NEAT1 inhibits the angiogenic activity of cerebral arterial endothelial cells by inducing the M1 polarization of microglia through the AMPK signaling pathway.

BACKGROUND: Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. METHODS: Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1ß, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. RESULTS: NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. CONCLUSIONS: NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.

LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3.

BACKGROUND: Recent studies revealed that long non-coding RNAs (lncRNAs) have significant roles in regulating the pathogenesis of ischemia stroke, and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell apoptosis. Aberrant expression of NEAT1 was found after the injury of ischemia-reperfusion, but the mechanism was not fully understood. METHODS: The expression of NEAT1 and Mfn2 were detected in BV-2 and N2a cell with or without OGD/R-induced by qRT-PCR. Inflammatory cytokines secretion was detected by enzyme-linked immunosorbent assay (ELISA). The oxidative stress was evaluated by the examination of ROS, MDA and SOD levels. Flow cytometry and apoptosis marker detection by western blot were performed to examined apoptosis. RESULTS: The expression of NEAT1 and Mfn2 were decreased in OGD/R-induced cell model. Overexpression of NEAT1 or Mfn2 reduced oxidative stress and apoptosis by OGD/R-induced in neuronal cells, while knockdown of Sirt3 reversed the protective effect of NEAT1 and Mfn2. NEAT1 stabilized Mfn2 mRNA via recruiting Nova. NEAT1 alleviates the oxidative stress and apoptosis by OGD/R-induced via activating Sirt3. CONCLUSION: LncRNA NEAT1 stabilizes Mfn2 mRNA via recruiting Nova, therefore increase the expression of Mfn2 and alleviates ischemia-reperfusion induced oxidative stress and apoptosis via Mfn2/Sirt3 pathway.

The Association of Blood Urea Nitrogen to Creatinine Ratio and the Prognosis of Critically Ill Patients with Cerebral Infarction: A Cohort Study.

Background: To evaluate the association between blood urea nitrogen (BUN) to creatinine (Cr) (BUN/Cr) ratio and the in-hospital mortality of critically ill patients with cerebral infarction in intensive care unit (ICU). Methods: In this cohort study, the data of 3059 participants with cerebral infarction were collected from the Medical Information Mart for Intensive Care (MIMIC)-III and the MIMIC-IV database. After propensity score matching (PSM) on age and gender, 2085 people were involved in and divided into the alive group (n = 1390) and the dead group (n = 695) based on the results of follow-up. Multivariate logistic analyses were applied to identify the confounders and the association between BUN/Cr and mortality of cerebral infarction. Results: The median follow-up time was 10.5 days. Among 2778 participants, 695 were dead at the end of follow-up. Univariate analysis revealed that BUN/Cr [risk ratio (RR) = 1.01, 95% confidence interval (CI): 1.01-1.02] might be associated with the in-hospital mortality of cerebral infarction patients. After adjusting for respiratory failure, malignant cancer, anticoagulation, liver disease, white blood cell (WBC), red cell distribution width (RDW), glucose, bicarbonate, and temperature, BUN/Cr had week correlation with the increased risk of in-hospital mortality of cerebral infarction patients (RR = 1.01, 95% CI: 1.01-1.02). Conclusion: This study evaluated the association between BUN/Cr and the in-hospital mortality of cerebral infarction patients in ICU and found that BUN/Cr had weak correlation with the increased risk of in-hospital mortality of patients with cerebral infarction in ICU especially in males and those with respiratory failure, malignant cancer, and without liver disease, as well as those receiving anticoagulation.

Training Session and Detraining Duration Affect Lower Limb Muscle Strength Maintenance in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.

Muscle strength after detraining is still higher than the level before training, which is an important issue for middle-aged and older adults. The purpose of the present study was to examine the effects of detraining duration (DD), resistance training duration (RTD), and intensity on the maintenance of resistance training (RT) benefits after detraining in middle-aged and older adults. A systematic search yielded 15 randomized control trails (n = 383) eligible for inclusion. The results showed that RTD ≥ 24 weeks and DD ≥ RTD, the RT benefits were still significantly maintained even with medium and low intensity (standardized mean difference = 1.16, 95% confidence interval, CI [0.38, 1.94], p = .004). When RTD < 24 weeks and DD ≤ RTD, only the high-intensity groups maintained the RT benefits (DD, 4-6 weeks: standardized mean difference = 0.71, 95% CI [0.34, 1.08], p = .0002; DD 8-16 weeks: standardized mean difference = 1.35, 95% CI [0.66, 2.04], p = .0001). However, when DD > RTD, the RT benefits were not maintained even with high intensity. In summary, when RTD was less than 24 weeks, RTD > DD was an important factor in maintaining muscle strength.

