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This meta-analysis aims to examine whether the XRCC3 polymorphisms are associated with ovarian cancer risk. Eligible case-control studies were identified through search in PubMed. Pooled odds ratios (ORs) were appropriately derived from fixed effects models. We therefore performed a meta-analysis of 5,302 ovarian cancer cases and 8,075 controls from 4 published articles and 8 case-control studies for 3 SNPs of XRCC3. No statistically significant associations between XRCC3 rs861539 polymorphisms and ovarian cancer risk were observed in any genetic models. For XRCC3 rs1799794 polymorphisms, we observed a statistically significant correlation with ovarian cancer risk using the homozygote comparison (T2T2 versus T1T1: OR = 0.70, 95% CI = 0.54–0.90, P = 0.005), heterozygote comparison (T1T2 versus T1T1: OR = 1.10, 95% CI = 1.00–1.21, P = 0.04), and the recessive genetic model (T2T2 versus T1T1+T1T2: OR = 0.67, 95% CI = 0.52–0.87, P = 0.002). For XRCC3 rs1799796 polymorphisms, we also observed a statistically significant correlation with ovarian cancer risk using the heterozygote comparison (T1T2 versus T1T1: OR = 0.91, 95% CI = 0.83–0.99, P = 0.04). In conclusion, this meta-analysis shows that the XRCC3 were associated with ovarian cancer risk overall for Caucasians. Asian and African populations should be further studied.

Blood–brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate Macaca fascicularis model with tMCAO. Thus, our study identifies compound LFHP-1c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption in vitro and in vivo , and provides a potentially therapeutics for brain ischemic stroke.

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