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Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1
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作者 Hui-Ying Jian Zi-Cheng Liang +2 位作者 Huan Wen Zhen Zhang Pu-Hua Zeng 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第6期2727-2741,共15页
BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study i... BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1(ACAT1)-regulated cellular stiffness.Through a series of experiments,we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1,lowering the level of cholesterol in the cell membrane,and altering the cellular stiffness,which provides a new idea for the research of traditional Chinese medicine against HCC.AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.METHODS HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice.The apoptotic rate and proliferative,invasive,and migratory abilities of control and SPXJ-treated HCC cells were compared.Atomic force microscopy was used to determine the cell surface morphology and the Young’s modulus values of the control and SPXJ-treated HCC cells.Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit.ACAT1 protein levels were estimated using western blotting.RESULTS Compared with the vehicle group,SPXJ serum considerably reduced proliferation of HCC cells,increased stiffness and apoptosis of HCC cells,inhibited migration and invasion of HCC cells,decreased plasma membrane cholesterol levels,and upregulated ACAT1 protein levels.However,treatment of HCC cells with the water-soluble cholesterol promoted proliferation,migration,and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels,but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control.CONCLUSION SPXJ formula inhibited proliferation,invasion,and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression. 展开更多
关键词 Shi-pi-xiao-ji formula Hepatocellular carcinoma Cellular stiffness Plasma membrane cholesterol level AcetylcoA acetyltransferase 1
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胰淀素作用于背外侧被盖核胆碱乙酰转移酶神经元调节小鼠体重