A community-based approach to lean body mass and appendicular skeletal muscle mass prediction using body circumferences in community-dwelling elderly in Taiwan.

BACKGROUND AND OBJECTIVES: To develop and validate the prediction equations for lean body mass (LBM) and appendicular skeletal muscle mass (ASM) using body circumference measurements of community-dwelling adults older than 50 years old. METHODS AND STUDY DESIGN: Four hundred and ninety-eight community-dwelling adults older than 50 years old were recruited for this study. Participants were randomly assigned to a development group (DG, n=332) and validation group (VG, n=166). Lean body mass and ASM were assessed using dualenergy x-ray absorptiometry along with the anthropometric parameters. The Pearson correlation coefficient was used to examine the associations between ASM, LBM and anthropometric parameters in the DG. Prediction equations for LBM and ASM were established from DG data using multiple regression analyses. Paired t-test and Bland-Altman test were used to validate the equations in the VG. RESULTS: Forearm circumference had the highest correlation with LBM and ASM. The developed prediction models were: LBM (kg) = 27.479 + 0.726 * weight (kg) - 3.383 * gender (male = 1, female = 2) - 0.672 * BMI + 0.514 * forearm circumference (cm) - 0.245 * hip circumference (cm)(r2=0.90); ASM (kg) = -4.287 + 0.202 * weight (kg) - 0.166 * hip circumference (cm) - 1.484 * gender (male = 1, female = 2) + 0.173 * calf circumference (cm) + 0.096 * height + 0.243 * forearm circumference (cm)(r2=0.85). CONCLUSIONS: Prediction equations using only a measuring tape provide accurate, inexpensive, practical methods to assess LBM and ASM in Asians older than 50 years old.

Effects of Dynamic Stretching with Different Loads on Hip Joint Range of Motion in the Elderly.

The purpose of this study was to investigate the immediate and sustained effects of static stretching (SS), dynamic stretching (DS) with no-load (DSNL), DS with a light load (DSLL, 0.25 kg), and DS with a heavy load (DSHL, 0.5 kg) on the hip joint range of motion (ROM). Sixteen participants (63.2 ± 7.13 years) were randomly assigned to perform SS, DSNL, DSLL, and DSHL exercises. The ROM for passive flexion and extension of the right hip joint was measured at pretest, as well as immediately after and at 60 min after completing the exercise. Additionally, the ROM of hip flexion and extension during the stretching exercise was evaluated by kinematic analysis of video-captured images. Passive ROM measurements reveals that the hip flexion ROM was higher after DSNL than after DSLL and DSHL at both time points (DSNL vs. DSLL, DSHL: 0 min: 7.0% vs. -1.8%, -3.9%; 60 min: 7.8% vs. -2.1%, -1.4%, p < 0.05), as well as higher than after SS at 60 min after exercise (DSNL vs. SS: 7.8% vs. 1.0%, p < 0.05). Compared to SS, all types of DS demonstrated a more sustained effect of ROM improvement at 60 min (DSNL, DSLL, DSHL vs. SS: 8.0%, 5.6%, 7.0% vs. 1.6%, p < 0.05). These results suggest that all DS modes can effectively improve hip extension ROM in the elderly. DSNL may be the most effective exercise for improving hip flexion ROM, providing sustained effect for over 60 min.

Effects of aerobic exercise on cognitive function in adults with major depressive disorder: A systematic review and meta-analysis.

