A Bioinformatics-Assisted Review on Iron Metabolism and Immune System to Identify Potential Biomarkers of Exercise Stress-Induced Immunosuppression.

The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to build a protein-protein interactions network for subsequent network topology analysis. Importantly, Fe is a sensitive double-edged sword where two extremes of its nutritional status may have harmful effects on innate and adaptive immunity. We identified clearly connected important hubs that belong to two clusters: (i) presentation of peptide antigens to the immune system with the involvement of redox reactions of Fe, heme, and Fe trafficking/transport; and (ii) ubiquitination, endocytosis, and degradation processes of proteins related to Fe metabolism in immune cells (e.g., macrophages). The identified potential biomarkers were in agreement with the current experimental evidence, are included in several immunological/biomarkers databases, and/or are emerging genetic markers for different stressful conditions. Although further validation is warranted, this hybrid method (human-machine collaboration) to extract meaningful biological applications using available data in literature and bioinformatics tools should be highlighted.

Development and Validation of Waist Girth-Based Equations to Evaluate Body Composition in Colombian Adults: Rationale and STROBE-Nut-Based Protocol of the F20 Project.

Waist girth (WG) represents a quick, simple, and inexpensive tool that correlates with excess of fat mass in humans; however, this measurement does not provide information on body composition. The evaluation of body composition is one of the main components in the assessment of nutritional status. Indeed, the use of anthropometry-based equations to estimate body fat and fat-free mass is a frequent strategy. Considering the lack of validation in the Colombian population, the aim of this research study (the F20 Project) is to externally validate WG-based equations (e.g., relative fat mass), and also to develop and validate new models that include WG to estimate body composition in Colombian adults compared to DXA. This cross-sectional study will be carried out following the guidelines for Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut). Using stratified probabilistic sampling, the study population will be adults with different levels of physical activity residing in Medellín and its metropolitan area. The results of this study will not only validate the estimation performance of the current WG-based equations, but they will also develop new equations to estimate body composition in the Colombian population. This will improve professional practice in health, exercise, and sports sciences (ClinicalTrials.gov ID #NCT05450588).

Profiling Physical Fitness of Physical Education Majors Using Unsupervised Machine Learning.

The academic curriculum has shown to promote sedentary behavior in college students. This study aimed to profile the physical fitness of physical education majors using unsupervised machine learning and to identify the differences between sexes, academic years, socioeconomic strata, and the generated profiles. A total of 542 healthy and physically active students (445 males, 97 females; 19.8 [2.2] years; 66.0 [10.3] kg; 169.5 [7.8] cm) participated in this cross-sectional study. Their indirect VO2max (Cooper and Shuttle-Run 20 m tests), lower-limb power (horizontal jump), sprint (30 m), agility (shuttle run), and flexibility (sit-and-reach) were assessed. The participants were profiled using clustering algorithms after setting the optimal number of clusters through an internal validation using R packages. Non-parametric tests were used to identify the differences (p < 0.05). The higher percentage of the population were freshmen (51.4%) and middle-income (64.0%) students. Seniors and juniors showed a better physical fitness than first-year students. No significant differences were found between their socioeconomic strata (p > 0.05). Two profiles were identified using hierarchical clustering (Cluster 1 = 318 vs. Cluster 2 = 224). The matching analysis revealed that physical fitness explained the variation in the data, with Cluster 2 as a sex-independent and more physically fit group. All variables differed significantly between the sexes (except the body mass index [p = 0.218]) and the generated profiles (except stature [p = 0.559] and flexibility [p = 0.115]). A multidimensional analysis showed that the body mass, cardiorespiratory fitness, and agility contributed the most to the data variation so that they can be used as profiling variables. This profiling method accurately identified the relevant variables to reinforce exercise recommendations in a low physical performance and overweight majors.

TRP Channels as Molecular Targets to Relieve Cancer Pain.

Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.

Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis.

