Introduction: To investigate whether tripotolide have direct effect on podocytes injured by AngII ? If so, how does it work?Methodology: Conditionally immortalized mouse podocytes were divided into three groups: negative control, positive control treated with AngII (10^-6, 10^-7, 10^-8mol/L) and pretreated with triptolide (1, 3, 10ng/ml) for 2 hours. F-actin and zonula occludens-1 (ZO-1) were observed by fluorescence microscopy. To explore the underlying mechanism，we observed reactive oxygen species (ROS) generation and the subsequent MAPK activation by flow cytometry and western blot.Results: Ang II induced actin cytoskeleton reorganization and ZO-1 redistribution in a dose-dependent manner. In untreated podocytes, the ZO-1 staining was peripherally distributed at contacts of adjacent cells as fine segments, while it appeared markedly fragmented in response Ang II, indicating tight junction loose and cell ruffling. Triptolide stabilized actin filaments and improved ZO-1 distribution in a dose dependent manner. At the dose of 10ng/ml, triptolide almost completely restored the normal cytoskeleton and cell contact in podocytes without affecting cell survival. AngII (10^-7mol/L) significantly increased ROS generation in podocytes. This effect was observed rapidly at 10min and maintained for 30min. Pretreatment of podocytes with triptolide (10ng/ml) or antioxidant NAC (10 mmol/L) before AngII exposure led to a significant reduction in the cellular ROS level. In addition, antioxidant NAC successfully reduced AngII-induced podocyte damage as showed by cytoskeleton staining, indicating that ROS generation mediates Ang-induced podocyte injury. Furthermore, triptolide effectively inhibited AngII-induced p38, ERK1/2 and JNK MAPK activation, which are the downstream signaling molecules of ROS. SB203580 and U0126, which are specific kinase inhibitor for p-38 and ERK MAPK, can block AngII induced podocyte injury.Conclusion: Triptolide showed dramatic protective effect in AngII induced podocyte injury. The protective effect of triptolide might partially due to the inhibition of ROS generation and the subsequent MAPK activation.

Abstract: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Ageing is associated with sarcopenia, and end-stage renal disease accelerates the normal physiological muscle wasting resulting in an increasing prevalence of sarcopenia, which is named uraemic sarcopenia. There are several mechanisms that may be involved in the onset and progression of uraemic sarcopenia, such as hormones, changes in immune and muscle cells, metabolic acidosis, reducing protein intake and so on. Uraemic sarcopenia presents a high probability for morbidity and mortality, and consequently a high priority for muscle wasting prevention and treatment in these patients.

Tolllike Receptor 9 (TLR9) is a member of Tolllike receptor family that use pathogen associated molecule patterns (PAMPs) as ligands. It is expressed in immune cells and senses bacterial DNA ligand to induce innate immune response. Recent studies have shown that TLR9 is also expressed in several nonimmune cells，including glomerular podocyte， and uses mitochondrial DNA as ligand to activate signaling pathways that lead to cell injury. Here, we will review the roles of TLR9 in immune cells and nonimmune cells and the underlying mechanisms.

ABSTRACT A 59 year-old man suffered from diabetes for 20 years. He had hypertension and hyperuricemia, and also had complications of diabetic nephropathy which presented with proteinuria, hypoalbuminemia, and renal insufficiency. One month ago, he received xylitol with a quotidian dose of 25g for 13 days, and then acute kidney injury occurred. A renal biopsy showed glomerular nodular lesions, and interstitial fibrosis and tubular atrophy. In addition, massive depositions of double refractive crystals located in the tubules of the renal cortex in the polarized light microscopy accompanied by necrosis of the tubular epithelium. The final diagnosis was acute calcium oxalate nephropathy superimposed on diabetic nephropathy.