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Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses
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Effects of traditional Chinese medicine salvianolate combined with alprostadil and reduced glutathione on delay of progression in patients with acute kidney injury has been confirmed, but the role of this combination therapy on the progression of chronic renal failure is uncertain.
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Objective To investigate the effect of parathyroid hormone (PTH) on the transition and connective tissue growth factor (CTGF) expression of human renal proximal tubular epithelial cell line HK-2 . Methods The expression of CTGF mRNA and protein of HK-2 cells were measured by real time RT-PCR and Western blot respectively . The effect of PTH on the phenotypic transformation of HK-2 cells was examined by light microscopy . The expression of α-smooth muscle actin (α-SMA) in HK-2 cells was detected by immunofluorescence . Results Basal level of CTGF mRNA and the protein expression were detected in HK-2 ceils . PTH upregulated the expression of CTGF mRNA and protein with the maximal response at the concentration of 10-10 mol/L and the best stimulating time was at 72 h . After exposure to PTH (10-10tool/L) for 12 hours, the highest level of luciferase activity was 1 .96 fold as compared to control (1 .888±0 .078 vs 0 .989±0 .030, P＜0 .01 ) . Untreated cells showed negligible expression of ±-SMA,whereas ±-SMA expression was significantly increased in cells treated with PTH . Conclusion PTH up-regulates CTGF expression and induces transition of HK-2 cells .
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OBJECTIVE: To evaluate the effect of integrated traditional Chinese and Western medicine therapy on the progression of acute renal failure in patients with chronic renal insufficiency. METHODS: Thirty-two patients with chronic renal insufficiency developed acute renal failure recently were treated with Chinese herbs and western drugs intravenously and clysterizing of Chinese herbs liquid for 30 minutes, and the treatment course was 14 days. Assessment of liver and renal function, blood routine, electrolytes and endogenous creatinine clearance rate (Ccr) was performed before and 2 weeks after the treatment. RESULTS: The levels of hemoglobin (HB), white blood cell count (WBC) and serum electrolytes showed no significant changes after the treatment. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) decreased, while the level of Ccr increased significantly (P<0.05) after the treatment. The total effective rate was 65.6%. CONCLUSION: The integrated traditional Chinese and Western medicine therapy can effectively delay the deterioration of renal function in patients with chronic renal insufficiency accompanied by acute renal failure.
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OBJECTIVE: To investigate the role of p27 in the inhibition of emodin on the mesangial cell (MC) proliferation induced by tumor necrosis factor-alpha(TNF-alpha). METHODS: p27 protein of MC was detected with western blotting analysis. The degree of MC proliferation was estimated through [(3)H] thymidine ([(3)H] TdR) incorporation. Different dosage of emodin (50 mg/L,100 mg/L) was added into MC stimulated by TNF-alpha. RESULTS: TNF-alpha (200 kU/L) decreased p27 level of MC cultured in serum-free DMEM for 24 hours and increased[(3)H] TdR incorporation. Emodin increased p27 level of MC stimulated by TNF-alpha and decreased [(3)H] TdR incorporation. The more the emodin was added, the greater the above-mentioned effect of emodin. CONCLUSION: The increment of p27 level maybe play an important role in the inhibition of emodin on MC proliferation induced by TNF-alpha.
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Objective Our study aimed at the role of p27 on the hypertrophy of mesangial cell (MC) cultured in high glucose. Methods The p27 protein of MC lysate was detected with western blotting analysis. The degree of cultured MC hypertrophy was estimated through [3H]-thymidine incorporation and [3H]-leucine incorporation. The effect of reducing p27 expression on cell hypertrophy was analysed with p27 antisense oligodeoxynucleotide (ODN) phosphorothioate. Results in MC cultured in high glucose (450mg/dl) serum-free DMEM compared with MC cultured in normal glucose (100mg/dl) serum-free DMEM, p27 increased, [3H]-leucine incorporation increased and[3H]-thymidine incorporation decreased;p27 antisense ODN transfection reduced [3H]leucine incorporation, increased [3H] thymidine incorporation of MC cultured in high glucose senumfree DMEM. Increasing medium osmolarity with D-mannitol failed to induce p27 expression of MC. Conclusion p27 protein increased in MC cultured in high glucose. High level of p27 played an important role in MC hypertrophy induced by high glucose. Because the cell cycle is controlled by the interaction between the positive cell cycle regulatory proteins(CCRP) and negative CCRP, further research is needed to study the expression of the positive and negative CCRP in MC in order to better understand the role of CCRP in MC hypertrophy.
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Objective:To observe the relationship between diabetic retinopathy (DR) and ? 3 adrenergic receptor (? 3 AR) gene polymorphism in Chinese patients with type 2 diabetes mellitus. Methods: The mutation of genotype of Trp64Arg in ? 3 AR gene was measured wit h PCR RFLP in 50 normal control and 196 patients with type 2 diabetes, while other clinical parameters [body mass index (BMI), blood pressure, fasting blood glucose, serum lipid levels and HbA1c] were all measured. Results: (1)There were no significant differences in the freque ncies of ? 3 AR phenotypes and alleles between type 2 diabetic patients and n ormal controls or between female patients and male patients; (2) The plasma triglyceride, diastolic blood pressure and BMI in female patients with mutation of ? 3 AR gene were higher than those in without mutation. There was no difference in male diabetic patients; (3)There was no difference in genotype frequencies or allele frequencies between diabetic patients with or without retinopathy. Genotype and allele frequencies didnot differ in proliferative diabetic retinopathy and non proliferative diabetic retinopathy. Conclusion: The mutation of Trp64Arg in ? 3 AR gene is associated with obesity, hypertension and dyslipideamia in femal e diabetic patients. Trp64Arg polymorphism in ? 3 AR gene is not associated with diabetic retinopathy in type 2 diabetes mellitus patients in Shanghai.
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Objective: To investigate the role of cyclin kinase inhibitor P27 on the proliferation of mesangial cell(MC) in Thy1 glomerulonephritis(GN) rats. Methods: The Thy1 model of experimental mesangial proliferative glomerulonephritis was induced by intravenous injection of rabbit anti-thymocyte plasma. The P27 protein of glomerular lysate was detected with Western blotting analysis. The P27 mRNA was determined with RT-PCR. The extracellular matrix (ECM) protein (fibronectin and type Ⅳ collagen) of glomerular lysate was examined with ELISA. Results: Glomerular P27 protein of Thy1 model rat decreased compared with that of normal rat. The level of P27 was associated with the degree of MC proliferation:P27 began to decrease on day 1 in Thy1 model, then reached the lowest on day 3 when MC proliferation was maximal, then returned to 60% of the baseline level on day 5 when MC proliferation began to resolute. Glomeruar P27 mRNA remained constant in Thy1 GN(3 d) rats. Glomerular fibronectin(Fn) and type Ⅳ collagen increased in Thy1 model: They reached the highest on day 3(P
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50% of that before treatment; (3)Normal control group( n =10). The urinary retinol binding protein(RBP) and N acetal D amino glucosidase(NAG)were measured by ELISA. The urinary osmosis, 24 h urinary protein excretion and serum creatinine (Cr) were measured. Results: (1) The urinary RBP[(0.54?0.19) mg/L], NAG[(112.84?42.82) U/L] and osmosis [(553.62?248.91) mmol/L] in PNS patients were significantly higher than normal control group ( P