A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.     

微小RNA-21在乳腺癌患者血清中的表达及其与临床病理特征的关系

目的 观察血清微小RNA(miRNA,miR)-214、miR-21和miR-195在乳腺癌患者和健康人血清中的表达,探讨这3个miRNA和乳腺癌的相关性.方法 收集40例乳腺癌患者和10例健康女性的血清,从血清中提取总RNA,应用实时荧光定量聚合酶链反应(FQ-PCR)技术检测这3个miRNA在两类人群中的表达.应用SPSS 21.0软件对血清中miRNAs的表达水平的差异采用Mann-Whitney U检验进行分析.结果 miR-21在乳腺癌患者血清中的表达量为0.120(0.043～0.299)和正常对照组血清中的表达量[0.011 (0.003 ～0.063)]比较显著上调(P＜0.01);且血清中miR-21与乳腺癌临床分期、淋巴结转移相关(P＜0.01).结论 血清miR-21和乳腺癌的临床病理特征明显相关.     

阿托伐他汀对心肌梗死后大鼠基质金属蛋白酶-2及微小RNA-21的作用

目的 观察阿托伐他汀对心肌梗死后大鼠基质金属蛋白酶(MMP)-2、微小RNA(miRNA,miR)-21表达的影响.方法 选取140只Wistar大鼠建立急性心肌梗死模型,分为假手术组、对照组、阿托伐他汀低剂量组和高剂量组,进行左室重量指数、心肌胶原容积分数、miRNA-21及MMP-2 mRNA表达测定.结果 阿托伐他汀治疗组左室重量指数、心肌胶原容积分数、梗死周边区miR-21 、MMP-2 mRNA的表达均降低(P＜0.05);各组梗死周边区miR-21表达量与MMP-2 mRNA水平呈正相关(r对照组=0.611,P＜0.05;r阿托伐他汀低剂量组=0.502,P＜0.05;r阿托伐他汀低剂量组=0.541,P＜0.05).结论 阿托伐他汀能降低梗死周边区MMP-2和miR-21的表达,发挥减轻心室重构的作用.     

Apoptosis and cell cycle arrest in oral lichen planus Hypothesis on their possible influence on its malignant transformation

The quantitative importance of cell cycle arrest and apoptosis mechanisms in oral lichen planus (OLP) was analysed in order to assess the cell response to T lymphocyte aggression and establish a hypothesis on the influence of these phenomena in the malignant transformation process. The TUNEL assay and immunohistochemical methods were used to detect caspase-3, bax, and p21 in 32 tissue samples of oral mucosa with OLP and in 20 samples of normal oral mucosa. Positivity for TUNEL, caspase-3 and p21 was significantly more frequent in cases than in controls (p<0.001). Both TUNEL and caspase-3 positivity was significantly greater in the basal versus suprabasal layer (p=0.004 and 0.052, respectively). The basal and suprabasal expression of p21 was significantly higher in cases with a more intense liquefaction degeneration (p<0.01). There was no significant difference in basal expression of bax between cases and controls. The quantitative importance of apoptosis was small in OLP. Epithelial cells attacked in OLP have a very low response to apoptosis and cell cycle arrest mechanisms, which may produce an epithelial substrate that favours malignant transformation.