Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling.

Regulatory T (Treg) cells require (interleukin-2) IL-2 for their homeostasis by affecting their proliferation, survival and activation. Here we investigated transcriptional and epigenetic changes after acute, periodic and persistent IL-2 receptor (IL-2R) signaling in mouse peripheral Treg cells in vivo using IL-2 or the long-acting IL-2-based biologic mouse IL-2-CD25. We show that initially IL-2R-dependent STAT5 transcription factor-dependent pathways enhanced gene activation, chromatin accessibility and metabolic reprogramming to support Treg cell proliferation. Unexpectedly, at peak proliferation, less accessible chromatin prevailed and was associated with Treg cell contraction. Restimulation of IL-2R signaling after contraction activated signature IL-2-dependent genes and others associated with effector Treg cells, whereas genes associated with signal transduction were downregulated to somewhat temper expansion. Thus, IL-2R-dependent Treg cell homeostasis depends in part on a shift from more accessible chromatin and expansion to less accessible chromatin and contraction. Mouse IL-2-CD25 supported greater expansion and a more extensive transcriptional state than IL-2 in Treg cells, consistent with greater efficacy to control autoimmunity.

IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells.

Low-dose IL-2 represents an immunotherapy to selectively expand regulatory T cells (Tregs) to promote tolerance in patients with autoimmunity. In this article, we show that a fusion protein (FP) of mouse IL-2 and mouse IL-2Rα (CD25), joined by a noncleavable linker, has greater in vivo efficacy than rIL-2 at Treg expansion and control of autoimmunity. Biochemical and functional studies support a model in which IL-2 interacts with CD25 in the context of this FP in trans to form inactive head-to-tail dimers that slowly dissociate into an active monomer. In vitro, IL-2/CD25 has low sp. act. However, in vivo IL-2/CD25 is long lived to persistently and selectively stimulate Tregs. In female NOD mice, IL-2/CD25 administration increased Tregs within the pancreas and reduced the instance of spontaneous diabetes. Thus, IL-2/CD25 represents a distinct class of IL-2 FPs with the potential for clinical development for use in autoimmunity or other disorders of an overactive immune response.

Sponges against miR-19 and miR-155 reactivate the p53-Socs1 axis in hematopoietic cancers.

Normal cell proliferation is controlled by a balance between signals that promote or halt cell proliferation. Micro RNAs are emerging as key elements in providing fine signal balance in different physiological situations. Here we report that STAT5 signaling induces the miRNAs miR-19 and miR-155, which potentially antagonize the tumor suppressor axis composed by the STAT5 target gene SOCS1 (suppressor of cytokine signaling-1) and its downstream effector p53. MiRNA sponges against miR-19 or miR-155 inhibit the functions of these miRNAs and potentiate the induction of SOCS1 and p53 in mouse leukemia cells and in human myeloma cells. Adding a catalytic RNA motif of the hammerhead type within miRNA sponges against miR-155 leads to decreased miR-155 levels and increased their ability of inhibiting cell growth and cell migration in myeloma cells. The results indicate that antagonizing miRNA activity can reactivate tumor suppressor pathways downstream cytokine stimulation in tumor cells.

Intermittent Fasting: Does It Affect Sports Performance? A Systematic Review.

Intermittent fasting is one of the most popular types of diet at the moment because it is an effective nutritional strategy in terms of weight loss. The main objective of this review is to analyze the effects that intermittent fasting has on sports performance. We analyzed physical capacities: aerobic capacity, anaerobic capacity, strength, and power, as well as their effect on body composition. For this, a bibliographic search was carried out in several databases where 25 research articles were analyzed to clarify these objectives. Inclusion criteria: dates between 2013 and present, free full texts, studies conducted in adult human athletes, English and/or Spanish languages, and if it has been considered that intermittent fasting is mainly linked to sports practice and that this obtains a result in terms of performance or physical capacities. This review was registered in PROSPERO with code ref. 407024, and an evaluation of the quality or risk of bias was performed. After this analysis, results were obtained regarding the improvement of body composition and the maintenance of muscle mass. An influence of intermittent fasting on sports performance and body composition is observed. It can be concluded that intermittent fasting provides benefits in terms of body composition without reducing physical performance, maintenance of lean mass, and improvements in maximum power. But despite this, it is necessary to carry out new studies focusing on the sports field since the samples have been very varied. Additionally, the difference in hours of intermittent fasting should be studied, especially in the case of overnight fasting.

The Effects of Melatonin Supplementation on Professional Football Player Performance: A Systematic Review.

