The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administratio...The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.展开更多
目的:探讨盐酸特拉唑嗪联合抗生素治疗Ⅲ型前列腺炎的临床效果。方法:将86例Ⅲ型前列腺炎患者随机分为观察组和对照组,分别给予盐酸特拉唑嗪(2 m g,每晚1次)+左氧氟沙星(200 m g,2次/d)和左氧氟沙星(200 m g,2次/d)治疗,8周后观察慢性...目的:探讨盐酸特拉唑嗪联合抗生素治疗Ⅲ型前列腺炎的临床效果。方法:将86例Ⅲ型前列腺炎患者随机分为观察组和对照组,分别给予盐酸特拉唑嗪(2 m g,每晚1次)+左氧氟沙星(200 m g,2次/d)和左氧氟沙星(200 m g,2次/d)治疗,8周后观察慢性前列腺炎症状指数(N IH-CPS I)评分及前列腺液(EPS)常规。结果:经过8周的治疗,观察组和对照组的N IH-CPS I评分、EPS常规中白细胞数目均有显著下降,但观察组下降的程度均较对照组明显。结论:盐酸特拉唑嗪联合左氧氟沙星治疗Ⅲ型前列腺炎比单用左氧氟沙星疗效明显,值得临床推广。展开更多
目的探讨载脂蛋白(apolipoprotein,apo)AⅠ-CⅢ基因簇的apoAⅠ/MspⅠ和apoCⅢ/SstⅠ基因多态性在心脑血管疾病低发的云南德宏傣族人群中的分布情况。方法2002年4～5月在云南德宏和昆明两地随机抽样168名傣族和72名汉族人,提取基因组DNA...目的探讨载脂蛋白(apolipoprotein,apo)AⅠ-CⅢ基因簇的apoAⅠ/MspⅠ和apoCⅢ/SstⅠ基因多态性在心脑血管疾病低发的云南德宏傣族人群中的分布情况。方法2002年4～5月在云南德宏和昆明两地随机抽样168名傣族和72名汉族人,提取基因组DNA后,应用聚合酶链反应-限制性片段长度多态性(PCR-restriction fragment length polym orphism,PCR-RFLP)技术检测apoAⅠ-CⅢ基因簇中apoAⅠ启动子区MspⅠ多态性(-75bpG/A和+83bpC/T)和apoCⅢ3′端非编码区的SstⅠ多态性。结果apoAⅠ-CⅢ基因簇的apoAⅠ/MspⅠ和apoCⅢ/SstⅠ的等位基因M1+、M1-、M2+、M2-、S+、S-在傣汉两民族的分布频率依次为傣族:0.735、0.265、0.938、0.062、0.310、0.690;汉族:0.715、0.285、0.917、0.083、0.347、0.653。apoAⅠ-CⅢ基因簇的这6个等位基因频率在傣汉两民族间无统计学意义(P>0.05)。比较分析21个不同人群apoAⅠ/MspⅠ基因多态性和35个不同人群apoCⅢ/SstⅠ基因多态性的结果表明,德宏傣族人群apoAⅠ-CⅢ基因簇多态性分布与同属于蒙古人种的人群接近,而与高加索人种和尼格罗人种有较大的差异性。结论apoAⅠ-CⅢ基因簇的apoAⅠ基因启动子区-75bp和+83bp位点的基因多态性可能是德宏傣族人群心脑血管疾病患病率较低的重要遗传因素。而apoCⅢ的S+等位基因在该人群中并不是心脑血管疾病患病的易感因子。傣族人群具有较低的心脑血管疾病患病率应归因于遗传因素和环境因素协同作用的结果。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82073934,81872937,and 81673513).
文摘The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.
文摘目的:探讨盐酸特拉唑嗪联合抗生素治疗Ⅲ型前列腺炎的临床效果。方法:将86例Ⅲ型前列腺炎患者随机分为观察组和对照组,分别给予盐酸特拉唑嗪(2 m g,每晚1次)+左氧氟沙星(200 m g,2次/d)和左氧氟沙星(200 m g,2次/d)治疗,8周后观察慢性前列腺炎症状指数(N IH-CPS I)评分及前列腺液(EPS)常规。结果:经过8周的治疗,观察组和对照组的N IH-CPS I评分、EPS常规中白细胞数目均有显著下降,但观察组下降的程度均较对照组明显。结论:盐酸特拉唑嗪联合左氧氟沙星治疗Ⅲ型前列腺炎比单用左氧氟沙星疗效明显,值得临床推广。
文摘目的探讨载脂蛋白(apolipoprotein,apo)AⅠ-CⅢ基因簇的apoAⅠ/MspⅠ和apoCⅢ/SstⅠ基因多态性在心脑血管疾病低发的云南德宏傣族人群中的分布情况。方法2002年4～5月在云南德宏和昆明两地随机抽样168名傣族和72名汉族人,提取基因组DNA后,应用聚合酶链反应-限制性片段长度多态性(PCR-restriction fragment length polym orphism,PCR-RFLP)技术检测apoAⅠ-CⅢ基因簇中apoAⅠ启动子区MspⅠ多态性(-75bpG/A和+83bpC/T)和apoCⅢ3′端非编码区的SstⅠ多态性。结果apoAⅠ-CⅢ基因簇的apoAⅠ/MspⅠ和apoCⅢ/SstⅠ的等位基因M1+、M1-、M2+、M2-、S+、S-在傣汉两民族的分布频率依次为傣族:0.735、0.265、0.938、0.062、0.310、0.690;汉族:0.715、0.285、0.917、0.083、0.347、0.653。apoAⅠ-CⅢ基因簇的这6个等位基因频率在傣汉两民族间无统计学意义(P>0.05)。比较分析21个不同人群apoAⅠ/MspⅠ基因多态性和35个不同人群apoCⅢ/SstⅠ基因多态性的结果表明,德宏傣族人群apoAⅠ-CⅢ基因簇多态性分布与同属于蒙古人种的人群接近,而与高加索人种和尼格罗人种有较大的差异性。结论apoAⅠ-CⅢ基因簇的apoAⅠ基因启动子区-75bp和+83bp位点的基因多态性可能是德宏傣族人群心脑血管疾病患病率较低的重要遗传因素。而apoCⅢ的S+等位基因在该人群中并不是心脑血管疾病患病的易感因子。傣族人群具有较低的心脑血管疾病患病率应归因于遗传因素和环境因素协同作用的结果。