Ashwagandha (Withania somnifera) is considered a potent adaptogen and anti-stress agent that could have some potential to improve physical performance. This preferred reporting items for systematic reviews and meta-analyses (PRISMA)-based comprehensive systematic review and Bayesian meta-analysis aimed to evaluate clinical trials up to 2020 from PubMed, ScienceDirect, and Google Scholar databases regarding the effect of Ashwagandha supplementation on physical performance in healthy individuals. Besides implementing estimation statistics analysis, we developed Bayesian hierarchical models for a pre-specified subgroup meta-analysis on strength/power, cardiorespiratory fitness and fatigue/recovery variables. A total of 13 studies met the requirements of this systematic review, although only 12 were included in the quantitative analysis. A low-to-moderate overall risk of bias of the trials included in this study was detected. All Bayesian hierarchical models converged to a target distribution (Ȓ = 1) for both meta-analytic effect size (µ) and between-study standard deviation (τ). The meta-analytic approaches of the included studies revealed that Ashwagandha supplementation was more efficacious than placebo for improving variables related to physical performance in healthy men and female. In fact, the Bayesian models showed that future interventions might be at least in some way beneficial on the analyzed outcomes considering the 95% credible intervals for the meta-analytic effect size. Several practical applications and future directions are discussed, although more comparable studies are needed in exercise training, and athletic populations are needed to derive a more stable estimate of the true underlying effect.

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose-response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.

Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V(600)E Lesion.

In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in a treatment naive patient, in which BRAF V(600)E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V(600)E to drive pathogenesis of malignant HCLc disease.

Molecular and metabolic insights of creatine supplementation on resistance training / Perspectivas moleculares y metabólicas de la suplementación con creatina en el entrenamiento de fuerza / Perspectivas moleculares e metabólicas da suplementação de creatina no treinamento de força

In recent years the research problem in the field of sports supplementation has changed to explain the metabolic mechanisms by which creatine (Cr) administration enhances the performance of certain sports or simply benefits the muscular adaptation. In this review for first time the biochemical mechanisms of Cr ingestion in a cell signaling insight were analyzed, focusing on energetic bioavailability enhancement and optimization of the temporal and spatial buffering of Cr/PCr/CK system. Moreover, intensification in proliferation and differentiation processes of muscle cells (IGF-I/PI3K/Akt-PKB, SPHK1/MAPK/p38/MRFs, mTOR, cellular swelling, mitotic activity of satellite cells, actin polymerization, and myoblast fusion) and inactivation and/or reduction in the expression of ergolitic metabolites (GSK3β, myostatin and AMPK regulation) were examined. In this way, we explained from a metabolic point of view the increase in muscle mass, strength, fatigue resistance, and performance of high intensity sports after Cr monohydrate supplementation.

En los últimos años el problema de investigación en el campo de la suplementación deportiva ha cambiado al punto de explicar los mecanismos metabólicos por los cuales la administración de creatina (Cr) incrementa el rendimiento en ciertos deportes o simplemente beneficia la adaptación muscular. Esta revisión analiza por primera vez los mecanismos bioquímicos de la ingesta de Cr desde la perspectiva de señalización celular, enfocándose en la mayor biodisponibilidad energética de Cr y optimización de la acción buffer espacial/temporal que ofrece el sistema Cr/PCr/CK. Además, se examinan aspectos relacionados con el incremento en los procesos de proliferación y diferenciación de células musculares (IGF-I/PI3K/Akt-PKB, SPHK1/MAPK/p38/MRFs, mTOR, hinchamiento celular, actividad mitótica de células satélite, polimerización de actina y fusión de mioblastos) y la inactivación y/o reducción en la expresión de proteínas con funciones ergolíticas (GSK3β, miostatina y regulación de AMPK). De esta manera, se explican el aumento de la masa muscular, la fuerza, la resistencia a la fatiga y el rendimiento en ejercicios de alta intensidad, producidos por la suplementación con monohidrato de Cr, desde un punto de vista metabólico.

Nos últimos anos, o problema de pesquisa no campo da suplementação de esportes mudou ao ponto de explicar os mecanismos metabólicos pelos quais a administração de creatina (Cr) aumenta o desempenho em alguns esportes ou benefícios de adaptação musculares. Neste artigo, vamos analisar primeiro os mecanismos bioquímicos de ingestão da Cr a partir da perspectiva de sinalização celular, com foco em maior biodisponibilidade de energia de Cr e otimização de tampão temporais/espacial ação oferecida pelo sistema Cr/PCr/CK. Além disso, são considerados aspectos relacionados com o aumento da os processos de proliferação e diferenciação de células musculares (IGF-I/PI3K/Akt-PKB, SPHK1/MAPK/p38/MRFs, mTOR, inchaço celular, atividade mitótica da célula satélite, a polimerização de actina e de fusão de mioblastos) e inativação e/ou a redução na expressão de proteínas com funções ergolíticas (GSK3, miostatina e regulação da AMPK). Desta maneira, é explicado o aumento da massa muscular, força, resistência à fadiga e desempenho em exercícios de alta intensidade, produzidos pela suplementação com Cr monohidratada, a partir de um ponto de vista metabólico.