Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.

Non-coding RNAs in exercise immunology:A systematic review

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,with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated,most of them after acute exercise training.In conclusion,our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution,function,and trafficking as well as production of(anti-)inflammatory cytokines.miRNAs miR-15,miR-29c,miR-30a,miR-142/3,miR-181a,and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

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

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.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

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

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 studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

An Innovative Approach towards Selecting Aerobic and Coordinative Exercises in Clinical Practice for Children and Young People with ADHD

A growing body of studies and systematic reviews show evidence of the beneficial effects of physical exercise on core symptoms of ADHD. Furthermore, studies indicate that physical exercise as an adjuvant can enhance the effects of medication in the treatment of ADHD. Aerobic and coordinative exercises improve executive functioning through their effect on neurocognitive domains that are implicated in ADHD. It is postulated that through their specific modus operandi, aerobic exercise, by raising cortical arousal levels, improves impaired alerting functions whereas coordinative exercises improve the regulation of inhibitory control through the involvement of a higher variety of frontal-dependent cognitive processes. The increasing use of routine neurocognitive testing with continuous performance tests (CPT), such as the QbTest, at clinical assessments for ADHD allows for an innovative approach to identify the assessment impairments in alerting function and inhibition control that are related to ADHD and accordingly choose aerobic or coordinative physical exercise in a more targeted fashion.

Study on the Influence of New Media on College Students’ Physical Exercise Behavior

New media is becoming an important method to promote physical exercise,and it is also an essential factor affecting the physical exercise behavior of college students.This study takes the influence of new media sports information on college students’physical exercise behavior as the research objective.By using a questionnaire survey and mathematical statistics,545 college students in Shandong Province of China are selected as research samples.Based on the theory of new media exposure,fitness behavior theory,and self-efficacy theory,this study systematically discusses the influence and mechanism of new media exposure on the physical exercise behavior of college students in Shandong Province,so as to help college students improve their physical exercise behavior.

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

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.

Who Benefits More from Physical Exercise?On the Relations between Personality,Physical Exercise,and Well-Being

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.

Effects of Physical Exercise and Music Therapy on Cognitive Aspects in Tunisian Patients with Mild Alzheimer’s Type Dementia

Aim: The objective of this research is to highlight the effectiveness of physical exercise and music therapy in older patients with Alzheimer’s disease (AD). Methods: Patients with a mild level of AD were included in this study, divided into the therapy group (TG;N = 30, aged 68 ± 3.2 years) and the control group (CG;N=30, aged 65 ± 2.6 years). The therapy group was enrolled in an exercise-training program (walking, resistance and balance exercises) combined with musical therapy for 10 weeks (three sessions of 60 minutes per week). The Control group was instructed to follow their daily rhythm of life (e.g., rest, reading) under the same conditions. The intervention program was enrolled under the supervision of;one psychologist;a neurologist;two music therapists, and two physiotherapists, all belonging to the same hospital unit. After 10 weeks of participation in the combined program, cognitive parameters were improved in the therapy group measured with the Behavior Pathology in Alzheimer Disease (BEHAVE-AD), (p < 0.05) for activity disturbance, diurnal rhythm disturbances, anxieties and phobias, affective disturbance. The percentage range of improvements is 1.07% to 2.96%. Results: Our results demonstrate that physical exercise combined with music therapy improves cognitive function in patients with Alzheimer’s disease. Conclusions: Physical exercise and music therapy are beneficial combined treatments for improving life quality in older patients. This approach may be useful to help patients with a mild level of Alzheimer’s disease improve their behavioral and psychological parameters.

The Positive Effects of Physical Exercise on Mental Health Among Chinese Students Under Great Competitive Pressure

Under an environment full of competitive stress,students tend to form negative emotions,and the time for them to engage in physical exercise is greatly limited due to overwhelming academic tasks.Therefore,in this paper,we focus on acknowledging the purpose of physical exercise,and how physical exercise affects the mental health of students under stressful circumstances but not in the context of leisure.Questionnaire was distributed to participants with an average age of 20,to investigate their preference,frequency,and reason for exercising,and their attitude towards it.Our results showed that participants think that exercise can strengthen the body,relieve stress,improve fitness and interpersonal relationship regardless of their purpose such as interests,emotional necessity and even out of non-subjective ideas.In conclusion,physical exercise helped to improve students’mental health especially under great pressure and ultimately,it will enhance their academics and bring about the unity of mind and body.

Management of non-alcoholic fatty liver disease:Lifestyle changes

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.

