Background and ObjectiveInterleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus.MethodsTwelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed.ResultsDb/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment.ConclusionsThe protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome. 相似文献
Cytochrome P450 (CYP) 2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which play a crucial role in either the detoxification or inactivation of potential carcinogens, or the bioactivation of some environmental procarcinogens to reactive DNA-binding metabolites. And smoking is a major risk factor for lung cancer. The purpose of this study is to explore the relationship between the interaction of CYP2C19*3 polymorphism and smoking and lung cancer in a Chinese population. In a Chinese case-control study of lung cancer patients (n?=?420) and healthy controls (n?=?420), we investigated the roles of CYP2C19*3 polymorphism in lung cancer risk using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We found that the frequency of CYP2C19*3 (AG + AA) genotype was significantly higher in lung cancer patients than that in control subjects (14.28 % versus 4.76 %; P?<?0.001). Multivariable logistic regression analysis showed that after adjustment of other risk factors, the A allele of CYP2C19*3 remains significantly associated with lung cancer. We also found that there was a significant interaction between CYP2C19*3 and smoking in increasing the risk for lung cancer (OR 5.121, 95 % confidence interval [CI] 4.321–10.124; P?=?0.001). The interaction between CYP2C19*3 polymorphism and smoking plays an important role in the mechanism of lung cancer in Chinese population. 相似文献
Aims Ischemic stroke (IS) is one of the most common diseases of neurology and the main cause of death and disability in Chinese population. CACNA1C was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of CACNA1C and ischemic stroke. Our study was designed to elucidate the relationship between four single-nucleotide polymorphisms (SNPs) variants in CACNA1C gene and the risk of large-artery atherosclerotic (LAA) stroke patients.
Methods A total of 384 subjects were enrolled in this study, including 192 LAA stroke cases and 192 healthy controls. And four SNPs variants in CNCNA1C gene were genotyped using in-house developed multiplex tagged-amplicon deep sequencing (TAm-Seq). Statistical analysis were conducted using χ2 test and binary logistic regression analysis.
Results We found one variant was significantly associated with LAA stroke in the allele models (rs10848683, p = 0.036, OR = 1.371, 95%CI: 1.021–1.841). And rs10848683 was also found to associate with LAA stroke under recessive model (p = 0.027, OR = 0.618, 95% CI: 0.403–0.947) after adjustment for gender and age. We also found that significant difference existed between haplotypes (rs229961-rs215976-rs216008-rs10848683) and LAA stroke (C-T-C-C, p = 0.017, OR = 2.265, 95%CI: 1.136–4.518; G-C-C-C, p = 0.046, OR = 1.891, 95% CI: 1.003–3.565; C-T-C-T, p = 0.001, OR = 0.256, 95%CI: 0.101–0.645).
Conclusion The results suggested that there was a potential association between CNCNA1C gene and the risk factor of LAA stroke in Chinese Han population. 相似文献