Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.

The complex role of physical exercise and reactive oxygen species on brain

Reactive oxygen species （ROS） are continuously generated during aerobic metabolism and at moderate level. They play a role in redox signaling, but in significant concentration they cause oxidative damage and neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain the normal redox state in different types of neuron cells. In last decade it became clear that regular exercise beneficially affects brain function, and can play an important preventive and therapeutic role in stroke, Alzheimer, and Parkinson diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillariszation, decreased oxidative damage, and increased proteolyfic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosinerelated kinase B （TrkB）, and cAMP response element binding protein, resulting in better function and increased neurogenesis. Therefore, it appears that exercise-induced modulation of the redox state is an important means, by which exercise benefits brain function, increases the resistance against oxidative stress, facilitates recovery from oxidative stress, and attenuates age-associated decline in cognition.

The effect of aerobic exercise on synaptic types in 3xTgAD mice

The aim of this study was to examine the effects of aerobic exercise on synaptic types in the hippocampus of APP/PS1/tau(3xTg)transgenic mice.At 6 months of age,3xTg Mice and C57BL/6J controls were randomly assigned to sedentary control groups(AS,CS)and exercise groups(AE,CE).AE and CE mice were subjected to moderate intensity treadmill running for 12 weeks.Synaptic numbers and morphology were assessed using the transmission electron microscopy.

Comparison of the effects of high-intensity interval and moderate-intensity continuous training on inflammatory markers,cardiorespiratory fitness,and quality of life in breast cancer patients

Background:As the effectiveness of breast cancer treatment has improved,a growing number of long-term breast cancer survivors are seeking help for unique health problems.These patients may be at increased risk of cardiovascular disease due to the side effects of treatment.The positive impact of most types of exercise has been repeatedly reported in people with cancer,but the most effective exercise approaches for maximum beneficial adaptations remain controversial.Thus,this study aimed to compare the effects of high-intensity interval training(HIIT)and moderate-intensity continuous training(MICT) on inflammatory indices,adipokines,metabolic markers,body composition,cardiorespiratory fitness,and quality of life in breast cancer patients during adjuvant endocrine therapy.Methods:Thirty non-metastatic breast cancer patients during adjuvant endocrine therapy who had been treated with chemotherapy and/or radiotherapy were recruited from Iran and randomized to HIIT,MICT,or control groups for a supervised exercise intervention that took place 3 times a week for 12 weeks.The training intensity was determed based on the peak oxygen uptake(VO2peak),and the volume of training was matched in HIIT and MICT based on the VO2peak.Body composition,functional capacity,cardiorespiratory fitness,metabolic indices,sex hormones,adipokines,and inflammatory markers were assessed before and after the intervention.Results:The VO2peakincreased by 16.8% in the HIIT group in comparison to baseline values(mean difference=3.61 mL/kg/min).HIIT significantly improved the VO2peakcompared to control(mean difference=3.609 mL/kg/min) and MICT(mean differences=2.974 mL/kg/min)groups.Both HIIT(mean difference=9.172 mg/dL) and MICT(mean difference=7.879 mg/dL) interventions significantly increased highdensity lipoprotein cholesterol levels compared to the control group.The analysis of covariance showed that physical well-being significantly improved in MICT compared to control group(mean difference=3.268).HIIT significantly improved the social well-being compared to the control group(mean difference=4.412).Emotional well-being subscale was significantly improved in both MICT(mean difference=4.248)and HIIT(mean difference=4.412) compared to the control group.Functional well-being scores significantly increased in HIIT group compared with control group(mean difference=3.35).Significant increase were also observed in total functional assessment of cancer therapy-General scores in both HIIT(mean difference=14.204) and MICT groups(mean difference=10.036) compared with control group.The serum level of suppressor of cytokine signaling 3 increased significantly(mean difference=0.09 pg/mL) in the HIIT group compared to the baseline.There were no significant differences between groups for body weight,body mass index,fasting blood glucose,insulin resistance,sex hormone binding globulin,total cholesterol,low-density lipoprotein cholesterol,adipokines,interleukin-6,tumor necrosis factor-a,or interleukin-10.Conclusion:HIIT can be used as a safe,feasible,and time-efficient intervention to improve cardiovascular fitness in breast cancer patients.Both HIIT and MICT modalities enhance quality of life.Further large-scale studies will help determine whether these promising results translate into improved clinical and oncological outcomes.

Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

Exercise-induced oxidative stress:Friend or foe?

