Effects of Acute Ingestion of Caffeine Capsules on Muscle Strength and Muscle Endurance: A Systematic Review and Meta-Analysis.

This study aimed to explore the effects of acute ingestion of caffeine capsules on muscle strength and muscle endurance. We searched the PubMed, Web of Science, Cochrane, Scopus, and EBSCO databases. Data were pooled using the weighted mean difference (WMD) and 95% confidence interval. Fourteen studies fulfilled the inclusion criteria. The acute ingestion of caffeine capsules significantly improved muscle strength (WMD, 7.09, p < 0.00001) and muscle endurance (WMD, 1.37; p < 0.00001), especially in males (muscle strength, WMD, 7.59, p < 0.00001; muscle endurance, WMD, 1.40, p < 0.00001). Subgroup analyses showed that ≥ 6 mg/kg body weight of caffeine (WMD, 6.35, p < 0.00001) and ingesting caffeine 45 min pre-exercise (WMD, 8.61, p < 0.00001) were more effective in improving muscle strength, with the acute ingestion of caffeine capsules having a greater effect on lower body muscle strength (WMD, 10.19, p < 0.00001). In addition, the acute ingestion of caffeine capsules had a greater effect in moderate-intensity muscle endurance tests (WMD, 1.76, p < 0.00001). An acute ingestion of caffeine capsules significantly improved muscle strength and muscle endurance in the upper body and lower body of males.

The effect of exercise on flow-mediated dilation in people with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Introduction: An increasing number of studies have investigated the effect of exercise on flow-mediated dilation (FMD) in people with type 2 diabetes mellitus (T2DM), while the findings were controversial. The primary aim of this systematic review and meta-analysis was to investigate the effect of exercise on FMD in T2DM patients, and the secondary aim was to investigate the optimal type, frequency, session duration, and weekly time of exercise for T2DM patients. Methods: Searches were conducted in PubMed, Cochrane Library, Scopus, Web of Science, Embase and EBSCO databases. The Cochrane risk of bias tool (RoB2) in randomized trial and Physiotherapy Evidence Database (PEDro) scale were used to assess the methodological quality of the included studies. Results: From the 3636 search records initially retrieved, 13 studies met the inclusion criteria. Our meta-analysis revealed that exercise had a significant effect on improving FMD in T2DM patients [WMD, 2.18 (95% CI, 1.78-2.58), p < 0.00001, I2 = 38%], with high-intensity interval training (HIIT) being the most effective intervention type [HIIT, 2.62 (1.42-3.82); p < 0.0001; aerobic exercise, 2.20 (1.29-3.11), p < 0.00001; resistance exercise, 1.91 (0.01-3.82), p = 0.05; multicomponent training, 1.49 (0.15-2.83), p = 0.03]. In addition, a higher frequency [> 3 times, 3.06 (1.94-4.19), p < 0.00001; ≤ 3 times, 2.02 (1.59-2.45), p < 0.00001], a shorter session duration [< 60 min, 3.39 (2.07-4.71), p < 0.00001; ≥ 60 min, 1.86 (1.32-2.40), p < 0.00001], and a shorter weekly time [≤ 180 min, 2.40 (1.63-3.17), p < 0.00001; > 180 min, 2.11 (0.82-3.40), p = 0.001] were associated with larger improvements in FMD. Conclusion: This meta-analysis provides clinicians with evidence to recommended that T2DM patients participate in exercise, especially HIIT, more than 3 times per week for less than 60 min, with a target of 180 min per week being reached by increasing the frequency of exercise. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023466575.

Effects of exercise in people with multiple sclerosis: a systematic review and meta-analysis.

