Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4.

Hypoxia-induced cardiomyocyte apoptosis plays an important role in the development of ischemic heart disease. MicroRNAs (miRNAs or miRs) are emerging as critical regulators of hypoxia-induced cardiomyocyte apoptosis. miR-200c is an miRNA that has been reported to be related to apoptosis in various pathological processes; however, its role in hypoxia­induced cardiomyocyte apoptosis remains unclear. In the present study, we aimed to investigate the potential role and underlying mechanism of miR-200c in regulating hypoxia­induced cardiomyocyte apoptosis. We found that miR-200c was significantly upregulated by hypoxia in cardiomyocytes, as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The lactate dehydrogenase, MTT, Annexin V/propidium iodide apoptosis and caspase-3 activity assays showed that downregulation of miR-200c markedly improved cell survival and suppressed the apoptosis of cardiomyocytes in response to hypoxia. Bioinformatics analysis and the dual-luciferase reporter assay demonstrated that miR-200c directly targeted the 3'-untranslated region of GATA-4, an important transcription factor for cardiomyocyte survival. RT-qPCR and western blot analysis showed that suppression of miR-200c significantly increased GATA-4 expression. Furthermore, downregulation of miR-200c upregulated the expression of the anti-apoptotic gene Bcl-2. However, the protective effects against hypoxia induced by the downregulation of miR­200c were significantly abolished by GATA-4 knockdown. Taken together, our results suggest that downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4, providing a potential therapeutic molecular target for the treatment of ischemic heart disease.

[Clinical efficacy of special effect san xiao decoction on type 2 diabetes mellitus].

OBJECTIVE: To investigate the clinical efficacies of the special effect San Xiao decoction on type 2 diabetes mellitus and its impact on inflammatory factors. METHODS: 116 patients with type 2 diabetes mellitus were randomly divided into control group and observation group from Aug. 2010 to Aug. 2012, and each group had 58 cases. Both of the two groups were given the conventional basic treatment and 0.5 g/time, oral, 2 times/d of metformin. The observation group was received 1 dose/d of special effect San Xiao decoction on the basis of the basic treatment, and the treatment course was 12 weeks. The fasting blood glucose (FBG), 2h postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 ( IL-6) and c-reactive protein (CRP) were observed after the treatment. RESULTS: The FBG, PBG, HbA1c and insulin sensitive index (ISI) of the observation group were better than those of the control group (P < 0.05 or P < 0.01); BMI and body weight of the observation group were lower than those of the control group (P < 0.05); The blood sugar control effect of the observation group was better than that of the control group (P < 0.05); The hypoglycemia incidence of the observation group was lower than that of the control group (P < 0.01); TNF-alpha, IL-6 and CRP of the observation group were lower than those of the control group (P < 0.01). CONCLUSION: The clinical efficacy of the special effect San Xiao decoction on type 2 diabetes mellitus is significant, it has the role of alleviating inflammatory response for diabetes and it also has less adverse reactions, which is worth to be applied in clinical.

[Effects of Guizhi Fuling Decoction on YKL-40 and hs-CRP of patients with non-ST segment elevation acute coronary syndrome].

OBJECTIVE: To investigate the changes of serum levels of chitinase-3-like-1 protein (YKL-40) and high-sensitivity C-reactive protein (hs-CRP) in patients with non-ST segment elevation acute coronary syndrome (ACS), to explore its correlation with its severity, and to observe the effects of Guizhi Fuling Decoction (GFD) on levels of blood lipids, YKL-40, and hs-CRP. METHODS: Recruited were 72 patients with unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI) at Department of Integrative Medicine, First Affiliated Hospital of Xinxiang Medical College from August 2010 to June 2011. They were randomly assigned to the treatment group (36 cases) and the control group (36 cases). All patients were treated by routine treatment, but patients in the treatment group took GFD additionally. The course of treatment was four weeks. According to the severity degree, all patients were graded to four ranks: low-risk group of UA, medium-risk group of UA, high-risk group of UA, and NSTEMI. The levels of YKL-40 and hs-CRP, and the correlation of severity degree were analyzed. Before and after treatment levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were measured. Before treatment, at two weeks, and after treatment the serum levels of YKL-40 and hs-CRP were detected. The relationship of YKL-40, hs-CRP and the severity of the disease were analyzed. RESULTS: Levels of YKL-40 and hs-CRP were positively correlated with the severity of the disease respectively (r = 0.729, P < 0.05; r = 0.655, P < 0.05). The positive correlation also existed between YKL-40 and hs-CRP (r = 0.848, P < 0.05). There was no statistical difference in the levels of blood lipids, YKL-40, or hs-CRP between the two groups before treatment (P > 0.05). Compared with before treatment, the levels of YKL-40 and hs-CRP significantly decreased in both groups after two weeks of treatment (P < 0.05). The levels of TG, TC, LDL-C, YKL-40, and hs-CRP significantly decreased, while the HDL-C level increased in both groups after treatment (P < 0.05). The level of HDL-C in the treatment group was higher, while levels of YKL-40 and hs-CRP were lower after treatment, when compared with the control group (all P < 0.05). CONCLUSION: On the basis of anti-inflammation and adjusting blood lipids by Western medicine, GFD could further reduce the serum levels of YKL-40 and hs-CRP of ACS patients, elevate the HDL-C level, and play anti-atherosclerosis effects.