RESUMO
BACKGROUND: Growth and differentiation factor 15 (GDF15) has been proved to regulate the process of Myocardial ischemia-reperfusion injury (MIRI), which is a serious complication of reperfusion therapy. The present study aimed to explore if GDF15 could regulate the MIRI-induced ferroptosis. METHOD: MIRI animal model was established by ligating the left anterior descending coronary artery. Oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to imitate MIRI in vitro. The indicators of ferroptosis including mitochondrial damage, GPX4, FACL4, XCT4, and oxidative stress markers were evaluated. RESULTS: Overexpression of GDF15 greatly inhibited MIRI, improved cardiac function, alleviated MIRI-induced ferroptosis. pc-DNA-GDF15 significantly inhibited the oxidative stress condition and inflammation response. The OGD/R-induced ferroptosis was also inhibited by pc-DNA-GDF15. CONCLUSION: We proved that the MIRI-induced ferroptosis could by inhibited by pc-DNA-GDF15 through evaluating mitochondrial damage, MDA, GSH, and GSSG. Our research provides a new insight for the prevention and treatment of MIRI, and a new understanding for the mechanism of MIRI-induced ferroptosis.
Assuntos
Ferroptose , Traumatismo por Reperfusão Miocárdica , Animais , Vasos Coronários , DNA , Glucose , Fator 15 de Diferenciação de Crescimento/metabolismo , OxigênioRESUMO
Aim: This study was conducted to investigate the effects of VKORC1, CYP2C9, CYP4F2 and EPHX1 and nongenetic factors on warfarin maintenance dose in a very elderly, frail Han-Chinese population. Materials & methods: 16 variants of VKORC1, CYP2C9, CYP4F2 and EPHX1 were genotyped. Univariate analysis and multivariable regression model were performed for the associations of gene variants and warfarin maintenance dose. Results & conclusion:EPHX1 rs2260863 nonvariant CC homozygotes required significantly lower daily warfarin dose than GC heterozygotes. In the multivariable model, VKORC1 rs9923231, CYP2C9 rs1057910, EPHX1 rs2260863, CYP4F2 rs2189784 and body surface area altogether explained 26.9% of dosing variability. This study revealed the main impact of genetic factors on warfarin response in this special population.
Assuntos
Povo Asiático/genética , Epóxido Hidrolases/genética , Idoso Fragilizado , Quimioterapia de Manutenção/métodos , Polimorfismo de Nucleotídeo Único/genética , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Humanos , Quimioterapia de Manutenção/efeitos adversos , Masculino , Varfarina/efeitos adversosRESUMO
OBJECTIVE: To compare the efficacy and safety of bioresorbable vascular stents (BVS) and drug-eluting stents (DES) in coronary heart disease. METHODS: The full text of clinical studies involving BVS and DES was retrieved in PubMed, Springer, EMBASE, Wiley-Blackwell, and Chinese Journal Full-text Database. Review Manager 5.3 was used for meta-analysis to evaluate the risk of target lesion failure, stent thrombosis and cardiac death in BVS and DES. RESULTS: Finally, 10 studies with 6383 patients were included in the meta-analysis. Compared with DES group, BVS group had significantly increased risk of target lesion failure (OR = 1.46, 95%CI 1.20-1.79, P = 0.0002; P Heterogeneity = 0.68, I2 = 0%), stent thrombosis (OR = 2.70, 95%CI 1.57-4.66, P = 0.0003; P Heterogeneity = 1.00, I2 = 0%) and cardiac death (OR = 2.19, 95%CI 1.17-4.07, P = 0.01; P Heterogeneity = 0.93, I2 = 0%). CONCLUSION: This study shows that DES is a safer treatment than BVS for coronary revascularization.
