日本血吸虫病患者γ干扰素及其受体检测意义

目的　研究γ干扰素 (IFNγ)及I型γ干扰素受体(IFNγR1)在慢性血吸虫病(慢血)及晚期血吸虫病(晚血)患者中表达水平,探讨IFNγ和IFNγR1表达的临床意义及其和肝纤维化的关系。　方法　用流式细胞术检测慢血及晚血患者外周血淋巴细胞IFNγR1的表达水平;用ELISA法检测慢血及晚血患者血清IFNγ水平;用放射免疫法检测血清中透明质酸(HA)、Ⅳ胶原(ⅣC)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)等肝纤维化指标。采用对比分析,观察IFNγR1、IFNγ及肝纤维化指标在慢血及晚血患者中的表达水平及相关性。　结果　慢血患者IFNγR1和IFNγ与健康对照组比较差异无显著性 (P>0.05);晚血未切脾患者IFNγR1表达明显低于其他组(P<0.05),而IFNγ增高(P<0.01);晚血切脾患者此两项指标又恢复正常;IFNγR1和IFNγ与HA、ⅣC、LN、PCⅢ之间无相关性(r分别为0.19、0.20、0.14、0.21)。结论　IFNγR1和IFNγ之间存在相互对应关系 ,IFNγR1的表达与血吸虫病的病程有关     

PPARγ激动剂对RSV感染的A549细胞TLR3、TNF-α表达的抑制作用

目的 探讨 A549细胞呼吸道合胞病毒（RSV）感染后Toll样受体3（TLR3）及肿瘤坏死因子-α（TNF-α） mRNA和蛋白表达及PPARγ激动剂15-脱氧前列腺素J2（15d-PGJ2）和罗格列酮的干预作用.方法 建立RSV感染的细胞模型,将传代培养的细胞随机分成6组：15d-PGJ2干预组（A）、罗格列酮干预组（B）、RSV组（C）、PDTC组（D）、GW9662组（E）及对照组（F）.各组在培养12、24和48 h后收获上清液和细胞,实时荧光RT-PCR检测TLR3和TNF-α mRNA表达,Western Blot检测TLR3蛋白表达,ELISA法检测上清中TNF-α蛋白水平.结果 与F组相比,各时间点C组TLR3和TNF-α mRNA及蛋白表达均明显升高（均P＜0.01）;与C组相比,A组、B组和D组TLR3和TNF-α mRNA及蛋白表达均明显降低（均P＜0.01）.15d-PGJ2和罗格列酮对TLR3和TNF-α mRNA和蛋白表达的抑制作用在12 h最明显;同一时间点A组和B组TLR3和TNF-α mRNA和蛋白的表达量均呈剂量依赖性下降.结论 RSV感染后TLR3和TNF-α mRNA及蛋白表达升高;罗格列酮和15d-PGJ2能以剂量依赖性方式抑制TLR3和TNF-α mRNA和蛋白表达.     

The synaptically evoked late hyperpolarisation in hippocampal CA1 pyramidal cells is resistant to intracellular EGTA

It has been suggested that the late hyperpolarisation following synaptic activation of hippocampal CA1 pyramidal neurons is activated by calcium influx. This hypothesis was examined using microelectrodes containing EGTA. Intracellular injection of EGTA blocked the afterhyperpolarisation which normally followed cell firing produced by injection of a depolarising current or the ionophoresis of glutamate onto the apical dendrites. In contrast, the hyperpolarisation following synaptic activation was resistant to EGTA. The results suggest that this potential is not dependent on intracellular Ca2+. Other possible mechanisms are discussed.     

健康体检者空腹血糖、胰岛素抵抗与血清谷氨酰转肽酶水平的相关性研究

目的 探讨健康体检者血清谷氨酰转肽酶（γ-GT）与FPG、IR间的关系. 方法 纳入793名健康体检者,根据FPG中位数5.42 mmol/L与胰岛素抵抗指数（HOMA-IR）中位数2.04,分为高FPG（HF）组和正常FPG（NF）组,IR组和IS组,比较各组γ-GT水平. 结果 HF、IR组γ-GT水平均高于NF、IS组（P＜0.01）.Spearman相关分析显示,γ-GT与FPG、FIns及HOMA-IR呈正相关.Logistic回归分析结果显示,FPG（OR=1.615,95％CI：1.208～2.158）、TG（OR=4.104,95％CI：2.650～6.357）、FIns（OR=2.866,95％CI：1.114～7.372）及饮酒情况（OR=3.068,95％CI：1.935～4.864）是γ-GT水平升高的危险因素. 结论 FPG、FIns与血清γ-GT水平相关,γ-GT可能成为T2DM发生风险的预测因素.     

