目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与...目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。展开更多
AIM： To evaluate the effect of mitochondrial tumor ne- crosis factor receptor-associated protein-1 （TRAP-l） on the lymph node metastasis （LNM） in Chinese colorectal cancer （CRC） patients, and develop potential ...AIM： To evaluate the effect of mitochondrial tumor ne- crosis factor receptor-associated protein-1 （TRAP-l） on the lymph node metastasis （LNM） in Chinese colorectal cancer （CRC） patients, and develop potential LNM- associated biomarkers for CRC using quantitative real- time polymerase chain reaction （RT-PCR） analysis. METHODS： Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM （LNM CRC） and without LNM （non-LNM CRC） were assessed in 96 Chinese colorectal carcinoma samples using quantita- tive RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diaclnostic biomarkers was also examined.RESULTS： TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immuno- histochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramati- cally higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM （90.2% in LNM group vs 22% in non-LNM group, P 〈 0.001）, the advanced tumor node metastasis stage （89.1% in LNM group vs 26.9% in non-LNM group, P 〈 0.001）, the increased 5-year recurrence rate （82.7% in LNM group vs 22.6% in non-LNM group, P 〈 0.001） and the decreased 5-year overall survival rate （48.4% in LNM vs 83.2% in non-LNM group, P 〈 0.001）. Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients （Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028）. CONCLUSION： Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential bio- marker for LNM and a prognostic factor in CRC. Over- expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients. 2012 Baishideng. All rights reserved展开更多
Interferon regulatory factor （IRF）3 is critical for the transcriptional induction of chemokines and cytokines during viral or bacterial invasion. The kinases Tank binding kinase （TBK）1 and Ikappa B kinase （IKK）...Interferon regulatory factor （IRF）3 is critical for the transcriptional induction of chemokines and cytokines during viral or bacterial invasion. The kinases Tank binding kinase （TBK）1 and Ikappa B kinase （IKK）ε can phosphorylate the C-terminal part of IRF3 and play important roles in IRF3 activation. In this study, we show that another kinase, c-Jun-NH2-terminal kinase （JNK）, phosphorylates IRF3 on its N-terminal serine 173 residue, and TAK1 can stimu- late IRF3 phosphorylation via JNK. JNK specific inhibitor SP600125 inhibits the N-terminal phosphorylation with- out affecting the C-terminal phosphorylation. In addition, IRF3-mediated gene expressions on lipopolysaccharide （LPS） or polyinosinic-cytidylic acid （polyI：C） treatment are severely impaired by SP600125, as well as for reporter gene assay of IRF3 activation. Knockdown of TAK1 further confirmed these observations. Interestingly, constitu- tive active IRF3（5D） can be inhibited by SP600125; JNK1 can synergize the action of IRF3（5D）, but not the S173A- IRF3（5D） mutant. More importantly, polyI：C failed to induce the phosphorylation of mutant S173A and SP600125 dramatically abrogated IRF3 phosphorylation and dimerization that was stimulated by polyhC. Thus, this study demonstrates that the TAK1-JNK cascade is required for IRF3 function, in addition to TBK1/IKKε, uncovering a new mechanism for mitogen-activated protein （MAP） kinase to regulate the innate immunity.展开更多
AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into ...AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into groups of sham-operation,bile duct ligation(BDL),BDL +L.plantarum,BDL+internal biliary drainage(IBD),and BDL+IBD+L.plantarum.Ten days after L.plantarum administration,blood and ileal samples were collected from the rats for morphological examination,and intestinal barrier function,liver function,intestinal oxidative stress and protein kinase C(PKC)activity measurement.The distribution and expression of the PKC and tight junction(TJ)proteins,such as occludin,zonula occludens-1,claudin-1,claudin-4,junction adhesion molecule-A and F-actin,were examined by confocal laser scanning microscopy,immunohistochemistry,Western blotting,real-time fluorescent quantitative polymerase chain reaction assay.RESULTS:L.plantarum administration substantially restored gut barrier,decreased enterocyte apoptosis,improved intestinal oxidative stress,promoted the activity and expression of protein kinase(BDL vs BDL+L.plantarum,0.295±0.007 vs 0.349±0.003,P<0.05;BDL+IBD vs BDL+IBD+L.plantarum,0.407±0.046 vs 0.465±0.135,P<0.05),and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice(BDL vs BDL+L.plantarum,0.266±0.118 vs 0.326±0.009,P<0.05).The protective effect of L.plantarum was more prominent after internal biliary drainage(BDL+IBD vs BDL +IBD+L.plantarum,0.415±0.105 vs 0.494±0.145,P<0.05).CONCLUSION:L.plantarum can decrease intestinal epithelial cell apoptosis,reduce oxidative stress,and prevent TJ disruption in biliary obstruction by activating the PKC pathway.展开更多
