Ginsenoside Rg1 promoted the wound healing in diabetic foot ulcers via miR-489-3p/Sirt1 axis.

PURPOSE: Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489-3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489-3p in wound closure of DFUs in vivo. RESULTS: Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489-3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489-3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489-3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489-3p/Sirt1 axis. CONCLUSIONS: Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489-3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.

Ginsenoside (Rg-1) promoted the wound closure of diabetic foot ulcer through iNOS elevation via miR-23a/IRF-1 axis.

BACKGROUND: Impaired wound healing in diabetes foot ulcers (DFUs) brings a great burden to diabetic patients. Pro-angiogenesis through elevating nitric oxide (NO) is beneficial to the wound healing process. Ginsenoside Rg1, the main active in Notoginseng, is reported to regulate the angiogenesis in endothelial cells through modulating miR-23a. However, the effect of Rg1 in diabetes remains elusive. METHODS: High fat diet combined with streptozotocin-induced diabetic rats were treated with Rg1. Then incision area and tissue NO level were measured to evaluate the wound closure efficacy of Rg1. Then high glucose cultured HUVECs were employed to mimic diabetic environment in vitro. Overexpression and knockdown plasmids of miR-23a or IRF-1 were constructed and transfected in HUVECs. qPCR and western blot were used to determine the mRNA and protein level, respectively. Dual-luciferase reporter assay was utilized to determine the interaction of IRF-1/miR-23a. RESULTS: Rg1 accelerated the wound closure speed in diabetic rats and increased NO level through elevating iNOS expression. Knockdown of iNOS reversed Rg1-induced VEGF expression, cell proliferation, anti-apoptotic efficacy and cell migration ability in high glucose cultured HUVECs. Further investigation revealed that Rg1 mediated iNOS through miR-23a. miR-23a inhibited the expression of IRF-1, a protein which could directly bind to the iNOS mRNA 3'UTR. CONCLUSION: Rg1 promoted angiogenesis in diabetic wound healing process through NO signaling via miR-23a, providing a novel candidate for DFUs treatment.

Expression of survivin and patients survival in non-small cell lung cancer: a meta-analysis of the published studies.

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44-2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.

Meta-analysis for cyclin E in lung cancer survival.

BACKGROUND: To assess the prognosis value of cyclin E expression in survival of patients with lung cancer (LC), we performed a systematic review of the literature with meta-analysis. METHODS: Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association of cyclin E expression with survival of LC patients. Heterogeneity and publication bias were also assessed. RESULTS: Fourteen studies (2606 cases) were eligible and subjected to analysis. Cyclin E over-expression was found to be a strong predictor of poor prognosis in LC patients (HR: 1.38, 95% CI: 1.07-1.79; P=0.014). When only non-small cell lung cancer (NSCLC) was considered, the combined HR was 1.53 (95% CI: 1.19-1.97, P=0.001). A significant association was also evident when the analysis was limited to studies involving adenocarcinoma (AD), but not squamous cell carcinoma (SQ). Publication bias was absent. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average.