Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.

Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.

Objective:To analyze the relationship of serum cartilage glycoprotein 39(YKL-40)and angiopoietin-like protein 3(ANGPTL3)with left ventricular dysfunction in elderly coronary heart disease(CHD)patients with heart failure(HF).Methods:The 84 elderly patients divided into group of CHD with HF, and 80 patients divided into group of CHD without HF treated in Shekou People's Hospital of Nanshan District, Shenzhen City from January 2018 to December 2019 were enrolled in this study.Evaluation of the left ventricular function meets the cardiac function classification standard of(NYHA). Serum YKL-40 and ANGPTL3 levels in all patients were detected.The relationships of serum YKL-40 and ANGPTL3 levels with the left ventricular dysfunction were analyzed in the two groups.Results:Serum levels of YKL-40 and ANGPTL3 were higher in the group of CHD with HF than in the group of CHD without HF[(81.24±6.32)μg/L vs.(69.33±5.89)μg/L, and(42.40±5.03)μg/L vs.(30.25±4.23)μg/L, t=12.469 and 16.700, both P<0.001]. Of 84 patients of CHD with HF assessed by NYHA heart function, 35 cases were in the mild group and 49 cases were in the severe group.Logistic regression analysis showed that the elevated serum level of serum YKL-40 and ANGPTL3 was positively correlated with the severity of left ventricular dysfunction in patients of CHD with heart failure( OR=1.548 and 1.854, P=0.002 and 0.001). The receiver operator characteristic(ROC)curve showed that the area under the ROC curve(AUC)of YKL-40, ANGPTL3 alone and the combined index in predicting left ventricular dysfunction in CHD with heart failure were >0.80, and the best predictive value could be obtained when the cut-off values of YKL-40 and ANGPTL3 were 79.535 μg/L and 40.805 μg/L, respectively. Conclusions:The elevated serum level of YKL-40 and ANGPTL3 may indicate the more severe left ventricular dysfunction in patients of CHD with heart failure.Early monitoring of serumYKL-40 and ANGPTL3 levels has an important clinical significance in guiding early prediction and intervention of left ventricular dysfunction in patients of CHD with heart failure.

Objective To investigate the inhibition of Hedyotic diffusa injection on the proliferation of hu-man osteosarcoma cell line MG -63 in vitro.Methods The human osteosarcoma cell line MG -63 was subcultivated aseptically in vitro.Different concentration of Hedyotic diffusa injection (50μL/mL,100μL/mL,200μL/mL,400μL/mL) successively acted on such cell .A total three time points were selected to determine the activity and numbers of cells by MTT assay including 12h,24h and 48h.Results The cellular proliferation inhibition rates of human osteosarcoma cell line MG-63 in drug groups of 50μL/mL concentration holes were (2.87 ±2.22)%,(13.42 ±2.14)% and (30.80 ±3.67)%after 12 h,24 h and 48 h.The rates of 100μL/mL concentration holes were (22.25 ±1.58)%, (43.34 ±2.84)%and (66.46 ±2.64)%,after 12 h,24 h and 48 h.The rates gradually increased and had statis-tical meaning,t12h =12.319,t24h =14.573,t48h =12.319,P<0.05;the cell in drug groups of 200μL/ml and 400μL/ml concentration holes was totally dead , and pathological findings showed that there were circular and floating cells in which nucleoplasmic ratio decreased and small fragments of cells increased .Conclusion Hedyotic diffusa extract has a certain inhibition in vitro on the proliferation of human osteosarcoma cell line MG -63.Moreover,the strength of its inhibition is relevant probably with drug concentration ,which deserves a further research .