Protective effect of umbilical cord mesenchymal stem cells combined with resveratrol against renal podocyte damage in NOD mice.

BACKGROUND: The role of chronic inflammation initiated by persistent hyperglycemia in podocyte injury has attracted increasing attention. The advanced glycation end products (RAGE) receptor- nuclear factor-kappa B (NF-кB) signaling pathway is involved in the occurrence of inflammation. We speculate that treatment with human umbilical cord mesenchymal stem cells (hUCMSCs) combined with resveratrol can block this signaling pathway and protect podocyte function. METHODS: Non obesity diabetes(NOD) mice were randomly divided into 5 groups: NOD-T1DM, Res, hUCMSCs, hUCMSCs + Res and insulin (INS)groups. Mice without diabetes were classified as NOD control group(NOD group). Blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(SCr), 24-h urine albumin excretion rate (UAER) were measured. The expression of nephrin, WT1 and RAGE, MCP-1 in renal tissues were detected by Western blot, expression of NF-кB protein(P65) was determined by immunohistochemistry. RESULTS: The combined treatment of hUCMSCs and Resveratrol can reduce BG, BUN, SCr, 24-h UAER, and the expression of the inflammatory factors MCP-1, RAGE and NF-кB; increase the number of podocytes and the expression of the podocyte-related proteins nephrin and WT1 in type 1 diabetes mellitus, and improve renal pathological structure. CONCLUSIONS: Combining of hUCMSCs and resveratrol can better protect renal podocyte function, and the effects on the reduction of blood glucose and renal injury are better than those obtained by insulin treatment. This indicated that the combination of Res and hUCMSCs may be a novel therapeutic method for the treatment of DN.

Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese.

Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 × 10(-10), RFX3) and 11p15.5 (rs179785, P=1.28 × 10(-8), KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.