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作者 曹晓娟 刘昊东 +10 位作者 李鹏辉 李嘉成 樊奇 王星 李彩琴 杨子程 郭永清 陈玉洁 张小宇 海日汗 杜晨光 《畜牧兽医学报》 CAS CSCD 北大核心 2024年第7期3185-3192,共8页
胰淀素(amylin)作用于背外侧被盖核(lateral dorsal tegmental nucleus,LDT),诱导减肥和抑食效应,并激活背肩胛棕色脂肪组织(interscapular brown adipose tissue,IBAT)产热。多种食欲激素受体与胆碱乙酰转移酶(choline acetyltransfera... 胰淀素(amylin)作用于背外侧被盖核(lateral dorsal tegmental nucleus,LDT),诱导减肥和抑食效应,并激活背肩胛棕色脂肪组织(interscapular brown adipose tissue,IBAT)产热。多种食欲激素受体与胆碱乙酰转移酶(choline acetyltransferase,ChAT)神经元共同定位于LDT中,以调节饱腹感和能量消耗。然而,LDT的ChAT神经元是否参与胰淀素介导的体重调节作用尚待探索。作者拟通过免疫荧光检测小鼠LDT中原癌基因蛋白(c-Fos)和ChAT神经元的表达,逆行示踪技术确认LDT的下游神经核团,神经元损伤试验分析胰淀素作用的神经机制。结果显示:腹腔注射胰淀素显著降低小鼠体重,并显著促进LDT和臂旁核(PBN)中c-Fos和ChAT神经元表达。ChAT和神经型一氧化氮合成酶(nNOS)神经元在LDT、PBN和迷走神经背侧核(DMV)中共表达。逆行示踪试验证明LDT向PBN神经元发送神经投射。此外,损伤LDT和PBN神经元可降低胰淀素的减肥效果。LDT是连接PBN的能量平衡调节中枢,ChAT神经元参与介导胰淀素的体重调节过程。 展开更多
关键词 肥胖 胆碱乙酰转移酶 胰淀素 下丘脑 背外侧被盖核
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硫醇乙酰基转移酶mshD对结核分枝杆菌生长和应对压力刺激的研究
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作者 张蓝月 王颖超 +5 位作者 刘唯夷 尚雪恬 贾红彦 朱传智 张宗德 潘丽萍 《中国防痨杂志》 CAS CSCD 北大核心 2024年第8期935-941,共7页
目的:探索硫醇乙酰基转移酶MshD对结核分枝杆菌在体外生长、应对压力刺激和活性氧(reactive oxygen species,ROS)水平的影响。方法:利用CRISPR-NHEJ基因编辑技术,构建结核分枝杆菌mshD基因敲除株(ΔmshD株)和回补株(ΔmshD::mshD株)。... 目的:探索硫醇乙酰基转移酶MshD对结核分枝杆菌在体外生长、应对压力刺激和活性氧(reactive oxygen species,ROS)水平的影响。方法:利用CRISPR-NHEJ基因编辑技术,构建结核分枝杆菌mshD基因敲除株(ΔmshD株)和回补株(ΔmshD::mshD株)。分别检测H37Rv野生株(WT)、ΔmshD株和ΔmshD::mshD株在液体培养基和固体培养基中的生长情况,以及外源添加L-半胱氨酸和过氧化氢酶对菌株生长的影响;检测3种菌株对不同刺激剂如H 2O 2、二硫苏糖醇(DTT)、十二烷基硫酸钠(SDS)的敏感性,以及外源添加过氧化氢酶对压力条件处理后菌株的恢复情况;采用流式细胞术检测SDS处理3种菌株前后菌株的ROS水平。结果:与WT和ΔmshD::mshD株相比,ΔmshD株在固体平板上的生长较为缓慢,外源添加过氧化氢酶可以恢复其生长趋势;ΔmshD株应对DTT[WT(6.96±2.02)%,ΔmshD(0.02±0.00)%,ΔmshD::mshD(6.64±0.77)%;F=29.700,P<0.001],H 2O 2[WT(0.23±0.06)%,ΔmshD(0.01±0.00)%,ΔmshD::mshD(0.26±0.06)%;F=25.520,P=0.001]和SDS[WT(0.12±0.03)%,ΔmshD(0.01±0.00)%,ΔmshD::mshD(0.18±0.04)%;F=19.540,P=0.002]刺激的存活率更低,差异均有统计学意义;外源添加过氧化氢酶可以恢复其存活率。ΔmshD株自身ROS水平高于WT(WT:95.100±2.553,ΔmshD:106.000±4.000,ΔmshD::mshD:94.667±3.055;F=11.650,P=0.009),SDS处理ΔmshD株的自身ROS水平进一步升高(WT:436.000±8.000,ΔmshD:533.667±4.726,ΔmshD::mshD:441.333±2.517;F=292.900,P<0.001),差异均有统计学意义。结论:mshD基因缺失在固体培养基中生长减慢,mshD基因协助结核分枝杆菌抵抗各种应激压力,ΔmshD菌株内源性ROS水平增加。外源添加过氧化氢酶可一定程度恢复mshD基因敲除株生长和存活缺陷。 展开更多
