BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence ...BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.展开更多
背景新辅助治疗有助于进一步提高直肠癌患者的术后疗效,降低肿瘤复发率,改善患者生活质量.准确评估其疗效意义重大.超声造影(contrast-enhanced ultrasound,CEUS)作为一种能实时显示目标组织微循环状态的超声新技术,能为临床评估疗效提...背景新辅助治疗有助于进一步提高直肠癌患者的术后疗效,降低肿瘤复发率,改善患者生活质量.准确评估其疗效意义重大.超声造影(contrast-enhanced ultrasound,CEUS)作为一种能实时显示目标组织微循环状态的超声新技术,能为临床评估疗效提供可靠的血流动力学参考.目的探讨CEUS定量评估新辅助治疗后直肠癌的微循环血流灌注状态变化,及其与微血管密度(microvessel density,MVD)相关性.方法选取在我院行新辅助治疗的进展期直肠癌患者106例,所有患者于治疗前后行CEUS检查,测定病灶微循环血流灌注参数,并与手术后标本MVD进行比较分析.结果新辅助治疗后病灶最大直径较治疗前明显减少,差异有统计学意义(P<0.05);新辅助治疗后病灶曲线下面积(area under the curve,AUC)、峰值强度(peak intensity,PI)较治疗前明显下降,差异有统计学意义(P<0.05);新辅助治疗后病灶PI、AUC分别与MVD呈正相关(r=0.82,P<0.05;r=0.79,P<0.05).结论CEUS能客观反映直肠癌微循环血流灌注状态,其血流灌注参数与MVD有较好相关性,可为临床评估直肠癌新辅助治疗效果提供血流动力学参考.展开更多
基金Supported by Chongqing Fundamental Research Funds,No.jbky20210001Key Programs of Technological Innovation and Application Development of Chongqing,China,No.cstc2021jscx-dxwtBX0016+2 种基金Natural Science Foundation of Chongqing,No.cstc2021jcyjmsxmX0793Science and Technology Project in Social Livelihood of Bishan District,Chongqing,China,No.BSKJ0078 and No.BSKJ0075Performance Incentive-oriented Project of Chongqing,No.jxjl20220007。
文摘BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
文摘背景新辅助治疗有助于进一步提高直肠癌患者的术后疗效,降低肿瘤复发率,改善患者生活质量.准确评估其疗效意义重大.超声造影(contrast-enhanced ultrasound,CEUS)作为一种能实时显示目标组织微循环状态的超声新技术,能为临床评估疗效提供可靠的血流动力学参考.目的探讨CEUS定量评估新辅助治疗后直肠癌的微循环血流灌注状态变化,及其与微血管密度(microvessel density,MVD)相关性.方法选取在我院行新辅助治疗的进展期直肠癌患者106例,所有患者于治疗前后行CEUS检查,测定病灶微循环血流灌注参数,并与手术后标本MVD进行比较分析.结果新辅助治疗后病灶最大直径较治疗前明显减少,差异有统计学意义(P<0.05);新辅助治疗后病灶曲线下面积(area under the curve,AUC)、峰值强度(peak intensity,PI)较治疗前明显下降,差异有统计学意义(P<0.05);新辅助治疗后病灶PI、AUC分别与MVD呈正相关(r=0.82,P<0.05;r=0.79,P<0.05).结论CEUS能客观反映直肠癌微循环血流灌注状态,其血流灌注参数与MVD有较好相关性,可为临床评估直肠癌新辅助治疗效果提供血流动力学参考.
