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Background The role of physical exercise in the prevention of Alzheimer’s disease (AD) has been widely studied. Microglia play an important role in AD. Triggering receptor expressed in myeloid cells 2 (TREM2) is expressed on microglia and is known to mediate microglial metabolic activity and brain glucose metabolism. However, the relationship between brain glucose metabolism and microglial metabolic activity during running exercise in APP/PS1 mice remains unclear. Methods Ten-month-old male APP/PS1 mice and wild-type mice were randomly divided into sedentary groups or running groups (AD_Sed, WT_Sed, AD_Run and WT_Run, n  = 20/group). Running mice had free access to a running wheel for 3 months. Behavioral tests, [18]F-FDG-PET and hippocampal RNA-Seq were performed. The expression levels of microglial glucose transporter (GLUT5), TREM2, soluble TREM2 (sTREM2), TYRO protein tyrosine kinase binding protein (TYROBP), secreted phosphoprotein 1 (SPP1), and phosphorylated spleen tyrosine kinase (p-SYK) were estimated by western blot or ELISA. Immunohistochemistry, stereological methods and immunofluorescence were used to investigate the morphology, proliferation and activity of microglia. Results Long-term voluntary running significantly improved cognitive function in APP/PS1 mice. Although there were few differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) showed enriched glycometabolic pathways in APP/PS1 running mice. Running exercise increased FDG uptake in the hippocampus of APP/PS1 mice, as well as the protein expression of GLUT5, TREM2, SPP1 and p-SYK. The level of sTREM2 decreased in the plasma of APP/PS1 running mice. The number of microglia, the length and endpoints of microglial processes, and the ratio of GLUT5 + /IBA1 + microglia were increased in the dentate gyrus (DG) of APP/PS1 running mice. Running exercise did not alter the number of 5-bromo-2′-deoxyuridine (BrdU) + /IBA1 + microglia but reduced the immunoactivity of CD68 in the hippocampus of APP/PS1 mice. Conclusions Running exercise inhibited TREM2 shedding and maintained TREM2 protein levels, which were accompanied by the promotion of brain glucose metabolism, microglial glucose metabolism and morphological plasticity in the hippocampus of AD mice. Microglia might be a structural target responsible for the benefits of running exercise in AD. Promoting microglial glucose metabolism and morphological plasticity modulated by TREM2 might be a novel strategy for AD treatment.

Background The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is a poor prognosis. Trastuzumab improves overall survival but is associated with cardiotoxicity, especially a decline in left ventricular ejection fraction (LVEF). In addition, chemotherapy and radiotherapy increase fatigue and pain, decrease physical capacity and health-related quality of life. To date, no study has evaluated the benefits of physical activity on the side effects of treatment in patients with HER2 positive breast cancer. The aim of this study is to evaluate the impact of 3 months’ exercise intervention on myocardial function and in particular on the rate of cardiotoxicity. Methods This multicenter, randomized clinical trial will include 112 patients treated by adjuvant trastuzumab for HER2 positive breast cancer to investigate the effects of a 3 months’ supervised exercise program (intermittent exercise, combining moderate and high intensities; 55 minutes duration, 3 times per week), on the rate of cardiotoxicity [defined by either a decrease of the LVEF under 50% or an absolute drop of LVEF of 10%] between baseline and at 3 months and on strength, aerobic capacity, metabolic, inflammatory and hormonal parameters. Health-related quality of life, fatigue, pain and level of physical activity will also be assessed. Participants are randomly allocated to one of the two groups (“training group” vs “standard oncological care”). Performance-based and self-reported outcomes are assessed at baseline, at the end of supervised exercise program and at six months follow-up. Discussion Although physical exercise is recommended to reduce the side effects of adjuvant treatments in breast cancer patients, no randomized study has been conducted to assess the benefits of a physical training program in patients with HER2 overexpressing breast cancer. Cardiac toxicity of trastuzumab may be minimized with an exercise program combining high and moderate intensities. This type of program may be safe, feasible and effective but also increase cardiorespiratory fitness and improve health-related quality of life. If these benefits are confirmed, this exercise intervention could be systematically proposed to patients during the course of treatment by trastuzumab in addition to standard oncological care. Trial registration National Clinical Trials Number ( NCT02433067 ); Registration 28 april 2015.

Background This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents. Methods A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren’s leisure-time physical activity practices. Results An inverse association between BMI and telomere length (β: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (β: 0.151; 95% CI: 0.029; 0.278) and neutrophils (β: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA. Conclusion The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity.

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO 2 coincides with an increase in certain species and the \"GABA shunt\" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity.

A new study shows that immune activation after infection involves competition for energy with physiological programmes such as maintaining a normal body temperature. This trade-off favours immune tolerance as a strategy for host defence.

Yoga targets psychological processes which may be important for long-term weight loss (WL). This study is the first to examine the feasibility, acceptability, and preliminary efficacy of yoga within a weight management program following WL treatment. 60 women with overweight or obesity (34.3±3.9 kg/m2, 48.1±10.1 years) were randomized to receive a 12-week yoga intervention (2x/week; YOGA) or a structurally equivalent control (cooking/nutrition classes; CON), following a 3-month behavioral WL program. Feasibility (attendance, adherence, retention) and acceptability (program satisfaction ratings) were assessed. Treatment groups were compared on weight change, mindfulness, distress tolerance, stress, affect, and self-compassion at 6 months. Initial WL (3-mo WL) was evaluated as a potential moderator. Attendance, retention, and program satisfaction ratings of yoga were high. Treatment groups did not differ on WL or psychological constructs (with exception of one mindfulness subscale) at 6 months. However, among those with high initial WL (≥5%), YOGA lost significantly more weight (-9.0kg vs. -6.7kg) at 6 months and resulted in greater distress tolerance, mindfulness, and self-compassion and lower negative affect, compared to CON. Study findings provide preliminary support for yoga as a potential strategy for improving long-term WL among those losing ≥5% in standard behavioral treatment.

Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.

The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect.

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment. Mitochondrial alterations play a key role in the development of DC, and microRNAs regulating mitochondrial function are emerging as potential biomarkers of metabolic stress in DC. L-Arginine (Arg) supplementation has been shown to be an effective strategy for improving mitochondrial function and energetics, with a significant impact on physical performance. The aim of the current study was to evaluate the effects of Arg supplementation on cardiac mitochondrial function, DC development, and relative phenotypes including exercise intolerance. We used db/db mice as a model of type II diabetes, chronically treated with Arg (1 mg/kg/day) for 12 weeks. Arg-treated db/db mice showed preserved diastolic function and left ventricular morphology compared with untreated diabetic mice. Arg supplementation also improved exercise tolerance and the propensity to physical activity. Mitochondrial respiration was significantly increased in cardiomyocytes isolated from treated db/db mice, as well as in diabetic cardiomyocytes treated with Arg in vitro. The improvement of cardiac mitochondrial function in db/db + Arg mice was associated with an increase in PGC-1-alpha levels, mitochondrial biogenesis, recycling, and antioxidant capacity. Arg treatment prevented the accumulation of circulating and cardiac miR-143 in db/db mice, which is an index of metabolic stress and activation of mitochondrial damage mechanisms. In conclusion, Arg supplementation is effective in preventing the development of DC, preserving diastolic function and exercise tolerance by improving mitochondrial fitness and homeostasis. Additionally, miR-143 could potentially be employed to monitor cardiac metabolic stress and the effects of Arg treatment in diabetes.