Background: Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder that impairs the cognitive function of individuals. Aerobic exercise stands out as a promising non-pharmacological intervention for enhancing cognitive function and promoting brain health.While positive impacts of aerobic exercise on executive function in adults with depression have been documented, a comprehensive understanding of its benefits on overall cognitive function, including memory, attention, and processing speed, along with key moderating factors in adults with MDD, remains unexplored. The purpose of the systematic review and meta-analysis was to investigate the effects of aerobic exercise on overall cognitive function in adults with MDD, and to explore whether cognitive sub-domains, aerobic exercise characteristics, and study and sample variables modify the effects of aerobic exercise on cognition. Methods: Six English electronic databases (Embase, Cochrane Central, Scopus, APA PsycInfo, PubMed, Web of Science) were searched from inception to 2 April 2023. Randomized trials, including adults aged 18 years or above with a diagnosis of clinical depression, of the effects of aerobic exercise on cognitive function in adults with MDD compared to non-aerobic exercise groups were included. A three-level meta-analysis was conducted utilizing a random-effects model in R. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The PROSPERO registration number is CRD42022367350. Results: Twelve randomized trials including 945 adults with MDD were included. Results indicated that aerobic exercise significantly improved overall cognitive function (g = 0.21; 95 % confidence intervals [CI] = 0.07, 0.34), and the sub-domains of memory (g = 0.25; 95 % CI = 0.06, 0.44) and executive function (g = 0.12; 95 % CI = 0.04, 0.20). Significant benefits in cognitive function were found from moderate-to-vigorous (mixed) intensity (g = 0.19; 95 % CI = 0.02, 0.37), aerobic exercise conducted 3 times per week (g = 0.23; 95 % CI = 0.10, 0.38), in sessions < 45 min (g = 0.59; 95 % CI = 0.28, 0.90), and 45-60 min (g = 0.16; 95 % CI = 0.07, 0.26), in aerobic exercise intervention ≤ 12 weeks (g = 0. 26; 95 % CI = 0.08, 0.44). Limitations: This review only included peer-reviewed English-language studies, which may lead to a language bias. The results of the Egger's test suggested a potential publication bias. Conclusions: Aerobic exercise is efficacious in improving overall cognitive function and the sub-domains of memory and executive function in adults with major depressive disorder.

Effects of exercise therapy on disability, mobility, and quality of life in the elderly with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. METHODS: We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. RESULTS: Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = - 1.75, 95% CI - 2.59, - 0.92, p < 0.05), Oswestry disability index (ODI) (WMD = - 9.42, 95% CI - 15.04, - 3.79, p < 0,005), short-form 36-item health survey physical composite summary (SF-36PCS) (WMD = 7.07, 95% CI 1.01, 13.14, p < 0.05), short-form 36-item health survey mental composite summary (SF-36MCS) (WMD = 7.88, 95% CI 0.09, 15.67, p < 0.05), and timed up and go test (TUG) (WMD = - 0.92, 95% CI - 2.22, 0.38, p < 0.005). CONCLUSION: Exercise therapy effectively improved VAS, ODI, and SF-36 indexes in the elderly. Based on the subgroup, when designing the exercise therapy regimen, aerobics, strength, and mind-body exercise (≥ 12 weeks, ≥ 3 times/week, ≥ 60 min) should be considered carefully, to ensure the safety and effectiveness for the rehabilitation of CLBP patients. More high-quality trials are needed in future to confirm the effect of exercise on SF-36 and TUG indexes.

Effects of Different Exercise Modes on Gait Performance of Parkinson's Disease Patients: A Systematic Review and Network Meta-Analysis.

Gait disturbances are among the main symptoms of Parkinson's disease (PD) and can increase fall risk. In this study we aimed to systematically evaluate the effects of different exercise modes on gait indexes of PD patients. We conducted a review and network meta-analysis of randomized controlled trials in studies listed in Web of Science, MEDLINE, EMBASE, PsycINFO, Cochrane Library, ClinicalTrailS.gov, and China National Knowledge Infrastructure databases from their inception to October 23, 2021. Eligible studies were randomized controlled trials investigating the effect of exercise on gait index by using the Timed Up and Go test, (TUG), stride length, stride cadence, or 6 Minutes Walking Test (6MWT). We used Review Manager 5.3 to evaluate the quality of the included literature, and we used Stata 15.1 and R-Studio for the network meta-analysis. We assessed the relative ranking of therapies by the surface under the cumulative ranking possibilities. In 159 studies, there were 24 exercise interventions. Compared with the control group, 13 exercises showed significant improvements on the TUG; six exercises were significantly better for improving stride length; only one exercise was better for improving stride cadence; and four exercises were better for improving the 6MWT. The surface under the cumulative ranking curves suggested that Pilates, body weight support treadmill training, resistance training, and a multidisciplinary exercise program were preferable for gains on TUG, stride length, stride cadence, and 6MWT. This meta-analytic review found that exercise therapies bring obvious benefits to gait indexes of patients with PD, and the efficacy of exercise therapies varied with different types of exercise and outcome indexes.

