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physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway

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Journal of Integrative Medicine 2023年第2期21卷 184-193页

作者： Chu-lan Xiao Zhi-peng Zhong Can Lü Bing-jie Guo Jiao-jiao Chen Tong Zhao Zi-fei Yin Bai Li Department of Rehabilitation Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Traditional Chinese Medicine The 920th Hospital of Joint Logistics Support ForceKunming 650000Yunnan ProvinceChina Second Team Graduate SchoolNaval Medical UniversityShanghai 200433China College of Integrated Traditional Chinese and Western Medicine Nanjing University of Traditional Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Military Traditional Chinese Medicine Faculty of Traditional Chinese MedicineNaval Medical UniversityShanghai 200433China

Objective:physical exercise,a common non-drug intervention,is an important strategy in cancer treatment,including hepatocellular carcinoma(HCC).However,the mechanism remains largely unknown.Due to the importance of hypoxia and cancer stemness in the development of HCC,the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.Methods:A physical exercise intervention of swimming(30 min/d,5 d/week,for 4 weeks)was administered to BALB/c nude mice bearing subcutaneous human HCC tumor.The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring,hematoxylin and eosin(HE)staining,and immunohistochemistry(IHC)detection of proliferating cell nuclear antigen(PCNA)and Ki67.The expression of stemness transcription factors,including Nanog homeobox(NANOG),octamer-binding transcription factor 4(OCT-4),v-Myc avian myelocytomatosis viral oncogene homolog(C-MYC)and hypoxia-inducible factor-1a(HIF-1a),was detected using real-time reverse transcription polymerase chain reaction.A hypoxia probe was used to explore the intratumoral hypoxia status.Western blot was used to detect the expression of HIF-1a and proteins related to protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway.The IHC analysis of platelet endothelial cell adhesion molecule-1(CD31),and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion.SMMC-7721 cells were treated with nude mice serum.The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors.The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1a.Further,the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.Results:Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor.HE staining and IHC results showed a lower necrotic area ratio as well as fewer

关键词： physical exercise Swimming Hepatocellular carcinoma Liver cancer Blood perfusion Hypoxia Cancer stemness Akt/GSK-3β/β-catenin

physical exercise protects muscle from accelerated aging induced by high-salt intake and muscle CG2196(salt)gene overexpression in Drosophila

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Food Science and Human Wellness 2023年第6期12卷 1948-1960页

作者： Dengtai Wen Yiling Chen Xu Tian Wenqi Hou Department of physical Education Ludong UniversityYantai 264025China College of physical Education Yichun UniversityYichun 336000China School of exercise and Health Shanghai University of SportShanghai 200438China

Aging decreases muscle mass,strength,and functional capacity.High-salt stress seems to promote muscle aging and decrease lifespan.However,exercise delays muscle aging and increases longevity,and it may protect muscle from rapid aging induced by high-salt intake(HSI),but the molecular mechanisms are poorly understood.In this study,the flies were fed a high-salt diet and trained to exercise.Muscle CG2196(salt)gene and dSir2 gene were over-expressed by building mef2-gal4/UAS system.The results showed that both physical exercise and muscle dSir2 gene overexpression prevented HSI-induced and muscle salt overexpression-induced accelerated age-related decline of climbing index,climbing endurance,muscle NAD^(+)level,SOD activity level,dSir2 expression,and dFOXO expression,and they also prevented HSI-induced and muscle salt overexpression-induced accelerated age-related increase in muscle ROS level,MDA level,and salt gene expression.physical exercise improved lifespan decrease induced by HSI and muscle salt overexpression.Therefore,current results indicated that high-salt stress accelerated muscle aging by decreasing muscular NAD^(+)/dSir2/dFOXO pathway activity and increasing oxidative stress.physical exercise protected muscle from accelerated aging induced by high-salt stress through activating muscle NAD^(+)/dSir2/dFOXO pathway and enhancing muscle oxidation resistance.The combination of exercise and muscle dSir2 overexpression had the best protective effect on muscle aging and lifespan in flies.

