1.Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CCl4-induced acute liver injury
Qinyu NI ; Jiacheng LIN ; Weifan HUANG ; Liu YANG ; Ran LI ; Tianzhi TU ; Guangfu HE ; Yueqiu GAO ; Xuehua SUN ; Xiaoni KONG ; Xiaojun ZHU
Liver Research 2024;8(4):269-281
Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.
2.A comparative study for Danielson procedure with and without prosthetic valve ring in treating Ebstein anomaly
Yi YANG ; Jianqun ZHANG ; Huili GAN ; Qinyu KONG ; Shenxun WANG ; Sihong ZHENG ; Ping BO ; Guohui HUANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(11):659-661
Objective To compare the results of Danielson procedure with and without prosthetic valve ring in treating Ebstein anomaly and to define the effect of prosthetic valve ring on the procedure.Methods From January 2006 to December 2009,31 cases of Ebstein anomaly over 10 years old were classified as type A or type B according the Carpentier's classification scheme.Patients were treated by Danielson procedure or Danielson procedure plus prosthetic valve ring at Anzhen hospital.They were retrospectively classified as Danielson procedure group (group A,n =19) and Danielson procedure plus prosthetic valve ring group (group B,n =12 ).Results There was 1 early in-hospital death due to lung infection and hypoxemia in group A,and no early death in group B ( Fisher exact test,P =0.51 ).The mean follow-up time was ( 23.0 ± 18.5 ) months (5 -41 months).The cumulative follow-up time was 59.42 patient-years.There was one late death in group A due to the redo tricuspid valve plastic procedure because of severe tricuspid regurgitation,and no late death in group B.With echocardiography inspection,11 patients had mild and 7 had moderate to severe tricuspid regurgitation in group A,and only 2 mild tricuspid regurgitation in group B.The tricuspid valve competence after surgery in group B was better than in group A ( Fisher exact test,P=0.024).The 6-minute walk distance test (6MWD) in group B was significantly better than in group A(415 ±41 )m vs ( 382 ± 46 ) m( t test,P =0.047 ).The New York heart functional class in group B was statistically better than in Group A ( P =0.024).Conclusion Although there was no significant difference in the early and late mortality rate between the two groups after surgery,Danielson procedure plus prosthetic valve ring was better than pure Danielson procedure in prevention of late tricuspid regurgitation recurrence,heart function and 6MWD test during follow-up.

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