Inhibition of miR-186-5p contributes to high glucose-induced injury in AC16 cardiomyocytes.

A growing body of evidence has demonstrated that microRNAs (miRs) have pivotal roles in the pathophysiological development mechanisms of diabetic cardiomyopathy (DCM). Previous studies have demonstrated that miR-186-5p was significantly decreased in DCM. In addition, it has recently been reported that an imbalance of miR-186 is associated with a variety of physiological and pathological processes. Therefore, the present study was designed to investigate the role of miR-186-5p in high glucose (HG)-induced cytotoxicity and apoptosis in AC16 cardiomyocytes. Reverse transcription-polymerase chain reaction was used to demonstrate the significant decrease in the level of miR-186-5p in HG-treated AC16 cells (P<0.05). Subsequently, it was clarified that pre-transfection with miR-186-5p mimic significantly ameliorated the effects of high glucose, which induced a significant decrease in the viability of AC16 cells (P<0.05) and increases in apoptosis, as evidenced by the appearance of apoptotic nucleus and the significant upregulation of apoptosis rate in AC16 cells (P<0.05). In addition, the significantly increased expression of caspase-3 induced by HG (P<0.01) was also reversed by miR-186-5p mimic (P<0.01). Conversely, transfection with miR-186-5p inhibitor significantly reduced the viability of AC16 cells (P<0.05) and promoted apoptosis (P<0.05) as well as the expression of caspase-3 in AC16 cells (P<0.01), indicating the beneficial role of miR-186-5p in the physiological process of HG-induced damage. In conclusion, these results suggest that the distribution of miR-186-5p contributes to HG-induced cytotoxicity and apoptosis in AC16 cardiomyocytes.

New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of Endogenous H2S Production and ER stress.

OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500µM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay. Cell viability was tested by using the cell counting kit-8 (CCK-8) kit. Glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP), caspase-3 and caspase-12 expressions were measured using western blot analysis. Lipid droplet was evaluated by Oil Red O staining. Apoptosis in hearts of DCM rats was analyzed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: H2S levels in serum of DCM patients and DCM rats were significant lower, H2S contents and cystathionine-γ-lyase (CSE) expression in heart tissues of DCM rats were also markedly lower. H2S levels in supernatants of PA-treated AC16 cardiac cells were decreased. Cardiac lipotoxicity demonstrated by increase in TUNEL positive cells and lipid deposit in vivo and in vitro accompanied by a decrease of H2S levels. Pretreatment AC16 cells with 100µmol/L of NaHS (a donor of H2S) could suppress the PA-induced myocardial injury similar to the effects of 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), leading to an increase in cell viability and preventing lipid deposit. Meanwhile, administration diabetic rats with NaHS or 4-PBA alleviated cardiac lipotoxicity, as evidenced by decrease in TUNEL positive cells, cleaved caspase-3 expression and lipid accumulation. CONCLUSION: Deficiency of endogenous H2S was involved in lipotoxicity-induced myocardial injury. Exogenous H2S attenuates PA-induced myocardial injury though inhibition of ER stress.

[Risk Assessment of Malaria in Libo County, Guizhou Province].

Data concerning malaria endemic situation during 2006-2012 and data concerning malaria transmission risk and malaria elimination capacity during 2010-2012 were collected. The results showed that during 2006-2012, malaria in Libo County was predominated by vivax malaria with the transmission vector of Anopheles sinensis, and malaria incidence declined year by year（3.72/10 000, 3.56/10 000, 5.76/10 000, 4.34/10 000, 2.54/10 000, 1.14/10 000, and 0, respectively）. In the residents surveyed during 2010-2012, >2% received blood test, 82.9%（29/35） received standard therapy, 93.3%（651/698）had usage of insect-resistant facilities, and 440 received medical training, with an awareness rate of 92.3%（738/800）in the residents. The malaria transmission risk index of Anopheles mosquito was 2, the area risk value was 10, and the malaria transmission risk index was 20, indicating a moderately-low level of risk.

[Measures and effect of malaria prevention and control in Libo County].

OBJECTIVE: To understand the implementation status and effect of prevention and control of malaria in Libo County, so as to provide the evidence for improving the malaria elimination working. METHODS: The data about malaria from the county CDC and county hospital were collected and 16 villages from 8 townships were randomly sampled and 10 villagers of each village were investigated. Other information about the prevention and control of malaria was also investigated. RESULTS: The incidence of malaria was decreasing annually, from 5.75 per 10,000 in 2008 to zero in 2012. The malaria monitoring could be well conducted in the county and township levels. The infection source could be controlled in time. The utilization rate of anti-mosquito facilities in the residents was 93.25% and the awareness rate of knowledge about malaria prevention and control was 40.13%. CONCLUSIONS: The implementation and effect of prevention and control of malaria are satisfactory in Libo County, but the medium control is limited and the active protection consciousness of the residents is not strong. Therefore, the task of malaria elimination is still very arduous.