关键词 分枝杆菌 结核 乙酰基转移酶类 过氧化氢酶 活性氧
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高温胁迫下刺参H3K9ac特征及HATs、HDACs的表达
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作者 张京京 徐冬雪 +2 位作者 宋文琦 夏斌 高勤峰 《中国海洋大学学报(自然科学版)》 CAS CSCD 北大核心 2024年第2期44-54,共11页
为了探索高温胁迫下刺参(Apostichopus japonicus)H3K9乙酰化水平的变化,研究组蛋白乙酰转移酶(Histone acetyltransferases,HATs)和去乙酰化酶(Histone deacetylases,HDACs)对刺参H3K9乙酰化的影响。本研究通过Western Blot技术研究高... 为了探索高温胁迫下刺参(Apostichopus japonicus)H3K9乙酰化水平的变化,研究组蛋白乙酰转移酶(Histone acetyltransferases,HATs)和去乙酰化酶(Histone deacetylases,HDACs)对刺参H3K9乙酰化的影响。本研究通过Western Blot技术研究高温胁迫条件下刺参肠道组织H3K9乙酰化特征,并对刺参基因组中4种组蛋白乙酰转移酶基因ajKAT2B、ajKAT5、ajKAT7、ajKAT8和4种组蛋白去乙酰化酶基因ajSIRT1、ajHDAC1、ajHDAC3、ajHDAC4进行结构解析和系统进化树分析;利用qRT-PCR定量研究在高温胁迫后刺参的8种基因表达量的变化模式。研究表明,通过Western Blot发现,在26℃胁迫下,H3K9ac水平在胁迫48 h后明显上升(P<0.05),在96 h后又迅速下降(P<0.05),表明其在高温胁迫下调控基因转录可能起到重要作用。基因结构解析发现HATs和HDACs含有保守的结构域,通过构建基因系统进化树发现其与物种进化树呈一致的趋势,也表现出功能上的高度保守。qRT-PCR结果表明:4种HATs基因在高温胁迫48 h后均有显著的上升(P<0.05),在胁迫96 h后,ajKAT2B和ajKAT8降低至对照组的表达水平,ajKAT5迅速下降至显著低于对照组水平,ajKAT7稍有降低但仍显著高于对照组。4种HDACs基因中,ajSIRT1在高温胁迫6 h后有明显的上升,在胁迫48 h后显著高于对照组(P<0.05),在胁迫96 h后降低至对照组的表达水平;ajHDAC1在高温胁迫6 h后有明显下降(P<0.05),在胁迫48 h后迅速上升至显著高于对照组水平(P<0.05),然后降低至对照组水平;ajHDAC3和ajHDAC4在高温胁迫6 h后均显著上升(P<0.05),在胁迫48 h后降至对照组水平并继续下降。研究结果表明,刺参H3K9ac乙酰化水平在高温胁迫下表现出明显动态变化,多种HATs和HDACs在mRNA水平上均有明显响应,这可能是导致H3K9ac变化的因素之一。 展开更多
关键词 刺参 高温胁迫 H3K9ac 组蛋白乙酰转移酶 组蛋白去乙酰化酶
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ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage
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作者 Yihua Zhang Ping Huang +4 位作者 Min Cao Yi Chen Xinhu Zhao Xuzhi He Lunshan Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1072-1077,共6页
MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are... MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage. 展开更多
关键词 acetylatedα-tubulin α-tubulin acetyltransferase 1(ATAT1) erythrophagocytosis hematoma absorption intracerebral hemorrhage MACROPHAGE MICROGLIA
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GNAT类乙酰转移酶调控水稻细菌性条斑病菌的生长和致病力