Effects of aquatic exercises on physical fitness and quality of life in postmenopausal women: an updated systematic review and meta-analysis.

Objective: In the present systematic review and meta-analysis, we aimed to evaluate and update the effects of aquatic exercise on physical fitness and quality of life (QoL) in postmenopausal women. Methods: The databases Cochrane Library, PubMed, Web of Science, and MEDLINE were searched for randomized controlled trials (RCTs) on the topic from inception to July 2022. The GetData software was used to extract data from the published images. RevMan5.4 software was used for statistical analysis. Data are expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). I2 index was employed for heterogeneity. Egger's test was used to assess publication bias. We evaluated the methodological quality of included studies using the Physiotherapy Evidence Database scale. Results: We included 594 participants in 16 RCTs (19 comparison groups). The results indicated that aquatic exercise can significantly improve lower limb strength (LLS), upper limb strength (ULS), agility, flexibility, and overall QoL. No significant effects were found on aerobic capacity. Subgroup-analysis results indicated that aquatic exercise only significantly improved LLS, ULS, agility, and flexibility in postmenopausal women < 65 years of age. However, aquatic exercise improves the overall QoL both in postmenopausal women < 65 years and ≥ 65 years. Aquatic resistance exercise significantly improves LLS, ULS, agility and flexibility. In addition, aquatic aerobic exercise can effectively increase LLS, and combined aquatic aerobic and resistance exercise can enhance the overall QoL. Conclusions: Aquatic exercise can effectively improve physical fitness and overall QoL in postmenopausal women, but has limited effects on aerobic capacity; thus, it is highly recommended in postmenopausal women.

Comparing the effects of different exercises on blood pressure and arterial stiffness in postmenopausal women: A systematic review and meta-analysis.

The present study aimed to compare the efficacy of different exercises on systolic blood pressure (SBP), diastolic blood pressure (DBP), and aortic pulse wave velocity (PWV) in postmenopausal women. We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, Web of Science, PubMed, and Cochrane library databases, up to July 2022. The randomized controlled trials (RCTs) were selected following the inclusion criteria. We assessed study quality with the PEDro scale. The Stata software was used for statistical analysis. Twenty-three papers (26 RCTs) and 729 participants were included. Meta-analysis demonstrated that exercise decreased SBP (WMD = -6.74 mmHg, 95%CI: -9.08, -4.41, p = 0.000), DBP (WMD = -4.13 mmHg, 95%CI: -5.78, -2.48, p = 0.000) and aortic PWV (WMD = -0.79 m/s, 95%CI: -1.02, -0.56, p = 0.000). Aerobic exercise can significantly decrease SBP (WMD = -7.97 mmHg, 95%CI: -12.99, -2.60, p = 0.003) and DBP (WMD = -5.97 mmHg, 95%CI: -8.55, -3.39, p = 0.000). Resistance exercise can significantly decrease SBP (WMD = -5.62 mmHg, 95%CI: -9.00, -2.23, p = 0.001), DBP (WMD = -1.87 mmHg, 95%CI: -2.75, -0.99, p = 0.000) and aortic PWV (WMD = -0.67 m/s，95%CI: -0.98, -0.36, p = 0.000). Combined aerobic and resistance exercise can significantly decrease SBP (WMD = -5.42 mmHg, 95%CI: -10.17, -0.68, p = 0.025). The efficacy of mind-body exercise (Tai Chi/Yoga) on SBP, DBP, and aortic PWV were not obvious (p > 0.05). Exercise significantly improved SBP, DBP, and aortic PWV in postmenopausal women. Aerobic exercise decreased SBP and DBP. Resistance exercise decreased SBP, DBP, and aortic PWV. Additionally, further research is required to confirm the efficacy of mind-body exercise (Tai Chi/Yoga) on blood pressure and arterial stiffness.