文摘目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。
基金Supported by The Grants from Shanghai Health Bureau,No.JG1103
文摘AIM： To evaluate the effect of mitochondrial tumor ne- crosis factor receptor-associated protein-1 （TRAP-l） on the lymph node metastasis （LNM） in Chinese colorectal cancer （CRC） patients, and develop potential LNM- associated biomarkers for CRC using quantitative real- time polymerase chain reaction （RT-PCR） analysis. METHODS： Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM （LNM CRC） and without LNM （non-LNM CRC） were assessed in 96 Chinese colorectal carcinoma samples using quantita- tive RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diaclnostic biomarkers was also examined.RESULTS： TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immuno- histochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramati- cally higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM （90.2% in LNM group vs 22% in non-LNM group, P 〈 0.001）, the advanced tumor node metastasis stage （89.1% in LNM group vs 26.9% in non-LNM group, P 〈 0.001）, the increased 5-year recurrence rate （82.7% in LNM group vs 22.6% in non-LNM group, P 〈 0.001） and the decreased 5-year overall survival rate （48.4% in LNM vs 83.2% in non-LNM group, P 〈 0.001）. Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients （Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028）. CONCLUSION： Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential bio- marker for LNM and a prognostic factor in CRC. Over- expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients. 2012 Baishideng. All rights reserved
文摘Interferon regulatory factor （IRF）3 is critical for the transcriptional induction of chemokines and cytokines during viral or bacterial invasion. The kinases Tank binding kinase （TBK）1 and Ikappa B kinase （IKK）ε can phosphorylate the C-terminal part of IRF3 and play important roles in IRF3 activation. In this study, we show that another kinase, c-Jun-NH2-terminal kinase （JNK）, phosphorylates IRF3 on its N-terminal serine 173 residue, and TAK1 can stimu- late IRF3 phosphorylation via JNK. JNK specific inhibitor SP600125 inhibits the N-terminal phosphorylation with- out affecting the C-terminal phosphorylation. In addition, IRF3-mediated gene expressions on lipopolysaccharide （LPS） or polyinosinic-cytidylic acid （polyI：C） treatment are severely impaired by SP600125, as well as for reporter gene assay of IRF3 activation. Knockdown of TAK1 further confirmed these observations. Interestingly, constitu- tive active IRF3（5D） can be inhibited by SP600125; JNK1 can synergize the action of IRF3（5D）, but not the S173A- IRF3（5D） mutant. More importantly, polyI：C failed to induce the phosphorylation of mutant S173A and SP600125 dramatically abrogated IRF3 phosphorylation and dimerization that was stimulated by polyhC. Thus, this study demonstrates that the TAK1-JNK cascade is required for IRF3 function, in addition to TBK1/IKKε, uncovering a new mechanism for mitogen-activated protein （MAP） kinase to regulate the innate immunity.
基金Supported by The National Natural Science Foundation of China,No.30471687Chinese Ministry of Science and Technology,No.2008CB517403
文摘AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into groups of sham-operation,bile duct ligation(BDL),BDL +L.plantarum,BDL+internal biliary drainage(IBD),and BDL+IBD+L.plantarum.Ten days after L.plantarum administration,blood and ileal samples were collected from the rats for morphological examination,and intestinal barrier function,liver function,intestinal oxidative stress and protein kinase C(PKC)activity measurement.The distribution and expression of the PKC and tight junction(TJ)proteins,such as occludin,zonula occludens-1,claudin-1,claudin-4,junction adhesion molecule-A and F-actin,were examined by confocal laser scanning microscopy,immunohistochemistry,Western blotting,real-time fluorescent quantitative polymerase chain reaction assay.RESULTS:L.plantarum administration substantially restored gut barrier,decreased enterocyte apoptosis,improved intestinal oxidative stress,promoted the activity and expression of protein kinase(BDL vs BDL+L.plantarum,0.295±0.007 vs 0.349±0.003,P<0.05;BDL+IBD vs BDL+IBD+L.plantarum,0.407±0.046 vs 0.465±0.135,P<0.05),and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice(BDL vs BDL+L.plantarum,0.266±0.118 vs 0.326±0.009,P<0.05).The protective effect of L.plantarum was more prominent after internal biliary drainage(BDL+IBD vs BDL +IBD+L.plantarum,0.415±0.105 vs 0.494±0.145,P<0.05).CONCLUSION:L.plantarum can decrease intestinal epithelial cell apoptosis,reduce oxidative stress,and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