BACKGROUND: Melatonin is a hormone that has shown anti-inflammatory actions, reduced oxidative stress, and has effects on physical performance, so the aim of this study was to review the effects of melatonin supplementation on the performance of professional soccer players. METHODS: Critical and systematic review. Data were obtained by performing searches in the following bibliographic databases: Web of Science, MEDLINE (via PubMed), Embase, Cochrane Library, and Scopus. The terms used were "Soccer Athlete", "Melatonin", and "Soccer Performance", using "Humans" as a filter. The search update was in May 2023. RESULTS: Having applied the inclusion and exclusion criteria, eight articles were selected out of 59 retrieved references. The dose of melatonin administered in the studies ranged between 5 and 8 mg. The outcomes showed a decrease in oxidative stress, muscle damage, and inflammatory markers in the melatonin-treated group. CONCLUSIONS: Exogenously administered melatonin seems to attenuate some of the effects derived from physical exercise, such as oxidative stress, inflammation, and muscle damage, in professional football players, and since it has no potential adverse effects, it could be interesting to apply it in this population. However, the direct effects of melatonin supplementation on physical performance have not been demonstrated, so more research is needed on the intervention period and effective dose and with larger participant populations.

Males Have a Higher Energy Expenditure than Females during Squat Training.

The main objective of this study was to determine the differences in energy expenditure (EE) according to sex during and after two different squat training protocols in a group of healthy young adults. Twenty-nine Sports Sciences students volunteered to participate in this study. They attended the laboratory on four different days and completed four sessions: two sessions with 3 sets of 12 repetitions at 75% of their one-repetition maximum (RM) and two sessions with 3 sets of 30 repetitions at 50% of their 1RM. Energy expenditure was evaluated using an indirect calorimeter. Males consistently demonstrated higher EE in all sessions and intensities. The linear regression model identified a significant association between sex, BMI, and total EE across all sessions and intensities. In conclusion, males exhibited higher EE in both protocols (50% and 75% of 1RM) throughout all sessions. Furthermore, sex and BMI were found to influence EE in healthy young adults. Therefore, coaches should consider sex when assessing EE, as the metabolic response differs between males and females.

Estimation of the Quality of the Diet of Mexican University Students Using DQI-I.

The quality of diet can be measured using diet quality indices, based on knowledge of associations between diet and health. The objective of this work was to evaluate whether the International Diet Quality Index is suitable for use as a diet quality index in populations of Mexican university girls. A cross-sectional nutritional survey was conducted at the University of Chihuahua (Mexico), collecting semi-quantitative nutritional information and socio-economic and lifestyle data from a representative sample of 400 women. Mean (Standard Deviation (SD)) age was 21.43 years (SD: 3.72); 59.1% were normal weight, 26.6% overweight, 15.3% obesity. The Diet Quality Index-International (DQI-I) was developed according to the method of Kim et al. (2003) and focused on major aspects of a high-quality diet (variety, adequacy, moderation and overall balance). The total score of Diet Quality Index-International reached 53.86% (SD: 11.43), indicating that the general diet of Mexican women a poor-quality diet. Adequacy scored highest, followed by moderation and variety. Overall balance scored the lowest. Variety: 26.3 % consumed less than 4 food groups daily, only 12.8% take more than 1 serving from each food group, and 50.6% consumed only one source of protein daily. Regarding adequacy, a large proportion of the population reported an intake of proteins, vitamin C, calcium, iron, and fruit greater than 50% of recommendation; the vegetables, fiber and grain groups were less 50%. Poor scores were obtained for total fat and SFA consumption (moderation). No statistically significant differences are observed for any of the variables under study and score of the Diet Quality Index-International: body mass index, weight, physical activity level, education level of father and mother, location of lunch, breakfast considered important, knowledge of nutrition, which allows us to consider a relatively uniform population in its eating habits. These people are close to a Westernized diet, and an intervention in nutritional education would be advisable to improve the intake of unprocessed foods, consume a greater variety of protein sources and significantly reduce consumption of sugary foods and soft drinks. Due to different methodological and cultural factors, the proposed Diet Quality Index-International dietary assessment method does not seem to be useful in the assessment of diet quality in the Mexican university population, so further research is needed to develop a diet quality index adapted to the Mexican population.

Dietary exposure to endocrine disruptors in gut microbiota: A systematic review.

Endocrine disrupting chemicals (EDCs) can interfere with hormonal actions and have been associated with a higher incidence of metabolic disorders. They affect numerous physiological, biochemical, and endocrinal activities, including reproduction, metabolism, immunity, and behavior. The purpose of this review was to elucidate the association of EDCs in food with the gut microbiota and with metabolic disorders. EDC exposure induces changes that can lead to microbial dysbiosis. Products and by-products released by the microbial metabolism of EDCs can be taken up by the host. Changes in the composition of the microbiota and production of microbial metabolites may have a major impact on the host metabolism.

