Osteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPARγ and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR-20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPARγ, Bambi and Crim1 would be potential targets of miR-20a. PPARγ is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPARγ, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPARγ, Bambi and Crim1, the negative regulators of BMP signaling.

CorrespondenceMiss Wen-tong Fang, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China. Tel.: +86 152 6186 4062 Fax: +86 025 8371 8836 E-mail: fwtfu@163.com ------------------------------------------ WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia, and AF is associated with relatively higher all-cause mortality in both men and women.• However, there are limited treatment options for AF.• Statins are hypothesized to have a benefit against arrhythmias in addition to well-established secondary prevention benefit for atherosclerotic coronary artery disease, yet the data are inconsistent WHAT THIS STUDY ADDS• Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF.• The benefit of statin therapy seemed more markedly in secondary prevention than primary prevention.• These results provided some evidence for the benefit of statins beyond their lipid-lowering activity AIMSThe use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF. METHODSMeta-analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed. RESULTSTwenty studies with 23 577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37-0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18-0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40-0.74; P < 0.0001). CONCLUSIONSStatin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention.

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Background: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. Results: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. Conclusions: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Tubeimoside-1 (TBMS1), a triterpenoid saponin isolated from the tuber of Bolbostemma paniculatum (Maxim) Franquet, serves an universal suppressive role in multiple cancer types, including lung cancer. However, the mechanism involved in non-small cell lung cancer (NSCLC) cells by which TBMS1 elicits its antitumor effects is not yet completely understood. The present study indicated that 10 µmol/l TBMS1 significantly enhanced apoptosis and notably blocked the migration and invasion of NCI-H1299 cells. These effects were reversed following transfection with miR-126-5p inhibitor into TBMS1-treated NCI-H1299 cells. Vascular endothelial growth factor-A (VEGF-A) is a target gene for miR-126-5p. Notably, results suggested that the downregulated VEGF-A and VEGFR-2 in TBMS1-treated NCI-H1299 cells were upregulated after inhibiting miR-126-5p, and overexpression of VEGF-A or VEGFR-2 could significantly reduce apoptosis and promote the migration and invasion of TBMS1-treated NCI-H1299 cells. Furthermore, TBMS1 combined with TBHQ (an ERK activator) dramatically suppressed TBMS1-induced apoptosis and stimulated TBMS1-reduced migration and invasion in NCI-H1299 cells, suggesting that TBMS1 inhibits the ERK signaling pathway and represses the growth and metastasis of NCI-H1299 cells. Further study demonstrated that either inhibiting miR-126-5p or overexpressing VEGF-A and VEGFR-2 in TBMS1-treated NCI-H1299 cells elevated the mRNA expression levels and phosphorylation levels of MEK1, as well as ERK. To conclude, TBMS1 increases miR-126-5p expression, whereas overexpressing miR-126-5p inactivates VEGF-A/VEGFR-2/ERK signaling pathway, which ultimately actuates the pro-apoptotic and anti-metastatic effects in NCI-H1299 cells. Therefore, the present findings provide a theoretical foundation for TBMS1 as a potential candidate in NSCLC treatment.