BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired t...Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of life.It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients.Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD patients.In addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis.Furthermore,irisin produces changes in the diversity of the microbiota.Therefore,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.展开更多
Diabetes mellitus, a type of chronic metabolic disease, is occurring more frequently and causes severe threats to human health. In vivo, exercise can stimulate skeletal muscle cells to secrete and release myokines int...Diabetes mellitus, a type of chronic metabolic disease, is occurring more frequently and causes severe threats to human health. In vivo, exercise can stimulate skeletal muscle cells to secrete and release myokines into blood circulation, which will participate in metabolism and act on multiple organs or systems. Recently, the relationship between myokines and diabetes mellitus was a hot research topic, and myokines may be potential targets for the diagnosis, monitoring, prevention and treatment of diabetes mellitus. In this review, we elucidated the multiple effects of common myokines in the pathogenesis and therapy of diabetes mellitus, which will provide a theoretical foundation of the mechanism in the positive effects of exercises on humans.展开更多
Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes assoc...Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding ofthe mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.展开更多
Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as myokines.Altered myokine levels are associated with metabol...Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as myokines.Altered myokine levels are associated with metabolic diseases,such as type 2 diabetes(T2D).The significance of interorgan crosstalk,particularly through myokines,has emerged as a fundamental aspect of nutrient and energy homeostasis.However,a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge.In this review,we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades,namely interleukin 6(IL-6),irisin,myostatin(MSTN),growth differentiation factor 11(GDF11),fibroblast growth factor 21(FGF21),apelin,brain-derived neurotrophic factor(BDNF),meteorin-like(Metrnl),secreted protein acidic and rich in cysteine(SPARC),β-aminoisobutyric acid(BAIBA),Musclin,and Dickkopf 3(Dkk3).Related to these,we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease.Despite significant advancements in myokine research,many myokines remain challenging to measure accurately and investigate thoroughly.Hence,new research techniques and detection methods should be developed and rigorously tested.Therefore,developing a comprehensive perspective on myokine biology is crucial,as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.展开更多
Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secret...Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.展开更多
Irisin is a chief myokine released during physical activity and has garnered attention for its potential therapeutic effects on different metabolic and cardiovascular disorders.This review explores the intricate conne...Irisin is a chief myokine released during physical activity and has garnered attention for its potential therapeutic effects on different metabolic and cardiovascular disorders.This review explores the intricate connections between irisin,physical activity,sarcopenia,type 2 diabetes mellitus(T2DM),and cardiovascular complications.Experimental data suggests that through irisin release,physical activity positively influences muscle health,metabolic regulation,and cardiovascular function.In individuals with sarcopenia,characterized by progressive muscle mass and function loss,irisin plays a pivotal role in maintaining muscle integrity and function.Additionally,irisin’s beneficial effects on insulin sensitivity and glucose metabolism suggest its involvement in the pathophysiology of T2DM.The review will examine how irisin may modulate the development of cardiovascular complications,particularly in the context of diabetes and aging.Additionally,it will explore its potential as a therapeutic target for managing sarcopenia,T2DM,and cardiovascular complications,underscoring the importance of physical activity in mitigating these interconnected health challenges.Further research is needed to elucidate the precise mechanisms by which irisin mediates these effects and assess its clinical applicability in preventing and treating metabolic and cardiovascular disorders.展开更多
The etiology,risk factors,and management of sarcopenia and metabolic dysfunction-associated steatotic liver disease(MASLD)are comparable,which prompted the investigators to search for a particular diagnostic or progno...The etiology,risk factors,and management of sarcopenia and metabolic dysfunction-associated steatotic liver disease(MASLD)are comparable,which prompted the investigators to search for a particular diagnostic or prognostic biomarker that was involved in both disorders.Peptides or proteins known as myokines,or exerkines,are produced and secreted by contracted muscles.Myokines work similarly to hormones in their actions.One common clinical hallmark of sarcopenia and MASLD is physical inactivity,which is associated with alterations in the levels of myokines.Irisin is a positive regulator of muscle size that is elevated in the biological fluids during exercise.Significantly low levels were observed in the pathological conditions associated with physical inactivity.The serum levels of irisin are significantly higher in MASLD patients,while their levels were lower in risk factors of MASLD,e.g.,diabetes mellitus,obesity,and insulin resistance.In sarcopenia with obesity(sarcopenic obesity)or with a normal build,serum irisin levels are significantly lower than in healthy subjects.Therefore,serial determination of irisin levels that showed a transition from higher to lower levels in MASLD indicated the development of sarcopenia in those patients.展开更多
Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicin...Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased survival.Several avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simplifies the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and hormones.However,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical oncology.To date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer cells.Nevertheless,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode.Insights for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.展开更多
Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate s...Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.展开更多
Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studie...Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.展开更多
BACKGROUND Currently, the findings about irisin as a novel myokine related to obesity are inconsistent in overweight/obese people. To our knowledge, no systematic analysis has been conducted to evaluate the relationsh...BACKGROUND Currently, the findings about irisin as a novel myokine related to obesity are inconsistent in overweight/obese people. To our knowledge, no systematic analysis has been conducted to evaluate the relationship between irisin levels and overweight/obesity. AIM To evaluate the association between circulating irisin levels and overweight/obesity. METHODS The Cochrane Library, MEDLINE, SCOPUS, and the ISI Web of Science were searched to retrieve all of the studies associated with circulating irisin levels and overweight/obesity. Standard mean difference values and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methodology. RESULTS A total of 18 studies were included in our meta-analysis containing 1005 cases and 1242 controls. Our analysis showed that the circulating irisin level in overweight/obese people was higher than that in overall healthy controls (random effects MD = 0.63;95%CI: 0.22-1.05;P = 0.003). In the subgroup analysis by ethnicity, the irisin level was higher in overweight/obesity people than that in controls in Africa (random effects MD = 3.41;95%CI: 1.23-5.59;P < 0.05) but not in European, Asian, or American populations. In addition, in a subgroup analysis by age, the results showed that obese children exhibited a higher irisin level than controls (random effects MD = 0.86;95%CI: 0.28-1.43;P < 0.05). CONCLUSION This meta-analysis provides evidence that circulating irisin is higher in obese individuals compared to healthy controls and it is important to identify the relationship between circulating irisin levels and overweight/obesity in predicting overweight/obesity.展开更多
An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus cen...An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus central to the process whereby organisms adapt to their respective environments.Mitochondria produce molecular energy via oxidative phosphorylation that then allows cells to biosynthetically respond and adapt to changes in their environment.Reactive oxygen species(ROS)are by-products of oxidative phosphorylation that can be either beneficial or damaging,depending on the context;ROS are hence both the conveyors of environmental stress as well as cellular“adaptogens”.Mitohormesis refers to the process whereby low levels of oxidative stress spur survival adaptations,whereas excessive levels stymie survival.Low energy and frequency pulsing electromagnetic fields have been recently shown capable of stimulating mitochondrial respiration and ROS production and instilling mitohormetic survival adaptations,similarly to,yet independently of,exercise,opening avenues for the future development of Magnetic Mitohormetic interventions for the improvement of human health.This viewpoint explores the possibilities and nuances of magnetic-based therapies as a form of clinical intervention to non-invasively activate magnetic mitohormesis for the management of chronic diseases.展开更多
Regular exercise improves physical function and quality of life and reduces fatigue in cancer survivors;these health benefits could be due to the anti-inflammatory effects of exercise. In this study we examined the ef...Regular exercise improves physical function and quality of life and reduces fatigue in cancer survivors;these health benefits could be due to the anti-inflammatory effects of exercise. In this study we examined the effects of a whole-body exercise programme and dragon boat paddling on the production of reactive oxygen species (ROMs), antioxidant capacity (BAP) and the circulating levels of several interleukins in breast cancer patients. Thirty four women surgically treated for breast cancer were enrolled in this study: 20 of them usually row dragon boats recreationally while 14 were sedentary. The 16-week training programme consisted of resistance and aerobic exercise, with the addition of dragon boat paddling for the last 8 weeks. Analyses of ROMs, cytokines and BAP were performed before and after 16 weeks of training. Results show a significant decrease in the ROMs value and significantly increased the BAP, IL-6, IL-8 and IL-15 levels. Exercise increased the BAP, IL-6, IL-8 and IL-15 values in the N+ patients, whereas only IL-6 and IL-8 were higher in the N0 patients. We demonstrated that muscle-derived cytokines are released after a training program and that the resulting decreased oxidative stress conditions underline the health-benefiting effects of such activity on breast cancer patients.展开更多
Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a ...Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.展开更多
Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.Howe...Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cell group were not significantly different from the external oblique muscle-fabricated nerve conduit group.Collectively,these data suggest that muscle-derived cells effectively accelerated peripheral nerve regeneration.This study was approved by the Animal Ethics Committee of Plastic Surgery Hospital,Chinese Academy of Medical Sciences(approval No.040)on September 28,2016.展开更多
Recently, glucagon-like peptide-1(GLP-1) receptor agonists have become a cornerstone for the treatment of obese patients with type 2 diabetes(T2D), exhibiting favorable effects on the cardiovascular outcome. In T2D, i...Recently, glucagon-like peptide-1(GLP-1) receptor agonists have become a cornerstone for the treatment of obese patients with type 2 diabetes(T2D), exhibiting favorable effects on the cardiovascular outcome. In T2D, impaired GLP-1 secretion/function is observed, and gut microbiota dysbiosis is related to the GLP-1 resistance. Prior research has revealed that exercise increases GLP-1 levels in healthy and obese individuals; however, the efficacy of exercise on GLP-1 levels in patients with T2D remains unclear. Exercise may improve GLP-1 resistance rather than GLP-1 secretion in patients with T2D. Exercise increases the gut microbiota diversity, which could contribute to improving the GLP-1 resistance of T2D. Furthermore, the gut microbiota may play a role in the correlation between exercise and GLP-1. The combination of exercise and GLP-1-based therapy may have a synergistic effect on the treatment of T2D. Although the underlying mechanism remains unknown, exercise potentiates the efficacy of GLP-1 receptor agonist treatment in patients with T2D.展开更多
The observation that physical activity(PA)reduces the risk of coronary heart disease dates back more than 70 years ago and it is now established that regular PA reduces all-cause mortality,in part,by reducing the risk...The observation that physical activity(PA)reduces the risk of coronary heart disease dates back more than 70 years ago and it is now established that regular PA reduces all-cause mortality,in part,by reducing the risk of numerous chronic diseases including coronary heart disease,stroke,cancer,type 2 diabetes,and Alzheimer's disease.During the past decade the increased use of activity tracking devices has significantly improved our understanding of the dose-response relationships between PA and all-cause mortality.Further,our appreciation of the impact that prolonged sitting has on all-cause mortality has increased.Moreover,new research provides key insight into the signaling mechanisms that connect PA to the reduced risk of disease in multiple organ systems.Therefore,given the recent advances in the study of PA and all-cause mortality,it is an appropriate time to review the latest evidence on this topic as well as the mechanisms responsible for the PA-induced protection against allcause mortality.Therefore,this review will summarize recent data on the dose-response association between PA on all-cause mortality and the negative impact that sedentary behavior has on all-cause mortality.Further,we also highlight potential mechanisms linking PA with the reduced risk of developing several chronic diseases.Finally,we conclude with a brief discussion of the emerging evidence that the health benefits associated with PA are derived,in part,from skeletal muscle-organ crosstalk involving muscle produced hormones(myokines)that exert their effects in either an autocrine,paracrine,or endocrine manner.展开更多
Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically s...Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.展开更多
Low-grade inflammation is emerging as a common feature of contemporary metabolic,psychiatric,and neurodegenerative diseases.Both physical inactivity and abdominal adiposity are associated with persistent systemic low-...Low-grade inflammation is emerging as a common feature of contemporary metabolic,psychiatric,and neurodegenerative diseases.Both physical inactivity and abdominal adiposity are associated with persistent systemic low-grade inflammation.Thus,the behavioral,biological,and physiological changes that cause a predisposition to obesity and other co-morbidities could have epigenetic underpinnings in addition to various evolutionary scenarios.A key assumption involves the potential for a mismatch between the human genome molded over generations,and the issue of adapting to the modern high calorie diet and common built environments promoting inactivity.This biological mismatch appears to have dire health consequences.Therefore,the goal of this article is to provide a brief overview on the importance of inflammation as part of human survival and how physical activity(PA)and physical inactivity are critical regulators of systemic inflammation.The review will highlight antiinflammatory effects of PA and exercise training from a metabolic and systemic signaling perspective,which includes skeletal muscle to utilization of fatty acids,TLR4 signaling,and myokine/adipokine effects.The available evidence suggests that PA,regular exercise,and weight loss offer both protection against and treatment for a wide variety of chronic diseases associated with low-grade inflammation through an improved inflammatory profile.展开更多
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
文摘Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of life.It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients.Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD patients.In addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis.Furthermore,irisin produces changes in the diversity of the microbiota.Therefore,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.
