“Upholding Virtue and Exercising Caution in Punishment”(Ming De Shen Fa in Chinese pinyin)is one of the core governance philosophies in ancient Chinese politics.This principle was explicitly proposed by Zhou Gongdan...“Upholding Virtue and Exercising Caution in Punishment”(Ming De Shen Fa in Chinese pinyin)is one of the core governance philosophies in ancient Chinese politics.This principle was explicitly proposed by Zhou Gongdan,a renowned statesman of the early Zhou Dynasty,though its intellectual roots can be traced back to the Yao and Shun periods.Although this principle might not be fully recognized by the rulers of the exploiting class throughout history due to their own limitations,the political ideas and rich connotations behind it,especially as a mature governance concept formed by ancient Chinese politicians more than 4,000 years ago,undoubtedly is of high academic value and theoretical and practical significance.Objectively,this principle has also had a profound impact on the political and legal thinking,moral values,and promotion of social legal civilization in later generations.The analysis and discussion around this concept will play a positive role in the in-depth study of ancient China’s human rights concepts and the construction of contemporary Chinese discourse system of human rights.This article attempts to provide a preliminary summary,collation,analysis,and research from the perspective of political philosophy on the basic meaning,ideological context,and historical origin of social understanding of this concept,especially the human rights ideas contained therein.展开更多
Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physi...Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the ac- tivity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.展开更多
Given the recent technological developments, ultra-sound Doppler can provide valuable measurements of arterial blood flow with high temporal resolution. In a clinical setting, measurements of hemodynamics is used to m...Given the recent technological developments, ultra-sound Doppler can provide valuable measurements of arterial blood flow with high temporal resolution. In a clinical setting, measurements of hemodynamics is used to monitor, diagnose and manage changes in blood velocity profile for cardiac valve disease, relatively large vessel stenosis and other cardiovascular diseases. In health science and preventive medicine for cardiovascular disease with exercise therapy, evaluation of cardiac and vascular function is a useful indicator not only at rest but also during exercise, leading to improved exercise tolerance as well as physical activity. During exercise, the increase in oxygen uptake (calculated as product of arterial blood flow to the exercising limb and the arteriovenous oxygen difference) is directly proportional to the work performed. The increased oxygen demand is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (major part in the whole exercising muscles) from the blood. Therefore, the determination of the local blood flow dynamics (potential oxygen supply) feeding to rhythmic muscle contractions can contribute to the understanding of the factors limiting the work capacity including, for instance the muscle metabolism, substance utilization and vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound the validity of evaluating blood velocity/flow in the fore- arm or lower limb conduit artery feeding to the mus- cle is demonstrated during rhythmic muscle exercise;however the exercising blood velocity profile (fast Fourier transformation) due to muscle contractions is always seen as a physiological variability or fluctuations in the magnitude in blood velocity due to the spontaneous muscle contraction and relaxation induced changes in force curve intensity. Considering the above mentioned variation in blood velocity in relation to muscle contractions may provide valuable information for evaluating the blood flow dynamics during exercise. This review presents the methodological concept that underlines the methodological considerations for determining the exercising blood velocity/flow in the limb conduit artery in relation the exercise model of dynamic leg exercise assessed by pulsed Doppler ultrasonography.展开更多
The story goes back to October 24, 2003 when Xiong Dem-ing, a woman living in a poverty-stricken village in southwest China, was on herway back home with a sack of pig feed on her shoulder. She happened to meet Premie...The story goes back to October 24, 2003 when Xiong Dem-ing, a woman living in a poverty-stricken village in southwest China, was on herway back home with a sack of pig feed on her shoulder. She happened to meet Premier Wen Jiabao, who was visiting her village in Yunyang County, Chongqing展开更多
Objective： To evaluate the effect of pharyngeal musculature and genioglossus exercising on obstructive sleep apnea and hypopnea syndrome （OSAHS）. Methods： We conducted a non-randomized retrospective clinical trial...Objective： To evaluate the effect of pharyngeal musculature and genioglossus exercising on obstructive sleep apnea and hypopnea syndrome （OSAHS）. Methods： We conducted a non-randomized retrospective clinical trial of 75 patients with OSAHS. Fifty-four patients were managed by exercising of the pharyngeal musculature and genioglossus （exercising group）. Twenty-one patients, who refused to undertake any treatment, were defined as the control group. We took the Epworth Sleepiness Scale （ESS）, checked patients＇ polysomnography, and took 320- detector computed tomography （CT） before treatment. Six and twelve months later, we made records of apnea hypopnea index （AHI）, lowest arterial oxygen saturation （LSaO2）, body mass index （BMI）, the shortest sagittal diameter, and transverse diameter, and the effective rates of exercising