The first report demonstrating that prolonged endurance exercise promotes oxidative stress in humans was published more than 4 decades ago.Since this discovery,many ensuing investigations have corroborated the fact that muscular exercise increases the production of reactive oxygen species(ROS)and results in oxidative stress in numerous tissues including blood and skeletal muscles.Although several tissues may contribute to exercise-induced ROS production,it is predicted that muscular contractions stimulate ROS production in active muscle fibers and that skeletal muscle is a primary source of ROS production during exercise.This contraction-induced ROS generation is associated with(1)oxidant damage in several tissues(e.g.,increased protein oxidation and lipid peroxidation),(2)accelerated muscle fatigue,and(3)activation of biochemical signaling pathways that contribute to exercise-induced adaptation in the contracting muscle fibers.While our understanding of exercise and oxidative stress has advanced rapidly during the last decades,questions remain about whether exercise-induced increases in ROS production are beneficial or harmful to health.This review addresses this issue by discussing the site(s)of oxidant production during exercise and detailing the health consequences of exercise-induced ROS production.

The Effect of Different Rest Intervals on the Sustainability of Squat and Bench Press Repetitions in Karate Men

The purpose of this study was to compare the effect of three different rest intervals on the sustainability of squat and bench press on consecutive sets at 90% with 1RM （1 repetition maximum）-loads. Design and methods： Fifteen karate men were chosen to participate in this study （age of 22/3 ± 2/1 years; height 172/6 ± 3/6 cm; weight 67/8 ± 5/2 kg）. All subjects performed 7 sessions of squat ＆ bench press with 48 h intervals. At the first session, IRM was measured. During the rest 6 sessions, athletes performed 4 times squat ＆ bench press with 90% （IRM） at each session, one of three different rest intervals （60, 180, 225 seconds） were used randomly between sets. Number of repetitions performed ＆ repetition sustainability between different rest intervals were recorded. Results with Boneferoni method showed that each three different rest intervals caused decline in repetitions in squat ＆bench press. The repetition decline was significant in the bench press and squat. Repetition sustainability in 225 s in compare to 60 ＆ 180 s was more significant. Repetition sustainability also was higher in 180 s in compare to 60 s. On basis of findings from this study, we can recommend for best performance in bench press ＆ squat, rest intervals of 225 s, to maintain consecutive repetitions.

Alterations in renin-angiotensin receptors are not responsible for exercise preconditioning of skeletal muscle fibers

Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise pre-conditioning.Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy.The mechanism(s)responsible for exercise preconditioning remain unknown and are explored in these experiments.Specifically,we investigated the impact of endurance exercise training on key components of the renin-angiotensin system(RAS).The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensinⅡtypeⅠreceptors(AT1Rs)promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors(MasRs)inhibits the atrophic signaling of the classical RAS pathway.Guided by prior studies,we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skeletal muscle fibers is a potential mechanism responsible for exercise preconditioning.Following endurance exercise training in rats,we examined the abundance of AT1Rs and MasRs in both locomotor and respiratory muscles.Our results indicate that endurance exercise training does not alter the protein abundance of AT1Rs or MasRs in muscle fibers from the diaphragm,plantaris,and soleus muscles compared to sedentary controls(p>0.05).Furthermore,fluorescent angiotensinⅡ(AngⅡ)binding analyses confirm our results that exercise pre-conditioning does not alter the protein abundance of AT1Rs in the diaphragm,plantaris,and soleus(p>0.05).This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial effects of exercise preconditioning in skeletal muscle fibers.

The Effect of 4 Weeks of Strength Training and Beta-Alanine Supplementation on Anaerobic Power and Carnosine Level in Boxer Players

Purpose The objective of this study was to investigate the effect of 4 weeks of strength training with beta-alanine supple-mentation on anaerobic power and carnosine level in boxer players.Methods Eighteen male boxer players participated in this study,randomly divided into two homogeneous groups(strength training+beta-alanine and strength training+placebo groups).The study design was double-blind,parallel,and placebo-controlled.An anaerobic Wingate test was performed by athletes before and after the intervention period(4 weeks).Par-ticipants received 0.3 g/kg of body mass of the supplement(maltodextrin or beta-alanine)per day during the intervention.Participants were also evaluated for anaerobic power,serum level of carnosine,and blood lactate before and after 4 weeks.Results Average power in both groups was significantly increased compared with pre-intervention,but fatigue index was significantly decreased only after beta-alanine supplementation;however,there were no significant differences with either average power or fatigue index between the beta-alanine and placebo groups.There was no significant difference in the interaction between the groups and time,as well as no significant difference between groups for lactic acid.Carnosine level in both groups was significantly increased compared with pre-intervention.When changes in serum carnosine for the two groups were examined,statistical analysis showed a significant difference between the beta-alanine and placebo groups.Conclusion Four weeks of strength training accompanied by beta-alanine supplementation had a likely beneficial effect on boxer players'anaerobic performance and carnosine level.