Inhibition of the leptin-induced activation of the p38 MAPK pathway contributes to the protective effects of naringin against high glucose-induced injury in H9c2 cardiac cells.

Leptin, a product of the obese gene, has been reported to contribute to the development of cardiomyocyte hypertrophy in patients with diabetes and to activate the p38 mitogen-activated protein kinase (MAPK) pathway in cardiomyocytes. In this study, we demonstrate that naringin, a citrus flavonone, protects cardiomyoblasts (H9c2 cells) against high glucose (HG)-induced apoptosis by modulating the activation of the p38 MAPK pathway. We investigated the hypothesis that naringin prevents HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway in H9c2 cells. Our results demonstrated that the exposure of H9c2 cells to HG (35 mmol/l) for a 24 h markedly upregulated the expression levels of both leptin and leptin receptors. However, the increase in the expression levels of leptin and leptin receptors was greatly attenuated by treatment of the H9c2 cells with 80 µmol/l naringin 2 h prior to exposure to HG. In addition, treatment of the cells with 50 ng/ml leptin antagonist (LA) for 24 h prior to exposure to HG markedly ameliorated the increased expression of phosphorylated (p)-p38 MAPK induced by HG. Of note, pre-treatment of the cells with either 80 µmol/l naringin or 50 ng/ml LA markedly inhibited the HG-induced injury, leading to an increase in cell viability and a decrease in the total number of apoptotic cells, preventing reactive oxygen species (ROS) generation, as well as the dissipation of mitochondrial membrane potential (MMP). In conclusion, the findings of the present study provide the first evidence that the leptin-induced activation of the p38 MAPK pathway is involved in HG-induced injury, including cytotoxicity, apoptosis, ROS generation and the dissipation of MMP in H9c2 cardiac cells. Our data demonstrate that naringin protects cardiac cells against HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway.

Angiographic and interventional management for a esophagopericardial fistula.

We reported a case of a 78-year-old patient with esophagopericardial fistula who was referred for angiographic and interventional management. Emergent implantation of the esophageal stent could not lengthen or even save the patient's life. One week later, the patient died of multiple organ failure, which was probably from formation of granulation tissue and stent migration. Therefore, if the inflammatory to the esophagopericardial fistula had been better controlled initially, and the implantation of the esophageal stent delayed, our patient would have survived.

[Expression of Toll-like receptor 4 and tumor necrosis factor-α on peripheral-blood mononuclear cells and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy].

OBJECTIVE: To explore the expression of Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNF-α) on peripheral-blood mononuclear cells (PBMCs) and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy (DCM). METHODS: The expression of TLR4 and TNF-α mRNA on PBMCs were examined by SYBR Green I real-time quantitative reverse transcription polymerase chain reaction (RT-PCR), the levels of TLR4 and TNF-α were examined by flow cytometric analysis and enzyme-linked immuno sorbent assay (ELISA) on DCM group (n = 20), Type 2 diabetic group (n = 22) and control group (n = 20). Myocardial perfusion was visualized by single-photon emission computed tomography (SPECT). RESULTS: The expressions of TLR4 and TNF-α mRNA/protein on PBMCs in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.05); summed stress score (SSS) and summed rest score (SRS) of myocardial perfusion in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.01). The expression of TLR4, TNF-α was positively correlated with SSS (r = 0.75, P < 0.05; r = 0.931, P < 0.005) and SRS (r = 0.78, P < 0.005; r = 0.789, P < 0.005). SSS and SRS in DCM group were also positively correlated with soluble vascular cell adhesion molecule-1 (sVCAM-1) (r = 0.728, P < 0.005; r = 0.738, P < 0.005) but there was no correlation between SSS and SRS and brain natriuretic peptide, LVEF, E/A, HbA1c, FBG, FIN and LDL-C (P > 0.05). CONCLUSION: The increased expression of TLR4 and TNF-α mRNA/protein on PBMCs and increased serum sVCAM-1 is linked with reduced myocardial perfusion in DCM group. TLR4 and TNF-α may thus play a critical role in the myocardial perfusion inflammation injury in these patients.