关键词： physical exercise high-salt intake muscle aging NAD^(+)/dSir2

Non-coding RNAs in exercise immunology:A systematic review

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Journal of Sport and Health Science 2024年第3期13卷 311-338,I0002页

作者： Mona Kotewitsch Melina Heimer Boris Schmitz Frank C.Mooren Department of Rehabilitation Sciences Faculty of HealthUniversity of Witten/HerdeckeWitten 58455Germany DRV Clinic Konigsfeld Center for Medical RehabilitationEnnepetal 58256Germany

Regular physical exercise has been recognized as a potent modulator of immune function,with its effects including enhanced immune surveillance,reduced inflammation,and improved overall health.While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs(ncRNAs)also involved in immune system regulation,heterogeneity in individual study designs and analyzed exercise protocols exists,and a condensed list of functional,exercise-dependent ncRNAs with known targets in the immune system is missing from the literature.A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise.Two combined approaches were used:(a)a systematic literature search for“ncRNA and exercise immunology”,(b)and a database search for microRNAs(miRNAs)(miRTarBase and DIANA-Tarbase v8)aligned with known target genes in the immune system based on the Reactome database,combined with a systematic literature search for“ncRNA and exercise”.Literature searches were based on PubMed,Web of Science,and SPORTDiscus;and miRNA databases were filtered for targets validated by in vitro experimental data.Studies were eligible if they reported on exercise-based interventions in healthy humans.After duplicate removal,95 studies were included reporting on 164 miRNAs,which were used for the qualitative synthesis.Six studies reporting on long-noncoding RNAs(lncRNAs)or circular RNAs were also identified.Results were analyzed using ordering tables that included exercise modality(endurance/resistance exercise),acute or chronic interventions,as well as the consistency in reported change between studies.Evaluation criteria were defined as“validated”with 100%of≥3 independent studies showing identical direction of regulation,“plausible”(≥80%),or“suggestive”(≥70%).For resistance exercise,upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible.For endurance exercise,15 miRNAs were categorized as validated,wit

关键词： Immune system Inflammation MicroRNA ncRNA physical exercise

Prevalence of Achilles tendinopathy in physical exercise:A systematic review and meta-analysis

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Sports Medicine and Health Science 2022年第3期4卷 152-159页

作者： Yahai Wang Huanhuan Zhou Zhibin Nie Sidong Cui Nanchang Normal College of Applied Technology NanchangJiangxiChina Soochow University SuzhouJiangsuChina physical Education College Yunnan Normal UniversityKunmingYunnanChina

This comprehensive systematic review and meta-analysis assessed the prevalence of Achilles tendinopathy(AT)in physical exercise(PE).Specifically,we estimate the overall risk of AT in physical exercise and compare sportspecific estimates of AT risk.PubMed,Web of Science,Cochrane Library,and SPORTDiscus were searched before the 1st of October 2021.Random-effects,subgroup analysis,sensitivity analysis and meta-regressions were conducted,involving 16 publications.This meta-analysis found that the overall prevalence of AT was 0.06(95%CI,0.04–0.07).The prevalence of Achilles tendon rupture was 0.03(95%CI,0.02–0.05).Subgroup analysis showed that the prevalence of AT increased with age,the highest among the group aged over 45(0.08;95%CI,0.04–0.11),and the lowest among the group under 18 years old(0.02;95%CI,0.01–0.03).The gymnastics and ball games had the highest prevalence of AT,at(0.17;95%CI,0.14–0.20)and(0.06;95%CI,0.02–0.11),respectively.The prevalence of AT in athletes(0.06;95%CI,0.04–0.08)was higher than that of amateur exercisers(0.04;95%CI,0.02–0.06)and there was no difference in the prevalence of AT between males and females.There are differences in the prevalence of AT in different ages,sport events and characteristics of participants.This systematic review and meta-analysis suggested that it was necessary to pay more attention to AT in people who were older or engaged in gymnastics.

