AIM To investigated the mechanism of the association between the TBX21 T-1993 C promoter polymorphism and autoimmune hepatitis type 1(AIH-1) development.METHODS In vivo,In vivo,and reporter analyses were performed to ...AIM To investigated the mechanism of the association between the TBX21 T-1993 C promoter polymorphism and autoimmune hepatitis type 1(AIH-1) development.METHODS In vivo,In vivo,and reporter analyses were performed to determine the function of transcription factors binding to the T-1993 C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor(T-bet) and interferon-γ(IFN-γ) expressions in CD4+ T cells,B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993 TC and 15-1993 TT genotype carriers,and healthy controls including 10-1993 TC and 25-1993 TT genotype carriers. Furthermore,a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients.RESULTS TBX21-1993 C allele created a strong Yin-Yang 1(YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells.Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the-1993 TC genotype and controls with the-1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with si RNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION The repression of TBX21 expression by high-affinity binding of YY1 to the-1993 C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.展开更多
AIM: To investigate the association between the polymorphism of TBX21 gene and the risk of gastric cancer in a Chinese population. METHODS: The -1993 polymorphism located in TBX21 gene promoter region was identified b...AIM: To investigate the association between the polymorphism of TBX21 gene and the risk of gastric cancer in a Chinese population. METHODS: The -1993 polymorphism located in TBX21 gene promoter region was identified by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) method. The risk between TBX21 gene genotype and gastric cancer was determined by multivariate logistic regression analysis in 220 gastric cancer patients and 262 cancer-free controls matched by age, sex and ethnicity. RESULTS: Compared with the TBX21 -1993TT genotype, the -1993CC genotype exhibited a significantly elevated risk for gastric cancer [Odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.41-8.31]. The relation-ship between the -1993 polymorphic genotype and the invasive status such as lymph node and distant metastasis was found among the gastric cancer patients (OR = 4.02, 95% CI: 1.87-8.66; OR = 7.02, 95% CI: 3.44-14.34, respectively). CONCLUSION: TBX21 -1993 polymorphism might contribute to the risk of gastric cancer, especially to the distant metastasis.展开更多
Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclea...Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclear cells were isolated.High throughput RNA-seq was used to identify the different genes between Behcet's disease and healthy subjects.Mouse model was constructed by shrimp myosin sensitization and treated with Sanwu Huangqin decoction.The levels of IFN-γand IL-17A in peripheral blood and mononuclear cells were detected by ELISA and flow cytometry.The expression level of TBX21 gene in spleen was detected by RT-PCR;Results:Compared with healthy subjects,31 differential genes were identified in BD patients,of which 19 genes were up-regulated and 12 genes were down regulated.PPI analysis showed that the top 5 genes were TBX21,STAT3,IL15,PRF1 and IFNG.The results of animal experiments showed that the levels of IFN-γand IL-17A in the peripheral blood and PBMC of the model group were significantly higher compared with the control group(P<0.01).Sanwu Huangqin decoction could significantly reduce the levels of IFN-γand IL-17A in the peripheral blood and PBMC of mice(P<0.05 or P<0.01).RT-PCR results showed that the expression of TBX21 mRNA in spleen tissue of model group was significantly higher than that of the control group(P<0.01).Sanwu Huangqin decoction could significantly down-regulate the expression of TBX21 mRNA in spleen(P<0.05 or P<0.01);Conclusion:Sanwu Huangqin decoction reduce the levels of IFN-γand IL-17A by inhibiting the expression of TBX21 mRNA,so as to achieve the effect of treating BD.展开更多
为了更加深入地了解牛TBX21基因的蛋白质结构和功能及其与该基因有关联的疾病,本研究以牛TBX21为目的基因,利用生物信息学方法对其编码蛋白质的基本理化性质、疏\亲水性、蛋白质翻译后的修饰位点、信号肽和跨膜结构域、亚细胞定位以及...为了更加深入地了解牛TBX21基因的蛋白质结构和功能及其与该基因有关联的疾病,本研究以牛TBX21为目的基因,利用生物信息学方法对其编码蛋白质的基本理化性质、疏\亲水性、蛋白质翻译后的修饰位点、信号肽和跨膜结构域、亚细胞定位以及蛋白质的高级结构等对其进行预测分析。结果表明,牛TBX21基因编码532个氨基酸,分子质量为58188.87,基因编码产物不稳定指数为57.26,理论等电点为5.88,分子式为C 2597 H 3892 N 714 O 781 S 18。亲水性氨基酸占比为78.63%,疏水性氨基酸占比为21.37%,平均分值为-0.655,为负值,表现为亲水性。该基因中没有信号肽和跨膜结构域,没有N-糖基化位点,但含有磷酸化位点52个。通过对其亚细胞的定位分析,显示TBX21基因编码的产物主要是在细胞核内发挥其生物学作用。该基因的蛋白质二、三级结构均由α-螺旋、β-折叠和无规则卷曲组成,其在生物合成、基因表达与调控等方面有重要作用。本研究结果可为牛TBX21基因深入研究奠定一定的基础。展开更多
基金Supported by National Natural Science Foundation of China,No.30972595
文摘AIM To investigated the mechanism of the association between the TBX21 T-1993 C promoter polymorphism and autoimmune hepatitis type 1(AIH-1) development.METHODS In vivo,In vivo,and reporter analyses were performed to determine the function of transcription factors binding to the T-1993 C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor(T-bet) and interferon-γ(IFN-γ) expressions in CD4+ T cells,B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993 TC and 15-1993 TT genotype carriers,and healthy controls including 10-1993 TC and 25-1993 TT genotype carriers. Furthermore,a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients.RESULTS TBX21-1993 C allele created a strong Yin-Yang 1(YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells.Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the-1993 TC genotype and controls with the-1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with si RNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION The repression of TBX21 expression by high-affinity binding of YY1 to the-1993 C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.