Background: A growing body of studies have examined the effect of exercise in people with multiple sclerosis (MS), while findings of available studies were conflicting. This meta-analysis aimed to explore the effects of exercise on balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Methods: We searched PubMed, Web of Science, Scopus, and Cochrane databases, through March 1, 2024. Inclusion criteria were: (1) RCTs; (2) included an intervention and control group; (3) had people with MS as study subjects; (4) had balance, walking ability, walking endurance, fatigue, or quality of life as the outcome measures. Exclusion criteria were: (1) non-English publications; (2) animal model publications; (3) review articles; and (4) conference articles. A meta-analysis was conducted to calculate weighted mean difference (WMD) and 95% confidence interval (CI). Cochrane risk assessment tool and Physiotherapy Evidence Database (PEDro) scale were used to evaluate the methodological quality of the included studies. Results: Forty studies with a total of 56 exercise groups (n = 1,300) and 40 control groups (n = 827) were eligible for meta-analysis. Exercise significantly improved BBS (WMD, 3.77; 95% CI, 3.01 to 4.53, P < 0.00001), TUG (WMD, -1.33; 95% CI, -1.57 to -1.08, P < 0.00001), MSWS-12 (WMD, -2.57; 95% CI, -3.99 to -1.15, P = 0.0004), 6MWT (WMD, 25.56; 95% CI, 16.34 to 34.79, P < 0.00001), fatigue (WMD, -4.34; 95% CI, -5.83 to -2.84, P < 0.00001), and MSQOL-54 in people with MS (WMD, 11.80; 95% CI, 5.70 to 17.90, P = 0.0002) in people with MS. Subgroup analyses showed that aerobic exercise, resistance exercise, and multicomponent training were all effective in improving fatigue in people with MS, with resistance exercise being the most effective intervention type. In addition, a younger age was associated with a larger improvement in fatigue. Furthermore, aerobic exercise and multicomponent training were all effective in improving quality of life in people with MS, with aerobic exercise being the most effective intervention type. Conclusion: Exercise had beneficial effects in improving balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Resistance exercise and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The effect of exercise on improving fatigue was associated with the age of the participants, with the younger age of the participants, the greater the improvement in fatigue. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371056, identifier: CRD42022371056.

Mea6/cTAGE5 cooperates with TRAPPC12 to regulate PTN secretion and white matter development.

Mutations of TRAPPC12 are associated with progressive childhood encephalopathy including abnormal white matter. However, the underlying pathogenesis is still unclear. Here, we found that Trappc12 deficiency in CG4 and oligodendrocyte progenitor cells (OPCs) affects their differentiation and maturation. In addition, TRAPPC12 interacts with Mea6/cTAGE5, and Mea6/cTAGE5 ablation in OPCs affects their proliferation and differentiation, leading to marked hypomyelination, compromised synaptic functionality, and aberrant behaviors in mice. We reveal that TRAPPC12 is associated with COPII components at ER exit site, and Mea6/cTAGE5 cKO disrupts the trafficking pathway by affecting the distribution and/or expression of TRAPPC12, SEC13, SEC31A, and SAR1. Moreover, we observed marked disturbances in the secretion of pleiotrophin (PTN) in Mea6-deficient OPCs. Notably, exogenous PTN supplementation ameliorated the differentiation deficits of these OPCs. Collectively, our findings indicate that the association between TRAPPC12 and MEA6 is important for cargo trafficking and white matter development.

Effects of different drop height training on lower limb explosive and change of direction performance in collegiate Sanda athletes.

The purpose of the present study was to examine the effects of 6 weeks of 40-, 60-, or 80-cm drop jump (DJ) training on lower limb explosive and change of direction (CoD) performance in collegiate Sanda athletes. Repeated-measure ANOVA revealed that there was a significant group × time interaction for standing long jump test (p = 0.006), counter movement jump test (p = 0.026), Illinois agility test (p = 0.003), square test (p = 0.018), Nebraska test (p = 0.027), t test (p = 0.032), and hexagon test (p = 0.012) due to the best performance observed at post-test compared with pre-test for DJ60 (effect size = 0.89-2.89), and the improvement was higher than that of the other groups. These findings suggest that 6 weeks of DJ training could improve the lower limb explosive and CoD performance in collegiate Sanda athletes and that 60 cm may be the optimal drop height.

