DNA methylation and mRNA expression of COL6A3 in antler mesenchyme of female and male reindeer.

BACKGROUD: Reindeer is the only deer species that both male and female produce antlers, which provides a particularly interesting case in studying the differences between antlers of the two sexes. Alpha 3(VI) Collagen Gene (COL6A3), forms a microfibrillar network associated with the structural integrity and biomechanical properties, has been found to be one of the differentially expressed genes in antler mesenchyme of female and male reindeer. OBJECTIVE AND METHODS: The promoter sequence of reindeer COL6A3 gene was obtained using the cloning technology and analyzed by the bioinformatics methods. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the COL6A3 promoter in reindeer antler mesenchyme. Real-time quantitative PCR was used to detect COL6A3 expression in the antler mesenchyme of female and male reindeer. RESULTS: Sequence analysis revealed that the reindeer COL6A3 partial promoter sequence was 983 bp including the possible promoter region at + 105 bp to + 155 bp. Homology and phylogenetic analysis indicated that the COL6A3 promoter of reindeer had the closest genetic distance with Bos taurus, Capra hircus and Ovis aries. BSP results indicated that the methylation level of COL6A3 promoter in the female reindeer antler mesenchyme was significantly higher than in the male. Correlating with increased methylation status, we also found that COL6A3 mRNA expression in female reindeer antler mesenchyme was significantly lower than in the male. CONCLUSION: The higher methylation level of the COL6A3 gene in female reindeer antler mesenchyme coincides with decreased COL6A3 mRNA expression, thereby affecting the transposon silencing mechanism and possibly contributing to apparent differences of antlers in female and male reindeer.

Comparative efficacy and safety of multiple antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack: A network meta-analysis.

BACKGROUND: Antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack (TIA) is a highly active research topic with five critical drugs obtained by visual analysis. We aimed to compare and rank multiple antiplatelet therapies using a network meta-analysis. METHODS: Relevant medical databases were searched. Eligible randomized controlled trials (RCTs) which examined any comparisons involving mono- or dual antiplatelet therapies, based on aspirin, clopidogrel, dipyridamole, ticlopidine, cilostazol and placebo for patients with noncardioembolic ischemic stroke or TIA, were included. 14 outcomes were assessed. Primary outcomes were stroke recurrence, composite events (stroke recurrence, myocardial infarction and vascular death), and intracranial hemorrhage. PROSPERO registered number CRD42017069728. RESULTS: 45 RCTs with 173,131 patients were included in network meta-analysis, involving eight antiplatelet therapies. Cilostazol and clopidogrel were statistically more efficacious than aspirin (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.47-0.88; OR = 0.77, 95%CI = 0.62-0.95) and dipyridamole (OR = 0.64, 95%CI = 0.44-0.93; OR = 0.76, 95%CI = 0.58-0.99) in reducing stroke recurrence, and showed significant benefits in reducing composite events compared with aspirin (OR = 0.63, 95%CI = 0.45-0.89; OR = 0.90, 95%CI = 0.83-0.97). No significant difference was found between cilostazol and clopidogrel in intracranial hemorrhage. Weighted regression suggested cilostazol was hierarchically the optimum treatment in consideration of both efficacy and safety, followed by clopidogrel. CONCLUSION: Cilostazol and clopidogrel are probably promising options for secondary prevention of ischemic stroke or TIA. Both of them reduce stroke recurrence similarly compared with aspirin or dipyridamole, and reduce composite events compared with aspirin. Further studies are needed to confirm this finding.