Beneficial Effects Of Exercise Research Articles

Roles of pigment epithelium-derived factor in exercise-induced suppression of senescence and its impact on lung pathology in mice.

Senescent cells contribute to tissue aging and underlie the pathology of chronic diseases. The benefits of eliminating senescent cells have been demonstrated in several disease models, and the efficacy of senolytic drugs is currently being tested in humans. Exercise training has been shown to reduce cellular senescence in several tissues; however, the mechanisms responsible remain unclear. We found that myocyte-derived factors significantly extended the replicative lifespan of fibroblasts, suggesting that myokines mediate the anti-senescence effects of exercise. A number of proteins within myocyte-derived factors were identified by mass spectrometry. Among these, pigment epithelium-derived factor (PEDF) exerted inhibitory effects on cellular senescence. Eight weeks of voluntary running increased Pedf levels in skeletal muscles and suppressed senescence markers in the lungs. The administration of PEDF reduced senescence markers in multiple tissues and attenuated the decline in respiratory function in the pulmonary emphysema mouse model. We also showed that blood levels of PEDF inversely correlated with the severity of COPD in patients. Collectively, these results strongly suggest that PEDF contributes to the beneficial effects of exercise, potentially suppressing cellular senescence and its associated pathologies.

Beneficial Effects of Exercise on Hypertension-Induced Cardiac Hypertrophy in Adolescents and Young Adults.

Hypertension-induced cardiac hypertrophy is widely known as a major risk factor for increased cardiovascular morbidity and mortality. Although exercise is proven to exert overall beneficial effects on hypertension and hypertension-induced cardiac hypertrophy, there are some concerns among providers about potential adverse effects induced by intense exercise, especially in hypertensive athletes. We will overview the underlying mechanisms of physiological and pathological hypertrophy and delineate the beneficial effects of exercise in young people with hypertension and consequent hypertrophy. Multiple studies have demonstrated that exercise training, both endurance and resistance types, reduces blood pressure and ameliorates hypertrophy in hypertensives, but certain precautions are required for hypertensive athletes when allowing competitive sports: Elevated blood pressure should be controlled before allowing them to participate in high-intensity exercise. Non-vigorous and recreational exercise are always recommended to promote cardiovascular health. Exercise-induced cardiac adaptation is a benign and favorable response that reverses or attenuates pathological cardiovascular remodeling induced by persistent hypertension. Exercise is the most effective nonpharmacological treatment for hypertensive individuals. Distinction between recreational-level exercise and competitive sports should be recognized by medical providers when allowing sports participation for adolescents and young adults.

Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.

Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored. To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals. Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise. Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice. Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes.

Diacylglycerol kinase delta overexpression improves glucose clearance and protects against the development of obesity

Background and aimDiacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments. MethodsWe generated a transgenic mouse model overexpressing human DGKδ2 under the myosin light chain promoter (DGKδ TG). We performed deep metabolic phenotyping of DGKδ TG mice and wild-type littermates fed chow or high-fat diet (HFD). Mice were also provided free access to running wheels to examine the effects of DGKδ overexpression on exercise-induced metabolic outcomes. ResultsDGKδ TG mice were leaner than wild-type littermates, with improved glucose tolerance and increased skeletal muscle glycogen content. DGKδ TG mice were protected against HFD-induced glucose intolerance and obesity. DGKδ TG mice had reduced epididymal fat and enhanced lipolysis. Strikingly, DGKδ overexpression recapitulated the beneficial effects of exercise on metabolic outcomes. DGKδ overexpression and exercise had a synergistic effect on body weight reduction. Microarray analysis of skeletal muscle revealed common gene ontology signatures of exercise and DGKδ overexpression that were related to lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways. ConclusionOverexpression of DGKδ induces adaptive changes in both skeletal muscle and adipose tissue, resulting in protection against high fat diet-induced obesity. DGKδ overexpression recapitulates exercise-induced adaptations on energy homeostasis and skeletal muscle gene expression profiles.

