Yongbin Hu’s research while affiliated with Red Cross and other places

Aims To explore the protective efficacies and potent mechanism of amygdalin on high glucose-cultured renal cell HBZY-1 in vitro and streptozotocin (STZ)-induced diabetic nephropathy (DN) rat in vivo. Main methods The cellar proliferation and generation of ROS in high-glucose cultured HBZY-1 cell were assessed by MTT and DCFH-DA assay, respectively. The fasting blood glucose levels, renal function and inflammation indexes as well as oxidative stress markers in STZ-induced diabetic rats were all measured. The histologic renal section was stained with Mason and periodic acid-Schiff (PAS) method. Immunohistochemistry and western blotting methods were applied to assess expression levels of extracellular matrix (ECM), epithelial-mesenchymal transition (EMT)-related as well as TGF-β1/Smad signaling pathway-related proteins. Key findings Firstly, amygdalin significantly suppressed the excessive cell proliferation and ROS generation in HBZY-1 cells cultured with high glucose. The hyperglycemia, 24 h-UP excretion, BUN and Scr of DN rats were significantly attenuated after the chronic treatment of amygdalin. Moreover, MDA, SOD, IFN-γ and IL-12 levels in kidney tissues were all effectively reduced. Besides, amygdalin can suppress the ECM accumulation and EMT transformation by inhibiting Smad/TGF-β pathway to alleviate the renal fibrosis in renal tissues of DN model rats. Significance Amygdalin ameliorates excessive oxidative stress, inflammation and renal tissue fibrosis of DN mainly by suppressing TGF-β1/Smad signaling pathway and regulating the key enzymes of ECM degradation.

Objective Glucose-dependent insulinotropic polypeptide receptor (GIPR) has been identified as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). Therefore, we developed the anti-GIPR antagonistic monoclonal antibody (mAb) alone and in combination with DPP-4 inhibitor as potential therapeutic strategy for treating obesity and dyslipidemia based on this genetic evidence. Methods Fully neutralized GIPR activity of GIPR-monoclonal antibody (mAb) was assessed by regulating the in vitro production of cAMP in the mouse GIPR stably expressing cells. Chronic efficacies of GIPR-mAb alone and in combination with DPP-4 inhibitor Sitagliptin in diabetic or DIO mice were both investigated. Multiple metabolic parameters including body weight, glucose level, fat mass, lipid metabolism-related indicators as well as H&E staining and immunohistochemical analysis were performed. Role of GIPR in pancreatic cells on regulating fat metabolism was explored in GIPR β-cell knockout mouse model. Results Chronic treatment of GIPR-mAb improved body weight control, glucose metabolism, and was associated with reduced fat mass, enhanced pancreatic function and exchange ratio of the resting respiratory in diabetic mice. In addition, further study of anti-GIPR mAb combined with Sitagliptin in DIO mice demonstrated significantly improved weight loss compare to the both monomer treatment. Furthermore, we demonstrated important role of GIPR in β-cell in regulating the fat mass and response to antagonistic GIPR-mAb in a conditional GIPR-knockout mouse. Conclusion Chronic treatment with anti-GIPR mAb alone and combined with DPP-4 inhibitor provide preclinical therapeutic approaches to treat obesity.

Background: Thyrotoxicosis is commonly classified into several entities according to different etiologies. Identifying the causes of thyroid dysfunction is critical for the subsequent selection of treatment. The free triiodothyronine to free thyroxine ratio (fT3/fT4) is widely used but is still a controversial diagnostic measurement. Methods: A total of 290 patients including 141 healthy control subjects, 86 patients with untreated Graves' disease (GD,) and 63 patients with subacute thyroiditis (SAT) were enrolled in the study. The main aim was to evaluate the diagnostic value of different indexes from serum testing including fT3, fT4, eosinophils (Eo) and monocytes (Mo). The diagnostic performance of multiple indexes was evaluated separately using receiver operating characteristic curve analysis. Results: Sensitivities and specificities of fT4/fT3, Mo/Eo ratios and Mo/Eo ratio + fT4/fT3 for diagnosing GD were 80.23 and 88.89, 82.56 and 60.32, and 74.4 and 87.3 with cut-off values of ≤ 2.841, ≤ 8.813 and >0.644, respectively. An equation of combined indicators including Mo, Eo, fT3, and fT4 data was developed to calculate a probability value and among all indexes studied the indicator combination formula gave the best diagnostic value, reaching sensitivity and specificity of 89.53 and 90.48%, respectively, with an optimum cut-off value at 0.561 for GD diagnosis. Conclusion: Compared to regular indexes (fT4/fT3 and Mo/Eo), a newly developed indicator combination formula provided a higher prediction probability and may serve as a simple, cost-effective tool for differentiating GD from SAT patients, especially in undeveloped regions of China.

Background: Transforming growth factor-beta 1(TGF-β1) T869C (rs1800470, the same below) gene polymorphism is notably relative with the development of Diabetic Nephropathy (DN), and CC/CT genotype diabetic have higher frequency of than TT genotype diabetic. To find out individual risk factors in the two genotypes especially in susceptible genotype could provide more efficient and targeted prevention. Methods: This was a prospective cohort study. A total of 251 type 2 diabetes mellitus (T2DM) patients [53.4% male, 56(52–67) years] were enrolled in this cohort study. Multiple concerned factors were collected and the relationship of these risk factors and development of DN were evaluated by Cox regression analysis. Hazard ratios of development of DN were calculated by Kaplan-Meier curves and the Cox proportional hazards model for CC/CT genotype versus TT genotype patients. Results: TGF-β1 T869C gene polymorphism was an independent predictor of DN in T2DM patients (HR, 2.08; 95%CI, 1.18–3.66; P=0.012). Hyperlipemia (HR, 1.91; 95%CI, 1.19–3.08; P=0.007), age (HR, 0.95; 95%CI, 0.93–0.98; P=0.001) and smoking status (HR, 2.36; 95%CI, 1.07–5.21; P=0.033) were risk indictors of the development of DN in CC/CT genotype patients. HbA1c (HR, 2.8; 95%CI, 1.07–7.30; P=0.036), hypertension (HR, 7.46; 95%CI, 1.38–40.29; P=0.02), and hyperlipemia (HR, 12.33; 95%CI, 1.05–145.39; P=0.046) were risk indictors for the development of DN in TT genotype patients. Conclusion: TGF-β1 T869C gene polymorphism was an independent predictor of DN for T2DM patients and CC/CT genotype had higher susceptibility to DN. CC/CT genotype and TT genotype patients had different risk indictors of DN.