Body Composition and Nutritional Status of the Spanish National Breaking Team Aspiring to the Paris 2024 Olympic Games.

Breaking is a sports dance modality that will debut for the first time at the Paris 2024 Olympic Games. This dance form combines street dance steps with acrobatics and athletic elements. It complies with gender equality, maintains aesthetic appeal, and is practised indoors. The objective of this study is to assess the characteristics of body composition and nutritional status of the athletes that make up the Breaking national team. This national team was recruited, and they underwent an analysis of body composition using bioimpedance measurement and a nutritional interview status with the completion of a survey on the frequency of the consumption of sports supplements and ergogenic aids. In addition, they completed a consumption questionnaire for a series of food groups with specified protein, lipid, and carbohydrate content. After that, parameters were analyzed in relation to their nutritional status during a complete medical examination at the Endocrinology and Nutrition Service of the Sports Medicine Center of CSD. A descriptive analysis of the results obtained was carried out to find the mean values of the variables analyzed. The analytical parameters described an adequate nutritional status, except for the mean capillary determination of 25-OH-vitamin D3, which was 24.2 ng/dL (SD: 10.3). Bone mineral density values were higher than those of the general population. This is the first time that a study of these characteristics has been carried out on Breakers, so it is highly relevant to increase knowledge in this area in order to conduct nutritional interventions aimed at improving the sports performance of these athletes.

Influence of BPA exposure, measured in saliva, on childhood weight.

Introduction: Endocrine disruptors such as bisphenol A (BPA), BPA glycidyl methacrylate, and other BPA acrylate-based derivatives have been related to type 2 diabetes, the metabolic syndrome, and obesity, among other metabolic disorders. The objective of this study is to examine the influence of BPA exposure by saliva analysis and daily physical activity on the risk of overweight/obesity in schoolchildren from southern Spain. Methods: The study included 300 children (53.5% girls) aged 7-10 years. Participants completed a questionnaire with four sections: participant data, including demographic information and life and family habits; semi-quantitative food frequency questionnaire; anthropometric variables; and physical activity variables. All participants underwent dental examination, when the presence of sealants/composites in each tooth and other dental alterations was recorded, and samples of whole saliva were collected for UHPLC-MS/MS analyses. Results: Risk of overweight/obesity was significantly influenced by body fat composition (OR = 10.77), not walking to and from school (OR = 1.38), lesser energy expenditure in sedentary activities (OR = 12.71), greater energy expenditure in sports (OR =1.62), and exposure to BPA from dental sealants/composites (OR = 1.38; p = 0.058). Discussion: Further research is warranted on this issue in children, who may be especially vulnerable to the negative health effects of endocrine disruption.

Influence of Alpine Skiing on Health-Related Quality of Life and Physical Self-Concept in Physically Active Adults over 55 Years of Age.

Background: Older adults have the highest rates of a sedentary lifestyle. Alpine skiing could be considered a suitable activity to encourage continued sports practice and improve the health of this population in winter. The aim of this study was to analyse the relationship between the practice of alpine skiing and health-related quality of life (HRQoL), physical self-concept (PSC), and sport motivation. Methods: The study design was cross-sectional and descriptive, involving 280 Spanish adults aged over 55 years and physically active (75.35% skiers). To assess physical activity, PSC, HRQoL, and sport motivation, we used the Rapid Assessment of Physical Activity Questionnaire (RAPA-Q), the Physical Self-Perception Profile (PSPP 30), the Health-Related Quality of Life (SF-36), and the Sport Motivation Scale (SMS) questionnaires, respectively. Results: In the skier's group, higher values were found for PSC (p < 0.001; d = 0.64), the physical component of HRQoL (p < 0.001, d = 0.48), physical function (p < 0.001, d = 61), and intrinsic motivation (p < 0.001; d = 0.85). The practice of alpine skiing was associated with higher levels of the physical health component (ORadj = 2.13, 95% CI 1.18−3.95, p = 0.013), PSC (ORadj = 2.92, 95% CI 1.58−5.52, p < 0.001), and intrinsic motivation (ORadj = 2.24, 95% CI 1.22−4.23, p = 0.010). Conclusions: The practice of alpine skiing is positively associated with higher values of HRQoL, PSC, and intrinsic motivation, and based on the above, it seems that alpine skiing can contribute to healthy ageing and improve the quality of life of older adults.

Evolution of Nutritional Habits Behaviour of Spanish Population Confined Through Social Media.

