Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance

AIM： To study the expression of suppressor of cytokine signaling-1 （SOCS-1） in the liver tissues of chronic hepatitis 13 （CHB） and the clinical significance of this expression. METHODS： The expression of SOCS-1 in liver tissues of 45 cases of CHB was investigated by immunohistochemical staining, and its correlations with inflammation grades and fibrosis stage were analyzed by SPSS statistics software. RESULTS： The result showed SOCS-1 expressing could be observed in the liver tissue of CriB. The expression of SOCS-1 was mainly distributed near the portal area in the liver tissue of mild inflammation CriB group, and was diffusely distributed in the liver tissue of moderate and severe inflammation groups. SOCS-1 positive stains mainly appear in the hepatocytes, only a few of liver interstitial cells were involved. Inside the hepatocyte, SOCS-1 positive stains are mainly distributed in the plasma. Some of the staining was observed on the membrane. The inclusion bodies in the plasma of hepatocytes were observed occasionally. There were both obvious correlations between the expression of SOCS-1 and the inflammatory grade, and that between the expression of SOCS-1 and the fibrosis stage, CONCLUSION： The distribution of SOCS-1 in the liver tissue of CriB is variable. This expression was correlated with the inflammation grade and fibrosis stage.     

STAT-3在大肠癌和小肠癌中的表达及意义

目的检测大、小肠癌中信号转导与转录活化因子3（STAT-3）的表达情况并探讨其相关性。方法用免疫组化法分别检测36例小肠癌和20例癌旁正常小肠黏膜,60例结直肠癌和22例癌旁正常大肠黏膜中STAT-3的表达情况。用半定量方法对免疫组化染色评分,结合临床和病理数据进行分析。结果 STAT-3定位于细胞质和胞核,在大、小肠癌中表达较癌旁正常组织增高（P〈0.01）;STAT-3表达与肠癌组织分化程度、淋巴结转移和TNM分期相关;STAT-3在大、小肠癌中的表达呈正相关（r=0.849,P〈0.05）。结论 STAT-3在肠癌组织中过度表达并与其发生发展有关,可能参与了大、小肠癌恶化的调控。     

前列腺癌组织中Ob—R和STAT3的表达变化及意义

目的观察瘦素受体（Ob—R）及信号转导和转录激活因子3（STAT3）在前列腺癌（PCa）组织中的表达,并探讨其临床意义。方法采用免疫组化法检测41例Pea（PCa组）、22例前列腺上皮内瘤（PIN,PIN组）、25例良性前列腺增生（BPH,BPH组）组织中Ob—R和STAT3。结果在BPH、PIN和PCa组中,Pb—R阳性表达率分别为56．00％（14／25）、72．73％（16／22）、90．24％（37／41）,PCa组与BPH组比较,P〈0．01,余组间两两比较,P均〉0．05;STAT3阳性表达率分别为60．00％（15／25）、81．82％（18／22）、87．80％（36／41）,PCa组与BPH组比较,P〈0．01,余组间两两比较,P均〉0．05。Oh-R的表达与PCa病理分级、临床分期无关,STAT3的表达仅与PCa病理分级有关（P〈0．05）。0b—R与STAT3表达呈正相关（r=0．6897,P〈0．01）。结论PCa组织中0b—R和STAT3呈高表达。Ob—R和STAT3可作为判断PCa生物学行为的指标。     

STAT3、Cyclin D1在大鼠肝癌组织中的表达变化及意义

目的观察信号转导和转录活化因子3（STAT3）和细胞周期素D1（Cyclin D1）在大鼠肝癌组织中的表达变化,并探讨其意义。方法将72只大鼠随机分为模型组和对照组各36只,模型组自由饮用0.1 mg/mL的二乙基亚硝胺（DEN）溶液,对照组饮用等量灭菌蒸馏水,连续饮用20周。处死大鼠取癌组织,用RT-PCR法检测STAT3、Cyclin D1 mRNA,Western blot法和免疫组化法检测STAT3、Cyclin D1蛋白。结果对照组STAT3、Cyclin D1mRNA表达水平分别为0.32±0.12、0.18±0.05,模型组分别为0.72±0.25、0.57±0.15,P均〈0.05。Western blot法检测模型组STAT3、Cyclin D1蛋白表达量分别为0.58±0.25、0.65±0.14,对照组分别为0.32±0.19、0.41±0.15,P均〈0.05。免疫组化法检测模型组STAT3、Cyclin D1蛋白IOD分别为2 373.87±258.79、668.44±63.10,对照组分别为487.81±55.31和138.86±31.50,P均〈0.05。结论 STAT3、Cyclin D1在肝癌大鼠癌组织中表达上调,二者可促进肝癌的发生和发展。     

