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Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease 被引量:5
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作者 Carsten Gnewuch Gerhard Liebisch +8 位作者 Thomas Langmann Benjamin Dieplinger Thomas Mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第25期3134-3141,共8页
AIM: To determine free and conjugated serum bile acid (BA) levels in inflammatory bowel disease (IBD) subgroups with defined clinical manifestations. METHODS: Comprehensive serum BA profiling was performed in 35... AIM: To determine free and conjugated serum bile acid (BA) levels in inflammatory bowel disease (IBD) subgroups with defined clinical manifestations. METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy con- trols by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the second- ary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased signifi- cantly. Total BA, total BA conjugate, and total BA glyco- conjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as signifi- cantly increased as the secondary BAs LCA, ursodeoxy- cholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode- oxycholic acid, were increased significantly compared to controls and patients without surgical interventions. CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diag- nostic characterization and differentiation of IBD sub- groups with defined clinical manifestations. 展开更多
关键词 Bile acids Liquid chromatography Tandem mass spectrometry Inflammatory bowel disease Crohn's disease Ulcerative colitis
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Non-alcoholic fatty liver disease:An early mediator predicting metabolic syndrome in obese children? 被引量:21
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作者 Jun-Fen Fu Hong-Bo Shi +6 位作者 Li-Rui Liu Ping Jiang Li Liang Chun-Lin Wang Hong-Bo Shi Ping Jiang Xi-Yong Liu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第6期735-742,共8页
AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese childre... AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening. 展开更多
关键词 Childhood obesity Non-alcoholic fatty liver disease Metabolic syndrome Liver B ultrasonography
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S腺苷蛋氨酸对肝癌细胞中GADD45β基因的表达诱导及其机制研究 被引量:4
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作者 邱伟华 Bingsen Zhou +6 位作者 陈皓 杨卫平 施敏敏 沈柏用 彭承宏 李宏为 Yun Yen 《中华肝胆外科杂志》 CAS CSCD 2008年第12期872-876,共5页
目的初步明确肝癌细胞中特异性表达缺失的GADD4513基因近端启动子活性调控中心,并探讨S腺苷蛋氨酸对肝癌细胞HepG2中GADD4513表达的影响及可能机制。方法以30-50个碱基的间隔,于体外人工合成GADD45β近端启动子序列(-618~-520),... 目的初步明确肝癌细胞中特异性表达缺失的GADD4513基因近端启动子活性调控中心,并探讨S腺苷蛋氨酸对肝癌细胞HepG2中GADD4513表达的影响及可能机制。方法以30-50个碱基的间隔,于体外人工合成GADD45β近端启动子序列(-618~-520),分别插入pGL3 basic荧光素表达质粒的荧光基因上游,以电穿孔法转染HepG2,根据启动子活性强度结合TRANSFAC数据库,分析可能存在的转录调节因子结合位点;实时荧光定量PCR比较S腺苷蛋氨酸作用前后HepG2细胞GADD45β表达,并在此基础上进一步比较S腺苷蛋氨酸对GADD45β启动子活性的诱导作用,探讨其可能作用机制,并为GADD45β近端启动子研究提供功能性证据。结果GADD45β近端启动子中含有3个NF-κB转录调节因子与启动子结合位点(-602/~593、-581/~572、-537/-528);S腺苷蛋氨酸能明显诱导HepG2中GADD45β的表达,并呈现出剂量-效应的正相关关系,同时其能相应明显诱导NF-κB的启动子活性。结论S腺苷蛋氨酸能明显诱导肝癌细胞中特异性缺失的GADD45β基因表达,增强转录调节因子NF-κB的活性水平是其可能的作用机制,该研究为S腺苷蛋氨酸的肝脏保护作用提供了新的实验依据。 展开更多
关键词 肝细胞 S腺苷蛋氨酸 GADD45Β 启动子
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羟基脲对肝癌细胞HepG2中GADD45β表达影响及其可能机制 被引量:3
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作者 邱伟华 Bingsen Zhou +3 位作者 Peiguo G.Chu 陈皓 施敏敏 Yun Yen 《中华肝胆外科杂志》 CAS CSCD 北大核心 2010年第4期290-294,共5页
目的 初步明确肝癌细胞中GADD45β基因近端启动子序列,探索羟基脲对人肝癌细胞HepG2的GADD45β表达影响及可能机制.方法 体外合成GADD45β近端启动子序列群(-618~-314),构建荧光素表达质粒,转染肝癌细胞株HepG2,根据启动子活性强度... 目的 初步明确肝癌细胞中GADD45β基因近端启动子序列,探索羟基脲对人肝癌细胞HepG2的GADD45β表达影响及可能机制.方法 体外合成GADD45β近端启动子序列群(-618~-314),构建荧光素表达质粒,转染肝癌细胞株HepG2,根据启动子活性强度结合数据库分析存在的转录调节因子结合位点;以实时荧光定量PCR比较羟基脲作用前后HepG2细胞GADD45β表达,并进一步比较羟基脲对GADD45β启动子活性的调控作用、分析羟基脲对HepG2的抑制效应,并通过Caspase-8、Caspase-9和Caspase-3的表达变化测定凋亡的发生和发展.结果 GADD4518近端启动子中含有3个NF-кB(-602/-593、-581/-572、-537/-528)和1个E2F-1(-470/-436)转录调节因子与启动子结合位点;羟基脲能明显诱导HepG2中GADD45β的表达,并呈现出剂量-效应的正相关关系,同时NF-кB和E2F-1启动子均明显增强.羟基脲能够明显抑制HepG2的DNA合成能力和细胞克隆形成能力,同时羟基脲能迅速启动HepG2凋亡的发生和发展.结论 羟基脲能明显诱导肝癌细胞中特异性缺失的GADD45β基因表达,增强转录调节因子的表达水平是其可能的作用机制. 展开更多
关键词 肝细胞 羟基脲 GADD45Β 启动子
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