Effect of RBP4 on neurocognitive function in diabetic nephropathy with silent cerebral infarction / 重庆医学

Objective To observe the impairment effect of retinol binding protein 4(RBP4) on neurocognitive function in diabetic nephropathy(DN) patients with silent cerebral infarction(SCI) and to explore its mechanism.Methods Sixty patients with newly diagnosed DN and 30 healthy volunteers were selected as the study subjects and the DN cases were divided into the complicating SCI group(SCI,n=30) and non-complicating SCI group(NSCI,n=30) according to the imaging results.The degrees of neurological function deficit and Montreal cognitive assessment(MoCA) were evaluated.Serum RBP4 level was determined by ELISA and expressions of Lp-PLA2 and C-X-C chemokine receptor type 4(CXCR4) were determined by Western blot.Results Compared with the NSCI group,the neurocognitive function in the SCI group was subsided,the expression levels of RBP4,Lp-PLA2 and CXCR4 were increased(P＜0.05).The RBP4 level was positively correlated with the neurocognitive function impairment in SCI patients,moreover,there existed a regression correlation between them.Conclusion Serum RBP4 may serve as the predictive factor of DN complicating SCI and is positively correlated with neurocognitive dysfunction.Lp-PLA2/CXCR4 pathway activation may be one of its pathogenesis.

The effects of rhBMP-2 and Treg/Th17 functional disequilibrium in uremic patients with cardiovascular complication after maintenance hemodialysis.

OBJECTIVES: We compared the correlation of regulatory T cell (Treg) and Th17 cell function disequilibrium with calcification in uremic patients on maintenance hemodialysis (MHD) with healthy controls, and investigated if their influence possibly increased the development and outcome of cardiovascular complications in uremic patients after MHD. METHODS: The extent of coronary artery calcification was assessed by coronary artery calcification scoring (CACS) in uremic patients with and without adverse cardiovascular events after MHD (MHD group 1 vs. MHD group 2, respectively). Peripheral blood mononuclear cells were incubated with rhBMP-2 as positive control. The Treg/Th17 cell frequencies, Foxp3 ROR-gt mRNA expressions, and MIP 3α/CCL20 concentrations were measured. RESULTS: The CACS score was significantly higher in MHD group 1 as compared group 2. In comparison with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremic patients, displayed higher Treg and Th17 frequencies, Foxp3 and ROR-gt expressions, and MIP3α/CCL20 concentrations. However, the up-regulations of Treg frequencies and Foxp3 expressions were significant in controls but not in MHD patients. It was also observed that Treg/Th17 functional disequilibrium was not only correlated with rhBMP-2 state but also consistent with the cardiovascular complications. Moreover, the CACS was negatively correlated with Treg cell frequencies but positively correlated with Th17 cell frequencies and MIP3a/CCL20 concentrations. CONCLUSIONS: Function disequilibrium of Treg/Th17 was related to the degree of the rhBMP-2 state. Function disequilibrium of the Treg/Th17 might act synergistically with rhBMP-2 in the high incidence of immune-mediated cardiovascular complications after MHD.

Effect of RNAi targetingp38MAPK on high glucose-induced apoptosis of osteoblast MC3T3-E1 cell line / 中华内分泌代谢杂志

Objective To examine the role of p38MAPK in high glucose-induced apoptosis of osteoblast MC3T3-E1 cell line, and to investigate its effect on the expressions of apoptosis-related molecules including caspase3, bax, and bcl-2. Methods The lentiviral vector containing short hairpin RNA targeting p38MAPK was constructed. The cultured osteoblast MC3T3-E1 cell were divided into 5 groups:normal control group(A group), high glucose group(B group), p38MAPK-shRNA transfection group(C group), signal transduction inhibitor group(D group), and transfection with negative control siRNA group(E group). RT-PCR was used to determine the p38MAPK mRNA expression levels in MC3T3-E1 cells. Flow cytometry(FCM)was employed to detect the cell apoptotic percentage. The protein levels of apoptosis-related molecules p38MAPK, p-p38MAPK, caspase-3, bax, and bcl-2 were assayed by Western blot. Ultrastructural alternation of MC3T3-E1 cell was observed under transmission electron microscopy(TEM). Results The lentiviral vector containing short hairp in RNA targeting p38MAPK was successfully constructed and transfected into MC3T3-E1 cells. RT-PCR result suggested that the siRNA targeting p38MAPK could effectively reduce the p38MAPK mRNA expression level induced by high glucose in MC3T3-E1 cell line. FCM showed siRNA significantly decreased high glucose-induced apoptosis percentage of MC3T3-E1 cells(P＜0.01). Meanwhile, we also found the siRNA significantly attenuated the proteins levels of p38MAPK, p-p38MAPK, caspase-3, and gene bax induced by high glucose in MC3T3-E1 cells, whereas the protein level of gene bcl-2 was enhanced remarkably when compared with high glucose group and negative control siRNA group(P＜0.01, P＜0.05).Conclusion The iRNA targeting p38MAPK suppressed high glucose-induced MC3T3-E1 cell apoptosis via inhibiting the activation of p38MAPK signaling pathway, thereby reducing the expressions levels of p-p38MAPK, caspase-3 and gene bax, and up-regulating the level of gene bcl-2.

Effect of Fox01 expression on islet β-celis apoptosis in diabetic rat / 中华内分泌代谢杂志

SD rats were injected with streptozotocin and fed with high fat diet,used as type 2 diabetic model. Transcription factor Fox01 [in nucleus (15.00±1. 15 vs 6.45±0. 62) %, P<0.05], Caspase-3 [(23.73 ±1.48 vs 6.30±2.20)% ,P<0.01] expressions in pancreatic istet β cells and the positive rate of islet β cells apoptosis[(22.29±1.84 vs 6.25±2.42) %, P<0.01] in diabetic rats were higher than those of control rats. The islet cells which highly expresed Fox01 (in nucleus)and caspase-3 were just the apoptotic islet cells. Therefore,Fox01 may be involved in regulating apoptosis of islet β cells in type 2 diabetes.