Xin Mou’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.

A stable hepatoma cell line(Hep G2 cell) insulin resistance model was established and used to analyze the effect of effective components of Mori Folium in alleviating insulin resistance,and preliminary explore the mechanism for alleviating insulin resistance. The Hep G2 insulin action concentration and the duration of action were investigated using the glucose oxidase method(GOD-POD method) to establish a stable Hep G2 insulin resistance model. Normal control group,model group,Mori Folium polysaccharide group,Mori Folium flavonoid group and rosiglitazone group were divided to determine the glucose consumption. The effect of Mori Folium effective components on Hep G2 insulin resistance was analyzed. The mRNA expressions of JNK,IRS-1 and PDX-1 in each group were detected by Real-time quantitative PCR(qRT-PCR). The protein expressions of p-JNK,IRS-1 and PDX-1 were detected by Western blot. And the mechanism of effective components of Mori Folium in alleviating insulin resistance was investigated. The results showed that the glucose consumption was significantly decreased in the insulin resistance cells after incubation with 25. 0 mg·L-1 insulin for 36 h(P<0. 01),and the model was relatively stable within 36 h. Mori Folium polysaccharides and flavonoids all alleviated insulin resistance,among which Mori Folium flavonoids had better effect in alleviating Hep G2 insulin resistance(P<0. 05). The qRT-PCR analysis showed that Mori Folium polysaccharides and flavonoids could inhibit JNK and IRS-1 mRNA expressions,while enhancing PDX-1 mRNA expression. Western blot analysis displayed that Mori Folium polysaccharides and flavonoids could inhibit p-JNK and IRS-1 protein expressions,while enhancing PDX-1 protein expression. Mori Folium polysaccharides and flavonoids can alleviate insulin resistance in Hep G2 cells,and its mechanism may be the alleviation of insulin resistance by inhibiting JNK signaling pathway.

The aim of the present study was to optimize flavonoid extraction from Chrysanthemum morifolium and to study the antitumor effects of flavonoids on human gastric cancer MKN45 cells in vitro. A single factor experiment was designed and the extraction process was optimized using an orthogonal test. MKN45 cells were treated with different concentrations of flavonoid from Chrysanthemum morifolium for 24 and 48 h and the inhibitory effect on the MKN45 cells was evaluated using an MTT assay. Following staining with Annexin V-fluorescein isothiocyanate/propidium iodide, flow cytometry was performed. The optimized flavonoid extraction conditions were as follows: Duration of ultrasonic treatment: 35 min; ethanol concentration: 75%; extraction temperature: 80°Cand liquid-to-solid ratio 25: 1. Under the above conditions, the extraction rate of flavonoids was 5.24%. When compared with a blank control group, flavonoids extracted from Chrysanthemum morifolium inhibited the proliferation of MKN45 cells in a dose- and time-dependent manner. Furthermore, in cell groups treated with low, moderate and high concentrations of flavonoid, it was observed that the proportion of apoptotic cells increased in a dose-dependent manner. The extraction process optimized by the orthogonal test achieved a high yield and satisfactory extraction efficiency. Additionally, the experiment demonstrated that flavonoids from Chrysanthemum morifolium inhibited the growth of MKN45 cells and induced their apoptosis. Thus, flavonoids from Chrysanthemum morifolium exerted antitumor effects on MKN45 cells, which may be exploited as a potential antitumor therapeutic for gastric cancer.

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.

Background: Abnormal expression of serum TGF-β1 was found in patients with diabetic nephropathy. However, the association of TGF-β1 with the risk of diabetic nephropathy remains unknown. The present study was undertaken to investigate whether such an association exists. Methods: We searched the Chinese VIP, Wangfang, China National Knowledge Infrastructure, PubMed, Embase, and Google Scholar databases for relevant studies and extracted all eligible data. Stata12 software was used for statistical analysis. Results: Nine reports met our criteria and were used for data extraction. There were 264 patients and 227 healthy controls from qualified reports in this meta-analysis. The results suggested that serum TGF-β1 levels were significantly up-regulated in patients with diabetic nephropathy; the instrumental variable was 3.94 (95% confidence interval 3.20-4.68, p<0.01). Conclusions: Meta-analysis suggested that elevated serum TGF-β level in patients with diabetes is associated with a high risk of nephropathy. Further studies are required to validate these observations.

