(5R)-5-hydroxytriptolide ameliorates diabetic kidney damage by inhibiting macrophage infiltration and its cross-talk with renal resident cells.

OBJECTIVE: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms. METHODS: The effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. RESULTS: In animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. CONCLUSIONS: The present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.

Effects of exercise therapy on type 2 diabetes patients in the working mode of ＂combination of physical and health＂ / 中国综合临床

Objective To evaluate the effect of aerobic exercise combined with resistance exercise on blood sugar and constitution in patients with type 2 diabetes mellitus.Methods Fifty eligible subjects in community type 2 diabetes database were randomly selected and a model intervention group of＂1+2+1＂ was established.The regular exercise intervention was conducted for six months by combining aerobic exercise with resistance exercise.The fasting blood sugar,blood pressure,heart rate,body mass and fat mass before and after intervention were compared by paired t test.Changes in related physical indicators.Results After 6 month of exercise therapy,fasting blood glucose of subjects reduced from (8.58±4.40) mmol／L to (6.29 ±1.72) mmol／L(P＝0.032).Body weight also reduced from (62.44±7.35) Kg to (60.70±7.54) Kg(P＝0.008). In physical quality related indexes, fat mass decreased significantly, while protein content increased significantly.There were no changes in muscle mass and fat free body weight.In addition, grip strength and flexion range of subjects significantly increased after exercise therapy.Comprehensive score of physical quality of subjects increased from (73.25± 5.65) to (75.48± 5.04) ( P＝0.010).Conclusion Exercise therapy of aerobic exercise combined with resistant exercise can effectively reduce blood glucose, body weight and fat mass,increase muscle strength,flexibility and physical quality.This also reflects that the community?led ＂health and physical integration＂ mode of work is an effective means to manage chronic diseases and enhance the physical fitness of residents.

Analysis of correlation between NLR family pyrin domain containing 3 and nonalcoholic fatty liver disease / 中国综合临床

Objective To explore the correlation between NLR family pyrin domain containing 3 (NLRP3) and nonalcoholic fatty liver disease (NALFD).Methods A cross-sectional study was conducted in this study.Eighty four cases of health examination personnel in Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital were included in the study randomly,and divided into NAFLD group (27cases) and normal control group (57cases) though liver ultrasound examination.Their general data (sex,height,weight),liver function,blood lipid,and blood glucose were analyzed.The level of NLRP3 in peripheral blood was analyzed by ELISA double antibody sandwich method.The relationship between NLRP3 and NAFLD was analyzed by Logistic regression.Results The prevalence of NAFLD was 32.1 ％ (27/84).The levels of serum cholesterol,triglyceride,low density lipoprotein cholesterol,fasting blood sugar,alanine aminotransferase,creatinine and uric acid in NAFLD group were higher than those in normal control group (all P＜0.01),while the level of serum high density lipoprotein cholesterol was lower than that in normal control group (P=0.023);the concentration of serum NLRP3 in NAFLD group was (5.1±1.8) μg/L,and that in normal control group was (3.9±1.4) μg/L.There was significant difference between the two groups (t =6.221,P =0.016).Logistic regression analysis showed that NLRP3 was a risk factor for NAFLD (OR =1.537,P =0.021).Conclusion The level of NLRP3 is up-regulated in the serum of NAFLD patients,which is related to the occurrence of NAFLD.

The protective effect of APPL1 on high glucose or cytokines-induced pancreatic β-cell apoptosis and dysfunction / 中华内分泌代谢杂志

Objective To determine the role of APPL1,an adaptor protein,played in pancreatic β-cell.Methods APPL1 was overexpressed in INS-1 cells with adenovirus encoding APPL1.Western blot was conducted to measure protein cxprcssion.Propidium iodide/Hoechst staining was used to determine the cell apoptosis.Insulin secretion was measured by ELISA.Results Exposure of INS-1 cells to 20 mmol/L glucose or 30U/ml interleukin-1 β plus 20 ng/ml TNF-α 48 h induced β-cell apoptosis (P＜0.01) and impaired 2 h glucosestimulated insulin secretion (P＜ 0.01).Overexpression of APPL1 in INS-1 decreased cell apoptosis by 34.16％-42.79％ (P＜0.01) and increased glucose-induced insulin secretion by 1.39-2.20 folds compared with control groups (P＜0.05).Conclusion APPL1 decreases β-cell apoptosis and increases glucose-stimulated insulin secretion,and thus protects β-cell against high glucose or cytokines-induced dysfunction.