紧密连接蛋白claudin-1对HCVcc易感性的影响

目的 利用HCV体外培养细胞模型,观察紧密连接蛋白claudin -1对于HCV易感性的影响.方法 构建pEGFP - claudin -1真核表达载体,脂质体转染293T细胞,观察claudin -1的表达,检测claudin -1对HCVcc感染性的影响;使用化学合成claudin -1 siRNA序列,抑制Huh -7.5细胞中claudin -1的表达,检测HCVcc感染性的变化.结果 293T细胞上外源性瞬时表达claudin -1后,获得对HCVcc的易感性,化学合成的siRNA序列可有效抑制Huh -7.5细胞上的claudin -1的表达,阻断HCVcc对Huh -7.5细胞的感染.结论 紧密连接蛋白claudin -1影响细胞对HCV的易感性,可能与HCV的嗜肝性有关.     

广东籍汉族人系统性红斑狼疮的易感性与补体C4零基因相关分析

目的 分析广东籍汉族人系统性红斑狼疮的易感性与补体Ｃ４零基因相关性。方法 采用国际参考实验室的方法及计算机凝胶图像光密度分析系统检测４５例广东籍汉族ＳＬＥ患者和７８例广东籍汉族正常人的Ｃ４同种异型，特别是Ｃ４＊Ｑ０基因。结果 ＳＬＥ患者组Ｃ４Ａ＊Ｑ０（０．２１９８）和Ｃ４Ｂ＊Ｑ０（０．２１９８）基因频率明显高于正常对照组Ｃ４Ａ＊Ｑ０（０．０４４９）和Ｃ４Ｂ＊Ｑ０（０．０５７７）（Ｐｃｏｒｒ〈０．０     

C型凝集素受体在寄生虫感染免疫调节中的作用

C型凝集素(C-type lectin)是一类钙依赖性糖结合蛋白,其受体依赖钙离子(Ca2+)的参与来识别碳水化合物配体。目前研究发现,该类受体可识别糖蛋白并激活下游免疫。本文总结了数种C型凝集素受体在寄生虫感染中的作用。     

甘露糖结合凝集素基因多态性与肺结核易感性关系的研究

目的研究甘露糖结合凝集素基因(MBL2)多态性与肺结核易感性的关系。方法采用PCR限制性片段长度多态性(PCR-RFLP)对112例肺结核患者和120例健康对照DNA样本中MBL2-221位点和外显子区54号位点进行基因分型。结果肺结核病人和健康对照-221各基因位点之间有显著性差异(P0.05)。在MBL2 6个单倍体型中,YA/YA基因型在肺结核病人和健康对照的比例分别为35.7%和49.2%,两者差异有统计学意义(P=0.038,OR值:0.57),XA/XA基因型则分别9.8%和1.7%(P=0.007,OR值:6.42),两者有显著性差异。肺结核病人-221位点和外显子区54号位点基因多态性除在不同年龄之间,初治与复治之间有显著性差异(P0.05)外,其余临床特征与各位点基因多态性无关(P0.05)。结论 YA/YA单倍体型可能是一种保护基因型,MBL基因多态性可能与肺结核易感性有关,并与肺结核病人复发等相关。     

CLEC4M与丙型肝炎病毒感染的研究进展

丙型肝炎病毒(HCV)是导致肝硬化、原发性肝癌的主要致病因素,全世界超过1.7亿人感染,丙型肝炎病毒携带者污染的血液是HCV感染的主要危险因素,大多数感染者不能清除病毒,最终发展成为慢性肝病,肝纤维化、肝硬化和原发性肝癌.     

