c-Abl stabilizes p73 by a phosphorylation-augmented interaction

The proapoptotic function of c-Abl is in part mediated by its functional interaction with p73, a p53 homologue. Although it has been shown that c-Abl-mediated p73 activation in response to genotoxic stress is associated with an increase of p73 protein levels, the underlying mechanism remains unclear. We show here that c-Abl increases the cellular p73 abundance through a mode of posttranslational regulation. Analogous to its functional activation of p73, the kinase activity is essential for c-Abl to up-regulate p73 protein levels. Analysis of phosphorylation-resistant mutants of p73 reveals that the effect of c-Abl is mediated by its direct phosphorylation on the p73 protein. Consequence to the phosphorylation is a marked increase of the association between c-Abl and p73 via the binding of tyrosine-phosphorylated p73 to the c-Abl Src homology 2 (SH2) domain. Of functional importance of this phosphorylation-induced interaction in p73 stabilization is the demonstration that expression of a c-Abl SH2 domain peptide, which impedes phosphorylation-dependent association, results in an almost complete abrogation of c-Abl-dependent p73 accumulation. Importantly, expression of the c-Abl SH2 domain peptide also leads to an efficient inhibition of cisplatin-induced accumulation of endogenous p73, highlighting the biological significance. In keeping with its retained phosphorylation sites, the NH(2)-terminal truncated (Delta N) isoforms of p73, which are antiapoptotic, are also phosphorylated and stabilized by c-Abl, suggesting a possibility that c-Abl contributes to either pro- or antiapoptotic process depending on the expression profile of p73 isoforms.     

BDNF对H2O2诱导人肺癌细胞YTMLC-90凋亡的抑制效应

背景与目的:已证实在神经系统内外多种细胞中均可合成神经营养因子,如神经生长因子(nerve growth factor,NGF)、脑源性神经营养因子(brain derivedneurotrophic factor,BDNF)和神经营养素3/4(NT-3/4).这些神经营养因子不仅能促进神经细胞的存活、增殖和凋亡,也与癌细胞侵犯神经组织的活性有关;但BDNF与肺癌细胞的生物学行为是否相关尚未见报道.本文旨在研究BDNF对过氧化氢(H2O2)诱导人肺癌细胞YTMLC-90凋亡的作用.方法:用含人Ⅰ型胶原al链(COLIA1)基因启动子和增强子元件及在其3′端接BDNF cDNA的微基因pSVCEPBFCAT,转染人肺癌细胞YTMLC-90并驱动BDNF异位表达,采用四甲基偶氮唑蓝(MTT)显色法检测细胞增殖,吖啶橙荧光染色显微镜和电镜观察细胞形态及其超微结构的改变,琼脂糖凝胶电泳检测染色质DNA断裂.结果:经200 μmol/L H2O2作用24 h,转染pSVCEPBFCAT的YTMLC-90细胞生长抑制率为30.0%,而未转染YTMLC-90和转染空载体pSVCEPCAT的YTMLC-90细胞生长抑制率分别为84.60%和80.00%,实验组与两个对照组之间的差异均有显著性(P＜0.01);对照组YTMLC-90细胞可见凋亡特有的形态学及生物化学改变,如胞浆和核固缩、染色质断裂、DNA电泳呈梯状条带,而转染pSVCEPBFCAT的YTMLC-90细胞未发现上述凋亡特征.结论:BDNF促进YTMLC-90细胞增殖和拮抗H2O2诱导凋亡,抑制H2O2对人肺癌细胞YTMLC-90的细胞毒性.     

食管内支架治疗恶性食管狭窄附8例临床分析

目的：用食管内支架治疗恶性食管狭窄。方法：对８例食管癌患者分别置入ＷＡＬＬＳＴＥＮＴ,ＳＴＲＥＣＫＥＲ ＳＴＥＮＴ及Ｚ－ＳＴＥＮＴ,共１０个支架。先用导丝探索通过狭窄段,经球囊扩张后置放支架。     

针刺与西药治疗肠易激综合征疗效对照观察

目的:比较针刺天枢、大肠俞为主与口服西药马来酸曲美布汀治疗肠易激综合征的疗效差异.方法:将40例患者随机分针刺组和西药组,每组20例.针刺组针刺天枢、大肠俞为主,采用子午捣臼法,每天1次;西药组口服马来酸曲美布汀胶囊,每次2粒,每日3次,两组均治疗4周后评定疗效.结果:两组患者治疗后腹痛时间、腹痛频率、排便形状异常比率、排便通过异常比率、黏液便比率、排便时腹胀或腹痛积分均较治疗前降低(均P＜0.01),且针刺组较西药组降低更显著(总积分:16.70±2.40 vs15.70±3.01,P＜0.01).针刺组总有效率为95.0%(19/20),优于西药组的70.0%(14/20)(P＜0.05).结论:针刺天枢、大肠俞为主可明显改善肠易激综合征患者的临床症状,其疗效优于口服西药马来酸曲美布汀.     

一种改良胚胎冻融法对冻融胚胎移植周期结局的影响

目的:探讨一种改良胚胎冻融法对冻融胚胎移植周期结局的影响。方法:回顾分析2003年1月～2008年6月,在本院生殖中心采用旧法冻融胚胎86个周期与改良法冻融胚胎95个周期胚胎的复苏存活率、胚胎完好率、周期妊娠率及胚胎种植率。结果:改良法冻融胚胎95个周期解冻胚胎248个,复苏存活率、胚胎完好率、周期妊娠率与胚胎种植率分别为93.1%、76.6%、38.9%和19.5%,均显著高于旧法冻融胚胎组(86个周期,解冻胚胎367个)的复苏存活率(53.4%)、胚胎完好率(12.8%)、周期妊娠率(20.9%)与胚胎种植率(9.7%),P<0.005。两种方法流产率差异无显著性(P>0.05)。结论:改良法冻融胚胎较旧法取得了更高的复苏胚胎存活率、胚胎完好率、周期妊娠率及胚胎种植率,达到国内较好中心水平,值得临床推广使用。     

Comprehensive profiling of phytochemicals in the fruits of Gardenia jasminoides Ellis and its variety using liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry

Journal of Natural Medicines - The fruits of Gardenia jasminoides Ellis are an important herb medicine in Traditional Chinese Medicine (TCM) and have been used for thousands of years for clearing...