BC047440基因在肝细胞癌中的表达及其意义

目的:探讨肝癌相关的新基因BC047440在肝细胞癌(HCC)中的表达及其病理学意义。方法：采用逆转录聚合酶链反应(RT-PCR)半定量检测36例HCC及其相应的癌旁肝组织中BC047440 mRNA的表达，并将该基因在HCC中的表达分为过高表达组及较高表达组，分析其与肿瘤病理变化的关系。〖KG(*8〗结果：36例HCC中BC047440基因mRNA的表达较癌旁肝组织高,其平均光密度比值分别为0.2594±0.0928和0.0942±0.0443,差异有极显著性意义（P<0.01）;过高表达组与较高表达组相比较，前者肝癌直径较大，门静脉受侵较严重，差异有显著性（P<0.05）。结论：BC047440基因与HCC的发生、发展和侵袭转移有关。     

JAK2/STAT3信号通路在肝细胞性肝癌中表达及意义

目的:探讨JAK2/STAT3信号通路在人肝细胞性肝癌(HCC)组织中的表达以及其意义。方法:用免疫组化法和Western blot法检测75例HCC组织及其相应的癌旁组织JAK2与STAT3蛋白的表达,分析两者与HCC患者病理特征及预后的关系。结果:JAK2与STAT3蛋白在HCC组织中的阳性表达率及表达量均高于相应的癌旁组织(62.7%vs.5.3%,69.3%vs.9.3%;均P0.05);JAK2与STAT3蛋白在HCC组织中的表达呈明显正相关(r=0.383,P0.01)。JAK2和STAT3蛋白的表达与肝硬化、门静脉癌栓、肿瘤分化程度、临床分期明显有关(均P0.05)。生存分析显示,JAK2与STAT3蛋白高表达患者的生存率及生存期均明显低于各自的低表达患者(χ2=13.591;χ2=6.842,均P0.05);Cox比例风险回归模型分析表明,JAK2与STAT3蛋白以及门静脉癌栓、肿瘤分化程度、临床分期均为影响HCC预后的独立危险因素(均P0.05)。结论:JAK2/STAT3信号通路在HCC组织中活性增高,且其活性高低与HCC患者预后密切相关。     

KAI-1基因在肝细胞癌中的表达及其临床意义

为研究KAI-1在肝细胞癌（HCC）中的表达及其与临床病理特征的关系，笔者对48例HCC手术切除的新鲜标本和10例正常肝组织经常规方法应用SABC免疫组化法，以KAI-1单克隆抗体对切片进行染色。检测KAI-1在HCC中的表达及其与临床病理特征的关系。结果显示 KAI-1在HCC癌组织中的阳性率为58.33%，明显低于癌旁及正常肝组织(P<0.05)，KAI-1在有转移与无转移HCC中的评分分别是1.76±1.51和2.90±1.82，前者明显低于后者(P<0.05)，而与其他临床病理特征无显著关系。提示KAI-1在HCC中的表达明显降低，且转移者明显低于不伴转移者。提示KAI-1可能抑制了HCC的发生发展和转移。     

TLR4/MyD88信号通路在膝骨关节炎滑膜炎中的作用

Toll样受体4是重要的固有免疫模式识别受体,通过识别损伤相关分子模式及病原相关分子模式,启动髓样分化因子 88依赖途径后激活NF-κB信号通路,引发炎性介质及细胞因子的分泌,触发固有免疫应答,在膝骨关节炎滑膜炎的发生中发挥作用。研究TLR4/MyD88信号通路在膝骨关节炎滑膜炎中的作用,以期更深入的阐明膝骨关节炎滑膜炎发病机制,为膝骨关节炎滑膜炎的诊疗提供理论依据和参考。     