文摘Diabetes mellitus, a type of chronic metabolic disease, is occurring more frequently and causes severe threats to human health. In vivo, exercise can stimulate skeletal muscle cells to secrete and release myokines into blood circulation, which will participate in metabolism and act on multiple organs or systems. Recently, the relationship between myokines and diabetes mellitus was a hot research topic, and myokines may be potential targets for the diagnosis, monitoring, prevention and treatment of diabetes mellitus. In this review, we elucidated the multiple effects of common myokines in the pathogenesis and therapy of diabetes mellitus, which will provide a theoretical foundation of the mechanism in the positive effects of exercises on humans.
文摘Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding ofthe mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.
基金supported by grants from the National Key Research and Development Program of China(2018YFA0800403 and 2021YFC2701903)the Training Program of the Major Research Plan of the National Natural Science Foundation of China(91857110)+3 种基金the National Natural Science Foundation of China(81670740,32000817,82100904,and 82300910)the National Natural Science Fund for Excellent Young Scholars of China(81722012)the Zhejiang Provincial Natural Science Foundation of China(LZ21H070001,LHDMD22H02001,and LHDMD24H030001)the Innovative Institute of Basic Medical Sciences of Zhejiang University,and the Fundamental Research Funds for the Central Universities.
文摘Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as myokines.Altered myokine levels are associated with metabolic diseases,such as type 2 diabetes(T2D).The significance of interorgan crosstalk,particularly through myokines,has emerged as a fundamental aspect of nutrient and energy homeostasis.However,a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge.In this review,we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades,namely interleukin 6(IL-6),irisin,myostatin(MSTN),growth differentiation factor 11(GDF11),fibroblast growth factor 21(FGF21),apelin,brain-derived neurotrophic factor(BDNF),meteorin-like(Metrnl),secreted protein acidic and rich in cysteine(SPARC),β-aminoisobutyric acid(BAIBA),Musclin,and Dickkopf 3(Dkk3).Related to these,we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease.Despite significant advancements in myokine research,many myokines remain challenging to measure accurately and investigate thoroughly.Hence,new research techniques and detection methods should be developed and rigorously tested.Therefore,developing a comprehensive perspective on myokine biology is crucial,as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.
基金the Biochemical Imaging Center at UmeåUniversity and the National Microscopy Infrastructure(VR-RFI 2019-00217),for providing assistance in microscopy.
文摘Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.
文摘Irisin is a chief myokine released during physical activity and has garnered attention for its potential therapeutic effects on different metabolic and cardiovascular disorders.This review explores the intricate connections between irisin,physical activity,sarcopenia,type 2 diabetes mellitus(T2DM),and cardiovascular complications.Experimental data suggests that through irisin release,physical activity positively influences muscle health,metabolic regulation,and cardiovascular function.In individuals with sarcopenia,characterized by progressive muscle mass and function loss,irisin plays a pivotal role in maintaining muscle integrity and function.Additionally,irisin’s beneficial effects on insulin sensitivity and glucose metabolism suggest its involvement in the pathophysiology of T2DM.The review will examine how irisin may modulate the development of cardiovascular complications,particularly in the context of diabetes and aging.Additionally,it will explore its potential as a therapeutic target for managing sarcopenia,T2DM,and cardiovascular complications,underscoring the importance of physical activity in mitigating these interconnected health challenges.Further research is needed to elucidate the precise mechanisms by which irisin mediates these effects and assess its clinical applicability in preventing and treating metabolic and cardiovascular disorders.
文摘The etiology,risk factors,and management of sarcopenia and metabolic dysfunction-associated steatotic liver disease(MASLD)are comparable,which prompted the investigators to search for a particular diagnostic or prognostic biomarker that was involved in both disorders.Peptides or proteins known as myokines,or exerkines,are produced and secreted by contracted muscles.Myokines work similarly to hormones in their actions.One common clinical hallmark of sarcopenia and MASLD is physical inactivity,which is associated with alterations in the levels of myokines.Irisin is a positive regulator of muscle size that is elevated in the biological fluids during exercise.Significantly low levels were observed in the pathological conditions associated with physical inactivity.The serum levels of irisin are significantly higher in MASLD patients,while their levels were lower in risk factors of MASLD,e.g.,diabetes mellitus,obesity,and insulin resistance.In sarcopenia with obesity(sarcopenic obesity)or with a normal build,serum irisin levels are significantly lower than in healthy subjects.Therefore,serial determination of irisin levels that showed a transition from higher to lower levels in MASLD indicated the development of sarcopenia in those patients.