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作者 陈雨 程雨果 +1 位作者 蔡静 陶均 《热带生物学报》 2024年第2期171-181,共11页
为探究GNAT乙酰转移酶在稻黄单胞菌稻生致病变种(Xanthomonas oryzae pv. oryzicola,Xoc)中的功能,本研究首先对GNAT家族蛋白进行了结构域分析,随后构建了GNAT编码基因的单突及多突突变体,并比较了野生型菌株和这些突变菌株间的生长速... 为探究GNAT乙酰转移酶在稻黄单胞菌稻生致病变种(Xanthomonas oryzae pv. oryzicola,Xoc)中的功能,本研究首先对GNAT家族蛋白进行了结构域分析,随后构建了GNAT编码基因的单突及多突突变体,并比较了野生型菌株和这些突变菌株间的生长速度、胞外酶活性和致病力的差异。结果发现:在营养缺乏条件下,除xoc_1598突变体和敲除全部GNAT类乙酰转移酶基因的6突突变体外,其他所有突变体的生长都弱于野生型,说明此类乙酰转移酶调控Xoc的生长。此外,所有GNAT类乙酰转移酶突变都导致Xoc致病力下降。同时还发现此类乙酰转移酶对运动性、胞外蛋白酶和淀粉酶活性也有调控作用。实验结果表明,乙酰化修饰是Xoc生长和致病力的重要调节机制。 展开更多
关键词 稻黄单胞菌 乙酰转移酶 胞外酶 致病性
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ACAT1和MTNR1B基因多态性与非酒精性脂肪性肝病易感性的关系
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作者 马磊 胡欣欣 +4 位作者 赵波 万强 周林 赵真真 辛永宁 《临床肝胆病杂志》 CAS 北大核心 2024年第4期700-705,共6页
目的本研究拟探讨乙酰辅酶A乙酰转移酶1(ACAT1)和褪黑激素受体1B(MTNR1B)基因多态性与非酒精性脂肪性肝病(NAFLD)疾病易感性的关系。方法本研究共纳入2020年12月—2022年6月就诊于青岛市市立医院的健康体检者164例、NAFLD患者228例。采... 目的本研究拟探讨乙酰辅酶A乙酰转移酶1(ACAT1)和褪黑激素受体1B(MTNR1B)基因多态性与非酒精性脂肪性肝病(NAFLD)疾病易感性的关系。方法本研究共纳入2020年12月—2022年6月就诊于青岛市市立医院的健康体检者164例、NAFLD患者228例。采用PCR及测序的方法对ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因多态性进行基因分型,并采集空腹静脉血进行生化检测。符合正态分布的计量资料两组间比较采用成组t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U非参数检验;计数资料两组间比较采用χ2检验。结果ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因型分布在NAFLD及健康对照组间无统计学差异(P值均>0.05),ACAT1 rs1044925 AA基因型携带者的LDL水平明显高于C等位基因携带者(Z=−2.08,P=0.04),MTNR1B rs10830963 G等位基因携带者空腹血糖水平明显高于CC基因型携带者(Z=−3.01,P<0.01)。结论ACAT1 rs1044925、rs1157651和MTNR1B rs10830963多态性与NAFLD易感性无明显相关,ACAT1 rs1044925和MTNR1B rs10830963位点分别与LDL和空腹血糖水平有关。 展开更多
关键词 非酒精性脂肪性肝病 乙酰CoA C-乙酰转移酶 受体 褪黑激素
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源于Halomonas sp.抗草甘膦EPSPS的克隆、鉴定及应用
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作者 丁宁 何云浩 +2 位作者 吴琳绯 李婵娟 吴高兵 《华中农业大学学报》 CAS CSCD 北大核心 2024年第3期158-166,共9页