were calculated and compared with the 21 patients without any treatment （control group） at the same time. SPSS 10.0 was used to analyze the data. Results： Before treatment, the ESS value was 7.67; 6 and 12 months later, the values were 3.54 and 3.25, respectively in the exercising group. AHI was decreased to 15.36 after 6 months and 13.79 after 12 months from 22.84 at the beginning. LSaO2 values were up to 81.18% after 6 months and 81.93% after 12 months from 74.05% at the beginning. There were significant differences in ESS scores, AHI, and LSaO2 between pre-treatment and post-treatment in the exercising group （P〈0.05）. However, there was no statistical difference in all the parameters between 6 and 12 months of exercising. The effective rates were 70.37% and 74.07% after 6- and 12-month exercising, respectively. There were significant differences between the exercising and control groups （P〈0.0001）. There was no statistical difference in the effective rate of the exercising group between 6 and 12 months of exercising （P〉0.05）. At 12 months of exercising, the compliance of the anteroposterior pharyngeal wall of the retropalatal area was lower （P〈0.01） than that before treatment. There was no significant change of BMI in either group. Conclusions： Exercising pharyngeal musculature and genioglossus is a kind of non-invasive and cost-effective method to treat some OSAHS patients, especially those who are old, without surgical complications, and especially mild and moderate OSAHS patients who do not want to take surgery and continuous positive airway pressure （CPAP） treatment. In addition, exercising pharyngeal musculature and genioglossus can be considered as remedial treatment of OSAHS to surgery and other therapies.展开更多
Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
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 ubiqu...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.展开更多
Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase bra...Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).展开更多
This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective f...Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity ...Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.展开更多
The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporat...The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.展开更多
Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exerc...Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exercise(RE)interventions in older adults with mild cognitive impairment(MCI).Methods This study is a 6-month pilot three-arm randomised controlled trial.Eligible participants(n=108)were recruited and randomised to the AE group,RE group or control(CON)group with a 1:1:1 ratio.Interventions were delivered at home with remote supervision.We evaluated participants’global cognition,memory,executive function,attention,physical activity levels,physical performance and muscle strength of limbs at baseline,3 months(T1)and 6 months(T2)after randomisation.A linear mixed-effects model was adopted for data analyses after controlling for covariates.Tukey’s method was used for adjusting for multiple comparisons.Sensitivity analyses were performed after excluding individuals with low compliance rates.Results 15(13.89%)participants dropped out.The median compliance rates in the AE group and RE group were 67.31%and 93.27%,respectively.After adjusting for covariates,the scores of the Alzheimer’s Disease Assessment Scale-Cognitive subscale in the AE group decreased by 2.04(95%confidence interval(CI)−3.41 to−0.67,t=−2.94,p=0.004)and 1.53(95%CI−2.88 to−0.17,t=−2.22,p=0.028)points more than those in the CON group at T1 and T2,respectively.The effects of AE were still significant at T1(estimate=−1.70,95%CI−3.20 to−0.21,t=−2.69,p=0.021),but lost statistical significance at T2 after adjusting for multiple comparisons.As for executive function,the Stroop time interference in the RE group decreased by 11.76 s(95%CI−21.62 to−1.90,t=−2.81,p=0.015)more than that in the AE group at T2 after Tukey’s adjustment.No other significant effects on cognitive functions were found.Conclusions Both remotely supervised AE and RE programmes are feasible in older adults with MCI.AE has positive effects on global cognition,and RE improves executive function.展开更多
Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise tra...Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.展开更多
文摘“Upholding Virtue and Exercising Caution in Punishment”(Ming De Shen Fa in Chinese pinyin)is one of the core governance philosophies in ancient Chinese politics.This principle was explicitly proposed by Zhou Gongdan,a renowned statesman of the early Zhou Dynasty,though its intellectual roots can be traced back to the Yao and Shun periods.Although this principle might not be fully recognized by the rulers of the exploiting class throughout history due to their own limitations,the political ideas and rich connotations behind it,especially as a mature governance concept formed by ancient Chinese politicians more than 4,000 years ago,undoubtedly is of high academic value and theoretical and practical significance.Objectively,this principle has also had a profound impact on the political and legal thinking,moral values,and promotion of social legal civilization in later generations.The analysis and discussion around this concept will play a positive role in the in-depth study of ancient China’s human rights concepts and the construction of contemporary Chinese discourse system of human rights.This article attempts to provide a preliminary summary,collation,analysis,and research from the perspective of political philosophy on the basic meaning,ideological context,and historical origin of social understanding of this concept,especially the human rights ideas contained therein.