文摘Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased survival.Several avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simplifies the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and hormones.However,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical oncology.To date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer cells.Nevertheless,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode.Insights for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.
文摘Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.
文摘Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.
基金Supported by the National Natural Science Foundation of China,No.81500351the Youth Medical Talent Project of Jiangsu Province,No.QNRC2016842+3 种基金the Jiangsu University Affiliated Hospital"5123"Talent Plan,No.51232017305the 169 Talent Project of Zhenjiang
文摘BACKGROUND Currently, the findings about irisin as a novel myokine related to obesity are inconsistent in overweight/obese people. To our knowledge, no systematic analysis has been conducted to evaluate the relationship between irisin levels and overweight/obesity. AIM To evaluate the association between circulating irisin levels and overweight/obesity. METHODS The Cochrane Library, MEDLINE, SCOPUS, and the ISI Web of Science were searched to retrieve all of the studies associated with circulating irisin levels and overweight/obesity. Standard mean difference values and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methodology. RESULTS A total of 18 studies were included in our meta-analysis containing 1005 cases and 1242 controls. Our analysis showed that the circulating irisin level in overweight/obese people was higher than that in overall healthy controls (random effects MD = 0.63;95%CI: 0.22-1.05;P = 0.003). In the subgroup analysis by ethnicity, the irisin level was higher in overweight/obesity people than that in controls in Africa (random effects MD = 3.41;95%CI: 1.23-5.59;P < 0.05) but not in European, Asian, or American populations. In addition, in a subgroup analysis by age, the results showed that obese children exhibited a higher irisin level than controls (random effects MD = 0.86;95%CI: 0.28-1.43;P < 0.05). CONCLUSION This meta-analysis provides evidence that circulating irisin is higher in obese individuals compared to healthy controls and it is important to identify the relationship between circulating irisin levels and overweight/obesity in predicting overweight/obesity.
基金supported by Lee Kong Chian MedTech Initiative,Singapore(N-176-000-045-001)the Institute for Health Innovation&Technology,iHealthtech,at the National University of Singaporefunded by Lee Kong Chian MedTech Initiative,Singapore.
文摘An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus central to the process whereby organisms adapt to their respective environments.Mitochondria produce molecular energy via oxidative phosphorylation that then allows cells to biosynthetically respond and adapt to changes in their environment.Reactive oxygen species(ROS)are by-products of oxidative phosphorylation that can be either beneficial or damaging,depending on the context;ROS are hence both the conveyors of environmental stress as well as cellular“adaptogens”.Mitohormesis refers to the process whereby low levels of oxidative stress spur survival adaptations,whereas excessive levels stymie survival.Low energy and frequency pulsing electromagnetic fields have been recently shown capable of stimulating mitochondrial respiration and ROS production and instilling mitohormetic survival adaptations,similarly to,yet independently of,exercise,opening avenues for the future development of Magnetic Mitohormetic interventions for the improvement of human health.This viewpoint explores the possibilities and nuances of magnetic-based therapies as a form of clinical intervention to non-invasively activate magnetic mitohormesis for the management of chronic diseases.
文摘Regular exercise improves physical function and quality of life and reduces fatigue in cancer survivors;these health benefits could be due to the anti-inflammatory effects of exercise. In this study we examined the effects of a whole-body exercise programme and dragon boat paddling on the production of reactive oxygen species (ROMs), antioxidant capacity (BAP) and the circulating levels of several interleukins in breast cancer patients. Thirty four women surgically treated for breast cancer were enrolled in this study: 20 of them usually row dragon boats recreationally while 14 were sedentary. The 16-week training programme consisted of resistance and aerobic exercise, with the addition of dragon boat paddling for the last 8 weeks. Analyses of ROMs, cytokines and BAP were performed before and after 16 weeks of training. Results show a significant decrease in the ROMs value and significantly increased the BAP, IL-6, IL-8 and IL-15 levels. Exercise increased the BAP, IL-6, IL-8 and IL-15 values in the N+ patients, whereas only IL-6 and IL-8 were higher in the N0 patients. We demonstrated that muscle-derived cytokines are released after a training program and that the resulting decreased oxidative stress conditions underline the health-benefiting effects of such activity on breast cancer patients.