凝集素样受体巨噬细胞诱导性C型凝集素样受体在类风湿关节炎患者巨噬/树突状细胞中表达及其临床意义

目的 研究巨噬细胞诱导性C型凝集素样受体(MINCLE)在健康者、类风湿关节炎(RA)和骨关节炎患者外周血及关节滑液中的表达特征,探讨其与RA发病的相关性.方法 ①采用实时定量聚合酶链反应(PCR)方法在mRNA水平检测RA患者(253例)及健康人(71名)外周血单个核细胞(PBMC)中MINCLE的表达;②采用流式细胞术在蛋白水平检测RA患者(18例)、骨关节炎患者(5例)及健康人(12名)外周血及关节滑液巨噬细胞、髓样树突状细胞(mDC)和浆细胞样树突状细胞(pDC)中MINCLE的表达;采用Mann-Whitney U检验或配对t检验统计分析MINCLE在健康者、骨关节炎患者和RA患者外周血及关节滑液之间的表达差异.结果 ①在mRNA水平,外周血PBMC中RA患者的MINCLE表达达高于健康对照组[(1.65±0.36)和(0.37±0.06),U=6057,P=2.75×10-5];②在蛋白水平,健康人及骨关节炎患者外周血巨噬细胞、mDC及pDC中未见MINCLE的表达;在骨关节炎关节滑液中,MINCLE仅低水平表达于mDC[(7.5±2.9)%]中,而MINCLE在RA患者关节滑液mDC中呈高表达[(34.8±4.4)%,U=0,P=2.6×10-3];MINCLE在RA患者的滑液巨噬细胞及mDC的表达均明显高于其在相对应的外周血中的水平[巨噬细胞(2.01±0.53)%和(0.27±0.51)%,t=4.879.P=2.23×10-6;mDC为(34.8±4.4)%和(21.7±5.5)%,t=2.535,P=0.017].结论 MINCLE的表达特征具有RA组织特异性,MINCLE很可能为RA发病的一个重要标记物.

Abstract：

Objective To determine the expression pattern of macrophage-inducible c-type lectin (MINCLE)on Macrophage(Mφ),myeloid dendritic cell (mDC)and plasmacytoid DC(pDC)in peripheral blood (PB)and synovial fluid(SF)in patients with rheumatoid arthritis (RA).Methods For mRNA expression of MINCLE,253 RA patients and 71 healthy control subjects were enrolled.The mRNA level of MINCLE was determined by real-time PCR.For protein expression of MINCLE,18 patients with RA,5 patients with osteoarthritis(OA)and 12 healthy control subjects were enrolled.The expression of MINCLE on Mφ,mDC and pDC were detected by flow cytometry.The differences of MINCLE expressions in PB between RA patients,OA patients and healthy controls,or differences between PB and SF in RA patients were analyzed using Mann-Whitney U test or paired-samples t test.Results ①Compared to the healthy controls,RA patients showed elevated mRNA expression level of MINCLE in PBMCs[(1.65±0.36)vs (0.37±0.06),U=6057,P=2.75×10-5].②At protein level,MINCLE was hardly detected in Mφ,mDC and pDC in PB of OA patients and healthy controls.In SF,MINCLE was highiy expressed on mDC in RA patients,compared with that in OA patients[(34.8±4.4)%,U=0,P=2.6×10-3].In RA patients,the expression level of MINCLE was remarkably elevated in Mφ,mDC and pDC in SF compared with that in PB[Mφ(2.01±0.53)%vs(0.273±0.51)%,t=4.879,P=2.23×10-6;mDC(34.8±4.4)%vs(22.7±5.5)%t=2.535.P=0.017].Conclusion MINCLE is selectively expressed on Mφ.mDC and pDC in SF in RA patients.MINCLE may serve as a potential important marker,or even target,for RA and possibly even for inflammation in general.     

甘露糖结合凝集素基因多态性与结核易感性关系的荟萃分析

目的综合评价甘露糖结合凝集素(mannose-bindinglectin,MBL)基因多态性与结核易感性关系。方法通过计算机检索中国知网、维普、万方、Pub Med、EMBASE、Web of Science、Cochrane图书馆截止2013年3月国内外公开发表的有关甘露糖结合凝集素基因多态性与结核易感性关系的相关文献。按Cochrane系统评价方法,采用Stata11.0进行Meta分析。结果入选21项病例对照研究包括4161例患者及4955例正常对照者,Meta分析结果显示等位基因模型(OR 0.88,95%CI 0.67~1.16),共显性模型OO vs.AA(OR 1.39,95%CI 0.80~2.41);AO vs.AA(OR 1.11,95%CI 0.90~1.38)隐形基因模型:(OR 1.36,95%CI 0.88~2.10),显性基因模型(OR 1.13,95%CI 0.89~1.44),总体上,MBL基因多态性与肺结核易感性无显著关联性,但按人种进行亚组分析显示,MBL多态性明显增加了亚洲人群的结核易感性(OO+AO/AA:OR 1.27 95%CI 1.03~1.56),但未发现与高加索人群、非洲人群相关。结论 MBL基因多态性增加了亚洲人群结核病易感性。     

