1.Impact of isoorientin on lipopolysaccharide-induced myocardial cell damage by regulating the HMGB1-RAGE signaling pathway
Journal of China Medical University 2025;54(8):727-732
Objective To investigate the effect of isoorientin(ISO)on lipopolysaccharide(LPS)-induced myocardial cell damage through regulation of the high-mobility group protein B1(HMGB1)receptor for the advanced glycation end-product(RAGE)signaling pathway.Methods H9c2 myocardial cells were incubated with LPS,and the cells were randomly assigned to an LPS induction group(Model group,1 μg/mL LPS),a low concentration ISO intervention group(ISO-L group,50 μmol/L ISO),a high concentration ISO interven-tion group(ISO-H group,100 μmol/L ISO),or a high concentration ISO+RAGE activator late glycation end-products(AGES)group(ISO-H+AGES group,100 μmol/L ISO+10 μg/mL AGES),with an additional control group(Control group).A cell counting kit 8 assay was used to determine the viability of the H9c2 cells.Flow cytometry was used to determine the rate of apoptosis of the H9c2 cells.An ELISA kit was used to determine the levels of oxidative stress-related factors,superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the H9c2 cells.ELISA method was also used to determine the levels of inflammatory factors,interleukin-1β(IL-1 β),tumor necrosis factor α(TNF-α),and lactate dehydrogenase(LDH)in the H9c2 cells.Western blotting was used to determine the expression levels of the HMGB1-RAGE signaling pathway and apoptosis-related proteins in the H9c2 cells.Results Compared with the Control group,the expression levels of optical density(OD)at 450 nm(48 h and 72 h),SOD,GSH-Px,and B-cell lymphoma-2(Bcl-2)proteins in the H9c2 cells in the Model group were significantly reduced(P<0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bcl-2 associated X protein(Bax),and cleaved caspase-3 proteins were significantly increased(P<0.05).Compared with the Model group,the expression levels of OD450(48 h and 72 h),SOD,GSH-Px,and Bcl-2 proteins in the H9c2 cells in the ISO-L and ISO-H groups were significantly increased(P<0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bax,and cleaved caspase-3 proteins were significantly decreased(P<0.05).AGES weakened the alleviating effect of ISO on LPS-induced H9c2 cell damage.Conclusion ISO alleviates LPS-induced myocardial cell damage by inhibiting excessive activation of the HMGB-RAGE signaling pathway.
2.Impact of isoorientin on lipopolysaccharide-induced myocardial cell damage by regulating the HMGB1-RAGE signaling pathway
Journal of China Medical University 2025;54(8):727-732
Objective To investigate the effect of isoorientin(ISO)on lipopolysaccharide(LPS)-induced myocardial cell damage through regulation of the high-mobility group protein B1(HMGB1)receptor for the advanced glycation end-product(RAGE)signaling pathway.Methods H9c2 myocardial cells were incubated with LPS,and the cells were randomly assigned to an LPS induction group(Model group,1 μg/mL LPS),a low concentration ISO intervention group(ISO-L group,50 μmol/L ISO),a high concentration ISO interven-tion group(ISO-H group,100 μmol/L ISO),or a high concentration ISO+RAGE activator late glycation end-products(AGES)group(ISO-H+AGES group,100 μmol/L ISO+10 μg/mL AGES),with an additional control group(Control group).A cell counting kit 8 assay was used to determine the viability of the H9c2 cells.Flow cytometry was used to determine the rate of apoptosis of the H9c2 cells.An ELISA kit was used to determine the levels of oxidative stress-related factors,superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the H9c2 cells.ELISA method was also used to determine the levels of inflammatory factors,interleukin-1β(IL-1 β),tumor necrosis factor α(TNF-α),and lactate dehydrogenase(LDH)in the H9c2 cells.Western blotting was used to determine the expression levels of the HMGB1-RAGE signaling pathway and apoptosis-related proteins in the H9c2 cells.Results Compared with the Control group,the expression levels of optical density(OD)at 450 nm(48 h and 72 h),SOD,GSH-Px,and B-cell lymphoma-2(Bcl-2)proteins in the H9c2 cells in the Model group were significantly reduced(P<0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bcl-2 associated X protein(Bax),and cleaved caspase-3 proteins were significantly increased(P<0.05).Compared with the Model group,the expression levels of OD450(48 h and 72 h),SOD,GSH-Px,and Bcl-2 proteins in the H9c2 cells in the ISO-L and ISO-H groups were significantly increased(P<0.05),and the apoptosis rate,MDA,IL-1β,TNF-α,and LDH levels,and the expression levels of HMGB1,RAGE,Bax,and cleaved caspase-3 proteins were significantly decreased(P<0.05).AGES weakened the alleviating effect of ISO on LPS-induced H9c2 cell damage.Conclusion ISO alleviates LPS-induced myocardial cell damage by inhibiting excessive activation of the HMGB-RAGE signaling pathway.
3.A comparative study of early warning score,blood glucose score and the two scores in predicting the prog-nosis of patients with acute diabetic complications
Xiaoyan LI ; Fanjie MENG ; Yulong DUAN ; Xuwei JIANG ; Min CHEN ; Yuna DU
The Journal of Practical Medicine 2018;34(3):397-400
Objective To compare the Modified Early Warning Score(MEWS),blood glucose value score and the two scores combined with the ability to predict the prognosis of patients with acute complication of diabetes mellitus,and to explore the most suitable assessment tools. Methods 419 patients with acute complica-tions were collected in diabetic mellitus. To put the admission time as the inital observation point,MEWS score, blood glucose value score and MEWS combined with blood glucose value were assessed and compared between the time point of admission and discharge by ROC curve.Results Using death as a prediction index,MEWS score of subjects operating characteristic area under the curve of AUCROC was 0.875 and the optimal cut-off value of was over 4 in the sensitivity of 78.43%,specificity of 85.60%,the positive predictive valueof 43.01% and the negative predictive value of 96.63% independently. The average score of blood glucose area under ROC curve AUCROC was 0.681 and the optimal cut-off value was 2 in the sensitivity of 50.98%,the specificity of 85.33% the positive predictive value of 73.4% and negative predictive value of 67.5% respectively. Two scores combined with area under ROC curve AUCROCwas 0.982,and the optimal cut-off value was over 7 in the sensitivity of 94.12%,the specificity of 95.65%,the positive predictive value of 75% and the negative predictive value of 99.15% individually. Conclusion For predicting the prognosis of patients with acute complications of diabetes,the combined scores are better than the pure MEWS score and blood glucose value.It is worth of clinical application.

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