基金supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (No. RGPIN 435807-13) to JPLthe ANZ-MASON foundation (to DB)supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (No. MSH-141980)
文摘Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.
基金financially supported by the National Natural Science Foundation of China,No.81671908(to ZLQ)and No.81571921(to XNY)the Fundamental Research Fund for the Central Universities of China,No.2016ZX310197(to ZLQ)+1 种基金the Union Youth Science&Research Foundation of China,No.3332015155(to XNY)the Science Fund of Plastic Surgery Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College of China,No.Q2015013(to XNY)
文摘Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cell group were not significantly different from the external oblique muscle-fabricated nerve conduit group.Collectively,these data suggest that muscle-derived cells effectively accelerated peripheral nerve regeneration.This study was approved by the Animal Ethics Committee of Plastic Surgery Hospital,Chinese Academy of Medical Sciences(approval No.040)on September 28,2016.
文摘Recently, glucagon-like peptide-1(GLP-1) receptor agonists have become a cornerstone for the treatment of obese patients with type 2 diabetes(T2D), exhibiting favorable effects on the cardiovascular outcome. In T2D, impaired GLP-1 secretion/function is observed, and gut microbiota dysbiosis is related to the GLP-1 resistance. Prior research has revealed that exercise increases GLP-1 levels in healthy and obese individuals; however, the efficacy of exercise on GLP-1 levels in patients with T2D remains unclear. Exercise may improve GLP-1 resistance rather than GLP-1 secretion in patients with T2D. Exercise increases the gut microbiota diversity, which could contribute to improving the GLP-1 resistance of T2D. Furthermore, the gut microbiota may play a role in the correlation between exercise and GLP-1. The combination of exercise and GLP-1-based therapy may have a synergistic effect on the treatment of T2D. Although the underlying mechanism remains unknown, exercise potentiates the efficacy of GLP-1 receptor agonist treatment in patients with T2D.
文摘The observation that physical activity(PA)reduces the risk of coronary heart disease dates back more than 70 years ago and it is now established that regular PA reduces all-cause mortality,in part,by reducing the risk of numerous chronic diseases including coronary heart disease,stroke,cancer,type 2 diabetes,and Alzheimer's disease.During the past decade the increased use of activity tracking devices has significantly improved our understanding of the dose-response relationships between PA and all-cause mortality.Further,our appreciation of the impact that prolonged sitting has on all-cause mortality has increased.Moreover,new research provides key insight into the signaling mechanisms that connect PA to the reduced risk of disease in multiple organ systems.Therefore,given the recent advances in the study of PA and all-cause mortality,it is an appropriate time to review the latest evidence on this topic as well as the mechanisms responsible for the PA-induced protection against allcause mortality.Therefore,this review will summarize recent data on the dose-response association between PA on all-cause mortality and the negative impact that sedentary behavior has on all-cause mortality.Further,we also highlight potential mechanisms linking PA with the reduced risk of developing several chronic diseases.Finally,we conclude with a brief discussion of the emerging evidence that the health benefits associated with PA are derived,in part,from skeletal muscle-organ crosstalk involving muscle produced hormones(myokines)that exert their effects in either an autocrine,paracrine,or endocrine manner.
文摘Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.
基金This work was supported by National Institutes of Health Grants R01 CA-121249(National Cancer Institute)and R21 CA-231131 to JAC.
文摘Low-grade inflammation is emerging as a common feature of contemporary metabolic,psychiatric,and neurodegenerative diseases.Both physical inactivity and abdominal adiposity are associated with persistent systemic low-grade inflammation.Thus,the behavioral,biological,and physiological changes that cause a predisposition to obesity and other co-morbidities could have epigenetic underpinnings in addition to various evolutionary scenarios.A key assumption involves the potential for a mismatch between the human genome molded over generations,and the issue of adapting to the modern high calorie diet and common built environments promoting inactivity.This biological mismatch appears to have dire health consequences.Therefore,the goal of this article is to provide a brief overview on the importance of inflammation as part of human survival and how physical activity(PA)and physical inactivity are critical regulators of systemic inflammation.The review will highlight antiinflammatory effects of PA and exercise training from a metabolic and systemic signaling perspective,which includes skeletal muscle to utilization of fatty acids,TLR4 signaling,and myokine/adipokine effects.The available evidence suggests that PA,regular exercise,and weight loss offer both protection against and treatment for a wide variety of chronic diseases associated with low-grade inflammation through an improved inflammatory profile.