Transfer of Exercise-Microbiome Is Suffcient to Induce a Shift in the Skeletal Muscle Metabolomic Profile without an Exercise Stimulus

Introduction: Skeletal muscle is a tissue that dynamically responds to disuse, which can induce rapid loss of mass and function. Identification of novel drug candidates will facilitate the development of supportive therapies for extended periods of decreased mobility, both planned and unanticipated. Recent findings from our lab as well as others indicate the important role of the gut microbiome in mediating the beneficial effects of exercise. Hypothesis: Transfer of microbiome from excise-trained mice into exercise-naïve mice will induce metabolic adaptations in the recipient skeletal muscle. Method: Sedentary and exercise-trained mice were used as donors for microbiome transfer. Exercise training consisted of 8-weeks of processive weighted wheel running. Exercise-naïve recipient mice were bowel cleansed with polyethylene glycol and transplanted with either sedentary (SED) or exercise-trained (EXER) donor microbiome. Recipient cecal content, serum, and gastrocnemius muscle were collected for untargeted metabolomics using liquid chromatography mass spectrometry. Results: Partial Least Squares Discriminant Analysis indicated significant metabolic discrimination between EXER and SED in all samples (cecal, serum, and muscle). Variable Importance in Projection scores identified several metabolites as significant discriminating metabolic features between EXER and SED, including ones involved in the TCA cycle, lysine and fatty acid degradation pathways. Conclusion: Transfer of microbial content from exercise-trained mice is suffcient to induce changes in muscle metabolite profile reminiscent of exercise in the absence of such a stimulus. Funding: This work is supported by the National Institute on Aging (AG071888). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

IGF1 promotes human myotube differentiation toward a mature metabolic and contractile phenotype.

Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations. We monitored the differentiation process starting from primary human CD56-positive myoblasts in the presence/absence of IGF1 in serum-free medium in daily collected samples for 10 days. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon electrical pulse stimulation following day 6. Myotubes without IGF1 were almost incapable of contraction. IGF1-treatment shifted the proteome toward skeletal muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7 and reduced MYH1/2 suggest a more oxidative phenotype further demonstrated by higher abundance of proteins of the respiratory chain and elevated mitochondrial respiration. IGF1-treatment also upregulated GLUT4 and increased insulin-dependent glucose uptake compared to myotubes differentiated without IGF1. To conclude, addition of IGF1 to serum-free medium significantly improves the differentiation of human myotubes that showed enhanced myofibril formation, response to electrical pulse stimulation, oxidative respiratory capacity and glucose metabolism overcoming limitations of previous standards. This novel protocol enables investigation of muscular exercise on a molecular level.

Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation

BackgroundExercise is an effective strategy to prevent sarcopenia, but high physical inactivity in the elderly requires alternative therapeutic approaches. Exercise mimetics are therapeutic compounds that simulate the beneficial effects of exercise on skeletal muscles. However, the toxicity and adverse effects of exercise mimetics raise serious concerns. PurposeWe aimed to search novel plant-based alternatives to activate exercise induced-signaling. MethodsWe used open databases and luciferase assays to identify plant-derived alternatives to activate exercise-induced signaling and compared its efficacy to mild intensity continuous training (MICT) in aged C57BL/6 mice. The nineteen-month-old mice were either fed an experimental diet supplemented with the isolated alternative or subjected to MICT for up to 21 mo of age. ResultsOur analysis revealed that Chrysanthemum zawadskii Herbich var latillobum (Maxim.) Kitamura (CZH), a medicinal plant rich in linarin, is a novel activator of peroxisome proliferator-activated receptor δ (PPARδ) and estrogen-related receptor γ (ERRγ), key regulators of exercise-induced positive effects on muscles. CZH supplementation ameliorated the loss of muscle function and mass, and increased PPARδ and ERRγ expression in mouse muscles. CZH also improved mitochondrial functions and proteostasis in aged mice, similar to MICT. Furthermore, CZH and linarin induced the activation of Sestrin 1, a key mediator of exercise benefits, in muscle. Silencing Sestrin 1 negated the increase in myogenesis and mitochondrial respiration by CZH and linarin in primary myoblasts from old mice. ConclusionOur findings suggest the potential of CZH as a novel plant-derived alternative to activate exercise-induced signaling for preventing sarcopenia in sedentary older adults. This could offer a safer therapeutic option for sarcopenia treatment.

The Influence of Exercise on Cancer Risk, the Tumor Microenvironment and the Treatment of Cancer.

There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.

Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats

Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer’s disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.