关键词： Achilles tendinopathy Prevalence physical exercise meta-Analysis

Sport and physical exercise in sustainable mental health care of common mental disorders:Lessons from the COVID-19 pandemic

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Sports Medicine and Health Science 2023年第2期5卷 151-155页

作者： Klaus W.Lange Yukiko Nakamura Andreas Reissmann Faculty of Human Sciences(Psychology Education and Sport Science)University of RegensburgRegensburgBavariaGermany

The large-scale disruptions to physical activity during the coronavirus pandemic have been found to be a leading predictor of common mental disorders.In addition,regular physical exercise has been found to alleviate anxiety,sadness and depression during the pandemic.These findings,together with numerous studies published before the pandemic on the effects of physical activity on mental health,should be considered in the provision of mental health care following the pandemic.Cross-sectional research has revealed that all types of exercise and sport are associated with a reduced mental health burden.Therefore,the effectiveness of exercise and sport participation in sustainable mental health care as well as the causal relationship between exercise,psychosocial health and common mental disorders merit further investigation.physical activity and sport,with their global accessibility,significant and clinically meaningful efficacy as well as virtual absence of adverse effects,offer a promising option for the promotion of mental health,including the prevention and treatment of common mental disorders.physical exercise and sport are likely to become valuable public mental health resources in the future.

关键词： Anxiety Depression Mental health physical exercise COVID-19

Who Benefits More from physical exercise?On the Relations between Personality,physical exercise,and Well-Being

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International Journal of Mental Health Promotion 2023年第10期25卷 1147-1157页

作者： Jialing Miao Wei Liao Baoguo Xie School of Entrepreneurship Wuhan University of TechnologyWuhan430070China School of Management Wuhan University of BioengineeringWuhan430415China School of Management Wuhan University of TechnologyWuhan430070China

Although employers believe that encouraging and supporting physical exercise activities by purchasing fitness equipment and building sports venues can improve employees’well-being,the utilization rate is rather low.Since most of the evidence of the well-being promotion in the workplace concentrated on the perspectives of organizational factors and psychosocial factors and focused on the reduction of the negative affect of well-being,it is still an open question whether physical exercise has benefits on both negative and positive affect of well-being and who benefits more from physical exercise.Thus,the purpose of this study is to investigate the impact of physical exercise on occupational well-being(job burnout and work engagement)and examine whether effectiveness depends on personality traits.Online questionnaires were distributed.The sample included 671 participants from different enterprises in China.Results showed that the effectiveness of physical exercise was also applicable to well-being in the workplace.physical exercise was negatively correlated with job burnout and positively correlated with work engagement.The effectiveness was different among employees with different personality traits.Contrary to our expectation,individuals with neuroticism were more likely to improve their work engagement through physical exercise.Extroversion and conscientiousness weakened the benefits of physical exercise.Therefore,differences of effectiveness among different personality traits emphasize the need for a more personalized strategy in physical exercise interventions.

关键词： physical exercise job burnout work engagement personal traits

Management of non-alcoholic fatty liver disease:Lifestyle changes

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World Journal of Gastroenterology 2024年第22期30卷 2829-2833页

作者： Hao Lv Yang Liu Department of General Surgery Xi'an Jiaotong University Second Affiliated HospitalXi'an 710004Shaanxi ProvinceChina

In this editorial,we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology.We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease(NAFLD).NAFLD is a hepatic manifestation of the metabolic syndrome,which ultimately leads to advanced hepatic fibrosis,cirrhosis,and hepatocellular carcinoma and affects more than 25%of the population globally.Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection,anti-inflammation,and regulating disease-related metabolic disorder symptoms.Although several drugs are in late-stage development,potent drugs against the diseases are lacking.Additionally,existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD.Intervening in patients’unhealthy lifestyles,such as weight loss through dietary changes and exercises to ameliorate patientassociated metabolic disorders and metabolic syndrome,is the first-line treatment for patients with NAFLD.With sufficient intrinsic motivation and adherence,the management of unhealthy lifestyles can reduce the severity of the disease,improve the quality of life,and increase the survival expectancy of patients with NAFLD.

关键词： Non-alcoholic fatty liver disease Lifestyle physical activity physical exercise Low-calorie diet Mediterranean diet

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

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Traditional Medicine Research 2024年第8期9卷 23-34页

作者： Yi Du Hong Liu Department of Critica Care Medicine Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical Sciences Tongji Shanxi HospitalTaiyuan 030032China Department of ICU First Hospital of Shanxi Medical UniversityTaiyuan 030001China

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo stud

关键词： ER stress diabetes physical exercise gene expression microRNA-149-5p MMP9 licorice glycoside E traditional physical therapy genomics insights