肝细胞肝癌中p15基因产物的表达及其意义

用免疫组织化学方法 (SABC法 )检测p15基因在 5 3例肝细胞肝癌 (HCC )标本中的表达。p15基因阳性表达率为 64 .2 % ( 3 4/5 3 )。病理I ,II级p15阳性率明显高于III级 (均为P <0 .0 5 ) ;临床分期T1 ,T2 期p15阳性率均明显高于T3期 (均为P <0 .0 5 )与T4 期 (均为P <0 .0 1)。提示p15基因的异常表达在HCC的发生、发展中可能起重要作用 ;p15基因表达可以作为病程、预后判断的候选检测指标 ,对HCC的基因治疗有潜在的价值和意义。     

STAT3在食管鳞状细胞癌中的表达和意义

目的研究STAT3蛋白表达与食管鳞状细胞癌临床病理特征的关系,探讨其在食管癌变中的可能作用。方法应用免疫组织化学S-P法检测60例食管鳞状细胞癌及其癌旁组织中STAT3蛋白的表达,结合临床资料进行分析。结果STAT3蛋白阳性反应主要定位于胞质。食管鳞状细胞癌组织中STAT3蛋白表达阳性率86.7%(平均灰度值为36.05±13.74)明显高于正常组织阳性率17.6%(平均灰度值为16.92±5.43)(P<0.05)。STAT3蛋白在低分化、中分化、高分化鳞癌组的阳性表达率分别是100%、95%、73.08%,平均灰度值分别是51.22±7.09、42.18±7.21、23.16±6.94,3组间差异有统计学意义(P<0.01)。肿瘤分化程度越高STAT3蛋白表达越低。有淋巴细胞转移的食管癌组织中STAT3表达的阳性率100%(平均灰度值45.36±10.36),明显高于无淋巴细胞转移的食管癌组织阳性率78.38%(平均灰度值30.26±12.41)(P<0.05)。结论STAT3蛋白在食管鳞状细胞癌组织中的高表达可能与食管鳞癌的发生有关系。     

NF-κB在肝细胞癌组织中的表达及意义

目的：探讨NF-κB基因在肝细胞癌组织中的表达及生物学意义。方法：采用逆转录聚合酶链反应(RT-PCR)、Western-blot免疫组织化学技术检测32例肝癌组织及癌旁肝组织中的NF-κB基因的mRNA和蛋白表达水平及蛋白定位。结果：NF-κB基因在肝癌组织中的表达较癌旁肝组织显著性增高(P<0.05)。免疫组化结果显示，NF-κB蛋白在肝癌细胞胞浆和胞核中均有表达，而在癌旁肝细胞中仅在胞浆中有表达。结论：NF-κB基因在肝癌组织中呈显著高表达，提示其可能参与了肝癌的发生发展。NF-κB表达定位在癌细胞和癌旁肝细胞中的差异，提示NF-κB活化后，进入胞核，通过调节下游基因的转录，促进肝癌的发生。     

肝细胞癌组织中p16,p27蛋白的表达及其意义

为探讨p16,p2 7蛋白在肝细胞癌 (HCC )中的表达情况、相互关系及其临床病理学意义。笔者应用免疫组织化学方法 (SABC法 ) ,检测 49例HCC组织及癌旁组织中 p16,p2 7蛋白表达水平。结果示 49例HCC中 ,p16,p2 7蛋白阳性表达率分别为 3 6.73 %和 40 .82 % ;而癌旁组织阳性表达率为89 .80 %和 91.84%。p16蛋白表达与HCC的分化程度密切相关 (P <0 .0 5 ) ,高分化I～II级中p16阳性率为 5 5 .5 6% ,显著高于III～IV级的 2 5 .81%。p2 7蛋白表达与HCC有无淋巴结、远处转移有显著相关性 (P <0 .0 1)。提示 p16与p2 7蛋白的表达缺失在HCC发生中可能起重要作用。p2 7蛋白可作为衡量HCC预后的有用指标。     