Does Physical Activity Affect Clinical Symptoms and the Quality of Life of Mild-Infected Individuals with COVID-19 in China? A Cross-Sectional Study.

BACKGROUND: Few studies have identified the links between physical activity (PA), clinical symptoms, and the quality of life (QoL) among mildly infected individuals with COVID-19. This cross-sectional study aims to evaluate how PA levels before infections affect the infectious symptoms and the QoL in mildly infected patients with COVID-19. METHODS: An online questionnaire link including participants' sociodemographic and anthropometric characteristics, clinical symptoms during the COVID-19 infectious period, the QoL of the worst symptomatic day, and PA in the last seven days before COVID-19 infections was disclosed. Logistic regression and multiple linear regression analyses were applied to assess the relationships between PA levels in the last seven days before infections and COVID-19-related outcomes. The level of statistical significance was set at p < 0.05. RESULTS: Compared to the low-PA-level group, the moderate-PA-level group presented a higher risk of headaches (OR = 1.34, 95% CI = 1.03 to 1.75, and p = 0.03) and the high-PA-level group presented a higher risk of muscle/body aches (OR = 1.42, 95% CI = 1.04 to 1.93, and p = 0.03). The adjusted linear regression analysis showed that no associations were found between PA levels in the last seven days before infections and the QoL index value on the worst symptomatic day (moderate-PA-level group: ß = -0.04, and p = 0.08; high-PA-level group: ß = -0.04, and p = 0.17). However, for the mobility and usual activities dimensions of EQ-5D-5L, the lower-PA-level group had a lower burden of QoL than the higher-PA-level group did on the worst-symptomatic day. CONCLUSIONS: Among mildly infected patients with COVID-19, a higher PA level is associated with a higher risk of experiencing clinical symptoms and a lower QoL.

Effects of rest interval and training intensity on jumping performance: a systematic review and meta-analysis investigating post-activation performance enhancement.

Background: There is no clear agreement regarding the ideal rest interval and training intensity to optimize post-activation performance enhancement (PAPE) after barbell squat (BS). Therefore, the aim of this study was to investigate the effects of rest interval and training intensity on jumping performance due to PAPE. Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: (1) eligible studies should be randomized controlled trials; (2) eligible studies should investigate the acute effect of barbell squat-induced PAPE on jump performance; (3) eligible studies should use countermovement jump, squat jump, or vertical jump as the outcome measure. Results: From 2518 search records initially identified, 19 studies were eligible for meta-analysis. Our meta-analysis results showed that BS had no significant effect on improving jumping performance due to PAPE (Cohen's d = 0.09, p = 0.08). Subgroup analysis showed that rest interval between 0-1 min was detrimental to jumping performance (Cohen's d = -0.33, p < 0.01), while rest intervals between 4-7 min (Cohen's d = 0.31, p < 0.01) and 8-9 min (Cohen's d = 0.26, p = 0.02) provided favorable jumping performance outcomes. In addition, low-intensity and moderate-intensity BS had no significant effect on jump performance, while high-intensity BS showed results consistent with rest interval. Conclusion: Our study indicated that both low-intensity and moderate-intensity BS failed to induce PAPE, and it is recommended that future studies use high-intensity BS to induce PAPE. A rest interval of 4-9 min had a beneficial impact on jump height, and an interval range of 4-7 min seems to be the best rest interval between conditioning activity and jumping performance.

