信号转导抑制因子-3与磷酸化信号转导转录活化因子-3在喉癌组织中的表达及与临床病理因素的关系

目的研究细胞因子信号转导抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)在喉鳞状细胞癌(LSCC)组织中的表达,并进一步探讨SOCS-3与磷酸化信号转导转录活化因子-3(phosphorylation signal transducer and activator of transcription 3,p-STAT3)的相关性及与喉癌临床病理因素的关系。方法收集2005年2月～2009年2月在白求恩国际和平医院耳鼻咽喉头颈外科接受手术的LSCC石蜡标本40例,并选取11例正常喉黏膜组织作为对照。采用免疫组化染色法检测SOCS-3、p-STAT3蛋白的表达情况。结果①LSCC组织中SCOS-3蛋白表达明显低于正常喉黏膜组织,两者之间差异具有统计学意义(P=0.000);p-STAT3蛋白在正常喉黏膜组织中的表达小于喉癌组织(P=0.000);②LSCC组织中SOCS-3与p-STAT3蛋白之间存在显著负相关(r=-0.459,P=0.003);③SOCS-3表达与患者年龄(P=0.223)、性别(P=0.849)、肿瘤T分级(P=0.193)无相关性,而与肿瘤病理分期(P=0.0 0 0),淋巴结转移(P=0.0 0 0)有关。结论①在喉正常黏膜组织中SOCS-3均呈阳性表达,而在LSCC组织中部分呈阳性表达;并与p-STAT3蛋白的表达情况呈负相关。提示SOCS-3可能在喉癌生长的过程通过抑制JAK/STAT3信号转导通路的持续活化从而抑制喉癌细胞增长,促进细胞凋亡;②SOCS-3的表达与患者年龄、性别、肿瘤T分级无相关性,而与喉癌病理分期及颈部淋巴结转移有关。

磷酸化蛋白50(EBP50)——一种新的抑癌蛋白

磷酸化蛋白50(ERM-binding phosphoprotein-50,EBP50)是由358个氨基酸组成的多功能连接蛋白.EBP50通过其PDZ-Ⅰ、PDZ-Ⅱ和ERM结合结构域与多种蛋白质结合,对PI3K/Akt、PLCβ等生长信号途径及对细胞迁移进行调控.目前有很多证据提示,ebp50是一种新的抑癌基因.在乳腺癌病人临床标本和细胞系中可检测到ebp50基因的杂合性丢失(LOH)和突变,其抑癌作用可能是通过它与多种抑癌蛋白(如抑癌蛋白PTEN、MERLIN和SYK)的相互作用并增强它们的稳定性,并与致癌蛋白结合从而抑制其致癌功能来达到的.通过对其分子结构、调控的信号途径及其与乳腺癌发生、发展的关系进行综述,为乳腺癌的防治提供新线索.

阿片类药物耐受机制的研究进展

以吗啡为代表的阿片类药物在治疗慢性疼痛病人时，可使机体对药物产生耐受与依赖。阿片类药物耐受性的形成涉及复杂的分子生物学机制。在受体水平，主要涉及u阿片受体；受体后机制则主要体现在神经细胞内信号转导途径的变化。

The roles of the proteasome pathway in signal transduction and neurodegenerative diseases

There are two degradation systems in mammalian cells, autophagy/lysosomal pathway and ubiquitin-proteasome pathway. Proteasome is consist of multiple protein subunits and plays important roles in degradation of short-lived cellular proteins. Recent studies reveal that proteasomal degradation system is also involved in signal transduction and regulation of various cellular functions. Dysfunction or dysregulation of proteasomal function may thus be an important pathogenic mechanism in certain neurological disorders. This paper reviews the biological functions of proteasome in signal transduction and its potential roles in neurodegenerative diseases.

The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling

Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons （IFNs） and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 （USP17） is required for virus-induced RIG-I- and melanoma differentiation-associated protein-5 （MDA5）-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly（I：C）- and poly（dA：dT）-induced activation of the IFN-β promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I- and MDA5-induced but not downstream activator-induced activation of the IFN-β promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.

Shafting misalignment fault diagnosis by means of motor speed signal and SVD-HT method

Aiming at the deficiency of diagnosis method based on vibration signal,a novel method based on speed signal with singular value decomposition and Hilbert transform(SVD-HT)is proposed.The fault diagnosis mechanism based on the speed signal is obtained by constructing the shaft misalignment fault model firstly.Then the SVD-HT method is applied to the processing of the speed signal.The accuracy of the SVD-HT method is verified by comparing the diagnosis results of the order spectrum method and the SVD-HT method.After that,the diagnosis results based on vibration signal and speed signal under no-load and load patterns are compared.Under the no-load pattern,the amplitudes of the speed signal components f_(r),2f_(r) and 4f_(r) are linear with the misalignment.In addition,under the load pattern,the amplitudes of the speed signal components f_(r),2f_(r) and 4f_(r) have a linear relationship with the load.However,the diagnosis result of the vibration signal does not have the above characteristics.The comparison results verify the robustness and reliability of the speed signal and SVD-HT method.The method presented in this paper provides a novel way for misalignment fault diagnosis.

Molecular variation and evolution of the tyrosine kinase domains of insulin receptor IRa and IRb genes in Cyprinidae

The insulin receptor （IR） gene plays an important role in regulating cell growth, differentiation and development. In the present study, DNA sequences of insulin receptor genes, IRa and IRb, were amplified and sequenced from 37 representative species of the Cyprinidae and from five outgroup species from non-cyprinid Cypriniformes. Based on coding sequences （CDS） of tyro- sine kinase regions of IRa and IRb, molecular evolution and phylogenetic relationships were analyzed to better understand the characteristics of IR gene divergence in the family Cyprinidae. 1Ra and IRb were clustered into one lineage in the gene tree of the IR gene family, reconstructed using the unweighted pair group method with arithmetic mean （UPGMA）. IRa and IRb have evolved into distinct genes after IR gene duplication in Cyprinidae. For each gene, molecular evolution analyses showed that there was no significant difference among different groups in the reconstructed maximum parsimony （MP） tree of Cyprinidae; IRa and 1Rb have been subjected to similar evolutionary pressure among different lineages. Although the amino acid sequences of IRa and IRb tyrosine kinase regions were highly conserved, our analyses showed that there were clear sequence variations between the tyrosine kinase regions of IRa and IRb proteins. This indicates that IRa and IRb proteins might play different roles in the insulin signaling pathway.