TUSC3基因在肝细胞癌中的表达及其临床意义

目的:探讨TUSC3基因在肝细胞癌(HCC)中的表达及临床意义。方法:收集92例行肝切除术且术后病理证实为HCC患者的石蜡组织标本及其临床病理资料,用免疫组化法检测TUSC3在HCC组织及相对应癌旁组织中的表达,分析TUSC3的表达情况与HCC患者临床病理因素的关系;用qRT-PCR及Western blot方法检测20对冷冻HCC及癌旁组织中TUSC3 mRNA与蛋白的表达。结果:92例石蜡组织标本的免疫组化结果显示,56例(60.9%)HCC组织中TUSC3表达下调,癌旁组织中33例(35.9%)TUSC3表达下调,差异有统计学意义(P0.001);TUSC3在HCC组织中的低表达与肿瘤Edmondson分级(P=0.008)、TNM分期(P=0.031)、肿瘤直径有关(P=0.0 2 0)。20对新鲜标本的qRT-PCR与Western blot检测结果显示,肝癌组织中TUSC3的mRNA[(0.99±1.46)vs.(1.96±2.18)]与蛋白[(0.49±0.35)vs.(1.04±0.43)]相对表达量均明显低于癌旁组织(均P0.05)。结论:TUSC3基因在HCC中的表达下调,其低表达可能与HCC的恶性进程密切相关。     

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway

Objectives: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism.

Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors.

Results: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p?p?p?p?Conclusion: Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.     

MyD88依赖途径在膝骨关节炎进程中的基因表达相关性研究

目的 :探讨MyD88依赖途径的相关基因TLR4、NF-κB与MyD88在膝骨关节炎(osteoarthritis,OA)不同病程下大鼠滑膜组织的表达特点及相关性。方法:将60只Wistar大鼠随机分为6组:空白组(N)、假手术组(F)和模型组[2周组(2W)、4周组(4W)、8周组(8W)、12周组(12W)],每组各10只。各模型组以Hulth法建立大鼠膝OA动物模型,空白组不予手术,假手术组仅打开关节腔。按上述设计时间收集样本,经总RNA的提取及反转录后,用Realtime PCR法对各组滑膜组织中TLR4、NF-κB及MyD88的相对表达量进行检测,分析其相关性。结果 :假手术组各基因的mRNA表达与空白组相比差异均无统计学意义((P0.05);而各模型组较空白组各基因表达增强(P0.05)。相关性分析显示:MyD88与TLR4及NF-κB的mRNA相关性系数分别为0.91和0.86,差异有统计学意义(P0.05)。结论:MyD88与TLR4、NF-κB的表达均呈显著的正相关性,在通路上起重要的枢纽作用,可通过其表达预测通路上其他基因的表达情况,进一步明确膝OA病理机制。     

skp2,C-myc在肝细胞肝癌中的表达及其意义

目的研究skp2和C—myc在肝细胞肝癌组织中的表达及其与临床病理指标的关系。方法用免疫组化PV9000二步法检测skp2和C—myc蛋白在48例肝细胞肝癌、20例肝硬化患者和16例正常肝组织中的表达。结果肝细胞肝癌组织中skp2的阳性表达率（33．3％）显著高于肝硬化组织（均为阴性表达）（P=0．008）和正常肝组织（均为阴性表达）（P=0．020）。skp2在肝细胞肝癌中的表达与组织分化程度及转移有关（P〈0．001及P=0．017），但与肿瘤大小无关（P=0．058），skp2在高分化肝细胞肝癌中无表达。肝细胞癌组织中C—myc蛋白的的阳性表达率为58．3％，显著高于肝硬化组织的15％（P=0．001）和正常肝组织（阴性表达）（P〈0．001）。C—myc蛋白阳性表达与组织分化程度、转移及肿瘤大小有关，组间差异依次为P〈0．001，=0．023及=0．007。肝细胞癌中skp-2蛋白的表达与C—myc的表达呈正相关（r=0．508，P〈0．001）。结论C—myc可能与肝细胞肝癌的发生发展有关。Skp2的表达提示预后不良。C—myc可能对skp2的表达起正性调节作用。     