The effect of exercise on cognitive function in people with multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: A growing body of research examining the effect of exercise on cognitive function in people with multiple sclerosis (MS), while findings of available studies were conflicting. We aimed to explore the effect of exercise on cognitive function in MS patients. METHODS: For this systematic review and meta-analysis, we searched PubMed, Web of Science, EBSCO, Cochrane, and Scopus electronic databases, through July 18, 2022. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. RESULTS: Twenty-one studies with a total of 23 experimental groups and 21 control groups met the inclusion criteria. There was a significant effect of exercise on improving cognitive function in MS patients, while the effect size was small (Cohen's d = 0.20, 95% CI 0.06-0.34, p < 0.001, I2 = 39.31%). Subgroup analysis showed that exercise significantly improved memory (Cohen's d = 0.17, 95% CI 0.02-0.33, p = 0.03, I2 = 7.59%). In addition, multicomponent training, exercise conducted 8 weeks and 10 weeks, up to 60 min per session, 3 times or more per week, 180 min or more per week increased cognitive function significantly. Furthermore, a worse basal MS status (defined by the Expanded Disability Status Scale) and an older age were associated with greater improvement in cognitive function. CONCLUSION: MS patients are recommended to participate in at least three multicomponent training sessions per week, with each session lasting up to 60 min, and the exercise goal of 180 min per week can be achieved by increasing the frequency of exercise. Exercise lasting 8 or 10 weeks is best for cognitive function improvement. Additionally, a worse basal MS status, or the older the age, the greater effect on cognitive function.

Effect of continuous aerobic exercise on endothelial function: A systematic review and meta-analysis of randomized controlled trials.

Background: Current research suggests that continuous aerobic exercise can be effective in improving vascular endothelial function, while the effect between different intensities and durations of exercise is unclear. The aim of this study was to explore the effect of different durations and intensities of aerobic exercise on vascular endothelial function in different populations. Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: 1) randomized controlled trials (RCTs); 2) including both an intervention and control group; 3) using flow-mediated dilation (FMD) as the outcome measure; and 4) testing FMD on the brachial artery. Results: From 3,368 search records initially identified, 41 studies were eligible for meta-analysis. There was a significant effect of continuous aerobic exercise on improving flow-mediated dilation (FMD) [weighted mean difference (WMD), 2.55, (95% CI, 1.93-3.16), p < 0.001]. Specifically, moderate-intensity [2.92 (2.02-3.825), p < 0.001] and vigorous-intensity exercise [2.58 (1.64-3.53), p < 0.001] significantly increased FMD. In addition, a longer duration [<12 weeks, 2.25 (1.54-2.95), p < 0.001; ≥12 weeks, 2.74 (1.95-3.54), p < 0.001], an older age [age <45, 2.09 (0.78-3.40), p = 0.002; 45 ≤ age <60, 2.25 (1.49-3.01), p < 0.001; age ≥60, 2.62 (1.31-3.94), p < 0.001], a larger basal body mass index (BMI) [20 < BMI < 25, 1.43 (0.98-1.88), p < 0.001; 25 ≤ BMI < 30, 2.49 (1.07-3.90), p < 0.001; BMI ≥ 30, 3.05 (1.69-4.42), p < 0.001], and a worse basal FMD [FMD < 4, 2.71 (0.92-4.49), p = 0.003; 4 ≤ FMD < 7, 2.63 (2.03-3.23), p < 0.001] were associated with larger improvements in FMD. Conclusion: Continuous aerobic exercise, especially moderate-intensity and vigorous-intensity aerobic exercise, contributed to improving FMD. The effect of continuous aerobic exercise on improving FMD was associated with duration and participant's characteristics. Specifically, a longer duration, an older age, a larger basal BMI, and a worse basal FMD contributed to more significant improvements in FMD. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=341442], identifier [CRD42022341442].

