SOD3 overexpression alleviates cerebral ischemia-reperfusion injury in rats.

BACKGROUND: Ischemic stroke is a deadly disease that poses a serious threat to human life. Superoxide dismutase 3 (SOD3, ECSOD) is the main antioxidant enzyme that removes superoxide anions from cells. This study aimed to investigate the effect of SOD3 overexpression on cerebral ischemia-reperfusion injury in rats. METHODS: GV230-EGFP-ECSOD, the recombinant SOD3-overexpressed vector, was constructed by genetic engineering technology, and mesenchymal stem cells (MSCs) were infected with lentiviral packaging. In animal experiment, cerebral ischemia-reperfusion injury model rats were successfully established. ECSOD-MSCs are the MSCs that successfully transfected with SOD3 overexpression vector. The animals were injected with ECSOD-MSCs (ECSOD-MSC group), normal MSCs (MSCs group), PBS (PBS group), and not do any processing (Model group) via the tail vein. Then MRI was used to detect the infarct volume of rats, modified Neurological Severity Scores (mNSS), and immunohistochemistry were used to evaluate the expression of neurological function and apoptosis-related genes in rats. RESULTS: Western blot analysis revealed that the SOD3 was highly expressed in MSCs. Animal experiments showed that the transplantation of ECSOD-MSCs significantly reduced the infarct volume of ischemic stroke rats (p < 0.05), significantly improved neurological function in rats (p < 0.05), and found proapoptotic gene, Bax, expression was significantly decreased (p < 0.05), the expression of anti-apoptotic gene, Bcl-2, was significantly increased (p < 0.05). The highly expressed SOD3 has no correction with brain infarct volume, and the highly expressed SOD3 has a positive correlation with cell apoptosis. It is speculated that overexpression of SOD3 affects the expression of Bax and Bcl-2, and improves apoptosis to alleviate ischemic stroke. CONCLUSION: Our results indicated that MSCs transfected with SOD3 can effectively alleviate cerebral ischemia-reperfusion injury in rats.

Genetic polymorphisms in the ALDH2 gene and the risk of ischemic stroke in a Chinese han population.

BACKGROUND: Previous studies have shown that aldehyde dehydrogenase 2 (ALDH2) plays a role in ischemic stroke progression. In recent years, the activation of the ALDH2 pathway have been reported serving as a useful index in the identification of stroke-prone participants, and the ALDH2 pathway may be a potential target for the therapeutic intervention in ischemic stroke. MATERIALS AND METHODS: We evaluated six tagging single-nucleotide polymorphisms (SNPs) of the ALDH2 gene in a case-control study from Hainan of China (488 cases, 503 controls). We used SPSS version 17.0 statistical software, Excel software and other analysis software to explore associations between SNPs and the risk of ischemic stroke various genetic models (additive, dominant, and recessive). RESULTS: Through statistical analysis, we found that ALDH2 rs886205 [odds ratio (OR) = 6.39; 95% confidence interval (CI) = 1.19-34.38; p = 0.03] and rs7296651 (OR = 9.29; 95% CI = 1.37-63.21; p = 0.02) were associated with increased risk of ischemic stroke in recessive model analysis. In addition, we established that the "AA" genotype (OR = 5.99; 95% CI = 1.11-32.23; p = 0.037) for rs886205 and the "AA" genotype (OR = 8.93; 95% CI = 1.31-60.78; p = 0.025) for rs7296651 were associated with increased ischemic stroke risk. CONCLUSIONS: Our results provide evidence that variants of ALDH2 gene polymorphisms influence the risk of developing ischemic stroke in Han Chinese population.

Association analysis of APO gene polymorphisms with ischemic stroke risk: a case-control study in a Chinese Han population.

This study aimed to assess the association of APO gene polymorphisms and ischemic stroke risk in a Chinese Han population. In this case-control study, we genotyped 14 single nucleotide polymorphisms (SNPs) in 3 APO genes in 488 cases and 503 controls using Sequenom Mass-ARRAY technology and evaluated their association with ischemic stroke using the χ2 and genetic model analysis. In the allelic model analysis, we determined three SNPs were significantly associated with ischemic stroke: rs693 with a p value of 0.042 (OR = 1.406; 95%CI = 1.011-1.956), rs651821 with a p value of 0.007 (OR = 0.760; 95%CI = 0.622-0.929) and rs662799 with a p value of 0.006 (OR = 0.755; 95%CI = 0.618-0.923). In the genetic model analysis, we found the minor allele "A" of rs693 was associated with an increased ischemic stroke risk in the additive model and dominant model. The minor allele "C" of rs651821 was associated with a decreased ischemic stroke risk in the additive model. The minor allele "G" of rs662799 was associated with a decreased ischemic stroke risk in the additive model. Additionally, strong linkage was found in 3 blocks constituted by rs1042034, rs676210, rs693, rs673548 in APOB; rs3791981, rs679899 in APOB; and rs651821, rs662799, rs17120035 in APOA5. Our data suggested that gene polymorphisms in the APO genes may exert influences ischemic stroke susceptibility in a Chinese Han population.

Hyperthermia influences fate determination of neural stem cells with lncRNAs alterations in the early differentiation.

BACKGROUND: Temperature is an important parameter in the microenvironment of neural stem cells (NSCs); however, little is known about the precise effects of hyperthermia on fate determination in NSCs or the role of long non-coding (lnc)RNAs in this process. This was addressed in the present study using NSCs cultured at two different temperatures. METHODS: NSCs were divided into 37NSC and 40NSC groups that were cultured at 37°C or 40°C, respectively, for 72 h. Neuronal or glial cell differentiation was evaluated by flow cytometry and western blotting. LncRNA expression was detected by quantitative real-time PCR. RESULTS: The numbers of cells positive for the neuronal marker Tuj-1 and the glial cell marker glial fibrillary acidic protein were higher in the 40NSC than in the 37NSC group. The two groups also showed distinct lncRNA expression profiles. CONCLUSION: Hyperthermia promotes neuronal and glial differentiation in NSCs, which involves specific lncRNAs.