Effects of Exercise Training on Executive Functioning in Adults with Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Exercise is a promising nonpharmacological intervention to improve executive function (EF). However, results from randomized trials and meta-analyses examining the effects of exercise on working memory in adults with depression are mixed, and the influence of exercise on EF, as well as the key moderators of the relationship, remain inconclusive. OBJECTIVE: The present systematic review with meta-analysis examined the influence of exercise interventions on EF in adults with depression, and the influence of key moderating variables. METHODS: Electronic searches were conducted using Embase, Cochrane Central, Scopus, Ovid MEDLINE, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Weipu Database up to 25 June 2022, and updated on 16 January 2023. Randomized controlled trials (RCTs) examining the effects of exercise training on EF in adults with depression were included. A three-level meta-analysis based on a random-effects model was applied in R. Study quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 14 RCTs that evaluated 1201 adults with depression were included. The results indicated that exercise significantly improved global EF [g = 0.180; 95% confidence intervals (CI) = 0.038, 0.323], and the subdomains of working memory (g = 0.182; 95% CI = 0.015, 0.350), cognitive flexibility (g = 0.222; 95% CI = 0.048, 0.395), and reasoning/planning (g = 0.889; 95% CI = 0.571, 1.206). In subgroup analyses, significant improvements in EF were only observed for aerobic exercise (g = 0.203; 95% CI = 0.023, 0.382), moderate-to-vigorous intensity exercise (g = 0.200; 95% CI = 0.022, 0.379), exercise performed three or more times per week (g = 0.207; 95% CI = 0.026, 0.388), in sessions ≤ 60 min (g = 0.173; 95% CI = 0.003, 0.343), and in program durations lasting at least 13 weeks (g = 0. 248; 95% CI = 0.034, 0.462). CONCLUSIONS: This meta-analysis demonstrates the benefits of exercise training for improving EF and the subdomains of working memory, cognitive flexibility, and reasoning/planning in adults with depression. Future randomized clinical trials are warranted to determine the therapeutic effects of exercise training on EF and cognitive symptoms in depressed patients.

LncRNA NEAT1 alleviates ischemic stroke via transcriptional inhibition of NLRP3 mediated by the miR­10b­5p/BCL6 axis.

Cerebral ischemic stroke (CIS) is a significant cause of disability and death. Inflammation usually occurs after CIS and accelerates cellular damage. NLRP3 plays a key role in the formation of CIS­associated inflammasome. Understanding how NLRP3 is regulated bears great importance. We hypothesized that lncRNA NEAT1 can downregulate NLRP3 expression by regulating the miR­10b­5p/BCL6 axis, and thus regulate microglia­driven inflammation. The expression of NEAT1 was analyzed in CIS patients and an in vitro model of oxygen and glucose deprivation/re­oxygenation (OGD/R). We assessed the levels of pro­inflammatory cytokines IL­18 and IL­1ß with ELISA. Interactions between NEAT1/miR­10b­5p and miR­10b­5p/BCL6 were determined by luciferase assay. The interaction of BCL6 and NLRP3 was identified by ChIP; RNA, and protein levels were evaluated by qRT­PCR and western blot, respectively. We found that NEAT1 level was decreased in CIS patients and OGD/R treated cells. OGD/R exerted pro­inflammasome effects by increasing the expression of inflammasome­associated proteins and ROS and malondialdehyde (MDA) while inhibiting SOD production. This effect was partially antagonized by NEAT1. We bioinformatically identified interactions between NEAT1/miR­10b­5p, BCL6/miR­10b­5p, and NLRP3­promoter/BCL6, and validated them by luciferase assay, qRT­PCR, and ChIP. NEAT1 inhibited miR­10b­5p and upregulated BCL6 by ceRNA mechanism and alleviated OGD/R induced cell damage. We also proved that BCL6 was a repressive transcription factor in the regulation of NLRP3 expression. Thus, lncRNA NEAT1 inhibited inflammasome activation by NLRP3 in microglia via the NEAT1/ miR­10b­5p/BCL6/NLRP3 regulatory axis, which alleviated deleterious outcomes of ischemic stroke.

