sensory neurons and create a positive feedback loop to further enhance their release. Among these mediators, the cytokines and neuropeptides are responsible for the crippling pain and the persistent neurogenic inflammation associated with RA. More importantly, specific proteins released either centrally or peripherally have been shown to play opposing roles in the pathogenesis of this disease: an inflammatory role that mediates and increases the severity of inflammatory response and/or an anti-inflammatory and protective role that modulates the process of inflammation. In this review, we will shed light on the neuroimmune function of different members of the heat shock protein (HSPs) family and the complex manifold actions that they exert during the course of RA. Specifically, we will focus our discussion on the duality in the mechanism of action of Hsp27, Hsp60, Hsp70, and Hsp90.

The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors.

Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary glands) that plays a role in tumor-cell biology. The chief components of the CS are the molecular chaperones, some of which belong to families of evolutionarily related molecules named heat shock protein (Hsp). We are quantifying and mapping these molecular chaperones in salivary glands to determine their possible role in the carcinogenetic mechanisms in these glands and to assess their potential as diagnostic biomarkers and therapeutic targets. Here, we report recent findings on Hsp10 and Hsp90 and show that the quantitative and topographic patterns of tissue Hsp90 are distinctive of malignant tumors and differentiate benign from malignant lesions. The Hsp90 results show a correlation between quantity of chaperone and tumor progression, which in turn calls for negative chaperonotherapy, namely, elimination/inhibition of the chaperone to stop the tumor. We found that in vitro, the Hsp90 inhibitor Ganetespib is cytotoxic for the salivary gland UM-HACC-2A cell line. The drug, by interfering with the pro-survival NF-κB pathway, hampers cellular proliferation and migration, and favors apoptosis, and can, therefore, be considered a suitable candidate for future experimentation to develop a treatment for salivary gland tumors.

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) functioning in favor of BC, using, for instance, Hsp inhibitors. The chaperones can also be employed in immunotherapy against BC as adjuvants, together with BC antigens. Extracellular vesicles (EVs) in BC diagnosis and management are also briefly discussed, considering their potential as easily accessible carriers of biomarkers and as shippers of anti-cancer agents amenable to manipulation and controlled delivery. The data surveyed from many laboratories reveal that, to enhance the understanding of the role of the CS in BS pathogenesis, one must consider the CS as a physiological system, encompassing diverse members throughout the body and interacting with the ubiquitin-proteasome system, the chaperone-mediated autophagy machinery, and the immune system (IS). An integrated view of the CS, including its functional partners and considering its highly dynamic nature with EVs transporting CS components to reach all the cell compartments in which they are needed, opens as yet unexplored pathways leading to carcinogenesis that are amenable to interference by anti-cancer treatments centered on CS components, such as the molecular chaperones.

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

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surgery, using Western blotting. Hsp27, Hsp60, and Hsp90 were increased in PC in comparison with PT and BG but no differences were found for Hsp70. Similarly, exosomal levels of Hsp27, Hsp60, and Hsp90 were higher in PC than in BG, and those in PC were higher before ablative surgery than after it. Hsp27, Hsp60, and Hsp90 show distinctive quantitative patterns in thyroid tissue and circulating exosomes in PC as compared with BG, suggesting some implication in the carcinogenesis of these chaperones and indicating their potential as biomarkers for clinical applications.

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

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 levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone.

Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice.

In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and quadriceps in each experimental group at all time points. Although morphological analysis showed unchanged total area of necrosis/regeneration in the diaphragm after training, there was a trend for larger areas of regeneration than necrosis in the diaphragm of mdx-EX compared to mdx-SD mice. However, the levels of Cx39, a protein associated with active regeneration in damaged muscle, were similar in the diaphragm of mdx-EX and mdx-SD mice. Hsp60 significantly decreased at 45 days in the diaphragm, but not in limb muscles, in both trained and sedentary mdx compared to WT mice. In limb muscles, but not in the diaphragm, Hsp70 and NF-kB p65 levels were increased in mdx mice irrespective of training at 30 and 45 days. Therefore, the diaphragm of mdx mice showed little inflammatory and stress responses over time, and appeared hardly affected by mild endurance training. J. Cell. Physiol. 232: 2044-2052, 2017. © 2016 Wiley Periodicals, Inc.

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

Conjugated linoleic acid (CLA) has been reported to improve muscle hypertrophy, steroidogenesis, physical activity, and endurance capacity in mice, although the molecular mechanisms of its actions are not completely understood. The aim of the present study was to identify whether CLA alters the expression of any of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) isoforms, and to evaluate the possible existence of fibre-type-specific hypertrophy in the gastrocnemius and plantaris muscles. Mice were randomly assigned to one of four groups: placebo sedentary, CLA sedentary, placebo trained, or CLA trained. The CLA groups were gavaged with 35 µl per day of Tonalin® FFA 80 food supplement containing CLA throughout the 6-week experimental period, whereas the placebo groups were gavaged with 35 µl sunflower oil each day. Each administered dose of CLA corresponded to approximately 0.7 g/kg or 0.5%, of the dietary daily intake. Trained groups ran 5 days per week on a Rota-Rod for 6 weeks at increasing speeds and durations. Mice were sacrificed by cervical dislocation and hind limb posterior muscle groups were dissected and used for histological and molecular analyses. Endurance training stimulated mitochondrial biogenesis by PGC1α isoforms (tot, α1, α2, and α3) but CLA supplementation did not stimulate PGC1α isoforms or mitochondrial biogenesis in trained or sedentary mice. In the plantaris muscle, CLA supplementation induced a fibre-type-specific hypertrophy of type IIx muscle fibres, which was associated with increased capillary density and was different from the fibre-type-specific hypertrophy induced by endurance exercise (of types I and IIb muscle fibres). J. Cell. Physiol. 232: 1086-1094, 2017. © 2016 Wiley Periodicals, Inc.