CLEC4L在人胎盘组织及滋养层细胞的分布与定位

目的细胞间黏附分子非整合素蛋白3(human C-type lectin domain family 4,memberL,CLEC4L)为主要分布在树突状细胞(DC)表面的一个外源性凝集素超家族分子,通过依赖Ca2+的碳水化合物识别区域(CRD)形成寡聚糖,增强与抗原的结合能力。CLEC4L作为丙型肝炎病毒(HCV)受体,对HCV感染和传播起重要作用。本研究旨在明确人胎盘组织及胎盘滋养层细胞中CLEC4L的分布与定位。方法免疫组织化学方法检测CLEC4L在人滋养层细胞内定位以证明CLEC4L的存在,同时免疫组织化学单染及荧光双染法检测不同孕期正常胎盘组织CLEC4L定位与表达。结果人胎盘滋养层细胞中检测到CLEC4L表达,主要分布于滋养层细胞表面;同样在早孕期的绒毛及足月胎盘中均检出CLEC4L的表达,但在足月胎盘中的表达明显低于早孕期的绒毛组织。结论实验显示不同孕期胎盘组织均可见CLEC4L的表达,其在孕早期表达较高。滋养层细胞上该受体可能与HCV胎盘宫内感染有关。     

姜黄素对Kvl．4钾通道C型失活的影响

目的 研究姜黄素对去N端Kv1.4(Kv1.4△N)通道C型失活特性的影响.方法 将Kv1.4△N的mR-NA注射入非洲爪蟾卵母细胞并于18～20℃下孵育,成功表达后使用双微电极钳制法记录电流,观察姜黄素对Kv1.4△N电流失活、复活的影响.结果 ①姜黄素对Kv1.4△N峰电流的抑制作用呈电压依赖性.②姜黄素对Kv1.4△N通道失活速度无明显影响.姜黄素灌流前后失活时间常数变化不大(2 765±118 ms vs 2 513±193 ms,n=5,P＞0.05).③通道失活后的恢复时间延长.结论 姜黄素抑制钾电流并延长其恢复时间,但对稳态失活并无明显影响.其机制可能与它对通道的开放状态比失活态有更高的亲和力有关.     

甘露糖结合凝集素(M B L)基因多态性与中国汉族肺结核易感性的研究

背景:MBL基因据认为在人类抗结核(TB)感染天然免疫应答中发挥作用.目的:探讨MBL基因多态性与中国汉族人群结核感染关联的可能性.设计:共有152名男性肺结核病人和293名健康男性对照纳入本研究.联合应用引物序列特异性PCR(PCR-SSP)和序列特异性寡核苷酸探针杂交(PCR-SSOP)方法对MBL基因六个单核苷酸多态性(SNPs)位点(A/B,A/C,A/O,H/L,Y/X和P/Q)进行基因型或单倍体型在病例组和对照组的分布进行比较,并进行非条件logistic回归分析.结果:当单独考虑时,5个位点的基因型和单倍体型与发病均无显著相关.然而,当重新分组后,和YA组相比,编码低水平MBL的XB单倍体组在病例组中有很高的出现频率(OR=1.57,95%CI:1.02-2.41,P＜0.05)结论:虽然低水平XB单倍型组在中国汉族人群肺结核感染中为一较弱的危险因素,但MBL多态性和肺结核之间的关联没有观察到令人信服的证据.     

