Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.

Interleukin- 18 gene polymorphism in patients with and without atherosclerotic coronary artery disease

Several studies have revealed that inflammation plays an important role in development of Coronary Artery Disease [CAD] and its other manifestations. IL-18 is a pleiotropic cytokine that enhances Th1 [T helper 1] or Th2 [T helper 2] immune response depending on its cytokine milieu and genetic background. It strongly induces formation of plaques in patients with CAD. Variation in the Il-18 gene found to influence both levels of IL-18 and clinical outcomes in individuals with history of heart disease. To investigate the association of two IL-18 promoter gene polymorphisms at -607C/A and - 137 G/D positions with CAD, and some CAD risk factors such as diabetes, arterial hypertension, hypercholesterolemia, cigarette smoking and obesity. Genomic DNA was extracted by the salting out method from the peripheral arterial blood of 280 patients with CAD documented by coronary angiography [143 with a documented history of myocardial infarction termed positive MI and 137 without myocardial infarction designated negative MI] and 140 age- sex matched persons with a normal coronary angiography [control group]. The genotype of both CAD and control groups were assessed by ASP-PCR method. Arlequin program was used for gametic phase estimation and haplotype analysis. There was no significant difference between patient and control groups either allelic, genotypic, and haplotypic for both variants[p>0.05]. Furthermore, no significant correlation was found between IL-18 genotypes and CAD risk factors in the patient group [P>0.05]. There results suggest that the investigated IL-18 gene promoter polymorphisms at -607 C/A and -137G/C positions are not associated with genetic susceptibility to CAD in southern Iran