基金Supported by National Natural Science Foundation, No.81000187
文摘AIM: To investigate the association between the polymorphism of TBX21 gene and the risk of gastric cancer in a Chinese population. METHODS: The -1993 polymorphism located in TBX21 gene promoter region was identified by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) method. The risk between TBX21 gene genotype and gastric cancer was determined by multivariate logistic regression analysis in 220 gastric cancer patients and 262 cancer-free controls matched by age, sex and ethnicity. RESULTS: Compared with the TBX21 -1993TT genotype, the -1993CC genotype exhibited a significantly elevated risk for gastric cancer [Odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.41-8.31]. The relation-ship between the -1993 polymorphic genotype and the invasive status such as lymph node and distant metastasis was found among the gastric cancer patients (OR = 4.02, 95% CI: 1.87-8.66; OR = 7.02, 95% CI: 3.44-14.34, respectively). CONCLUSION: TBX21 -1993 polymorphism might contribute to the risk of gastric cancer, especially to the distant metastasis.
基金General Project of Natural Science Funds of Heilongjiang Province(No.H2017064)
文摘Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclear cells were isolated.High throughput RNA-seq was used to identify the different genes between Behcet's disease and healthy subjects.Mouse model was constructed by shrimp myosin sensitization and treated with Sanwu Huangqin decoction.The levels of IFN-γand IL-17A in peripheral blood and mononuclear cells were detected by ELISA and flow cytometry.The expression level of TBX21 gene in spleen was detected by RT-PCR;Results:Compared with healthy subjects,31 differential genes were identified in BD patients,of which 19 genes were up-regulated and 12 genes were down regulated.PPI analysis showed that the top 5 genes were TBX21,STAT3,IL15,PRF1 and IFNG.The results of animal experiments showed that the levels of IFN-γand IL-17A in the peripheral blood and PBMC of the model group were significantly higher compared with the control group(P<0.01).Sanwu Huangqin decoction could significantly reduce the levels of IFN-γand IL-17A in the peripheral blood and PBMC of mice(P<0.05 or P<0.01).RT-PCR results showed that the expression of TBX21 mRNA in spleen tissue of model group was significantly higher than that of the control group(P<0.01).Sanwu Huangqin decoction could significantly down-regulate the expression of TBX21 mRNA in spleen(P<0.05 or P<0.01);Conclusion:Sanwu Huangqin decoction reduce the levels of IFN-γand IL-17A by inhibiting the expression of TBX21 mRNA,so as to achieve the effect of treating BD.
文摘为了更加深入地了解牛TBX21基因的蛋白质结构和功能及其与该基因有关联的疾病,本研究以牛TBX21为目的基因,利用生物信息学方法对其编码蛋白质的基本理化性质、疏\亲水性、蛋白质翻译后的修饰位点、信号肽和跨膜结构域、亚细胞定位以及蛋白质的高级结构等对其进行预测分析。结果表明,牛TBX21基因编码532个氨基酸,分子质量为58188.87,基因编码产物不稳定指数为57.26,理论等电点为5.88,分子式为C 2597 H 3892 N 714 O 781 S 18。亲水性氨基酸占比为78.63%,疏水性氨基酸占比为21.37%,平均分值为-0.655,为负值,表现为亲水性。该基因中没有信号肽和跨膜结构域,没有N-糖基化位点,但含有磷酸化位点52个。通过对其亚细胞的定位分析,显示TBX21基因编码的产物主要是在细胞核内发挥其生物学作用。该基因的蛋白质二、三级结构均由α-螺旋、β-折叠和无规则卷曲组成,其在生物合成、基因表达与调控等方面有重要作用。本研究结果可为牛TBX21基因深入研究奠定一定的基础。