为培育高抗草甘膦作物以应对草甘膦杂草进化,从海洋细菌中筛选到1株高抗草甘膦的盐单胞菌属菌株(Halomonassp.),通过基因组测序及生物信息学分析,确定该菌株的EPSPS基因,在Escherichiacoli(DE3)中对fHoEPSPS、mfHoEPSPS(G384A位点突变)... 为培育高抗草甘膦作物以应对草甘膦杂草进化,从海洋细菌中筛选到1株高抗草甘膦的盐单胞菌属菌株(Halomonassp.),通过基因组测序及生物信息学分析,确定该菌株的EPSPS基因,在Escherichiacoli(DE3)中对fHoEPSPS、mfHoEPSPS(G384A位点突变)和mHoEPSPS(mfHoEPSPS N端缺失PDT)进行重组表达和纯化,并运用自切割肽LP4/2A介导的基因聚合策略,将抗草铵膦的酶(Repat)置于mHoEPSPS的N端,构建了双抗草甘/铵膦酶(RLH),将其编码基因导入烟草后赋予草甘/铵膦复合抗性。结果显示,该菌株的EPSPS基因(fHoEPSPS)可编码一个N段融合了预苯酸脱水酶(PDT)的双功能酶。草甘膦抗性分析显示mfHoEPSPS的抗性比fHoEPSPS提高了19倍,将mHoEPSPS基因导入烟草后可赋予烟草3倍推荐剂量的草甘膦耐受性,转RLH基因的烟草能够耐受3~5倍推荐剂量的草甘/铵膦复合除草剂。结果表明,源于Halomonas sp.的抗草甘膦EPSPS是一种新型草甘膦耐受酶,通过G384A的位点突变可提高酶活;利用自切割肽介导的基因堆叠策略获得的转RLH基因烟草表现出较高草甘/铵膦复合抗性。 展开更多
关键词 抗除草剂作物 抗草甘膦5-烯醇式莽草酸-3-磷酸合成酶 草铵膦乙酰转移酶 双抗除草剂作物 基因聚合
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血清胆碱乙酰转移酶与中青年股骨颈骨折切开复位内固定术后股骨头坏死的关系
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作者 姚有榕 魏强强 +1 位作者 罗正理 王刚 《中国医药导报》 CAS 2024年第15期71-74,共4页
目的 观察血清胆碱乙酰转移酶(ChAT)与中青年股骨颈骨折切开复位内固定术后股骨头坏死的关系。方法 采用回顾性研究,收集2020年1月至2022年9月于中国人民解放军陆军第七十二集团军医院接受切开复位内固定治疗的83例中青年股骨颈骨折患... 目的 观察血清胆碱乙酰转移酶(ChAT)与中青年股骨颈骨折切开复位内固定术后股骨头坏死的关系。方法 采用回顾性研究,收集2020年1月至2022年9月于中国人民解放军陆军第七十二集团军医院接受切开复位内固定治疗的83例中青年股骨颈骨折患者的临床资料,根据其术后6个月是否发生股骨头坏死分为发生组(20例)、未发生组(63例)。比较血清ChAT和基线资料,使用logistic回归分析明确血清ChAT和相关指标与术后股骨头坏死的关系,采用受试者操作特征(ROC)曲线评估血清ChAT与相关指标对患者术后股骨头坏死的预测价值。结果 发生组血清ChAT、一氧化氮(NO)水平低于未发生组(P<0.05)。多因素logistic回归分析显示,血清ChAT(OR=0.811,95%CI:0.716~0.918)与NO(OR=0.845,95%CI:0.732~0.976)是股骨颈骨折患者术后股骨头坏死的影响因素(P<0.05)。ROC曲线显示,血清ChAT对股骨颈骨折患者术后出现股骨头坏死具有良好的预测价值,曲线下面积为0.760;NO对患者术后出现股骨头坏死的预测价值较低,曲线下面积为0.679。结论 血清ChAT、NO是股骨颈骨折患者术后出现股骨头坏死的影响因素,且血清ChAT对其术后出现股骨头坏死具有良好的预测价值。 展开更多
关键词 股骨颈骨折 胆碱乙酰转移酶 切开复位内固定术 股骨头坏死
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大黄素调控组蛋白乙酰化促进HpG2肝癌细胞焦亡及凋亡的发生
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作者 刘国旗 李程程 +1 位作者 刘声菊 朱丽英 《天津医药》 CAS 2024年第1期56-60,共5页
目的 研究天然产物大黄素是否能够影响HpG2肝癌细胞中组蛋白乙酰化水平,进而加速肝癌细胞焦亡和凋亡,为肝癌的治疗提供新的靶点。方法 CCK-8法检测不同浓度大黄素对Hp G2细胞活力的影响;生物信息学分析TCGA数据库中肝癌患者组蛋白乙酰... 目的 研究天然产物大黄素是否能够影响HpG2肝癌细胞中组蛋白乙酰化水平,进而加速肝癌细胞焦亡和凋亡,为肝癌的治疗提供新的靶点。方法 CCK-8法检测不同浓度大黄素对Hp G2细胞活力的影响;生物信息学分析TCGA数据库中肝癌患者组蛋白乙酰化相关基因表达情况,验证候选基因赖氨酸乙酰基转移酶2A(KAT2A)与细胞凋亡通路的相关性;实时荧光定量PCR(q PCR)检测Hep G2细胞与L02细胞KAT2A m RNA水平;酶联免疫吸附试验(ELISA)检测大黄素对Hp G2细胞中组蛋白乙酰转移酶(HAT)、组蛋白去乙酰转移酶(HDAC)、白细胞介素(IL)-1β、IL-18的影响;流式细胞术检测大黄素对肝癌细胞凋亡的影响;Western blot检测细胞凋亡、细胞焦亡相关蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl-2-相关X蛋白质(Bax)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶1(Caspase-1)、Gasdermin家族成员D N端(GSDMD-N)及KAT2A的表达情况。