文摘Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the ac- tivity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.
基金supported by the Danish National Research Foundation Grant 504-14,Uehara Memorial Foundation in 2002,a Grant-in-Aid for Young Scientists(B)in Scientific Research(No.16700471)the“Excellent Young Researchers Overseas Visit Program”in Scientific Research(No.21-8285)2010 from MEXT and JSPS.
文摘Given the recent technological developments, ultra-sound Doppler can provide valuable measurements of arterial blood flow with high temporal resolution. In a clinical setting, measurements of hemodynamics is used to monitor, diagnose and manage changes in blood velocity profile for cardiac valve disease, relatively large vessel stenosis and other cardiovascular diseases. In health science and preventive medicine for cardiovascular disease with exercise therapy, evaluation of cardiac and vascular function is a useful indicator not only at rest but also during exercise, leading to improved exercise tolerance as well as physical activity. During exercise, the increase in oxygen uptake (calculated as product of arterial blood flow to the exercising limb and the arteriovenous oxygen difference) is directly proportional to the work performed. The increased oxygen demand is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (major part in the whole exercising muscles) from the blood. Therefore, the determination of the local blood flow dynamics (potential oxygen supply) feeding to rhythmic muscle contractions can contribute to the understanding of the factors limiting the work capacity including, for instance the muscle metabolism, substance utilization and vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound the validity of evaluating blood velocity/flow in the fore- arm or lower limb conduit artery feeding to the mus- cle is demonstrated during rhythmic muscle exercise;however the exercising blood velocity profile (fast Fourier transformation) due to muscle contractions is always seen as a physiological variability or fluctuations in the magnitude in blood velocity due to the spontaneous muscle contraction and relaxation induced changes in force curve intensity. Considering the above mentioned variation in blood velocity in relation to muscle contractions may provide valuable information for evaluating the blood flow dynamics during exercise. This review presents the methodological concept that underlines the methodological considerations for determining the exercising blood velocity/flow in the limb conduit artery in relation the exercise model of dynamic leg exercise assessed by pulsed Doppler ultrasonography.
文摘The story goes back to October 24, 2003 when Xiong Dem-ing, a woman living in a poverty-stricken village in southwest China, was on herway back home with a sack of pig feed on her shoulder. She happened to meet Premier Wen Jiabao, who was visiting her village in Yunyang County, Chongqing
基金supported by the Social Development of Science and Technology Program of Ningbo City(No.2010C50031)the Ningbo Natural Science Foundation(No.2013A610261),China
文摘Objective： To evaluate the effect of pharyngeal musculature and genioglossus exercising on obstructive sleep apnea and hypopnea syndrome （OSAHS）. Methods： We conducted a non-randomized retrospective clinical trial of 75 patients with OSAHS. Fifty-four patients were managed by exercising of the pharyngeal musculature and genioglossus （exercising group）. Twenty-one patients, who refused to undertake any treatment, were defined as the control group. We took the Epworth Sleepiness Scale （ESS）, checked patients＇ polysomnography, and took 320- detector computed tomography （CT） before treatment. Six and twelve months later, we made records of apnea hypopnea index （AHI）, lowest arterial oxygen saturation （LSaO2）, body mass index （BMI）, the shortest sagittal diameter, and transverse diameter, and the effective rates of exercising were calculated and compared with the 21 patients without any treatment （control group） at the same time. SPSS 10.0 was used to analyze the data. Results： Before treatment, the ESS value was 7.67; 6 and 12 months later, the values were 3.54 and 3.25, respectively in the exercising group. AHI was decreased to 15.36 after 6 months and 13.79 after 12 months from 22.84 at the beginning. LSaO2 values were up to 81.18% after 6 months and 81.93% after 12 months from 