食管癌组织中STAT3通路相关调控基因的表达及临床意义

目的探讨转录信号传导子与激活子-3(Stat3)及CyclinD1、p53、c-fos在食管癌发生发展过程中的作用及意义。方法采用免疫组化方法检测100份食管癌组织及60份正常食管黏膜组织中Stat3、CyclinD1、p53及c-fos蛋白的表达情况。结果 Stat3蛋白在正常食管黏膜、食管癌组织中的阳性表达率分别为6.7%、94.0%,P<0.05;食管癌组织CyclinD1、p53、c-fos蛋白均明显高于正常食管组织(P<0.05)。Stat3与CyclinD1、p53、c-fos表达呈正相关(P<0.05)。结论 Stat3过度表达在食管癌发生发展过程中起重要作用;CyclinD1、p53、c-fos蛋白在调控食管癌癌变过程中可能起协同作用。     

宫颈鳞癌组织中pSTAT3、Cyclin D1、VEGF表达变化及意义

目的 观察宫颈鳞癌组织中磷酸化信号转导和转录激活因子3 （pSTAT3）、细胞周期素D1（Cyclin D1）及血管内皮生长因子（VEGF）蛋白的表达变化,并探讨其临床意义.方法 采用免疫组化SP法检测40例宫颈鳞癌（癌症组）、20例宫颈上皮内瘤变（CIN组）和15例正常宫颈鳞状上皮（对照组）组织中的pSTAT3、Cyclin D1和VEGF蛋白.结果 在癌症组及CIN组,pSTAT3过表达率分别为20.0％、62.5％ （P ＜0.05）,Cyclin D1过表达率分别为30.0％、72.5％ （P ＜0.05）,VEGF过表达率分别为40.0％、82.5％（P＜0.05）;对照组均无过表达者.pSTAT3、Cyclin D1蛋白过表达与宫颈鳞癌病理分级、临床分期及淋巴结转移有关（P均＜0.05）,VEGF蛋白过表达与宫颈鳞癌病理分级、淋巴结转移有关（P均＜0.05）.宫颈鳞癌组织中,pSTAT3与Cyclin D1及VEGF蛋白过表达呈正相关（r分别为0.531、0.618,P均＜0.05）.结论 宫颈鳞癌组织中pSTAT3、Cyclin D1及VEGF蛋白表达增高,三者共同参与了宫颈鳞癌的发生、发展.     

Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS)

The aim of this study was to evaluate the role of markers of bone remodelling, and osteoclast activation/function in patients with monoclonal gammopathy of undetermined significance (MGUS). We have measured serum levels of soluble RANKL (sRANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alpha), markers of bone resorption [N-telopeptide of collagen type-I (NTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)] and bone formation [bone-alkaline phosphatase (bALP)] in 40 MGUS patients. These parameters were compared with those of 42 newly diagnosed myeloma patients, and 45 healthy, gender- and age-matched controls. MGUS patients had elevated levels of NTX, sRANKL, and sRANKL/OPG ratio compared with controls (P < 0.0001). Furthermore, TRACP-5b, MIP-1alpha and NTX were decreased in patients with MGUS compared with myeloma patients (P < 0.001), while OPG and bALP were increased (P < 0.001). Serum levels of MIP-1alpha, as well as TRACP-5b, and sRANKL/OPG ratio were reduced, while bALP was increased in MGUS patients, even when compared with myeloma patients who had stage I/II disease. These results demonstrate that increased osteoclastogenesis leading to increased bone resorption is present in MGUS but seems to be compensated for by normal bone formation, which is absent in MM. Furthermore MIP-1alpha, bALP, and sRANKL/OPG may be useful tools for distinguishing between cases of MGUS and early myeloma.     

Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma

The role of serum macrophage inflammatory protein-1 alpha (MIP-1alpha) in bone disease and survival was evaluated in 85 newly diagnosed multiple myeloma (MM) patients. MIP-1alpha was elevated in MM patients and correlated with the extent of bone disease, bone resorption markers and levels of soluble receptor activator of nuclear factor-kappaB (RANK) ligand. MIP-1alpha was also associated with survival; the 3-year probability of survival was 85% and 44% for MIP-1alpha levels below and above 48 pg/ml respectively (P = 0.021). This suggests that MIP-1alpha contributes to the pathogenesis of bone disease in MM and possibly in tumour growth, as reflected by its impact on survival.     