Introduction: In Spain, on 14 March 2020, a state of alarm is declared to face the health emergency situation caused by the COVID-19 coronavirus, limiting the freedom of movement of people. The Spanish population is confined. Objective: With this situation, "NUTRITIONAL HEALTH IS NOT CONFINED" arises a research project that seeks to promote nutritional education based on the pattern of the Mediterranean diet (MD) using new computer technologies. It is about providing the population with the information of general interest about the promotion of a healthy diet through social networks and analysing the impact of its dissemination, in the form of a longitudinal intervention study of the Spanish nutritional evolution during confinement, with a daily survey format, and it is intended to assess food consumption during the period of confinement. Materials and methods: In total, 936 participants were asked every day. Short publications were published every day based on the scientific evidence (FAO, WHO, AECOSAN) through social media such as Instagram, accompanied by a questionnaire of 11 questions (yes/no) where it was intended to assess the evolution of daily consumption. Results and Discussion: The diffusion through social media has allowed to have a greater reach of the population. We observed that mood throughout confinement generally improves. There are certain eating habits from the MD that are well established in the daily diet of our population, such as the consumption of fruits, vegetables, legumes, dairy products, and eggs. It seems that enjoying good health is a growing concern in pandemic situations, which is why inappropriate behaviours such as "snacking" between meals or the consumption of processed foods such as snacks, industrial pastries, soft drinks, and sweets are avoided, increasing the amount of healthy food such as meat and fish. This study opens up future avenues of research promoting MD and implements new cohort nutritional databases, especially about young adult people, who are adept at navigating digital spaces and therefore using social media.

Acute Lipopolysaccharide-Induced Inflammation Lowers IL-2R Signaling and the Proliferative Potential of Regulatory T Cells.

IL-2R signaling is essential for the development and homeostasis of CD4+Foxp3+ regulatory T cells (Tregs). Low-dose IL-2 is being advanced as a therapy for autoimmune diseases because of its ability to expand Tregs. Although Treg stability and function is diminished by chronic inflammation, the impact of inflammation on proximal IL-2R signaling and/or responsiveness to low-dose IL-2 is poorly understood. In this study, we show that acute inflammation induced by LPS, analogous to responses to acute bacterial infection, led to decreased endogenous STAT5 signaling and proliferative potential as measured by Ki67 in mouse Tregs. This impaired Treg activity was transient, did not lead to a reduction in Treg numbers or function, and was due to TLR signaling by non-Tregs. Although acute LPS induced high levels of IL-1 and IL-6, these cytokines did not solely mediate dysregulated Treg activity. Global gene expression analyses demonstrated that acute LPS-induced inflammation substantially and rapidly altered the Treg transcriptome. In the presence of an IL-2R agonist, the mouse IL-2/CD25 fusion protein (mIL-2/CD25), this type of inflammatory response tempered the transcription of IL-2R-dependent genes in vivo. Gene enrichment and pathway analyses are consistent with LPS attenuating mIL-2/CD25-dependent genes related to the cell cycle, DNA replication, and cholesterol biosynthesis while enhancing mRNAs that mediated Treg suppression in vivo. Acute LPS-induced inflammation diminished some responses by Tregs to mIL-2/CD25 treatment in vivo. Together, these results suggest a role for persistent IL-2R signaling in mitigating some but not all of the deleterious effects of inflammation on Treg proliferation while supporting their function.

CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.

The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA-mediated depletion of CHES1 increases tumor cell proliferation. Growth suppression depends on the CHES1 forkhead DNA-binding domain and correlates with the nuclear localization of CHES1. CHES1 represses the expression of multiple genes, including the kinases PIM2 and DYRK3, which regulate protein biosynthesis, and a number of genes in cilium biogenesis. CHES1 binds directly to the promoter of PIM2, and in cells expressing CHES1 the levels of PIM2 are reduced, as well as the phosphorylation of the PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, indicating that PIM2 and protein biosynthesis are important targets of the antiproliferative effect of CHES1. In several human hematopoietic cancers, CHES1 and PIM2 expressions are inversely correlated, suggesting that repression of PIM2 by CHES1 is clinically relevant.

Identification of nuclear proteins of small cell lung cancer cell line H82: An improved procedure for the analysis of silver-stained proteins.

An efficient method for digestion and extraction of proteolytic peptides from silver-stained proteins was applied to the characterization of nuclear proteins from the small cell lung cancer H82 (ATCC HTB 175) cell line previously separated by high-resolution large format two-dimensional gel electrophoresis. From 68 spots, evenly distributed on the gel area and representing a wide range of spot intensities, 63 (92%) were successfully identified by matrix-assisted laser desorption/ionization (MALDI) or electrospray ionozation-mass spectrometry (ESI-MS). In five cases where the identification was not possible, the presence of an intense background apparently due to the leakage of polymers from the microtubes or other plastics, was detected. Extensive analysis of peptide sequences by ESI MS/MS experiments allowed the identification of post-translational modifications, such as acetylation, phosphorylation, deamidation of asparagine residues and the presence of isoaspartic acid. A new protein variant not reported in sequence databases was also detected.