Aerobic interval training preconditioning protocols inhibit isoproterenol-induced pathological cardiac remodeling in rats:Implications on oxidative balance,autophagy,and apoptosis

This study aimed to investigate the potential cardioprotective effects of moderate and high-intensity aerobic interval training(MIIT and HIIT)preconditioning.The focus was on histological changes,pro-oxidant-antioxidant balance,autophagy initiation,and apoptosis in myocardial tissue incited by isoproterenol-induced pathological cardiac remodeling(ISO-induced PCR).Male Wistar rats were randomly divided into control(n=6),ISO(n=8),MIIT(n=4),HIIT(n=4),MIIT+ISO(n=8),and HIIT+ISO(n=8)groups.The MIIT and HIIT protocols were administered for 10 weeks,followed by the induction of cardiac remodeling using subcutaneous injection of ISO(100 mg/kg for two consecutive days).Alterations in heart rate(HR),mean arterial pressure(MAP),rate pressure product(RPP),myocardial oxygen consumption(MVO_(2)),cardiac hypertrophy,histopathological changes,prooxidant-antioxidant balance,autophagy biomarkers(Beclin-1,Atg7,p62,LC3Ⅰ/Ⅱ),and apoptotic cell distribution were measured.The findings revealed that the MIIT+ISO and HIIT+ISO groups demonstrated diminished myocardial damage,hemorrhage,immune cell infiltration,edema,necrosis,and apoptosis compared to ISO induced rats.MIIT and HIIT preconditioning mitigated HR,enhanced MAP,and preserved MVO_(2)and RPP.The pro-oxidant-antioxidant balance was sustained in both MIIT+ISO and HIIT+ISO groups,with MIIT primarily inhibiting pro-apoptotic autophagy progression through maintaining pro-oxidant-antioxidant balance,and HIIT promoting pro-survival autophagy.The results demonstrated the beneficial effects of both MIIT and HIIT as AITs preconditioning in ameliorating ISO-induced PCR by improving exercise capacity,hemodynamic parameters,and histopathological changes.Some of these protective effects can be attributed to the modulation of cardiac apoptosis,autophagy,and oxidative stress.

The Road to the Beijing Winter Olympics and Beyond: Opinions and Perspectives on Physiology and Innovation in Winter Sport

Beijing will host the 2022 Winter Olympics,and China strengthens research on various aspects to allow their athletes to compete successfully in winter sport.Simultaneously,Government-directed initiatives aim to increase public participation in recreational winter sport.These parallel developments allow research to advance knowledge and understanding of the physiological determinants of performance and health related to winter sport.Winter sport athletes often conduct a substan-tial amount of training with high volumes of low-to-moderate exercise intensity and lower volumes of high-intensity work.Moreover,much of the training occur at low ambient temperatures and winter sport athletes have high risk of developing asthma or asthma-related conditions,such as exercise-induced bronchoconstriction.The high training volumes require optimal nutrition with increased energy and dietary protein requirement to stimulate muscle protein synthesis response in the post-exercise period.Whether higher protein intake is required in the cold should be investigated.Cross-country ski-ing is performed mostly in Northern hemisphere with a strong cultural heritage and sporting tradition.It is expected that innovative initiatives on recruitment and training during the next few years will target to enhance performance of Chinese athletes in classical endurance-based winter sport.The innovation potential coupled with resourcing and population may be substantial with the potential for China to become a significant winter sport nation.This paper discusses the physiological aspects of endurance training and performance in winter sport highlighting areas where innovation may advance in athletic performance in cold environments.In addition,to ensure sustainable development of snow sport,a quality ski patrol and rescue system is recommended for the safety of increasing mass participation.

Supporting tumor therapy by exercise:boosting T cell immunity by myokines

In a recent study published in Cancer Cell,Kurz et al.reported how exercise induces inhibitory effects on tumor growth by immuno-logical processes.1The investigation of these mechanisms is particularly signifcant because lifestyle factors are becoming increasingly important as adjunctive therapy for cancer.

