The active participation of p22phox-214T/C in the formation of intracranial aneurysm and the suppressive potential of edaravone.

Oxidative stress reactions play an important role in the pathogenesis of intracranial aneurysm (IA). p22phox is involved in the oxidative stress reaction, and it is a critical subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The present study investigated the association of genetic variants within the gene encoding p22phox­214T/C with IA. The p22phox­214T/C gene polymorphisms in 192 cases of IA and 112 controls were analyzed by polymerase chain reaction­restriction fragment length polymorphism (PCR­RFLP). The mRNA expression of NADPH oxidase was also analyzed by RT­PCR. The results of RT­PCR were validated by ELISA. In a rabbit model of elastase­induced aneurysm, we used edaravone for anti­oxidative stress treatment to observe the curative effects. In the clinical cases, a significant difference in p22phox­214T/C allele frequencies in the IA group was observed compared with the control group (P<0.001). The expression level of NADPH oxidase was differed significantly between the IA group and the control group. In the rabbit model of elastase­induced aneurysm, the success rate of the aneurysmal model in the edaravone group and the wound ulcer rate were lower than those in the control group. In addition, the diameter of the aneurysm was smaller than in the edaravone group than in the control group (3.26±0.13 mm vs. 3.85±0.07 mm), and the expression of matrix metalloproteinase­9 (MMP­9) was significantly lower than that in the control group (P<0.0001). Thus, these data suggest the active participation of p22phox­214T/C in the formation of IA and the suppressive potential of edaravone against IA formation.

Cytochrome P450 2E1 RsaI/PstI polymorphism and risk of esophageal cancer: A meta-analysis of 17 case-control studies.

The aim of this study was to explore the cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and risk of esophageal cancer (EC) in mainland Chinese populations. A systematic search of PubMed, EMBASE, Web of Science, CBM, CNKI and VIP databases for publications on the CYP2E1 RsaI/PstI polymorphism and risk of EC was performed. and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity and assessment of publication bias were performed. The search yielded 17 studies including 18 trails involving 1,663 cases and 2,603 controls. The meta-analyses showed a significant association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population (c2 vs. c1: OR=0.64; 95% CI, 0.50-0.81; P<0.001; c2/c2 vs. c1/c1: OR=0.73; 95% CI, 0.57-0.93; c2/c2 vs. c1/c1+c1/c2: OR=0.76; 95% CI, 0.60-0.96; P=0.02; c1/c2 vs. c1/c1: OR=0.54; 95% CI, 0.38-0.75; P<0.001; c1/c2+c2/c2 vs. c1/c1: OR=0.48; 95% CI, 0.34-0.70; P<0.001). An increased cancer risk in all genetic models was identified following stratification by ethnicity, source of controls and tumor type. In conclusion, in all genetic models, the association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population was significant. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism is a risk factor for EC, and the c2 allele is a factor that lowers the possibility of EC in the mainland Chinese population and this association did not change due to ethnic differences in genetic backgrounds and the environment.