RESUMO
Toll-like receptor 3 (TLR3) variants in mainland northern Chinese patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) were investigated. The complete genes of TLR3, including all exons and the promoter region, were assessed using direct sequencing technology of 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients, and 96 controls. Six single nucleotide polymorphisms were identified: rs5743303, rs5743305, rs5743312, rs3775291, rs3775290, and rs6830345. The distribution of TLR3 genotypes for nAMD and PCV was not significantly different compared with normal controls. This study indicates that the TLR3 gene polymorphism is not associated with nAMD and PCV in northern Chinese patients.
Assuntos
Doenças da Coroide/genética , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Idoso , Estudos de Casos e Controles , China , Éxons , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
Excessive oxidative stress in pancreatic ß cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.
RESUMO
Excessive oxidative stress in pancreatic β cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.
RESUMO
We investigated the association between the LOC387715/ARMS2 polymorphism (rs10490924 G>T) and susceptibility to polypoidal choroidal vasculopathy (PCV) through a meta-analysis of 1446 cases and 3255 controls from eight case-control studies. The genetic effect of the LOC387715/ARMS2 rs10490924 G>T polymorphism on PCV was assessed by calculating pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). We found that elevated PCV risk was significantly associated with the GG genotype (GG vs TT, OR = 4.23, 95%CI = 3.53-5.06), and heterozygous genotype TG appeared to have a minor effect on PCV risk (TG vs TT, OR = 1.47, 95%CI = 1.26-1.71). Patients with the T allele were 2.09 times more likely to have PCV than those with the G allele (95%CI = 1.906-2.288). A further subgroup analysis by ages also showed that the genetic effect of the LOC387715/ARMS2 rs10490924 G>T polymorphism on PCV is stronger among patients with mean age <73 years. Our meta-analysis strengthened the evidence that the LOC387715/ARMS2 rs10490924 G>T polymorphism plays an important role in PCV susceptibility.