The Effect of Aerobic Exercise on Cognitive Function in People with Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A growing body of research has examined the effect of aerobic exercise on cognitive function in people with Alzheimer's Disease (AD), but the findings of the available studies were conflicting. The aim of this study was to explore the effect of aerobic exercise on cognitive function in AD patients. Searches were performed in PubMed, Web of Science, and EBSCO databases from the inception of indexing until 12 November 2021. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1942 search records initially identified, 15 randomized controlled trials (RCTs) were considered eligible for systematic review and meta-analysis. Included studies involved 503 participants in 16 exercise groups (mean age: 69.2-84 years) and 406 participants (mean age: 68.9-84 years) in 15 control groups. There was a significant effect of aerobic exercise on increasing mini-mental state examination (MMSE) score in AD patients [weighted mean difference (WMD), 1.50 (95% CI, 0.55 to 2.45), p = 0.002]. Subgroup analyses showed that interventions conducted 30 min per session [WMD, 2.52 (95% CI, 0.84 to 4.20), p = 0.003], less than 150 min per week [WMD, 2.10 (95% CI, 0.84 to 3.37), p = 0.001], and up to three times per week [WMD, 1.68 (95% CI, 0.46 to 2.89), p = 0.007] increased MMSE score significantly. In addition, a worse basal cognitive status was associated with greater improvement in MMSE score. Our analysis indicated that aerobic exercise, especially conducted 30 min per session, less than 150 min per week, and up to three times per week, contributed to improving cognitive function in AD patients. Additionally, a worse basal cognitive status contributed to more significant improvements in cognitive function.

A systematic review and meta-analysis on effects of aerobic exercise in people with Parkinson's disease.

Previous studies have shown that aerobic exercise is an effective way to improve symptoms of Parkinson's disease (PD). The aim of this study [PROSPERO CRD42022340730] was to explore the effects of aerobic exercises on balance, gait, motor function, and quality of life in PD patients. Searches were performed in PubMed, Web of Science, and EBSCO electronic databases. The Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1287 search records initially identified, 20 studies were considered eligible for systematic review and meta-analysis. There was a significant effect of aerobic exercise on improving timed up and go test [standardized mean difference (SMD), -0.41 (95% CI, -0.61 to -0.22), p < 0.00001], Berg Balance Scale [0.99 (95% CI, 0.76 to 1.23), p < 0.00001], stride/step length [0.32 (95% CI, 0.03 to 0.61), p = 0.03], gait velocity [0.49 (95% CI, 0.20 to 0.78), p = 0.0009], Unified Parkinson's Disease Rating Scale Part-III [-0.40 (95% CI, -0.55 to -0.24), p < 0.00001], and 6-minute walking test [0.35 (95% CI, 0.13 to 0.56), p = 0.002] in people with PD, but not in step cadence [-0.08 (95% CI, -0.43 to 0.27), p = 0.65] and Parkinson's Disease Questionnaire-39 [-0.113 (95% CI, -0.39 to 0.13), p = 0.32]. Aerobic exercise had beneficial effects in improving balance, gait (velocity and stride/step length), and motor function in PD patients. However, aerobic exercise had no significant associations with the step cadence and quality of life in PD patients.

The effect of aerobic exercise on pulse wave velocity in middle-aged and elderly people: A systematic review and meta-analysis of randomized controlled trials.