原发性肝癌中STAT1，STAT2与hMLH1，hMSH2的表达关

目的　探讨肝细胞癌中STAT1,STAT2与hMLH1,hMSH2的表达关系及意义。方法　利用SABC免疫组织化学方法检测 3 7例原发性肝癌及癌旁组织标本中的STAT1,STAT2,hMLH1,hMSH2蛋白的表达。结果　HCC组织中STAT1,STAT2 ( 2. 3 0±1. 8 1, 2. 4 9±2. 1 3 )和hMSH1,hMSH2 ( 2. 2 4±1. 7 7, 1. 6 5±1. 7 0 )蛋白阳性率和阳性信号显著低于癌旁肝组织 ( 3. 7 3±0. 9 9, 3. 6 2±1. 8 5, 3. 3 8±1. 3 2, 3. 30±1. 3 7 ) (P < 0. 0 5 ); 4种蛋白活性在癌组织的分化程度中高分化阳性表达 ( 4. 1 5±2. 4 5, 4. 35±2. 4 5, 3. 5 2±1. 7 3, 4. 3 9±1. 5 0 )显著高于低分化者 ( 1. 8 0±2. 2 0, 2. 0 3±2. 1 4,1. 78±1. 6 2, 1. 5 8±1. 8 4 ) (P< 0. 0 5 ),癌旁组织中STAT1与hMSH2,STAT2与hMLH1,hMSH2表达呈正相关 (P< 0. 0 5, P< 0. 0 1 )。结论　STAT1,STAT2和hMLH1,hMSH2均可能在细胞早期的恶性转化中起重要作用。     

Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects

BackgroundToll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet–induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure.ObjectivesTo explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes.SettingAnimal- based study.MethodWe performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions.ResultsWe demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients.ConclusionTLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.     

STAT3在小鼠胚胎肝脏的表达

目的　探讨STAT3在胚胎肝脏发育中的作用。方法　应用免疫组化技术观察STAT3在小鼠胚胎肝脏中期发育中的表达。结果　STAT3蛋白在E13.5d鼠胚肝脏中出现较强表达 ;在E14 .5d和E15 .5d鼠胚肝脏中的表达有所下降。结论　STAT3可能参与了胚胎肝脏中期发育的调控 ,并可能涉及胚胎肝脏的造血功能。     

Dispensable role of myeloid differentiation primary response gene 88 (MyD88) and MyD88-dependent toll-like receptors (TLRs) in a murine model of osteoarthritis

ObjectivesThe aim of our study was to evaluate the role of cell-membrane expressed TLRs and the signaling molecule MyD88 in a murine model of OA induced by knee menisectomy (surgical partial removal of the medial meniscus [MNX]).MethodsOA was induced in 8–10 weeks old C57Bl/6 wild-type (WT) female (n = 7) mice and in knockout (KO) TLR-1 (n = 7), -2 (n = 8), -4 (n = 9) -6 (n = 5), MyD88 (n = 8) mice by medial menisectomy, using the sham-operated contralateral knee as a control. Cartilage destruction and synovial inflammation were evaluated by knee joint histology using the OARSI scoring method. Apoptotic chondrocytes and cartilage metabolism (collagen II synthesis and MMP-mediated aggrecan degradation) were analyzed using immunohistochemistry.ResultsOperated knees exhibited OA features at 8 weeks post-surgery compared to sham-operated ones. In menisectomized TLR-1, -2, -4, and -6 deficient mice, cartilage lesions, synovial inflammation and cartilage metabolism were similar to that in operated WT mice. Accordingly, using the same approach, we found no significant protection in MyD88-deficient mice in terms of OA progression as compared to WT littermates.ConclusionsDeficiency of TLRs or their signalling molecule MyD88 did not impact on the severity of experimental OA. Our results demonstrate that MyD88-dependent TLRs are not involved in this murine OA model. Moreover, the dispensable role of MyD88, which is also an adaptor for IL-1 receptor signaling, suggests that IL-1 is not a key mediator in the development of OA. This latter hypothesis is strengthened by the lack of efficiency of IL-1β antagonist in the treatment of OA.