‘Prediabetes’ as a practical distinctive window for workable fruitful wonders: Prevention and progression alert as advanced professionalism

Diabetes is a devastating public health problem.Prediabetes is an intermediate stage in the disease processes leading to diabetes,including types 1 and 2 diabetes.In the article“Prediabetes in children and adolescents:An updated review,”the authors presented current evidence.We simplify and systematically clearly present the evidence and rationale for a conceptual framework we term the‘3ASs’:(1)Awareness Sensible;(2)Algorithm Simple;and(3)Appealing Strategies.Policy makers and the public need to be alerted.The prevalence of prediabetes should send alarm bells ringing for parents,individuals,clinicians,and policy makers.Prediabetes is defined by the following criteria:impaired fasting glucose(100-125 mg/dL);impaired glucose tolerance(2 h postprandial glucose 140-199 mg/dL);or hemoglobin A1c values of 5.7%–6.4%.Any of the above positive test alerts for intervention.Clinical guidelines do not recommend prioritizing one test over the others for evaluation.Decisions should be made on the strengths and shortfalls of each test.Patient preferences and test accessibility should be taken into consideration.An algorithm based on age,physiological stage,health status,and risk factors is provided.Primordial prevention targeting populations aims to eliminate risk factors through public education and encouraging practices through environmental modifications.Access to healthy foods is provided.Primary prevention is for individuals with a prediabetes diagnosis and involves a structured program to reduce body weight and increase physical activity along with a healthy diet.An overall methodical move to a healthy lifestyle for lifelong health is urgently needed.Early energetic prediabetes action is necessary.

Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?

Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.

Roles and molecular mechanisms of physical exercise in cancer prevention and treatment

Exercise can enhance motivation to change lifestyle behaviors,improve aerobic fitness,improve physical function,control fatigue,and enhance quality of life.Studies have demonstrated the benefits to be gained from physical exercise,highlighting the importance of popularizing the concept of physical exercise for individuals and making professional exercise-treatment programs available to patients with cancer.However,the correlation between physical exercise and carcinogenesis is easily overlooked,and exercise interventions are not routinely provided to patients with cancer,especially those with advanced cancer.In this article,we present a literature review of the effects of exercise on cancer development and progression and give recent evidence for the type of exercise best suited for different types of cancer and in different disease stages.Moreover,the molecular mechanisms about regulating metabolism and systemic immune function in cancer are summarized and discussed.In conclusion,physical exercise should be considered as an important intervention for preventing and treating cancer and its complications.

Exercise interventions for older adults: A systematic review of meta-analyses

Background:The evidence concerning which physical exercise characteristics are most effective for older adults is fragmented.We aimed to characterize the extent of this diversity and inconsistency and identify future directions for research by undertaking a systematic review of metaanalyses of exercise interventions in older adults.Methods:We searched the Cochrane Database of Systematic Reviews,PsycInfo,MEDLINE,Embase,CINAHL,AMED,SPORTDiscus,and Web of Science for articles that met the following criteria:(1)meta-analyses that synthesized measures of improvement(e.g.,effect sizes)on any outcome identified in studies of exercise interventions;(2)participants in the studies meta-analyzed were adults aged 65+or had a mean age of 70+;(3)meta-analyses that included studies of any type of exercise,including its duration,frequency,intensity,and mode of delivery;(4)interventions that included multiple components(e.g.,exercise and cognitive stimulation),with effect sizes that were computed separately for the exercise component;and(5)meta-analyses that were published in any year or language.The characteristics of the reviews,of the interventions,and of the parameters improved through exercise were reported through narrative synthesis.Identification of the interventions linked to the largest improvements was carried out by identifying the highest values for improvement recorded across the reviews.The study included 56 meta-analyses that were heterogeneous in relation to population,sample size,settings,outcomes,and intervention characteristics.Results:The largest effect sizes for improvement were found for resistance training,meditative movement interventions,and exercise-based active videogames.Conclusion:The review identified important gaps in research,including a lack of studies investigating the benefits of group interventions,the characteristics of professionals delivering the interventions associated with better outcomes,and the impact of motivational strategies and of significant others(e.g.,carers)on intervention delivery and outcomes.