结果 大黄素能降低Hp G2细胞活性,半抑制浓度(IC_(50))95%置信区间为58.12~66.52μmol/L。与正常肝组织相比,组蛋白乙酰化相关基因m RNA水平在肝癌组织中表达增高,且KAT2A变化倍数最大[log_2(Fold Change)=2.010,P<0.01];在肝癌组织中,KAT2A m RNA的表达与细胞凋亡通路呈负相关(r_s=-0.230,P<0.01)。与L02细胞相比,KAT2A m RNA在Hep G2中表达升高(P<0.05);与对照组相比,大黄素干预组HAT和HDAC的表达水平下降,IL-18、IL-1β表达水平水平增高,细胞凋亡率升高,KAT2A、BAX的表达降低,Bcl-2、NLRP3、GSDMD-N及Caspase-1表达水平升高(P<0.05)。结论 大黄素可抑制肝癌细胞活力,加速细胞凋亡和焦亡,其机制可能与调控KAT2A表达相关。 展开更多
关键词 大黄素 肝细胞 乙酰化作用 乙酰基转移酶类 组蛋白类 细胞焦亡 细胞凋亡 KAT2A
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铜死亡相关基因DLAT在胰腺癌中的表达及临床意义
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作者 张钦泉 匡鹏 +4 位作者 董毅 王理承 毛连春 李中虎 金炜东 《联勤军事医学》 CAS 2024年第2期105-112,共8页
目的 探讨铜死亡相关基因在胰腺癌中发挥的作用,构建预后模型,筛选并验证铜死亡相关基因在胰腺癌中发挥的重要作用。方法 利用生物学数据库分析胰腺癌中铜死亡相关基因的表达水平、预后分析并构建预后模型。结果 以二氢硫辛酰胺S-乙酰... 目的 探讨铜死亡相关基因在胰腺癌中发挥的作用,构建预后模型,筛选并验证铜死亡相关基因在胰腺癌中发挥的重要作用。方法 利用生物学数据库分析胰腺癌中铜死亡相关基因的表达水平、预后分析并构建预后模型。结果 以二氢硫辛酰胺S-乙酰转移酶(dihydrolipoamide S-acetyltransferase, DLAT)为代表的铜死亡相关基因在胰腺癌中高表达(P均<0.05)。以铜死亡相关基因构建预后模型,与低风险评分胰腺癌患者相比,高风险评分胰腺癌患者预后较差(P<0.05)。公共数据库及临床数据的免疫组织化学法验证了DLAT在胰腺癌中高表达不利于胰腺癌患者预后,其表达水平可作为胰腺癌患者病情进展的独立危险因素(P均<0.05)。结论 铜死亡相关基因可以作为胰腺癌患者潜在的预后预测因子。以DLAT为代表的铜死亡相关基因可能为胰腺癌治疗提供新的途径。 展开更多
关键词 铜死亡相关基因 二氢硫辛酰胺S-乙酰转移酶 胰腺癌 免疫组织化学 预后
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中枢胆碱能神经元变性对小鼠肝叶切除术后认知功能的影响
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作者 文进秋 郑敏 +4 位作者 李新灵 阎晨 刘涛 王博 刘玉婷 《山东医药》 CAS 2024年第8期39-42,共4页
目的观察中枢胆碱能神经元变性对小鼠肝叶切除术后认知功能的影响。方法将C57BL/6小鼠随机分为麻醉组、手术组、多奈哌齐组、mu-p75-sap组、对照组,每组5只。麻醉组动物吸入2.6%七氟烷、30%氧气、70%氮气混合气体6 h麻醉;手术组、多奈... 目的观察中枢胆碱能神经元变性对小鼠肝叶切除术后认知功能的影响。方法将C57BL/6小鼠随机分为麻醉组、手术组、多奈哌齐组、mu-p75-sap组、对照组,每组5只。麻醉组动物吸入2.6%七氟烷、30%氧气、70%氮气混合气体6 h麻醉;手术组、多奈哌齐组、mu-p75-sap组采用同法麻醉并接受肝叶切除手术,其中多奈呱齐组术前给予选择性可逆中枢乙酰胆碱酯酶(AChE)抑制剂多奈哌齐5 mg/kg灌胃4周,mu-p75-sap组麻醉后向小鼠各侧脑室双侧各注射免疫毒素mu-p75-sap 0.8μg制作胆碱能神经元变性模型。对照组动物不进行手术和麻醉操作。采用Morris水迷宫实验检测小鼠学习和记忆能力,采用考马斯亮兰蛋白测定试剂盒检测各组海马组织中枢胆碱能神经生物标志物[胆碱乙酰转移酶(ChAT)、AChE、乙酞胆碱(Ach)]。结果与对照组相比,手术组逃逸潜伏期延长,AChE表达增高,停留时间、穿越平台次数和海马组织ChAT、Ach表达减少(P均<0.05)。与手术组相比,多奈哌齐组逃逸潜伏期缩短、停留时间和穿越平台次数增多、AChE表达降低、ChAT和Ach表达增高,mu-p75-sap组小鼠逃逸潜伏期延长、停留时间和穿越平台次数减少、ChAT和Ach表达降低、AChE表达增高(P均<0.05)。结论肝叶切除术可影响小鼠术后认知功能,中枢胆碱能神经元变性可加重对术后认知功能的影响,可能会导致术后认知障碍的发生发展。 展开更多