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells.

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9 µM concentration of nandrolone and return to the basal level a 15.6 µM 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 15.6 µM 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.

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 electron microscopy, biochemical tests, and Western blot analysis. RESULTS: Hsp60 was found to be increased in cancerous tissue, in which it was localized in the tumor cell plasma membrane, and in the interstitium associated with cells of the immune system, in which it was associated with exosomes liberated by tumor cells and, as such, circulated in the blood. An interesting finding was that these parameters returned to normal shortly after tumor removal. CONCLUSIONS: The data from the current study suggested that Hsp60 is a good candidate for theranostics applied to patients with large bowel carcinoma and encourage similar research among patients with other tumors in which Hsp60 has been implicated.

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling.

A physiological mechanism of programmed cell death called eryptosis occurs in aged or damaged red blood cells (RBCs). Dysregulated eryptosis contributes to abnormal microcirculation and prothrombotic risk. Cigarette smoke extract (CSE) induces a p38 MAPK-initiated, Fas-mediated eryptosis, activating the death-inducing signaling complex (DISC). Indicaxanthin (Ind) from cactus pear fruits, is a bioavailable dietary phytochemical in humans and it is able to incorporate into RBCs enhancing their defense against numerous stimuli. This in vitro work shows that Ind, at concentrations that mimic plasma concentrations after a fruit meal, protects erythrocytes from CSE-induced eryptosis. CSE from commercial cigarettes was prepared in aqueous solution using an impinger air sampler and nicotine content was determined. RBCs were treated with CSE for 3 h in the absence or presence of increasing concentrations of Ind (from 1 to 5 µM). Cytofluorimetric measurements indicated that Ind reduced CSE-induced phosphatidylserine externalization and ceramide formation in a concentration-dependent manner. Confocal microscopy visualization and coimmunoprecipitation experiments revealed that Ind prevented both CSE-triggered Fas aggregation and FasL/FADD/caspase 8 recruitment in the membrane, indicating inhibition of DISC assembly. Ind inhibited the phosphorylation of p38 MAPK, caspase-8/caspase-3 cleavage, and caspase-3 activity induced by CSE. Finally, Ind reduced CSE-induced ATP depletion and restored aminophospholipid translocase activity impaired by CSE treatment. In conclusion, Ind concentrations comparable to nutritionally relevant plasma concentrations, can prevent Fas-mediated RBC death signaling induced by CSE, which suggests that dietary intake of cactus pear fruits may limit the deleterious effects of cigarette smoking.

Vitamin D Deficiency in Professional Football Players during Competitive Season of Italian First Division (Serie A).

BACKGROUND: Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D in athletes. Indeed, vitamin D acts on the skeletal muscles and plays a fundamental role in numerous physiological processes involved in immune function. Many factors such as sun exposure, skin tone, body mass index and chronic illness affect vitamin D levels. The aim of the study is to evaluate vitamin D levels in professional football players in Italy and investigate the variations in vitamin D values in footballers who train at different latitudes. METHODS: The study performed is a retrospective observational study analyzing 25-OH vitamin D values in professional football players of the Italian First Division (Serie A). Two teams during the competitive season were selected: team A (latitude of 41° N in southern Italy) and team B (latitude of 45° N in northern Italy). Three time periods were identified and were classified as follows: the first quarter (May, June, July, and August), the second quarter (September, October, November, and December) and the third quarter (January, February, March, and April). The purpose of this was to study the average values of vitamin D during the year corresponding to different levels of sunlight exposure. Each athlete was subjected to at least one sampling during the three quarters of the competitive season. RESULTS: Both vitamin D insufficiency (10.1%) and overt deficiency (1.93%) were found in Italian Serie A players. Insufficient vitamin D values are between 20 ng/mL and 29 ng/mL and overt deficiency values <20 ng/mL. At the same time, the data demonstrated a significant variation in vitamin D values depending on the period of the competitive season and the latitude of the cities of the two teams. In detail, there was no significant difference in the first quarter, while there was a significant increase in vitamin D values in team B in the second and third quarter, at p < 0.01 and p < 0.05, respectively. CONCLUSIONS: Latitude and seasons have a significant impact on vitamin D levels. Therefore, it is essential to measure vitamin D in professional football players, especially during the spring and winter months, so as to monitor changes in levels in relation to the season and latitude and evaluate any supplements. Further studies should be performed to evaluate the relationship between vitamin D deficiency and football players' athletic performance.

Probiotics as Potential Therapeutic Agents: Safeguarding Skeletal Muscle against Alcohol-Induced Damage through the Gut-Liver-Muscle Axis.

Probiotics have shown the potential to counteract the loss of muscle mass, reduce physical fatigue, and mitigate inflammatory response following intense exercise, although the mechanisms by which they work are not very clear. The objective of this review is to describe the main harmful effects of alcohol on skeletal muscle and to provide important strategies based on the use of probiotics. The excessive consumption of alcohol is a worldwide problem and has been shown to be crucial in the progression of alcoholic liver disease (ALD), for which, to date, the only therapy available is lifestyle modification, including cessation of drinking. In ALD, alcohol contributes significantly to the loss of skeletal muscle, and also to changes in the intestinal microbiota, which are the basis for a series of problems related to the onset of sarcopenia. Some of the main effects of alcohol on the skeletal muscle are described in this review, with particular emphasis on the "gut-liver-muscle axis", which seems to be the primary cause of a series of muscle dysfunctions related to the onset of ALD. The modulation of the intestinal microbiota through probiotics utilization has appeared to be crucial in mitigating the muscle damage induced by the high amounts of alcohol consumed.