Effects of a multimodal exercise protocol on functional outcomes,epigenetic modulation and brain-derived neurotrophic factor levels in institutionalized older adults:a quasi-experimental pilot study

Epigenetic changes have been shown to be associated with both aging process and aging-related diseases.There is evidence regarding the benefits of physical activity on the functionality,cognition,and quality of life of institutionalized older adults,however,the molecular mechanisms involved are not elucidated.The purpose of this pilot study was to investigate the effects of a multimodal exercise intervention on functional outcomes,cognitive performance,quality of life(QOL),epigenetic markers and brain-derived neurotrophic factor(BDNF)levels among institutionalized older adult individuals.Participants(n=8)without dementia who were aged 73.38±11.28 years and predominantly female(87.5%)were included in this quasi-experimental pilot study.A multimodal exercise protocol(cardiovascular capacity,strength,balance/agility andflexibility,perception and cognition)consisted of twice weekly sessions(60 minutes each)over 8 weeks.Balance(Berg Scale),mobility(Timed Up and Go test),functional capacity(Six-Minute Walk test),cognitive function(Mini-Mental State Examination)and QOL(the World Health Organization Quality of Life-BREF Scale questionnaire)were evaluated before and after the intervention.Blood sample(15 mL)was also collected before and after intervention for analysis of biomarkers global histone H3 acetylation and brain-derived neurotrophic factor levels.Significant improvements were observed in cognitive function,balance,mobility,functional capacity and QOL after the intervention.In addition,a tendency toward an increase in global histone H3 acetylation levels was observed,while brain-derived neurotrophic factor level remained unchanged.This study provided evidence that an 8-week multimodal exercise protocol has a significant effect on ameliorating functional outcomes and QOL in institutionalized older adult individuals.In addition,it was also able to promote cognitive improvement,which seems to be partially related to histone hyperacetylation status.The Ethics Research Committee of Centro Universitário Metodista-IPA,Brazil approved the current study on June 6,2019(approval No.3.376.078).

Updated overview on interplay between physical exercise,neurotrophins,and cognitive function in humans

The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the variousmechanisms underlying the association between physical exercise and brain health, recent evidence attests that neurotrophin receptor signalingmay have an important role, because the activation of this pathway leads to growth and differentiation of new neurons and synapses, supportsaxonal and dendritic growth, fosters synaptic plasticity, and preserves survival of existing neurons. In this review of published evidence, we highlightthat a positive relationship exists between physical exercise and circulating brain-derived neurotrophic factor levels and that the postexercisevariation of this molecule is associated with improvement of neurocognitive functioning. Less clear evidence has instead been published forother neurotrophins, such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Overall, promotion of adequate volumes and intensities ofphysical exercise (i.e., approximately 3 months of moderate-intensity aerobic exercise, with 2—3 sessions/week lasting not less than 30 min)may hence be regarded as an inexpensive and safe strategy for boosting brain-derived neurotrophic factor release, thus preserving or restoringcognitive functions.

The effects of exercise on self-rated sleep among adults with chronic sleep complaints

Purpose： The purpose of this study was to evaluate whether and to what extent the observed effects on self-rated sleep in a previous study using a combined treatment program with physical exercise and sleep education can be attributed by the physical activity （PA） component. Methods： The present study reports supplementary analysis of an already described and published study. Data were provided by a nonclinical sample of 98 normal-active adults with chronic initiating and the maintaining of sleep complaints. The additional analysis included sleep log, exercise log, and daily pedometer data which were collected during a baseline week and 6-week of a combined intervention. Results： The results indicate that the number of steps （p -- 0.02） and the duration of PA （p = 0.01） is significantly related to the improvement in subjective sleep measures and therefore reveal an independent effect within this combined sleep program. Sleep diary data （recuperation of sleep, number of awakenings after sleep onset, and wake time after sleep onset time） improved significant （all p 〈 0.01） over the intervention program. About 50% of the participants stated that the PA had an effect on their improvement. Conclusion： Improvements on subjective sleep quality after a combined intervention cannot be attributed to the cognitive component alone, but PA has an independent effect. Adults with chronic sleep complaints benefit from exercise. Therefore structured PA should be implemented in any sleep management programs.

AHP-FCE Based Physical Exercise Risk Evaluation Model

Exercise is a highly proven and beneficial health promotion modality, But it is very difficult to determine whether the person during exercise is safe. A unique and comprehensive approach is proposed to perform physical exercise risk evaluation （PERE）, in which personalized factors are deterrrdned basing on grey correlation analysis, analytic hierarchy process （AHP） method is used to structure the large numbers of risk factors, and fuzzy comprehensive evaluation （FCE） is applied to fuzzify the factors and compute the exercise risk level. Finally, an actual calculation example is used to verify the feasibility of the method.