RNA-mediated epigenetic regulation in exercised heart: Mechanisms and opportunities for intervention

Physical exercise has been widely acknowledged as a beneficial lifestyle alteration and a potent non-pharmacological treatment for heart disease. Extensive investigations have revealed the beneficial effects of exercise on the heart and the underlying mechanisms involved. Exercise is considered one of the key factors that can lead to epigenetic alterations. The increasing number of identified molecules in the exercised heart has led to many studies in recent years that have explored the cellular function of ncRNAs and RNA modifications in the heart. Investigating the regulatory role of RNA-mediated epigenetic regulation in exercised hearts will contribute to the development of therapeutic strategies for the management of heart diseases. This review aims to summarize the positive impact of exercise on cardiac health. We will first provide an overview of the mechanisms through which exercise offers protection to the heart. Subsequently, we will delve into the current understanding of ncRNAs, specifically miRNAs, lncRNAs, and circRNAs, as well as RNA modification, focusing on RNA m6A and RNA A-to-I editing, and how they contribute to exercise-induced benefits for the heart. Lastly, we will explore the emerging therapeutic strategies that utilize exercise-mediated RNA epigenetic regulation in the treatment of heart diseases, while also addressing the challenges faced in this field.

Effect of Physical Activity during Pregnancy on the Risk of Hypertension Disorders and Gestational Diabetes: Evidence Generated by New RCTs and Systematic Reviews.

Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are the most common medical complications in pregnancy. Physical exercise is considered to be safe and beneficial during pregnancy. Moreover, pregnancy could be considered as an opportunity for healthcare providers to promote positive lifestyle behavior and optimize the well-being of pregnant women. Since there are few up-to-date reviews evaluating the role of exercise and the risks of developing obstetrical complications, we performed a review to investigate the effects of physical activity and exercise during pregnancy compared to a control group, focusing on the risk of development of HDP and GDM. We searched Medline and Web of Science, including only randomized controlled trials (RCTs) and systematic reviews. This review supports a beneficial effect of exercise and provides evidence that it significantly decreases the risk of HDP and GDM.

Impact of 8-week cold-and warm water swimming training combined with cinnamon consumption on serum METRNL, HDAC5, and insulin resistance levels in diabetic male rats

ObjectiveNumerous studies have reported the beneficial effects of exercise and the use of herbal supplements in improving type 2 diabetes and insulin resistance. However, there are still many unanswered questions about the effects of cold and hot water, exercise, and herbal supplements on meteorine-like protein (METRNL), which is considered one of the key factors influencing insulin resistance improvement in this condition. Hence, the current study aimed to address these knowledge gaps and investigate the effects of 8 weeks of warm and cold-water swimming exercise with cinnamon consumption on serum levels of METRNL, histone deacetylase-5 (HDAC5), and insulin resistance in diabetic male rats. MethodsFor this purpose, 70 diabetic male rats were randomly divided into seven groups (10 rats in each group) H ealthy control (HC) , Diabetic control , swimming training in cold water (temperature 5 °C) , swimming training at 5‌‌ °C + cinnamon consumption (200 mg/kg body weight) , swimming training in warm water (temperature 36-35 °C) , swimming training in warm water (temperature 36-35 °C) + consumption of cinnamon, and consumption of cinnamon only. ResultsThe present study revealed a significant increase in serum METRNL concentration in the cold-water swimming + cinnamon consumption group (p < 0.05). However, no significant changes were observed in insulin levels and HOMA-IR across the different groups (p > 0.05). Additionally, noteworthy findings included a significant reduction in HDAC5 levels in both the cold-water swimming group and the cold-water swimming + cinnamon consumption group, as well as a significant decrease in fasting blood sugar (FBS) levels in all groups compared to the HC group (p < 0.05). ConclusionsThe results of the present study demonstrate that the combination of cold-water swimming exercises and cinnamon extract consumption led to notable increases in serum METRNL concentration. Additionally, significant reductions were observed in HDAC5 and FBS levels. These findings highlight the potential effectiveness and benefits of the combination of cold-water swimming exercises and cinnamon extract consumption as an approach to improve diabetes-related indices.

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial

IntroductionPersonalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the...

The Role of the Myokine Irisin in the Protection and Carcinogenesis of the Gastrointestinal Tract.

Recently discovered irisin, a member of the myokines family, is a potential mediator of exercise-induced energy metabolism and a factor promoting browning of the white adipose tissue. Recent evidence indicates that this myokine, released from contracting muscles, can mediate the beneficial effects of exercise on health. Irisin may be a potential therapeutic agent against obesity and has been shown to play an important role in the protection of various cells, tissues, and organs due to its anti-inflammatory, antioxidative, and anti-cancer properties. Our aim was to review the recent experimental and clinical studies on irisin and its expression, release into the bloodstream, tissue targets, and potential contribution to the protective effects of exercise in the gastrointestinal tract. Particular emphasis was placed on inflammatory bowel disease, intestinal ischemia/reperfusion injury, periodontitis, and other digestive tract disorders, including carcinogenesis. Overall, irisin holds significant potential as a novel target molecule, offering a safe and therapeutic approach to treating various gastrointestinal diseases.

Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism.

Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression is influenced by factors like oxidative stress, inflammation, cell death, and fibrosis. Compared to drug treatment, exercise offers a cost-effective and low-risk approach to slowing down DN progression. Through multiple ways and mechanisms, exercise helps to control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects of exercise on DN improvement and highlights its potential mechanisms for ameliorating DN. In-depth understanding of the role and mechanism of exercise in improving DN would pave the way for formulating safe and effective exercise programs for the treatment and prevention of DN.

The effectiveness of exercise interventions targeting sleep in older adults with cognitive impairment or Alzheimer's disease and related dementias (AD/ADRD): A systematic review and meta-analysis.

Sleep loss is associated with reduced health and quality of life, and increased risk of Alzheimer's disease and related dementias. Up to 66% of persons with Alzheimer's disease and related dementias experience poor sleep, which can predict or accelerate the progression of cognitive decline. Exercise is a widely accessible intervention for poor sleep that can protect against functional and cognitive decline. No previous systematic reviews have investigated the effectiveness of exercise for sleep in older adults with mild cognitive impairment or Alzheimer's disease and related dementias. We systematically reviewed controlled interventional studies of exercise targeting subjectively or objectively (polysomnography/actigraphy) assessed sleep in persons with mild cognitive impairment or Alzheimer's disease and related dementias. We conducted searches in PubMed, Embase, Scopus and Cochrane-Library (n = 6745). Nineteen randomised and one non-randomised controlled interventional trials were included, representing the experiences of 3278 persons with mild cognitive impairment or Alzheimer's disease and related dementias. Ten had low-risk, nine moderate-risk, and one high-risk of bias. Six studies with subjective and eight with objective sleep outcomes were meta-analysed (random-effects model). We found moderate- to high-quality evidence for the beneficial effects of exercise on self-reported and objectively-measured sleep outcomes in persons with mild cognitive impairment or Alzheimer's disease and related dementias. However, no studies examined key potential moderators of these effects, such as sex, napping or medication use. Our results have important implications for clinical practice. Sleep may be one of the most important modifiable risk factors for a range of health conditions, including cognitive decline and the progression of Alzheimer's disease and related dementias. Given our findings, clinicians may consider adding exercise as an effective intervention or adjuvant strategy for improving sleep in older persons with mild cognitive impairment or Alzheimer's disease and related dementias.

Interaction between type 2 diabetes polygenic risk and physical activity on cardiovascular outcomes.

The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes. Using the UK Biobank cohort, we investigated the effect of type 2 diabetes genetic risk-physical activity interaction on 3-point and 4-point major adverse cardiovascular events (MACE), in 25,701 diabetic participants. We used a polygenic risk score for type 2 diabetes (PRS_T2D) as a measure of genetic risk for type 2 diabetes. We observed significant interaction between PRS_T2D and physical activity on cardiovascular outcomes (3-point MACE: P trend for interaction = 0.0081; 4-point MACE: P trend for interaction = 0.0037). Among participants whose PRS_T2D was in the first or second quartile, but not in the third or fourth quartile, each 10 metabolic equivalents (METs) hours per week of physical activity decreased the risk of 3-point or 4-point MACE. Furthermore, restricted cubic spline analysis indicated that intense physical activity (>80 METs hours per week, which was self-reported by 12.7% of participants) increased the risk of cardiovascular outcomes among participants whose PRS_T2D was in the fourth quartile. Subgroup analysis suggested that negative impact of intense physical activity was observed only in non-insulin users. The beneficial effect of physical activity on cardiovascular outcomes were disappeared among those with high genetic risk for type 2 diabetes.