74.05% at the beginning. There were significant differences in ESS scores, AHI, and LSaO2 between pre-treatment and post-treatment in the exercising group （P〈0.05）. However, there was no statistical difference in all the parameters between 6 and 12 months of exercising. The effective rates were 70.37% and 74.07% after 6- and 12-month exercising, respectively. There were significant differences between the exercising and control groups （P〈0.0001）. There was no statistical difference in the effective rate of the exercising group between 6 and 12 months of exercising （P〉0.05）. At 12 months of exercising, the compliance of the anteroposterior pharyngeal wall of the retropalatal area was lower （P〈0.01） than that before treatment. There was no significant change of BMI in either group. Conclusions： Exercising pharyngeal musculature and genioglossus is a kind of non-invasive and cost-effective method to treat some OSAHS patients, especially those who are old, without surgical complications, and especially mild and moderate OSAHS patients who do not want to take surgery and continuous positive airway pressure （CPAP） treatment. In addition, exercising pharyngeal musculature and genioglossus can be considered as remedial treatment of OSAHS to surgery and other therapies.
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘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.
基金supported by the STI 2030-Major Projects,No. 2021ZD0200500 (to XS)。
文摘Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).
文摘This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
基金supported by Cure Alzheimer’s Fund(to RET and SHC)JPB Foundation(to RET),and R56AG072054(to SHC)。
文摘Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
文摘Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.
文摘The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.
基金funded by the National Natural Science Foundation of China(81871854,72374014)the National Key R&D Program of China(2020YFC2008804)+1 种基金the Shanghai Jiao Tong University Young Talent Cultivation Program in Liberal Arts(2024QN041)the Shanghai Jiao Tong University School of Medicine:Nursing Development Program(SJTUHLXK2024).
文摘Background Evidence on the effects of different exercise interventions on cognitive function is insufficient.Aims To evaluate the feasibility and effects of remotely supervised aerobic exercise(AE)and resistance exercise(RE)interventions in older adults with mild cognitive impairment(MCI).Methods This study is a 6-month pilot three-arm randomised controlled trial.Eligible participants(n=108)were recruited and randomised to the AE group,RE group or control(CON)group with a 1:1:1 ratio.Interventions were delivered at home with remote supervision.We evaluated participants’global cognition,memory,executive function,attention,physical activity levels,physical performance and muscle strength of limbs at baseline,3 months(T1)and 6 months(T2)after randomisation.A linear mixed-effects model was adopted for data analyses after controlling for covariates.Tukey’s method was used for adjusting for multiple comparisons.Sensitivity analyses were performed after excluding individuals with low compliance rates.Results 15(13.89%)participants dropped out.The median compliance rates in the AE group and RE group were 67.31%and 93.27%,respectively.After adjusting for covariates,the scores of the Alzheimer’s Disease Assessment Scale-Cognitive subscale in the AE group decreased by 2.04(95%confidence interval(CI)−3.41 to−0.67,t=−2.94,p=0.004)and 1.53(95%CI−2.88 to−0.17,t=−2.22,p=0.028)points more than those in the CON group at T1 and T2,respectively.The effects of AE were still significant at T1(estimate=−1.70,95%CI−3.20 to−0.21,t=−2.69,p=0.021),but lost statistical significance at T2 after adjusting for multiple comparisons.As for executive function,the Stroop time interference in the RE group decreased by 11.76 s(95%CI−21.62 to−1.90,t=−2.81,p=0.015)more than that in the AE group at T2 after Tukey’s adjustment.No other significant effects on cognitive functions were found.Conclusions Both remotely supervised AE and RE programmes are feasible in older adults with MCI.AE has positive effects on global cognition,and RE improves executive function.
基金supported by funding provided to BJG from the Natural Sciences and Engineering Research Council of Canada(NSERCgrant no.402635).
文摘Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.