Effects of Low Back Pain Exercises on Pain Symptoms and Activities of Daily Living: A Systematic Review and Meta-Analysis.

Our objective in this paper was to systematically review evaluations of the effects of exercises on pain symptoms and activities of daily living (ADL) in middle-aged and elderly patients with low back pain (LBP). We searched Web of Science, PubMed, EBSCO, and China National Knowledge Internet (CNKI) databases for randomized controlled trials (RCTs) on this topic. We evaluated the methodological quality of included articles using the Physiotherapy Evidence Database (PEDro) scale, and we statistically analyzed these studies using RevMan software. We reviewed 18 RCTs (23 comparison groups) with a total of 910 participants, and our meta-analysis confirmed that exercises significantly improved both pain and ADLs measured on visual analog scales (VAS) (SMD = -0.91, 95% CI: [-1.3, -0.52], p < 0.00001) and on the Oswestry Disability Index (ODI) (SMD = -2.07, 95% CI: [-3.19, -0.96], p < 0.00001). We conclude that exercises can reduce pain severity and improve ADL capacity in middle-aged and elderly persons with LBP, confirming that exercise can serve as a medical intervention for these indivdiuals. However, given the high heterogeneity of responses among individual participants, there remains a need for further study.

Mitochondrial Dysfunction in Oxidative Stress-Mediated Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by-product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress-mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD.

Effects of Acute Aquatic High-Intensity Intermittent Exercise on Blood Pressure and Arterial Stiffness in Postmenopausal Women with Different ACE Genotypes.

The present study investigated the effects of acute aquatic high-intensity intermittent jumping (HIIJ) on blood pressure (BP) and arterial stiffness in postmenopausal women with different angiotensin-converting enzyme genotypes (ACE). We recruited 12 postmenopausal women carrying the ACE deletion/deletion (DD) genotype and 61 carrying the insertion/insertion or insertion/deletion (II/ID) genotype. The participants performed 12 trials of 30 s, 75% heart rate reserve (HRR) jumping, and 60 s, 50% HRR recovery, and 3 trials of 40 s upper limb resistance exercises were performed as fast as possible. The heart rate (HR) and BP were measured before exercise, immediately, 10 min, and 45 min after exercise. The brachial-ankle pulse wave velocity (baPWV) was measured before and after exercise. The systolic blood pressure (SBP) of the DD genotype increased more significantly than those with the II/ID genotype post-exercise (30.8 ± 4.48 vs. 20.4 ± 2.00 mmHg, p = 0.038). The left and right sides of baPWV increased significantly after exercise (1444.8 ± 29.54 vs. 1473.4 ± 32.36 cm/s, p = 0.020; 1442.1 ± 30.34 vs. 1472.0 ± 33.09, p = 0.011), and there was no significant difference between the two groups. The HIIJ increased baPWV. The postmenopausal women with the DD genotype have a higher SBP increased post-exercise than those with II/ID genotype. These findings suggest that the aquatic exercise program has better effects in decreasing blood pressure in postmenopausal women with the II/ID genotype. Those with the DD genotype should pay attention to the risk of increasing blood pressure after aquatic HIIJ exercise.

Aquatic Exercise for Health Promotion: A 31-Year Bibliometric Analysis.

The present study aimed to review the research literature on aquatic exercise for health promotion using bibliometric methods and CiteSpace software. The number of studies related to this topic are constantly expanding, with the USA, Brazil, and Australia the centers of this research. Most published papers fall within Sports Science, but the disciplines of Physiology, Psychology, and Rehabilitation were also found to be dominant domains for this literature. The seven most prolific authors were from Brazil or Spain. The most frequently cited references focused on sub-topics of physiology, biochemistry, physical fitness, psychological health, cardiovascular disease, and joint disease. New research trends have shifted to the promotion of cardiovascular health in clinical populations (stroke, overweight, hypertension, endothelium dysfunctional, obese, inflammation, antioxidant, heart failure). Overall, this review found that research hot spots and trends in this realm have focused on improving cardiovascular health with aquatic exercise.