Machine learning extracts oncogenic-specific γ-H2AX foci formation pattern upon genotoxic stress

H2AX is a histone H2A variant that becomes phosphorylated upon genotoxic stress. The phosphorylated H2AX (γ-H2AX) plays an antioncogenic role in the DNA damage response and its foci patterns are highly variable, in terms of intensities and sizes. However, whether characteristic γ-H2AX foci patterns are associated with oncogenesis (oncogenic-specific γ-H2AX foci patterns) remains unknown. We previously reported that a defect in the acetyltransferase activity of TIP60 promotes cancer cell growth in human cell lines. In this study, we compared γ-H2AX foci patterns between TIP60 wild-type cells and TIP60 HAT mutant cells by using machine learning. When focused solely on the intensity and size of γ-H2AX foci, we extracted the TIP60 HAT mutant-like oncogenic-specific γ-H2AX foci pattern among all datasets of γ-H2AX foci patterns. Furthermore, by using the dimensionality reduction method UMAP, we also observed TIP60 HAT mutant-like oncogenic-specific γ-H2AX foci patterns in TIP60 wild-type cells. In summary, we propose the existence of an oncogenic-specific γ-H2AX foci pattern and the importance of a machine learning approach to extract oncogenic signaling among the γ-H2AX foci variations.     

Human mast cells present antigen to autologous CD4+ T cells

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Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome

Metabolic syndrome is characterized by obesity, elevated blood pressure (BP), insulin resistance, and hypercholesterolemia. Recently an animal model of this disorder has been proposed in rats selectively bred based on their performance on a treadmill-running task. Accordingly, low capacity runner (LCR) rats exhibited all of the diagnostic criteria for metabolic syndrome, including elevated BP, as compared to their high capacity runner (HCR) counterparts [U. Wisløff, S.M. Najjar, O. Ellingsen, P.M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S.J. Lee, L.G. Koch, S.L. Britton, Cardiovascular risk factors emerge after artificial selection for low aerobic capacity, Science 307 (2005) 418–420]. Previous studies have highlighted the importance of GABAergic neurotransmission in the medullary cardiovascular-regulatory areas in the central control of BP. Thus, we hypothesized a dysregulation in GABAergic transmission in the medullary cardiovascular-regulatory nuclei of LCR rats. To begin testing this hypothesis we carried out experiments examining expression of the GABA synthetic enzymes, GAD65 and GAD67, mRNAs in the two rat strains via radioactive in situ hybridization. Our results showed GAD65 and GAD67 mRNAs were widely expressed throughout the brainstem; quantification revealed increased GAD65 mRNA expression in LCR animals in the caudal nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (VLM) as compared to HCR rats. Conversely, no differences in the expression of GAD67 were detected in these regions. These data are consistent with the notion of altered GABAergic neurotransmission in the NTS and VLM in metabolic syndrome, and point to the importance of these regions in cardiovascular regulation.     

SLE患者外周血IFN-γ水平与疾病活动性的相关研究

以IFN-γ为靶点,探讨它与SLE疾病活动性和肾脏损害的关系,从而探讨SLE的发病机制。32例SLE患者,根据活动指数评分,将病人分为活动期和稳定期两组。同时,按24 h尿蛋白定量等将SLE患者分为狼疮肾炎(lupus nephritis,LN)组和非肾炎组。另设健康志愿者为对照组。采用三色流式细胞术检测32例SLE患者外周血IFN-γ水平。流式细胞仪检测细胞培养后CD45+IFN-γ+的百分率情况;IFN-γ表达百分率在不同分组中表达:SLE活动组>SLE稳定组>对照组。在合并肾脏损害患者中,总淋巴细胞表达IFN-γ的阳性百分率:LN组>非LN组。IFN-γ水平与SLEDAI评分呈正相关(P<0.01)。表明IFN-γ水平增高与SLE疾病活动性呈正相关,建议可作为判断SLE疾病活动临床参考指标之一;抗Blys单抗下调IFN-γ的表达可作为检测该单抗干扰SLE免疫功能的靶点之一。