JAK2/STAT3信号通路介导小鼠骨性关节炎中软骨细胞代谢和抗氧化应激的研究

目的 在小鼠骨性关节炎（OA）模型中观察Janus酪氨酸蛋白激酶2/信号转导子与转录激活子蛋白3（JAK2/STAT3）信号通路对软骨细胞代谢的影响以及线粒体抗氧化应激能力的改变,探讨JAK2/STAT3信号通路在此过程中的作用。方法 将10只C57BL/6小鼠随机分为两组,选择其中一组小鼠建立OA模型,3周后取材,培养软骨细胞作为实验组,其余小鼠正常培养细胞作为对照组。在对照组和实验组中分别加入JAK2/STAT3信号通路激动剂SC-39100,运用蛋白印迹法（Western blotting）检测各组细胞p-JAK2、p-STAT3、B淋巴细胞瘤?2（Bcl-2）蛋白和Bax蛋白的表达,同时检测各组线粒体氧化应激指标琥珀酸脱氢酶（SDH）、细胞色素c氧化酶（COX）、丙二醛（MDA）改变。结果 与对照组相比,OA模型组软骨细胞p-JAK2、p-STAT3、Bcl-2蛋白的表达偏低（P＜0.05）、Bax蛋白的表达水平偏高（P＜0.05）,且OA模型组软骨细胞SDH和COX的表达水平均偏低（P＜0.05）、MDA的含量偏高（P＜0.05）;当OA模型组加入SC-39100后,p-JAK2、p-STAT3、Bcl-2表达均较OA模型组升高（P＜0.05）、Bax蛋白表达下降（P＜0.05）,SDH和COX的表达水平均较OA模型组升高（P＜0.05）,MDA的含量较OA模型组降低（P＜0.05）;对照组中加入SC-39100后的各指标与加入SC-39100前比较,差异均无统计学意义（P＞0.05）;OA模型加入SC-39100组后的各指标与对照组加入SC-39100比较,差异均有统计学意义（P＜0.05）。结论 JAK2/STAT3信号通路和OA中软骨细胞变化密切相关,JAK2/STAT3信号通路激活后可抑制软骨细胞的凋亡;当激活的JAK2/STAT3信号通路活化时会增加软骨细胞线粒体抗氧化应激能力。     

STAT3在非小细胞肺癌患者外周血中的表达及其诊断价值初探

目的 通过检测信号转导及转录活化因子3 (STAT3)在非小细胞肺癌(NSCLC)患者外周血中的表达水平,探讨STAT3作为潜在肿瘤标志物对NSCLC的诊断价值.方法 采用Real time PCR 检测STAT3 mRNA、ELISA方法检测STAT3蛋白在NSCLC患者、肺良性疾病患者、正常人外周血中的表达;应用ROC曲线评价STAT3的诊断价值.结果 STAT3 mRNA、STAT3蛋白在肺癌组的表达水平高于肺良性疾病组及正常对照组(P ＜0.05或P＜0.01);STAT3 mRNA和STAT3蛋白的ROC曲线下面积(Az)分别为0.870、0.860,两者的Az比较,差异无统计学意义(P=0.500).结论 STAT3 在NSCLC患者外周血中呈异常高表达,其对NSCLC具有中等的诊断价值,有可能成为一种新的NSCLC相关标志物.     

沉默CDKN2B-AS1调控miR-98-5p、STAT3对高糖诱导的人脐静脉内皮细胞损伤的影响

目的]探讨细胞周期蛋白依赖性激酶抑制剂2B反义RNA 1(CDKN2B-AS1)是否通过靶向miR-98-5p影响高糖诱导的人脐静脉内皮细胞(HUVEC)损伤。 [方法]将HUVEC分为对照组(含5 mmol/L葡萄糖的DMEM培养)、模型组(含33.5 mmol/L葡萄糖的DMEM培养)、模型＋si-NC组、模型＋si-CDKN2B-AS1组、模型＋miR-NC组、模型＋miR-98-5p模拟物组、模型＋si-CDKN2B-AS1＋anti-miR-NC组、模型＋si-CDKN2B-AS1＋anti-miR-98-5p组。运用实时定量聚合酶链反应检测HUVEC的CDKN2B-AS1、miR-98-5p表达;Western blot检测信号转导及转录激活因子3(STAT3)蛋白表达;流式细胞术检测细胞凋亡;超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)、丙二醛(MDA)试剂盒检测SOD、LDH、MDA水平。双荧光素酶报告实验分析miR-98-5p与CDKN2B-AS1、STAT3的靶向结合。 [结果]高糖使HUVEC中CDKN2B-AS1、STAT3表达、凋亡率、LDH、MDA水平升高,miR-98-5p表达、SOD水平降低(P＜0.05)。沉默CDKN2B-AS1或过表达miR-98-5p后,高糖诱导的HUVEC中CDKN2B-AS1、STAT3表达、凋亡率、LDH、MDA水平降低,miR-98-5p表达、SOD水平升高(P＜0.05)。双荧光素酶报告实验显示,CDKN2B-AS1靶向miR-98-5p,miR-98-5p靶向STAT3。抑制miR-98-5p逆转了沉默CDKN2B-AS1对高糖诱导的HUVEC凋亡、氧化应激、STAT3蛋白表达的抑制作用。 [结论]沉默CDKN2B-AS1通过调节miR-98-5p/STAT3轴抑制高糖诱导的HUVEC氧化应激和凋亡,CDKN2B-AS1可作为糖尿病相关血管并发症的候选治疗靶标。