MYCBP在原发性肝细胞癌中的变化与临床病理特征的关系及临床意义

目的 分析MYCBP在原发性肝细胞癌(HCC)中的变化与临床病理特征的关系及临床意义。方法 采用免疫组化法检测62例HCC患者术后肿瘤组织和癌旁组织中MYCBP相对含量(IRS评分),分析多个临床病理特征与无病生存期(DFS)、 MYCBP含量的关系。结果 肿瘤组织MYCBP的IRS评分明显高于癌旁组织(P<0.05)。MYCBP含量与病理分化程度、病灶数量、门静脉癌栓形成等临床病理特征相关(P<0.05)。MYCBP低含量组的术后DFS明显长于MYCBP高含量组(P<0.05)。结论 MYCBP含量在HCC中增加,并与某些临床病理指标及术后DFS存在关联,对HCC预后判断有一定临床意义。

An atypical ubiquitin ligase at the heart of neural development and programmed axon degeneration

The degeneration of nerve fibres following injury was first described by Augustus Waller over 170 years ago.Initially assumed to be a passive process,it is now evident that axons respond to insult via regulated cellular signaling events resulting in their programmed degeneration.Pro-survival and prodegenerative factors have been identified and their regulato ry mechanisms are beginning to emerge.The ubiquitin system has been implicated in the pro-degenerative process and a key component is the ubiquitin E3 ligase MYCBP2(also known as PHR1).Ubiquitin E3 ligases are tasked with the transfer of the small protein modifier ubiquitin to substrates and consist of hundreds of members.They can be classified as single subunit systems or as multi-subunit complexes.Their catalytic domains can also be assigned to three general architectures.Hints that MYCBP2 might not conform to these established formats came to light and it is now clear from biochemical and structural studies that MYCBP2 is indeed an outlier in terms of its modus operandi.Furthermore,the unconventional way in which MYCBP2 transfe rs ubiquitin to substrates has been linked to neurodevelopmental and pro-degenerative function.Herein,we will summarize these research developments relating to the unusual features of MYCBP2 and postulate therapeutic strategies that prevent Walle rian degeneration.These have exciting potential for providing relief from pathological neuropathies and neurodegenerative diseases.

microRNA-22在特发性肺动脉高压发病机制中的作用

目的研究血浆microRNA．22（miR一22）在特发性肺动脉高压（IPAH）诊断中的价值及发病机制中的作用。方法应用real-timePCR方法检测IPAH患者及匹配健康人血浆miR-22表达水平，结合生物信息学方法分析miR-22靶基因MYCBP，并采用eGFP报告基因对靶基因进行实验验证。结果IPAH患者血浆miR-22表达水平明显降低（P〈0．01），ROC曲线下面积（AUC）为0．744；生物信息学分析及eGFP报告基因验证，MYCBP是miR-22的靶基因之一。结论血浆miR-22在IPAH患者表达明显下调，可作为IPAH诊断分子标志物，miR-22通过靶基因MYCBP激活c—Myc信号通路，促进细胞增殖相关基因转录，是导致IPAH患者肺动脉中膜平滑肌增殖及肺血管重构的可能机制之一。