During the past decade, an increasing number of prospective studies have focused on the association between vitamin D and cardiovascular disease (CVD). However, the evidence on the relation between serum 25-hydroxyvitamin D [25(OH)D] and the risk of overt CVD is inconclusive. We performed a dose-response meta-analysis to summarize and prospectively quantify the RR of low serum 25(OH)D concentration and total CVD (events and mortality). We identified relevant studies by searching PubMed and EMBASE up to December 2015 and by hand-searching reference lists. Prospective studies based on the general population and reported RRs and 95% CIs were included. A random-effects model was used to calculate the pooled RRs. Nonlinear association was assessed by using restricted cubic spline analyses. A total of 34 publications with 180,667 participants were eligible for the meta-analysis. We included 32 publications (27 independent studies) for total CVD events and 17 publications (17 independent studies) for CVD mortality. We observed an inverse association between serum 25(OH)D and total CVD events and CVD mortality, and the pooled RRs per 10-ng/mL increment were 0.90 (95% CI: 0.86, 0.94) for total CVD events and 0.88 (95% CI: 0.80, 0.96) for CVD mortality. A nonlinear association was detected for total CVD events (-nonlinear < 0.001) and CVD mortality (-nonlinear = 0.022). Serum 25(OH)D concentration was inversely associated with total CVD events and CVD mortality from the observed studies.
Background: Fetal growth restriction (FGR) is a worldwide problem, and a major cause of perinatal morbidity. The precise molecular mechanisms involved in placental development and function during FGR remain poorly understood. Circular RNAs (circRNAs) are important biological molecules associated with disease pathogenesis. However, the role of circRNAs in FGR has not been well studied. Methods: circRNA expression profiles in placental tissues with and without FGR were identified by circRNA microarray. circRNA expression was verified by quantitative reverse-transcription PCR (RT-qPCR) assay. The effect of hsa_circ_0000848 and hsa-miR-6768-5p on HTR-8 cell apoptosis, migration, and invasion was evaluated. The association between hsa_circ_0000848 and hsa-miR-6768-5p was confirmed by dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays. Protein levels were examined via western blotting. Results: RT-qPCR results showed that hsa_circ_0000848 expression was significantly down-regulated in FGR placenta. Hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor suppressed apoptosis, and promoted cell migration and invasion. In addition, hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor increased the protein abundance of BCL2, MMP2 and MMP9, and decreased the protein abundance of cleaved caspase-3, cleaved caspase-9, and BAX, whereas hsa_circ_0000848 knockdown caused the opposite effect. Moreover, a significant increase in hsa-miR-6768-5p expression and a negative correlation between hsa_circ_0000848 and hsa-miR-6768-5p were identified in the FGR tissues. Luciferase reporter and RIP assay results revealed binding of hsa-miR-6768-5p to hsa_circ_0000848. Furthermore, hsa-miR-6768-5p overexpression eliminated the effect of hsa_circ_0000848 overexpression in HTR-8 cells.
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