Objective To evaluate the effect of Ji Tang Zhi on glucose metabolism in insulin resistance (IR) HepG 2 cell line,and to explore the related mechanism.Methods The HepG2 cells were incubated in culture medium addition of 10-7 mol/L insulin for 24 h to establish the IR cell model.Effect of Ji Tang Zhi on rate of glucose absorption in HepG2 cell was detected by the method of glucose oxidase-peroxidase (GOD-POD).We performed an MTT assay to determine cytotoxicity effects of Ji Tang Zhi on HepG2 cell line.The expression of p-IRS-1 Ser307,PI3K and GLUT-4 were detected by Western blotting.Results Incubated with 10-7 mol/L insulin for 24 h,the insulin resistance cell model had been built.Compared with model group,the rate of glucose absorption of cell treated with JTZ (30 ～ 120 μg/mL) was significantly improved.According to model cells,the expression of GLUT-4 and PI3K decreased significantly compared to control cells.While the expression of p-IRS-1 Ser 307 was inhibited and GLUT-4 and PI3K expression were increased in IR cells after treated with JTZ (30 ～ 120 μtg/mL).Conclusion JTZ exert beneficial effects on hyperglycosemia in IR cell line possibly through regulating the levels of GLUT-4,p-IRS-1 Ser307 and PI3K in HepG2 cell.

Objective To identify the effect of glucose regulating protein 75 expression in PC12 cells under glucose deprivation.Methods MTT method was used to monitor the cell viability.The leakage of LDH was represented as the index of cell injury.Flow cytometry was applied for cell cycle analysis,apoptosis and necrosis.Using RT-PCR detected and quantified mRNA.Western blot to measure relative amounts of the protein.Results Cell viability decreased and the LDH leakage increased.While the treated PC12 cells had two main forms of apoptosis and necrosis.GRP75 mRNA and protein levels were upregulated.Conclusion GRP75 has protective function during glucose deprivation.

Objective To investigate the genetic association between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)using bidirectional two-sample Mendelian randomization(MR),as well as the causal relationship between NAFLD and T2DM across different body mass index(BMI)categories.Methods The data were derived from genome-wide association studies conducted in European populations,with a sample size of 32 941 cases for NAFLD,312 646 cases for T2DM,and 681 275 cases for BMI.The univariate and multivariate MR methods were used to assess the bidirectional causal relationship between NAFLD and T2DM in the general population and across different BMI subtypes.The methods of inverse-variance weighting,MR-Egger regression,constrained maximum likelihood and model averaging,and weighted median were used to conduct the MR analysis,and MR-Pleiotropy Residual Sum and Outlier,radial MR,the MR-Egger intercept method,and the Cochrane Q test were used for sensitivity analysis.Results The univariate MR analysis revealed a bidirectional causal relationship between NAFLD and T2DM in the general population(forward analysis:odds ratio[OR]=9.75,95%confidence interval[CI]:2.57-37.00,P＜0.001;reverse analysis:OR=1.01,95%CI:1.00-1.01,P＜0.01).After adjustment for BMI,the multivariate MR analysis showed that the causal relationship between NAFLD and T2DM remained significant in the general population(OR=33.12,95%CI:7.57-144.95,P＜0.000 1).The subgroup analysis showed a causal relationship between NAFLD and T2DM across all BMI subtypes(lean subgroup:OR=12.19,95%CI:3.35-44.40,P＜0.001;overweight subgroup:OR=4.30,95%CI:1.69-10.92,P＜0.01;obese subgroup:OR=1.67,95%CI:1.14-2.44,P＜0.01).Conclusion This study reveals the causal relationship between NAFLD and T2DM in the general population of NAFLD and across different BMI subtypes from a genetic perspective.

Objective: To investigate the effects of retinoid-related orphan receptor γ (RORγ) gene on proliferation and metastasis of human colon cancer cells． Methods: RORγ knockdown cell lines were constructed and the knockdown efficiency was detected by RT-qPCR and Western blot assays ; MTT，colony formation，Transwell and wound healing assays were used to detect cell proliferation and metastasis ; the expression of epithelial-mesenchymal transition (EMT) related proteins was detected by Western blot．The relationship between RORγ gene expression and immune cell infiltration in tumor microenvironment was analyzed using TIMER 2. 0 database. Results : The knockdown of RORγ enhanced the viability (F = 157. 40，P＜0. 01) ，clonogenesis (F = 61. 35，P＜0. 01) ，migration (F = 13. 00，P＜0. 01) ，invasion (F = 21. 26，P＜0. 01) and wound healing ability (F = 877. 2，P＜0. 01) of colon cancer cells，inhibited the expression of E-Cadherin，and promoted the expression of vimentin and N-Cadherin．TIMER 2. 0 database analysis showed that RORγ expression in colon adenocarcinoma ( COAD) tissues was associated with multiple immune cell infiltrates． Conclusion Downregulation of RORγ expression promoted the proliferation and metastasis of colon cancer cells.