Effect of sitagliptin on tubulointerstitial Wnt/ß-catenin signalling in diabetic nephropathy.

AIM: To investigate the effect of sitagliptin on Wnt/ß-catenin signalling in the tubulointerstitium of diabetic nephropathy. METHODS: Forty male Wistar rats were divided into normal control (NC), diabetic model (DM), low and high-dose sitagliptin intervention groups (ST1 and ST2, respectively). Changes in the biochemical parameters and tubulointerstitial fibrosis index were observed. The levels of protein and gene expression of different indicators were detected via immunohistochemistry and real-time polymerase chain reaction. NRK-52E cells were divided into the normal control group, mannitol control group, high glucose group (HG), high glucose plus sitagliptin intervention group (HG + ST) and high glucose plus Wnt/ß-catenin inhibitor group (HG + XAV939). The relevant indicators were examined by Western blot or enzyme-linked immunosorbent assay. RESULTS: Compared with the NC group, the blood glucose, glycosylated haemoglobin, 24 h urinary albumin, creatinine clearance and tubulointerstitial fibrosis index were significantly increased in the DM group. These parameters were decreased in the ST1 and ST2 groups compared to the DM group. Compared with the NC group, the levels of Wnt4, ß-catenin, dipeptidyl peptidase-4 and α-smooth muscle actin were higher and E-cadherin was lower in the DM group. Sitagliptin treatment reversed these changes. In the high glucose-stimulated NRK-52E cells, sitagliptin and XAV939 inhibited the elevated expression of Wnt4, ß-catenin, dipeptidyl peptidase-4, α-smooth muscle actin, transforming growth factor-ß and fibronectin and restored E-cadherin activity. CONCLUSION: Sitagliptin may inhibit the tubulointerstitial Wnt/ß-catenin signalling pathway in diabetic nephropathy and provide renal protection by alleviatinge renal tubulointerstitial transdifferentiation and fibrosis.

Influence of Dipeptidyl Peptidase-IV Inhibitor Sitagliptin on Extracellular Signal-Regulated Kinases 1/2 Signaling in Rats with Diabetic Nephropathy.

The protective effects of sitagliptin on the kidneys of rats with diabetic nephropathy (DN) and its influence on extracellular signal-regulated kinases 1/2 (ERK1/2) signaling were investigated. Male Wistar rats (n = 40) were randomly assigned to normal control, DN, low-dose sitagliptin intervention (ST1), or high-dose sitagliptin intervention (ST2) groups. Animals were euthanized after a 16-week treatment, and blood glucose (BG), glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (AER), serum creatinine (Scr), creatinine clearance rate (Ccr), active glucagon-like peptide-1 (GLP-1) levels, kidney hypertrophy index, and renal pathohistology were determined. Immunohistochemical methods and real-time polymerase chain reaction (PCR) were used to detect protein and mRNA expression of podocalyxin, ERK1/2, GLP-1 receptor (GLP-1R) and transforming growth factor-ß (TGF-ß). After 16 weeks, BG, AER, Scr, HbA1c and the kidney hypertrophy index were all significantly decreased (p < 0.05) in ST1 and ST2 groups, while Ccr and active GLP-1 levels were increased (p < 0.05), with changes more pronounced in ST2 (p < 0.05). Glomerular pathological lesions were also improved following sitagliptin treatment, especially in ST2. Immunohistochemical and real-time PCR revealed that protein and mRNA expression levels of podocalyxin and GLP-1R were increased significantly in ST1 and ST2, while expression of ERK1/2 and TGF-ß was decreased (p < 0.05). Sitagliptin therefore delayed DN progression, possibly via the inhibition of ERK1/2 signaling and promotion of the interaction between GLP-1 and the GLP-1R.

The quality of life and associated factors in patients on maintenance hemodialysis - a multicenter study in Shanxi province.

OBJECTIVES: To assess the quality of life (QOL) and factors affecting QOL in hemodialysis patients so as to improve QOL of dialysis patients and provide the basis for better clinical care. METHODS: A retrospective study was performed to assess the QOL and factors affecting QOL in hemodialysis patients. We recruited 125 patients who had been receiving hemodialysis for at least 2 years in the dialysis units of nine hospitals in Shanxi Province, China, and conducted a multi-center questionnaire survey between 1 May 2015 and 1 July 2016. We investigated the patients' general condition and clinical data and used the Short Form-36 (SF-36) scale to measure QOL in these patients. RESULTS: The overall SF-36 score was 107.55 ± 14.50 in patients who had received hemodialysis for more than 2 years. Age (p < .05, F = 4.972) and gender (p < .01, t = 3.993) significantly affected the overall QOL score in these patients. Education level was also an influencing factor (p < .05, Z= -0.838), especially on the mental health of these patients. In addition, residual urine volume (p < .05, Z= -2.465) and diabetic nephropathy (p < .05, Z= -2.062) were important factors that affected the physical strength and QOL score in these patients. However, sources of medical expenses, marital status and different methods of dialysis, had no effect on the QOL score. CONCLUSION: The overall score of QOL in patients who have received maintenance hemodialysis for more than 2 years is higher in Shanxi Province than that in other provinces of China. Only a few factors influenced the QOL of these patients.

Study on Protection of Human Umbilical Vein Endothelial Cells from Amiodarone-Induced Damage by Intermedin through Activation of Wnt/ß-Catenin Signaling Pathway.

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti-inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone-induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone-induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone-induced endothelial cell apoptosis, improved amiodarone-induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/ß-catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/ß-catenin inhibitor IWR-1-endo, and si-RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone-induced endothelial injury via activating the Wnt/ß-catenin pathway. Thus, IMD could be used as a potential agent for the treatment of phlebitis.

Effectiveness and acceptance of acupuncture in patients with chronic low back pain: results of a prospective, randomized, controlled trial.

OBJECTIVE: To investigate the effectiveness of additional acupuncture in patients with chronic low back pain participating in an inpatient rehabilitation program. DESIGN: Patients were randomly assigned to one of two groups (A and B), both receiving a standard rehabilitation program according to German guidelines. Patients in group A additionally underwent acupuncture twice weekly, conducted by two Chinese physicians with education in Traditional Chinese Medicine (TCM). At the beginning and end of the program, as well as at 3 months after, patients completed questionnaires about health-related quality of life (Short-Form 36 Health Survey [SF-36]), sociodemographic and clinical data, attitude towards TCM, pain, and adverse events. SETTING: Inpatient rehabilitation clinic in Germany. PATIENTS: Patients with chronic low back pain participating in an inpatient rehabilitation program. OUTCOME MEASURES: Acceptance of acupuncture, health-related quality of life, and pain/symptoms. RESULTS: One hundred and forty-three patients were analyzed: 74 in group A (intervention) and 69 in group B (controls); 67% were men and 33% were women, with a mean age of 50.7 years. Acceptance of TCM was excellent: 89% of the patients would want TCM to be integrated into standard inpatient rehabilitation, and 83% would even have paid for TCM if necessary. Responses to SF-36 questionnaires showed that group A reported significantly better physical functioning, general health, vitality, and emotional role than group B. Pain outcomes in group A were superior to those in group B. Specifically, pain with sitting/standing, pain upon carrying loads of 10 kg or more, and prickling in hands and feet were significantly diminished. CONCLUSION: Acupuncture was highly accepted and had positive effects in patients with chronic low back pain. These results show that acupuncture can be an effective, well-tolerated therapy with no major adverse events.