Bone marrow mesenchymal stem cells-derived extracellular vesicles carrying microRNA-221-3p protect against ischemic stroke via ATF3.

OBJECTIVE: We aim to explore the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNA-221-3p (miR-221-3p) on ischemic stroke (IS) by targeting activating transcription factor 3 (ATF3). METHODS: The middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) neuron model were established. Extracellular vesicles were isolated from BMSCs (BMSC-EVs) and transfected with altered miR-221-3p or ATF3 to treat the MCAO mice and OGD-treated neurons. MiR-221-3p and ATF3 expression were determined, and the contents of inflammatory factors were detected. The pathological changes and apoptosis in mice brain tissues were observed. In cellular experiments, the viability and apoptosis of OGD-treated neurons were evaluated. Binding relationship between miR-221-3p and ATF3 was determined. RESULTS: MiR-221-3p was down-regulated and ATF3 was up-regulated in MCAO mice and OGD-treated neurons. BMSC-EVs and BMSC-EVs carrying up-regulated miR-221-3p attenuated inflammation, pathological changes and apoptosis in MCAO mice brain tissues, and also promoted viability and repressed apoptosis of OGD-treated neurons. ATF3 was verified as a target of miR-221-3p. CONCLUSION: BMSC-EVs carrying miR-221-3p protect against IS by inhibiting ATF3. This study may be helpful for exploring therapeutic strategies of IS.

Association of Brain-Derived Neurotrophic Factor rs6265 G>A polymorphism and Post-traumatic Stress Disorder susceptibility: A systematic review and meta-analysis.

BACKGROUND: Previous studies have shown that the brain-derived neurotrophic factor (BDNF) rs6265 G > A polymorphism is closely related post-traumatic stress disorder (PTSD) risk. However, the results were not consistent. We therefore conducted a meta-analysis to explore the underlying relationships between BDNF rs6265 G > A polymorphism and PTSD risk. MATERIALS AND METHODS: Five online databases were searched, and all related studies were reviewed up to July 1, 2020. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of each genetic model. In addition, heterogeneity, sensitivity accumulative analysis, and publication bias were examined to check the statistical power. RESULT: Overall, 16 publications involving 5,369 subjects were included in this systematic review and 11 case-control studies were analyses in meta-analysis. The pooled results indicated an increasing risk of A allele mutations with PTSD risk. Moreover, the sequential subgroup analysis also demonstrated some similar situations in Asian populations and other groups. CONCLUSION: Current meta-analysis suggests that the BDNF rs6265 G > A polymorphism might be involved in PTSD susceptibility.

Association Between Aldehyde dehydrogenase-2 Polymorphisms and Risk of Alzheimer's Disease and Parkinson's Disease: A Meta-Analysis Based on 5,315 Individuals.

Objective: A number of studies have reported that aldehyde dehydrogenase-2 (ALDH2) polymorphisms maybe associated with the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). However, the results of such studies are inconsistent. We therefore conducted a meta-analysis to clarify the association between ALDH2 polymorphisms and the risk of AD and PD. Methods: Five online databases were searched and the relevant studies were reviewed from inception through May 10, 2018. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated in each genetic model of the general population and various subgroups. Furthermore, we simultaneously performed heterogeneity, cumulative, sensitivity, and publication bias analyses. Results: Overall, nine case-control studies involving 5,315 subjects were included in this meta-analysis. Potential associations were found between the ALDH2 rs671 G>A polymorphism and the risk of AD (A vs. G: OR = 1.46, 95%CI = 1.01-2.11, P = 0.05, I 2 = 84.2%; AA vs. GG: OR = 2.22, 95%CI = 1.03-4.77, P = 0.04, I 2 = 79.2%; AA vs. GG+GA: OR = 1.94, 95%CI = 1.03-3.64, P =0.04, I 2 = 71.1%). In addition, some similar results were observed in other subgroups. Moreover, no significant association between ALDH2 polymorphisms and PD risk. Conclusions: In conclusion, our meta-analysis indicated that the ALDH2 rs671 G>A polymorphism plays an important role in AD development.