Anthropometric Characteristics of Elite Male Taekwondo Players Based on Weight Categories

Purpose The aim of this study was to investigate the anthropometric characteristics of elite taekwondo players based on weight categories,and to determine if the length of the lower extremities might influence player’s success-level.A total of 59 elite male taekwondo players(22.02±3.07 years)participated in this study.Methods All anthropometric assessments were performed according to the standards and methodology of the International Society for Advancement of Kinanthropometry.The 18 anthropometrical variables were measured for each athlete and compared between 7 different weight categories.The players were also divided into two groups(national and international)and the ratios of sitting-height to stature were compared.Results There were significant differences(P<0.05)between weight divisions in stature,body mass index,percentage of body fat,endomorphy,and mesomorphy,which were greater(P<0.05)in heavy weight groups than light weight groups,and ectomorphy,which was greater(P<0.05)in very light weight groups compared with the other weights.There was no significant difference in lean mass index(P>0.05)between weight groups.Sitting height/stature ratio was significantly dif-ferent(P<0.05)between the two groups,where the international group had longer lower extremities than the national group.Conclusion The findings of this study provide a valuable framework to support talent identification programmes and the development of specialised preparatory strategies for different weight divisions with the sport.

Blood flow restriction during the resting periods of high-intensity resistance training does not alter performance but decreases MIR-1 and MIR-133A levels in human skeletal muscle

Blood flow restriction(BFR)during exercise bouts has been used to induce hypertrophy of skeletal muscle,even with low loads.However,the effects of BFR during the rest periods between sets are not known.We have tested the hypothesis that BFR during rest periods between sets of high-intensity resistance training would enhance performance.Twenty-two young adult male university students were recruited for the current study,with n=11 assigned to BFR and n=11 to a control group.The results revealed that four weeks training at 70%of 1 RM,five sets and 10 repetitions,three times a week with and without BFR,resulted in similar progress in maximal strength and in the number of maximal repetitions.The miR-1 and miR-133a decreased significantly in the vastus lateralis muscle of BFR group compared to the group without BFR,while no significant differences in the levels of miR133b,miR206,miR486,and miR499 were found between groups.In conclusion,it seems that BFR restrictions during rest periods of high-intensity resistance training,do not provide benefit for enhanced performance after a four-week training program.However,BFR-induced downregulation of miR-1 and miR-133a might cause different adaptive responses of skeletal muscle to high intensity resistance training.

Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension:Therapeutic Implications

Myogenic contraction of vascular smooth muscle cells(VSMCs)in resistance arteries and arterioles plays a critical role in regulating peripheral resistance.Ion channels expressed in VSMCs control ion influx or efflux from the plasma membrane and endoplasmic reticulum to regulate membrane potential,which contributes to the regulation of vascular tone.With the depolarization of VSMC membranes,an elevation of intracellular calcium ion(Ca^(2+))concentration is mediated by voltage-gated Ca^(2+)channels and can trigger a vasoconstrictive response.In addition,potassium ion(K^(+))efflux through K^(+)channels can hyperpolarize VSMCs,resulting in vasodilation.However,in the pathophysiological progression of diseases such as hypertension,VSMCs undergo a wide range of pathological changes,among them is"electrical remodeling",which refers to changes in ion channels.Under physiological or pathological conditions,exercise has a profound impact on the human body,and ion channels are an essential target of the beneficial adaptive responses.This review provides insight on the physi-ological function of ion channels in VSMCs,including Cav1.2 channels,voltage-gated K^(+)channels,large-conductance Ca^(2+)-activated K^(+)channels,and inward-rectifier K^(+)channels,and the changes of these ion channels during hypertension.Focus is given to the effects of exercise on these ion channels and its implications in disease treatment.

Heart Rate Variability from Underwater Spiroergometry:How Meaningful?

Cardiovascular fitness of divers is overwhelmingly performed using bicycle ergometry.A more sport-specific alternative presents fit2dive,an underwater spiroergometry system.Purpose of this exploratory study:using fit2dive to investigate the diagnostic value of measures of heart rate variability(HRV)after markedly increasing physical load.Ten scuba divers employed the fit2dive system and increased fin-swimming speed until exhaustion.Breathing gas consumption(VE)and heart rate(HR)were measured.A three-lead ECG was recorded to analyze for time and frequency domain HRV-measures.VE increased from 16.5±6.5 to 68.3±26.6 L/min.HR increased from 96±13 beats/min(mean±SD)at rest to 170±14 beats/min before exhaustion.Global variability(SDNN:132±42 vs.54±17 ms)decreased along with two measures of parasympathetic activity(RMSSD:59±31 vs.24±16 ms;pNN50:22%±12%vs.3%±3%).Measures from the frequency domain decreased[low frequency(LF):3167±2651 vs.778±705 ms_(2)]or remained unaltered[high frequency(HF):885±652 vs.431±463 ms^(2)].Thus,LF/HF decreased from 4.3±2.3 to 2.5±1.4.The sports-specific fit2dive can help assessing diving fitness by employing HRV measures.However,this study supports the view that these measures much depend on HR.Thus,HRV measures regarding altered autonomic control during exercise will lead to serious misinterpretation:as HR increases,variability decreases.