A growing body of research examines the effect of aerobic exercise on pulse wave velocity (PWV) in middle-aged and elderly people, while findings of available studies were conflicting. The aim of this study was to explore the effect of aerobic exercise on PWV in middle-aged and elderly people. Searches were performed in PubMed, Web of Science, and EBSCO databases. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. We included studies that satisfied the following criteria: (1) eligible studies should be randomized controlled trials (RCTs); (2) eligible studies should include both an intervention and a control group; (3) eligible studies should use the middle-aged or elderly people as subjects; and (4) eligible studies should use PWV as the outcome measure. From 972 search records initially identified, 11 studies with a total of 12 exercise groups (n = 245) and 11 control groups (n = 239) were eligible for meta-analysis. There was a significant effect of aerobic exercise on reducing PWV in middle-aged and elderly people [weighted mean difference (WMD), -0.75 (95% CI, -1.21 to -0.28), p = 0.002]. Specifically, a higher intensity [vigorous-intensity, -0.74 (-1.34 to -0.14), p = 0.02; moderate-intensity, -0.68 (-1.49 to 0.12), p = 0.10], a younger age [45 years ≤ age < 60 years, -0.57 (-0.78 to -0.37), p < 0.00001; age ≥ 60 years, -0.91 (-2.10 to 0.27), p = 0.13], a better health status [healthy, -1.19 (-2.06 to -0.31), p = 0.008; diseased, -0.32 (-0.64 to -0.01), p = 0.04], and a lower basal body mass index (BMI) [BMI < 25, -1.19 (-2.06 to -0.31), p = 0.008; 25 ≤ BMI < 30, -0.52 (-0.92 to -0.12), p = 0.01; BMI ≥ 30, -0.09 (-0.93 to 0.76), p = 0.84] were associatedwith larger reductions in PWV. Aerobic exercise, especially vigorous-intensity aerobic exercise, contributed to reducing PWV in middle-aged and elderly people. The effect of aerobic exercise on improving PWV was associated with characteristics of the participants. Specifically, a younger age, a better health status, and a lower basal BMI contributed to more significant reductions in PWV. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337103], identifier [CRD42022337103].

Treadmill Exercise Prevents Decline in Spatial Learning and Memory in 3×Tg-AD Mice through Enhancement of Structural Synaptic Plasticity of the Hippocampus and Prefrontal Cortex.

Alzheimer's disease (AD) is characterized by deficits in learning and memory. A pathological feature of AD is the alterations in the number and size of synapses, axon length, dendritic complexity, and dendritic spine numbers in the hippocampus and prefrontal cortex. Treadmill exercise can enhance synaptic plasticity in mouse or rat models of stroke, ischemia, and dementia. The aim of this study was to examine the effects of treadmill exercise on learning and memory, and structural synaptic plasticity in 3×Tg-AD mice, a mouse model of AD. Here, we show that 12 weeks treadmill exercise beginning in three-month-old mice improves spatial working memory in six-month-old 3×Tg-AD mice, while non-exercise six-month-old 3×Tg-AD mice exhibited impaired spatial working memory. To investigate potential mechanisms for the treadmill exercise-induced improvement of spatial learning and memory, we examined structural synaptic plasticity in the hippocampus and prefrontal cortex of six-month-old 3×Tg-AD mice that had undergone 12 weeks of treadmill exercise. We found that treadmill exercise led to increases in synapse numbers, synaptic structural parameters, the expression of synaptophysin (Syn, a presynaptic marker), the axon length, dendritic complexity, and the number of dendritic spines in 3×Tg-AD mice and restored these parameters to similar levels of non-Tg control mice without treadmill exercise. In addition, treadmill exercise also improved these parameters in non-Tg control mice. Strengthening structural synaptic plasticity may represent a potential mechanism by which treadmill exercise prevents decline in spatial learning and memory and synapse loss in 3×Tg-AD mice.

Effects of Different Intensities and Durations of Aerobic Exercise on Vascular Endothelial Function in Middle-Aged and Elderly People: A Meta-analysis.

