Knockdown of SEMA7A alleviates MPP+ -induced apoptosis and inflammation in BV2 microglia via PPAR-γ activation and MAPK inactivation.

INTRODUCTION: The inflammation mediated by microglial cells plays an important role in the process of neurodegenerative diseases. Recent evidence indicates that semaphorin 7A (SEMA7A) is implicated in various neurodegenerative diseases, but whether it plays a role in Parkinson's disease (PD) remains unclear. METHODS: In this study, 1.0 mmol/L 1-methyl-4-phenylpyridinium (MPP+ )-stimulated mouse microglia (BV2) cells were used as an in vitro model of PD. The expression of SEMA7A was detected by quantitative polymerase chain reaction. Cell Counting Kit-8 and apoptosis kits were used to analyze the viability and apoptosis of BV-2 cells. The content of IL-6, IL-ß, and tumor necrosis factor-α was determined by ELISA (enzyme-linked immunosorbent assay) kit. Western blot was used to detect the protein expression level of the inducible NO synthase and cyclooxygenase-2. RESULTS: Our findings indicated that SEMA7A expression in BV2 cells was upregulated after MPP+ stimulation. Knockdown of SEMA7A promoted cell viability while it inhibited apoptosis and the expression of proinflammatory enzymes and proinflammatory cytokines. Silencing SEMA7A-induced peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation and mitogen-activated protein kinase (MAPK) signaling pathway inactivation. Furthermore, a PPAR-γ inhibitor and an MAPK activator promoted the effect of MPP+ on cell viability, apoptosis, and inflammation of BV2 cells; what is more, the PPAR-γ inhibitor and MAPK activator blocked the inhibitory effect of SEMA7A downregulation on MPP+ -induced injury. CONCLUSION: In general, knockdown of SEMA7A inhibits MPP+ -induced BV2 cell apoptosis and inflammation via PPAR-γ activation and MAPK inactivation, which may provide a new therapy target for PD.

Safety and efficacy study of prourokinase injection during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction.

OBJECTIVES: To evaluate the efficacy and safety of intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions in patients with acute ST-segment elevation myocardial infarction. METHODS: Acute ST-segment elevation myocardial infarction patients underwent primary percutaneous coronary interventions were randomly divided into two groups: intracoronary prourokinase group (n = 125) and control group (n = 135). During primary percutaneous coronary interventions, prourokinase or saline was injected to the distal end of the culprit lesion via balloon catheter after balloon catheter dilatation. Demographic and clinical characteristics, infarct size, myocardial reperfusion, and cardiac functions were evaluated and compared between two groups. Hemorrhagic complications and major averse cardiovascular events (MACE) occurred in the 6-months follow-up were recorded. RESULTS: No significant differences were observed between two groups with respect to baseline demographic, clinical, and thrombolysis in myocardial infarction grade (P > 0.05). In the intracoronary prourokinase group, more patients had ST-segment resolution (>50%) compared with control group (P < 0.05). Patients in the intracoronary prourokinase group showed lower levels of serum CK, creatine kinase-MB fraction, and troponin I than those in control group (P < 0.05). No significant differences in bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was no statistically different of MACE between the two groups (P > 0.05). CONCLUSIONS: Intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions effectively improved myocardial perfusion and no increased bleeding in ST-segment elevation myocardial infarction patients.

Ethanol Extract of Chinese Hawthorn (Crataegus pinnatifida) Fruit Reduces Inflammation and Oxidative Stress in Rats with Doxorubicin-Induced Chronic Heart Failure.

BACKGROUND Chinese hawthorn (Crataegus pinnatifida) fruit is a traditional Chinese medicine for treatment of digestive system and cardiovascular diseases. The fruit contains polyphenol compounds, such as epicatechin, that have anti-inflammatory activity. This study aimed to investigate the effects of an alcohol extract of hawthorn fruit (HAE) on inflammation and oxidative stress in rats with doxorubicin-induced chronic heart failure (CHF). MATERIAL AND METHODS Rats were intraperitoneally injected with doxorubicin to induce CHF and subsequently treated with HAE intragastrically once daily for 6 weeks. At the end of the experiment, echocardiographic and hemodynamic parameters were assessed, and enzyme-linked immunoassays were used to detect the levels of cardiac injury markers (brain natriuretic peptide, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, copeptin, and adrenomedullin), oxidative stress markers (glutathione peroxidase and malondialdehyde), and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-1ß, and tumor necrosis factor-a). The IL-1ß, IL-6, glutathione peroxidase-1, and catalase mRNA levels were also measured by quantitative real-time polymerase chain reaction. RESULTS Our findings indicated that HAE exerts a cardioprotective effect, as shown by improved echocardiographic and hemodynamic parameters, decreased activity of serum myocardial enzymes, reduced serum levels of CHF markers, and inhibited inflammatory response in cardiac tissue. In addition, HAE treatment downregulated the mRNA expression of IL-1ß and tumor necrosis factor-alpha and upregulated the mRNA expression of glutathione peroxidase-1 and catalase compared with untreated doxorubicin-induced CHF rats. CONCLUSIONS HAE shows promise for the prevention and treatment of CHF. The cardioprotective effect of HAE appears to be related to inhibition of both the inflammatory response and oxidative stress in vivo.