白细胞介素4和受体基因多态性与乙型肝炎肝硬化易感性的关系

目的：探讨白细胞介素4（IL-4）及受体（IL-4R）基因多态性与乙型肝炎肝硬化易感性的关系。方法：应用聚合酶链反应．限制性片断长度多态性（PCR—RFLP）分析方法，检测124例健康人群和100例乙型肝炎肝硬化患者IL-4基因启动区．589C／T及IL-4Rα链576位点谷氨酰胺／精氨酸（Q／R）这两个多态性位点，确定其基因型和等位基因频率的分布。结果：肝硬化组与对照组IL-4-589C／T位点其基因型和等位基因频率差异无显著性意义（P〉0．05），而肝硬化组IL-4Rα仅576R中RR基因型和R576等位基因频率与对照组相比差异具有显著性意义（P〈0．05，P〈0．01），Q等位基因相对于R等位基因患肝硬化的机会比为0．569（95％CI：0．332～0．963）。结论：IL-4Rα亚单位Q576R与乙型肝炎肝硬化易感有关，RR基因型携带者肝硬化易感性高，而IL-4—589位点基因多态性与乙型肝炎肝硬化无相关性。     

Toxic effects of Microgramma vacciniifolia rhizome lectin on Artemia salina, human cells,and the schistosomiasis vector Biomphalaria glabrata

The present study evaluated the toxicity of Microgramma vacciniifolia rhizome lectin (MvRL) to Artemia salina, human tumour cell lines (larynx epidermoid carcinoma Hep-2, NCI-H292 lung mucoepidermoid carcinoma, and chronic myelocytic leukaemia K562), and normal peripheral blood mononuclear cells (PBMCs), as well as to Biomphalaria glabrata embryos and adults. MvRL was toxic to A. salina (LC₅₀ = 159.9 μg/mL), and exerted cytotoxic effects on NCI-H292 cells (IC₅₀ = 25.23 μg/mL). The lectin (1–100 μg/mL) did not affect the viability of K562 and Hep-2 tumour cells, as well as of PBMCs. MvRL concentration of 1, 10, and 100 μg/mL promoted malformations (mainly exogastrulation) in 7.8%, 22.5%, and 27.7% of embryos, respectively, as well as delayed embryo development in 42.0%, 69.5%, and 54.7% of embryos, respectively. MvRL at a concentration of 100 μg/mL killed B. glabrata embryos (17.7%) and adults (25%). Further, MvRL damaged B. glabrata reproductive processes, which was evidenced by observations that snails exposed to the lectin (100 μg/mL) deposited fewer eggs than those in the control group, and approximately 40% of the deposited eggs exhibited malformations. Comparison of these results with that from A. salina assay indicates that MvRL is adulticidal at the concentration range which is toxic to environment. In conclusion, the cytotoxicity of MvRL on tumour cell and absence of toxicity to normal cell indicate its potential as chemotherapeutic drug. Also, the study revealed that the lectin is able to promote deleterious effects on B. glabrata embryos at environmentally safe concentrations.     

Glutathione-S-transferase M1 polymorphisms on the susceptibility to esophageal cancer among three Chinese minorities： Kazakh, Tajik and Uygur

~~Glutathione-S-transferase M1 polymorphisms on the susceptibility to esophageal cancer among three Chinese minorities:Kazakh,Tajik and Uygur1 Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94:…     

Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training

Aims/hypothesis  

Insulin-mediated glucose disposal rates (R _d) are reduced in type 2 diabetic patients, a process in which intrinsic signalling defects are thought to be involved. Phosphorylation of TBC1 domain family, member 4 (TBC1D4) is at present the most distal insulin receptor signalling event linked to glucose transport. In this study, we examined insulin action on site-specific phosphorylation of TBC1D4 and the effect of exercise training on insulin action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic patients.     

Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese

OBJECTIVE: Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of prebeta-high-density lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D. METHODS: Single nucleotide polymorphisms (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non-diabetic control subjects were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Single marker analysis for SNP T-778C indicated that T2D patients had increased frequency of C allele in comparison with non-diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non-diabetic controls, the carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T-778C variant independently of the haplotype context. CONCLUSION: The present study provided the first evidence that SNP T-778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D among Han Chinese.