BACKGROUND: Previous studies have found that aerobic exercise was more effective in improving vascular endothelial function than resistance training, high-intensity interval training (HIIT), and other types of exercise, while the effects between different intensities and durations of aerobic exercise were unclear. Therefore, we performed this meta-analysis to investigate the effects of different intensities and durations of aerobic exercise on the vascular endothelial function of middle-aged and elderly people. METHODS: Databases were searched up to April 2021 for studies evaluating the influences of different intensities and durations of aerobic exercise on endothelial function assessed by flow-mediated dilation (FMD) among healthy middle-aged and elderly people. Data were pooled using random-effects models to obtain the weighted mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: A total of 9 studies involving 221 participants fulfilled the inclusion criteria. Aerobic exercise improved the overall FMD of healthy middle-aged and elderly people [WMD, 1.33 (95% CI, 0.37-2.28), P < 0.05]. Specifically, vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.10 (95% CI, 0.27-1.93), P < 0.05], while moderate-intensity exercise had no significant association with FMD [WMD, 1.49 (95% CI, -0.62 to 3.60), P = 0.17]. In addition, long-term (8 weeks or above) aerobic exercise increased the FMD in healthy middle-aged and elderly people [WMD, 1.63 (95% CI, 0.61-2.66), P < 0.05], while one-time acute aerobic exercise had no significant association with FMD of healthy middle-aged and elderly people [WMD, 0.89 (95% CI, -1.47 to 3.24), P = 0.46]. Specifically, 8 weeks or above of vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.48 (95% CI, 1.06-1.90), P < 0.01], while 8 weeks or above of moderate aerobic exercise had no significant association with FMD [WMD, 1.49 (95% CI, -0.62 to 3.60), P = 0.17]. CONCLUSION: Aerobic exercise, especially 8 weeks or above of vigorous-intensity aerobic exercise, improved the endothelial function in healthy middle-aged and elderly people.

Angiotensin-Converting Enzyme Gene D/I Polymorphism in Relation to Endothelial Function and Endothelial-Released Factors in Chinese Women.

Many studies have investigated the relationship between angiotensin-converting enzyme (ACE) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect to ACE D/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22-75 years) were enrolled and divided into pre-menopause group and post-menopause group. After ACE D/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies of ACE D/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD (P = 0.032), and age-dependent in both genotypes (DD, P = 0.0472; DI/II, P < 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II (P < 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II (P = 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO, P = 0.032; ET-1, P = 0.017; Ang II, P = 0.002), but only with Ang II in women of DI/II (P = 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD (P = 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease.

Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles.

BACKGROUND: The development of 3D cerebral organoid technology using human-induced pluripotent stem cells (iPSCs) provides a promising platform to study how brain diseases are appropriately modeled and treated. So far, understanding of the characteristics of organoids is still in its infancy. The current study profiled, for the first time, the electrophysiological properties of organoids at molecular and cellular levels and dissected the potential age equivalency of 2-month-old organoids to human ones by a comparison of gene expression profiles among cerebral organoids, human fetal and adult brains. RESULTS: Cerebral organoids exhibit heterogeneous gene and protein markers of various brain cells, such as neurons, astrocytes, and vascular cells (endothelial cells and smooth muscle cells) at 2 months, and increases in neural, glial, vascular, and channel-related gene expression over a 2-month differentiation course. Two-month organoids exhibited action potentials, multiple channel activities, and functional electrophysiological responses to the anesthetic agent propofol. A bioinformatics analysis of 20,723 gene expression profiles showed the similar distance of gene profiles in cerebral organoids to fetal and adult brain tissues. The subsequent Ingenuity Pathway Analysis (IPA) of select canonical pathways related to neural development, network formation, and electrophysiological signaling, revealed that only calcium signaling, cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling in neurons, glutamate receptor signaling, and synaptogenesis signaling were predicted to be downregulated in cerebral organoids relative to fetal samples. Nearly all cerebral organoid and fetal pathway phenotypes were predicted to be downregulated compared with adult tissue. CONCLUSIONS: This novel study highlights dynamic development, cellular heterogeneity and electrophysiological activity. In particular, for the first time, electrophysiological drug response recapitulates what occurs in vivo, and neural characteristics are predicted to be highly similar to the human brain, further supporting the promising application of the cerebral organoid system for the modeling of the human brain in health and disease. Additionally, the studies from these characterizations of cerebral organoids in multiple levels and the findings from gene comparisons between cerebral organoids and humans (fetuses and adults) help us better understand this cerebral organoid-based cutting-edge platform and its wide uses in modeling human brain in terms of health and disease, development, and testing drug efficacy and toxicity.