The relationship between T cell immunoglobulin domain and mucin domain protein 3（Tim-3）/Galectin（Gal）-9 pathway and recurrent spontaneous abortion（RSA） was studied. Thirty-one pregnant women with RSA and 27 norm...The relationship between T cell immunoglobulin domain and mucin domain protein 3（Tim-3）/Galectin（Gal）-9 pathway and recurrent spontaneous abortion（RSA） was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin（IL）-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）, but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）. It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.展开更多
目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联...目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联免疫吸附法检测EBV mi R-BART17-3p、T细胞免疫球蛋白黏蛋白3(Tim-3)、叉头框蛋白P3(Fox P3)、白细胞介素17A(IL-17A)和转化生长因子-β(TGF-β)的m RNA、蛋白表达水平及含量。采用双荧光素酶报告基因实验考察EBV mi R-BART17-3p对Tim-3表达水平的影响。将15只BALB/C小鼠随机分为空白对照组、模型组、观察组,各5只。腹腔注射抗血小板抗体MWReg30以复制ITP小鼠模型,建模4 d后观察组小鼠予尾静脉注射携带EBV mi R-BART17-3p inhibitor的腺病毒载体。细胞染色并观察形态,检测外周血中TGF-β、IL-17A含量及血小板计数,采用流式细胞仪分别检测CD_(4)^(+)T细胞中Th17和Treg水平,并计算二者百分比。结果与对照组比较,ITP组患儿外周血EBV mi R-BART17-3p表达水平显著升高,Tim-3和TGF-βm RNA表达水平显著降低(P<0.05);Tim-3 m RNA表达水平与EBV mi R-BART17-3p表达水平呈显著负相关(r=-0.732,P<0.001)。Tim-3慢病毒载体p LKO.1-sh-Tim-3(sh-Tim-3)可显著降低Tim-3、Fox P3、TGF-β水平(P<0.05)。mi R-BART17-3p mimic显著升高了CD_(4)^(+)T细胞中mi R-BART17-3p的表达水平,并显著降低了Tim-3、Fox P3、TGF-βm RNA和蛋白表达水平(P<0.05);mi R-BART17-3p mimic可显著降低TGF-β含量,Tim-3+mi R-BART17-3p过表达逆转了mi R-BART17-3p mimic对TGF-β的抑制作用。动物实验结果显示,沉默EBV mi R-BART17-3p可促进Treg分化,减少脾脏和骨髓组织中的巨核细胞计数,并显著增加外周血中血小板计数。结论EBV mi R-BART17-3p可通过Fox P3/Tim-3途径调节ITP患儿Treg/Th17的免疫失衡。展开更多
目的分析湖北地区汉族人群T细胞免疫球蛋白域黏蛋白域蛋白4（T cells immunoglobulin domin and mucin domain protein 4，TIM4）基因8570G〉A、11515C〉A单核苷酸多态性，探讨其与变应性哮喘易感性之间的关系。方法采用聚合酶链反应和...目的分析湖北地区汉族人群T细胞免疫球蛋白域黏蛋白域蛋白4（T cells immunoglobulin domin and mucin domain protein 4，TIM4）基因8570G〉A、11515C〉A单核苷酸多态性，探讨其与变应性哮喘易感性之间的关系。方法采用聚合酶链反应和限制性片段长度多态性对145例变应性哮喘患者和130名健康对照T／M4基因8570G〉A和11515C〉A多态性进行分析，计算基因型和等位基因频率。结果湖北地区健康人群TIM48570G〉AGG、GA和AA基因型频率分别是0．985、0．015和0，而哮喘患者其频率分别为0．931、0．069、0，基因型和等位基因频率在病例组与对照组间差异有统计学意义（P=0．030，P=0．032）；未检测到T／M4基因11515C〉A的多态性。结论湖北汉族人群T／M4基因8570G〉A存在单核苷酸多态性变异，可能与湖北地区汉族变应性哮喘易感性有关。展开更多
To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the p...To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymor- phisms （SNPs） in the promoter region of TIM4 were detected, including two new SNPs （at positions -1609, -153） and two reported SNPs （rs6874202, rs6882076）. The frequency distribution of rs6882076 was different among different races （P〈0.05）. In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.展开更多
目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104...目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104例健康个体Tim-1基因-1637A>G、-1454G>A、-416G>C和-232A>G共4个SNP位点进行检测,对各基因位点基因型频数、等位基因频数及单倍型分布情况进行比较和分析。结果:健康对照组与RA患者组-1637、-232位点基因型频数分布差异有统计学意义,在RA患者中-1637位点等位基因A的频数高于等位基因G(P<0.01)。4个位点共检出15种单倍型,单倍型AGCA(OR值9.611,95% CI 3.13～29.52)、AGCG(OR值4.361,95% CI 2.12～8.96)在宁夏回族RA患者组中的频数高于健康人群(P<0.01);而单倍型GGCA(OR值0.374,95% CI 0.22～0.64)、GGCG(OR值0.199,95% CI 0.08～0.49)及GAGA(OR值0.023,95%CI 0.002～0.26)在宁夏回族人群RA患者组中的频数低于健康对照组(P<0.01)。结论:-1637位点A>G的突变与宁夏回族人群RA发生有关,等位基因A的存在可增加RA发病风险,而等位基因G对RA的发生具有保护作用;AGCA、AGCG这2种单倍型可增加宁夏回族人群RA发生的风险,而单倍型GGCA、GGCG、GAGA对宁夏回族人群RA的发生具有保护作用。展开更多
基金supported by grants from the National Science Foundation of China(Nos.30973205 and 81172464)the National "Twelfth-Five Year" Research and Development Program of China(No.2014BAI05B05)
文摘The relationship between T cell immunoglobulin domain and mucin domain protein 3（Tim-3）/Galectin（Gal）-9 pathway and recurrent spontaneous abortion（RSA） was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin（IL）-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）, but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）. It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.
