Heterogenous circulating miRNA changes in ME/CFS converge on a unified cluster of target genes: A computational analysis.

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome is a debilitating, multisystem disease of unknown mechanism, with a currently ongoing search for its endocrine mediators. Circulating microRNAs (miRNA) are a promising candidate for such a mediator and have been reported as significantly different in the patient population versus healthy controls by multiple studies. None of these studies, however, agree with each other on which specific miRNA are under- or over-expressed. This discrepancy is the subject of the computational study presented here, in which a deep dive into the predicted gene targets and their functional interactions is conducted, revealing that the aberrant circulating miRNAs in ME/CFS, although different between patients, seem to mainly target the same specific set of genes (p ≈ 0.0018), which are very functionally related to each other (p ≲ 0.0001). Further analysis of these functional relations, based on directional pathway information, points to impairments in exercise hyperemia, angiogenic adaptations to hypoxia, antioxidant defenses, and TGF-ß signaling, as well as a shift towards mitochondrial fission, corroborating and explaining previous direct observations in ME/CFS. Many transcription factors and epigenetic modulators are implicated as well, with currently uncertain downstream combinatory effects. As the results show significant similarity to previous research on latent herpesvirus involvement in ME/CFS, the possibility of a herpesvirus origin of these miRNA changes is also explored through further computational analysis and literature review, showing that 8 out of the 10 most central miRNAs analyzed are known to be upregulated by various herpesviruses. In total, the results establish an appreciable and possibly central role for circulating microRNAs in ME/CFS etiology that merits further experimental research.

Sclerostin as a biomarker of physical exercise in osteoporosis: A narrative review.

Osteoporosis, a disease of low bone mass, is characterized by reduced bone mineral density (BMD) through abnormalities in the microarchitecture of bone tissue. It affects both the social and economic areas, therefore it has been considered a lifestyle disease for many years. Bone tissue is a dynamic structure exhibiting sensitivity to various stimuli, including mechanical ones, which are a regulator of tissue sclerostin levels. Sclerostin is a protein involved in bone remodeling, showing an anti-anabolic effect on bone density. Moderate to vigorous physical activity inhibits secretion of this protein and promotes increased bone mineral density. Appropriate exercise has been shown to have an osteogenic effect. The effectiveness of osteogenic training depends on the type, intensity, regularity and frequency of exercise and the number of body parts involved. The greatest osteogenic activity is demonstrated by exercises affecting bone with high ground reaction forces (GRF) and high forces exerted by contracting muscles (JFR). The purpose of this study was to review the literature for the effects of various forms of exercise on sclerostin secretion.

The Role of Satellite Cells in Skeletal Muscle Regeneration-The Effect of Exercise and Age.

The population of satellite cells (mSCs) is highly diversified. The cells comprising it differ in their ability to regenerate their own population and differentiate, as well as in the properties they exhibit. The heterogeneity of this group of cells is evidenced by multiple differentiating markers that enable their recognition, classification, labeling, and characterization. One of the main tasks of satellite cells is skeletal muscle regeneration. Myofibers are often damaged during vigorous exercise in people who participate in sports activities. The number of satellite cells and the speed of the regeneration processes that depend on them affect the time structure of an athlete's training. This process depends on inflammatory cells. The multitude of reactions and pathways that occur during the regeneration process results in the participation and control of many factors that are activated and secreted during muscle fiber damage and at different stages of its regeneration. However, not all of them are well understood yet. This paper presents the current state of knowledge on satellite cell-dependent skeletal muscle regeneration. Studies describing the effects of various forms of exercise and age on this process were reviewed.

What factors affect the length of hospitalization in patients with erysipelas? A 10-year retrospective study of patients hospitalized in Lower Silesia, Poland.

BACKGROUND: Erysipelas is an acute skin infection caused by group A and G streptococci. This infection is associated with many comorbidities and often requires hospitalization. OBJECTIVES: The aim of this study was to identify the factors related to the length of hospitalization in patients with erysipelas. MATERIAL AND METHODS: This retrospective study included 153 admissions of 135 patients (63 women and 72 men) hospitalized due to erysipelas from January 2010 to December 2019. Clinical symptoms, test results, comorbidities, and antibiotic treatments were taken into consideration as factors affecting the length of hospital stay. RESULTS: The median length of hospitalization was 10 days (interquartile range (IQR) = 7-14). Women spent less time in the ward, but the difference was not significant. Features such as tinea pedis (15.5 days, IQR = 13.5-20; p = 0.002), anemia (11 days, IQR = 9-15; p = 0.02), chills (12 days, IQR = 9-15; p = 0.03), elevated serum C-reactive protein (CRP) level over 100 mg/L (11 days, IQR = 8-17; p = 0.02), and leukocytosis (11 days, IQR = 8-15, p = 0.005) were identified as prolonged hospitalization factors. Moreover, patients with erysipelas localized to the legs (p = 0.01) and with a gangrenous variant of erysipelas (p = 0.03) were hospitalized longer. The first-choice antibiotic was not significant in terms of prolonged hospitalization. Patients treated with clindamycin during hospitalization, regardless of whether it was a first-line or subsequent antibiotic, stayed in the ward significantly longer (p = 0.005). CONCLUSION: Patients suffering from erysipelas with the features identified above, have a higher risk of a prolonged stay in the hospital. Significantly increased inflammatory factors, anemia and tinea pedis contributed to prolonged hospitalization.

An application of QSRR approach and multiple linear regression method for lipophilicity assessment of flavonoids.

The analysis of quantitative structure-retention relationships (QSRR) is useful tool for assessment of compound's lipophilicity/hydrophobicity due to similarity between its retention in chromatographic system and ability to permeation through biological membranes. The main goal of this study was to compare usefulness of two reversed-phase chromatographic columns (Synergy POLAR and Synergy-FUSION) for lipophilicity assessment of 30 structurally diverse flavonoids using the QSRR approach and multiple linear regression method. The developed MLR models included the mechanistically interpretable geometrical descriptors: 3D Molecule Representation of Structure based on Electron diffraction (3D-MoRSE) and Radial Distribution Function (RDF). Both models were evaluated by the internal and external validation and selected descriptors were further interpreted. According to obtained results the FUSION-RP column can be recommended to log kw prediction of flavonoids. The comprehensive interpretation of molecular descriptors was used to present the molecular mechanisms and structural features governing the chromatographic retention of tested compounds.