Phase Angle as a Marker of Physical Function in Non-Sarcopenic Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Most patients with RA face a barrier to participation in social activities or exercise due to joint pain, despite the beneficial effects of exercise and physical activity. Thus, RA may be a risk factor for sarcopenia in the clinical field. Bioelectrical impedance analysis-derived phase angle (PhA) reflects cellular health and is correlated with the prognosis of various diseases. However, its association with physical function in non-sarcopenic RA female patients remains unclear. We evaluated the association between PhA values and various physical function measures in female patients with non-sarcopenic RA. Methods: Thirty-five participants with RA were screened. One met the criteria for sarcopenia. Finally, 34 patients with non-sarcopenic RA were enrolled. This cross-sectional retrospective study evaluated upper- and lower-extremity strengths, cross-sectional area of rectus femoris, 6 min walking test, Borg scale score, sit-to-stand test, and physical function and mental health from 36-Item Short Form Health Survey scores. Results: In total, 34 female participants (mean age = 49.74 ± 8.15 years) were enrolled. In non-sarcopenic RA patients, PhA was significantly correlated with BMI and ASM/(height)2. Multicollinearity was not detected among the independent variables (VIF < 5). The final multivariable regression model identified ASM/height2 as a significant predictor of PhA among non-sarcopenic RA patients. Conclusion: Multivariable linear regression analyses identified appendicular skeletal muscle mass as a significant predictor of PhA. Bioelectrical impedance analysis-derived PhA is a valuable guidance tool for RA management. PhA can be a useful clinical biomarker of muscle status in non-sarcopenic RA patients.

The Impact of Physical Exercise on microRNAs in Hemodialysis Patients: A Review and a Protocol for an Ancillary Study.

Physical inactivity is considered a significant risk factor for mortality and morbidity among chronic hemodialysis (HD) patients. Therefore, physical exercise is recommended in the treatment of HD patients. Although the beneficial effects of physical exercise in HD patients are well-described in the literature, the underlying physiological mechanisms still need to be fully understood. Recently, microRNAs (miRNAs) have emerged as potential mediators of the therapeutic effects of physical exercise in healthy individuals. miRNAs are short, single-stranded, noncoding RNAs involved in gene expression regulation. Specifically, upon forming the RNA-induced silencing complex, miRNAs selectively bind to specific miRNAs within cells, reducing gene expression. miRNAs can be secreted by cells in an accessible form or enclosed within exosomes or extracellular vesicles. They can be detected in various body fluids, including serum (circulating miRNAs), facilitating the study of their diverse expression. Currently, there is no available data regarding the impact of physical exercise on the expression of miRNAs involved in osteogenic differentiation, a fundamental mechanism in the development of vascular calcification, for HD patients. Therefore, we have designed an observational and longitudinal case-control study to evaluate the expression of miR-9 and miR-30b in HD patients participating in a 3-month interdialytic physical exercise program. This paper aims to present the study protocol and review the expression of circulating miRNAs in HD patients and their modulation through physical exercise.

Evaluation of skeletal muscle function in male rats with doxorubicin-induced myopathy following various exercise techniques: the significant role of glucose transporter 4

A common anthracycline antibiotic used to treat cancer patients is doxorubicin (DOX). One of the effects of DOX therapy is skeletal muscle fatigue. Our goal in this research was to study the beneficial effect of exercise on DOX-induced damaged muscle fibers and compare the effect of different exercise strategies (prophylactic, post- toxicity and combined) on DOX toxicity. Five groups were created from 40 male rats: group I, control group; group II, DOX was administered intraperitoneally for 2 weeks over 6 equal injections (each 2.5 mg/kg); group III, rats trained for 3 weeks before DOX; group IV, rats trained for 8 weeks after DOX; and group V, rats were trained for 3 weeks before DOX followed by 8 weeks after. Measures of oxidative damage (H2O2, catalase), inflammation (TNF-α), and glucose transporter 4 (GLUT4) expression on skeletal muscle were assessed. Also, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was estimated. Skeletal performance was evaluated by contraction time (CT), half relaxation time (1/2 RT), and force-frequency relationship by the end of this research. The current study demonstrated a detrimental effect of DOX on skeletal performance as evidenced by a significant increase in CT and 1/2 RT compared to control; in addition, H2O2, TNF-α, and HOMA-IR were significantly increased with a significant decrease in GLUT4 expression and catalase activity. Combined exercise therapy showed a remarkable improvement in skeletal muscle performance, compared to DOX, CT, and 1/2 RT which were significantly decreased; H2O2 and TNF-α were significantly decreased unlike catalase antioxidant activity that significantly increased; in addition, skeletal muscle glucose metabolism was significantly improved as GLUT4 expression significantly increased and HOMA-IR was significantly decreased. Exercise therapy showed significant improvement in all measured parameters relative to DOX. However, combined exercise therapy showed the best improvement relative to both pre-exercise and post-exercise groups.