文摘目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联免疫吸附法检测EBV mi R-BART17-3p、T细胞免疫球蛋白黏蛋白3(Tim-3)、叉头框蛋白P3(Fox P3)、白细胞介素17A(IL-17A)和转化生长因子-β(TGF-β)的m RNA、蛋白表达水平及含量。采用双荧光素酶报告基因实验考察EBV mi R-BART17-3p对Tim-3表达水平的影响。将15只BALB/C小鼠随机分为空白对照组、模型组、观察组,各5只。腹腔注射抗血小板抗体MWReg30以复制ITP小鼠模型,建模4 d后观察组小鼠予尾静脉注射携带EBV mi R-BART17-3p inhibitor的腺病毒载体。细胞染色并观察形态,检测外周血中TGF-β、IL-17A含量及血小板计数,采用流式细胞仪分别检测CD_(4)^(+)T细胞中Th17和Treg水平,并计算二者百分比。结果与对照组比较,ITP组患儿外周血EBV mi R-BART17-3p表达水平显著升高,Tim-3和TGF-βm RNA表达水平显著降低(P<0.05);Tim-3 m RNA表达水平与EBV mi R-BART17-3p表达水平呈显著负相关(r=-0.732,P<0.001)。Tim-3慢病毒载体p LKO.1-sh-Tim-3(sh-Tim-3)可显著降低Tim-3、Fox P3、TGF-β水平(P<0.05)。mi R-BART17-3p mimic显著升高了CD_(4)^(+)T细胞中mi R-BART17-3p的表达水平,并显著降低了Tim-3、Fox P3、TGF-βm RNA和蛋白表达水平(P<0.05);mi R-BART17-3p mimic可显著降低TGF-β含量,Tim-3+mi R-BART17-3p过表达逆转了mi R-BART17-3p mimic对TGF-β的抑制作用。动物实验结果显示,沉默EBV mi R-BART17-3p可促进Treg分化,减少脾脏和骨髓组织中的巨核细胞计数,并显著增加外周血中血小板计数。结论EBV mi R-BART17-3p可通过Fox P3/Tim-3途径调节ITP患儿Treg/Th17的免疫失衡。
文摘目的分析湖北地区汉族人群T细胞免疫球蛋白域黏蛋白域蛋白4（T cells immunoglobulin domin and mucin domain protein 4，TIM4）基因8570G〉A、11515C〉A单核苷酸多态性，探讨其与变应性哮喘易感性之间的关系。方法采用聚合酶链反应和限制性片段长度多态性对145例变应性哮喘患者和130名健康对照T／M4基因8570G〉A和11515C〉A多态性进行分析，计算基因型和等位基因频率。结果湖北地区健康人群TIM48570G〉AGG、GA和AA基因型频率分别是0．985、0．015和0，而哮喘患者其频率分别为0．931、0．069、0，基因型和等位基因频率在病例组与对照组间差异有统计学意义（P=0．030，P=0．032）；未检测到T／M4基因11515C〉A的多态性。结论湖北汉族人群T／M4基因8570G〉A存在单核苷酸多态性变异，可能与湖北地区汉族变应性哮喘易感性有关。
基金the National Natural Sciences Foundation of China (No. 30672008)
文摘To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymor- phisms （SNPs） in the promoter region of TIM4 were detected, including two new SNPs （at positions -1609, -153） and two reported SNPs （rs6874202, rs6882076）. The frequency distribution of rs6882076 was different among different races （P〈0.05）. In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.
文摘目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104例健康个体Tim-1基因-1637A>G、-1454G>A、-416G>C和-232A>G共4个SNP位点进行检测,对各基因位点基因型频数、等位基因频数及单倍型分布情况进行比较和分析。结果:健康对照组与RA患者组-1637、-232位点基因型频数分布差异有统计学意义,在RA患者中-1637位点等位基因A的频数高于等位基因G(P<0.01)。4个位点共检出15种单倍型,单倍型AGCA(OR值9.611,95% CI 3.13～29.52)、AGCG(OR值4.361,95% CI 2.12～8.96)在宁夏回族RA患者组中的频数高于健康人群(P<0.01);而单倍型GGCA(OR值0.374,95% CI 0.22～0.64)、GGCG(OR值0.199,95% CI 0.08～0.49)及GAGA(OR值0.023,95%CI 0.002～0.26)在宁夏回族人群RA患者组中的频数低于健康对照组(P<0.01)。结论:-1637位点A>G的突变与宁夏回族人群RA发生有关,等位基因A的存在可增加RA发病风险,而等位基因G对RA的发生具有保护作用;AGCA、AGCG这2种单倍型可增加宁夏回族人群RA发生的风险,而单倍型GGCA、GGCG、GAGA对宁夏回族人群RA的发生具有保护作用。