PRISMA 2009 Checklist. (DOC)

Objective: To explore the Chinese medicine (CM) syndrome discipline in patients with antituberculosis drug (ATBD)-induced liver injury to provide the basis of the standard Chinese medicine treatment for the disease with latent variable analysis. Methods: Epidemiological investigation method was adopted. Two hundred and sixty-one patients with ATBD-induced liver injury were investigated using CM syndrome questionnaire. The syndrome types were determined with exploratory factor analysis (EFA), and the latent variables were analyzed by confirmatory factor analysis (CFA). Results: Totally 26 indexes related to CM syndrome differentiation were obtained from the 261 eligible cases, among them, 5 were as the latent dependent variables, which corresponded to 5 common syndrome types, including dampness encumbering the Spleen (Pi), Liver (Gan)-qi stagnation, Spleen and Stomach (Wei) deficiency, stasis-toxin accumulation, and qi-yin deficiency. CFA indicated that the indexes with loading coefficient [Symbol: see text]0.6 exactly reflected the connotation of its corresponding syndrome type. Conclusions: Five CM syndrome types are the most common in patients with ATBD-induced liver injury, which relate to their corresponding indexes for differentiation. It is feasible to apply combined EFA and CFA for explaination and measurement of the existence of CM syndrome under specific diseases.

Objective: To explore the relationship between Chinese medicine (CM) constitutive susceptibility and syndrome diversity in diabetic nephropathy (DN). Methods: Epidemiologic investigation on constitution adopting the "Constitution in Chinese Medicine Questionnaire" (CCMQ), and survey on syndrome type by CM syndrome scale (preliminary) were carried out in 180 DN patients. Cluster analysis on symptom items was used to determine the syndrome type, and canonical correlation analysis was used to analyze the relationship between patients' constitution and syndrome. Results: Baseline levels in all enrolled patients were not different statistically. Cluster analysis showed 8 syndromes existed in DN patients, namely: I, qi-yin deficiency with qi-stagnancy type; II, yin-yang deficiency with heat-water-blood stasis type; III, qi-yin deficiency with dampness-heat type; IV, yin-yang deficiency with blood-stasis and heat type; V, qi-yin deficiency with stagnant heat type; VI, yin-yang deficiency with inner dampness-heat stagnancy type; VII, yin deficiency with heat stagnancy type; and VIII, Kidney (Shen)-Spleen (Pi) deficiency with stagnant heat type. Correlation analysis on the 8 syndromes and the 9 constitutions showed statistical significant correlations between syndrome III and dampness-heat constitution (P=0.0001); syndrome IV and blood-stasis constitution (P=0.0001); and syndrome VII and yin-deficiency constitution (P=0.0180). Conclusion: Certain relationship revealed between CM constitutions and syndrome types; constitution decides the disease genesis, its syndrome type and prognosis, as well as the change of syndromes.

To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy (DN) and transforming growth factor (TGF)-β1 (T869C) gene polymorphism. TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was screened for 180 DN cases and 180 type 2 diabetic mellitus (T2DM) cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire (CCMQ). Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1 (T869C) gene polymorphisms. The DN group has a higher frequency of TGF-β1 (T869C) gene polymorphism than the T2DM group, and CC/CT genotypes than the T2DM group [CC, CT, TT (DN group): 88, 87, 5 (cases) versus (T2DM group) 71, 73, 36 (cases), P<0.05]. The phlegm-dampness constitution, damp-heat constitution, and blood stasis constitution have correlations with TGF-β1 (T869C) gene polymorphism. Chinese medicine constitutions were associated with TGF-β1 (T869C) gene polymorphism, a potential predictor of susceptibility to DN in T2DM patients.