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Previous studies reported the oral administration ofNaja naja atravenom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin fromNaja naja atravenom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

Previous studies have proposed that albuminuria is involved in the activation of intrarenal renin angiotensin system (RAS), while its potential mechanism is still unclear. We investigated the influence of albumin on the expression of ACE/ACE2 and generation of Ang II in HK2 cells.The mRNA and protein expression of ACE and ACE2 was determined by RT-PCR and western blot respectively. Cellular localization of ACE and ACE2 was shown by laser scanning confocal microscope (LSCM). The concentration of Ang II in the supernatant was detected by radioimmunoassay (RIA).Treatment of HK-2 cells to BSA led to a significant increasing expression of ACE mRNA in dose and time dependent manner. The overexpression of ACE protein induced by BSA was consistent with its mRNA expression. Meanwhile, the mRNA and protein expression of ACE2 upon the stimulation of BSA was significantly downregulated in dose and time dependent manner. BSA could significantly increase the production of Ang II in the supernatant (p0.05). Captopril, however, attenuated the expression of ACE but increased expression of ACE2 induced by BSA.These findings suggested a novel insight on the albuminuria induced activation of intrarenal RAS by upregulation of ACE and downregulation of ACE2.

We report the first large genome-wide association study (GWAS) in a Chinese population to identify susceptibility variants for psoriasis using a two-stage case-control design. In the first stage, we carried out a genome-wide association analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for replication in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry. In addition to the strong replication for two known susceptibility loci MHC (rs1265181, P = 1.93 x 10(-208), OR = 22.62) and IL12B (rs3213094, P(combined) = 2.58 x 10(-26), OR = 0.78), we identified a new susceptibility locus within the LCE gene cluster on 1q21 (rs4085613, P(combined) = 6.69 x 10(-30), OR = 0.76).