Effects of Chinese Mind-Body Exercises on Executive Function in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.

Chinese mind-body exercises (CMBEs) are positively associated with executive function (EF), but their effects on EF, from synthesized evidence using systematic and meta-analytic reviews, have not been conducted. Therefore, the present systematic review with meta-analysis attempted to determine whether CMBEs affect EF and its sub-domains, as well as how exercise, sample, and study characteristics moderate the causal relationship between CMBEs and EF in middle-aged and older adults. Seven electronic databases were searched for relevant studies published from the inception of each database through June 2020 (PubMed, Web of Science, Embase, Cochrane Controlled Trials Register, Wanfang, China National Knowledge Infrastructure, and Weipu). Randomized controlled trials with at least one outcome measure of CMBEs on EF in adults of mean age ≥ 50 years with intact cognition or mild cognitive impairment (MCI) and with or without chronic diseases were included. A total of 29 studies (N = 2,934) ultimately were included in this study. The results indicated that CMBEs improved overall EF (Standardized Mean Differences = 0.28, 95% CI 0.12, 0.44), as well as its sub-domains of working memory and shifting. The beneficial effects of CMBEs on EF occurred regardless of type (Tai Chi, Qigong), frequency of group classes (≤2 time, 3-4 time, ≥5 times), session time (≤45 min, 46-60 min), total training time (≥150 to ≤300 min, >300 min), and length of the CMBEs (4-12 week, 13-26 week, and >26 week), in addition to that more frequent participation in both group classes and home practice sessions (≥5 times per week) resulted in more beneficial effects. The positive effects of CMBEs on EF were also demonstrated, regardless of participants mean age (50-65 years old, >65 years old), sex (only female, both), and cognitive statuses (normal, MCI, not mentioned), health status (with chronic disease, without chronic disease), as well as training mode (group class, group class plus home practice) and study language (English, Chinese). This review thus suggests that CMBEs can be used as an effective method with small to moderate and positive effects in enhancing EF, and that more frequent group classes and home practice sessions may increase these effects. However, certain limitations, including strictly design studies, limited ES (effect size) samples for specific variables, and possible biased publications, required paying particular attention to, for further exploring the effects of CMBEs on EF.

Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K-AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53-Nedd4-Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

LncRNA NEAT1 facilitates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs) via targeting miR-377 and upregulating SIRT1, VEGFA, and BCL-XL.

OBJECTIVE: The present study was designed to investigate the mechanism by which lncRNA NEAT1 regulates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). METHODS: OGD-treated BMECs were used to mimic cerebral ischaemia in vitro. The expression of lncRNA NEAT1 and miR-377 and proteins including VEGFA, SIRT1, and BCL-XL were measured by real-time quantitative PCR (qRT-PCR) and western blot, respectively. Cell viability and caspase 3 activity of BMECs under different conditions were determined using MTT and caspase activity assays, respectively. Matrigel-based angiogenesis assays were employed to evaluate the effect of lncRNA NEAT1 on angiogenesis. A dual-luciferase reporter assay was used to validate direct binding of miR-377 to putative targets. RESULTS: OGD exposure reduced the cell viability of BMECs. Upregulation of lncRNA NEAT1 and downregulation of miR-377 were also observed under OGD conditions. Knockdown of lncRNA NEAT1 inhibited angiogenesis and aggravated apoptosis in OGD-induced BMECs. Meanwhile, the expression level of miR-377 was upregulated while its downstream targets (VEGFA, SIRT1, and BCL-XL) were downregulated after lncRNA NEAT1 knockdown. Furthermore, miR-377 inhibited the angiogenesis and survival of OGD-induced BMECs. The expression of VEGFA, SIRT1, and BCL-XL were all attenuated by miR-377 overexpression. The dual-luciferase reporter assay proved miR-377 targeted the 3' UTR sequences of lncRNA NEAT1, VEGFA, SIRT1, and BCL-XL. CONCLUSION: lncRNA NEAT1 facilitated the survival and angiogenesis of OGD-induced BMECs via targeting miR-377 and promoting the expression of VEGFA, SIRT1, and BCL-XL, suggesting that lncRNA NEAT1 could be a promising target for cerebral ischaemia treatment.