关键词 胆碱能神经元变性 术后认知功能 肝叶切除术 乙酰胆碱酯酶 胆碱乙酰转移酶 乙酞胆碱
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高糖诱导HT-22小鼠海马神经元代谢记忆细胞模型的构建及影响
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作者 段云峰 许永劼 +4 位作者 杨婷婷 黄昶煜东 朱丽英 李兴 潘卫 《天津医药》 CAS 2024年第1期44-50,共7页
目的 体外构建高糖诱导HT-22小鼠海马神经元“代谢记忆”细胞模型,探究“代谢记忆”对HT-22细胞凋亡和组蛋白乙酰化的影响。方法 以高糖培养基(葡萄糖浓度为55 mmol/L)和常规糖培养基(葡萄糖浓度为25 mmol/L)培养HT-22细胞,分为常糖组(N... 目的 体外构建高糖诱导HT-22小鼠海马神经元“代谢记忆”细胞模型,探究“代谢记忆”对HT-22细胞凋亡和组蛋白乙酰化的影响。方法 以高糖培养基(葡萄糖浓度为55 mmol/L)和常规糖培养基(葡萄糖浓度为25 mmol/L)培养HT-22细胞,分为常糖组(NG 4、6、8组,25 mmol/L葡萄糖分别培养4、6、8 d),高糖组(HG 4、6、8组,高糖培养4、6、8 d),代谢记忆组(HG2NG2、HG2NG4、HG2NG6、HG4NG2、HG4NG4组,即高糖2 d转25 mmol/L葡萄糖培养2、4或6 d,高糖4 d转25 mmol/L葡萄糖培养2 d或4 d)。CCK-8法检测细胞活力变化,检测细胞培养上清液中乳酸脱氢酶(LDH)释放量,筛选出建立“代谢记忆”模型的最佳作用时间。后续将细胞分为NG4组、NG8组、HG4组、HG4NG4组和HG8组,光学显微镜观察各组细胞形态;流式细胞术检测各组细胞凋亡率;酶联免疫吸附试验(ELISA)检测去乙酰化酶(HDAC)和组蛋白乙酰转移酶(HAT)活性;Western blot检测组蛋白去乙酰化酶4(HDAC4)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和胱天蛋白酶3(Caspase-3)蛋白表达情况。结果 HG4NG4组为理想的高糖“代谢记忆”细胞模型;NG4、NG8组细胞交织成致密网状,生长状态良好,细胞呈梭形,突触结构明显。而HG4、8组细胞胞体变圆,突触结构消失,生长受抑,HG4NG4组细胞数量增多但形态受损;流式细胞术结果显示,与NG8组相比,HG8、HG4NG4组凋亡率增加(P<0.05);ELISA结果表明,与NG8组相比,HG8组及HG4NG4组HAT和HDAC的水平均增高(P<0.05),与HG8组相比,HG4NG4组HAT和HDAC差异无统计学意义;Western blot结果显示,与NG8组相比,HG8组、HG4NG4组HDAC4、Bax和Caspase-3蛋白表达增加,Bcl-2蛋白表达水平降低(P<0.05),与HG8组相比,HG4NG4组蛋白表达差异无统计学意义。结论 HT-22小鼠海马神经元细胞经高糖55 mmol/L培养4 d后,再以25 mmol/L葡萄糖培养4 d是理想的高糖“代谢记忆”细胞模型。其机制可能与高糖模型中HDAC、HAT活性及HDAC4表达升高有关。 展开更多
关键词 糖尿病 脑疾病 细胞凋亡 组蛋白乙酰转移酶 组蛋白脱乙酰基酶类 HT-22 代谢记忆
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N-乙酰基转移酶10通过催化赖氨酸残基和胞嘧啶碱基的乙酰化修饰在多种生物学过程和疾病中发挥作用
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作者 周锐 隋亚奇 赵文会 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第2期160-169,共10页
N-乙酰基转移酶10(N-acetyltransferase 10,NAT10)是一种具有乙酰基转移酶活性的核仁蛋白质,可催化蛋白质赖氨酸残基和RNA胞嘧啶碱基的乙酰化修饰。近年来,大量研究表明,这些乙酰化修饰在端粒酶活性调节、细胞基本且核心功能的调节、细... N-乙酰基转移酶10(N-acetyltransferase 10,NAT10)是一种具有乙酰基转移酶活性的核仁蛋白质,可催化蛋白质赖氨酸残基和RNA胞嘧啶碱基的乙酰化修饰。近年来,大量研究表明,这些乙酰化修饰在端粒酶活性调节、细胞基本且核心功能的调节、细胞胁迫响应、DNA损伤修复、细胞周期调控、核糖体RNA的生物学合成、mRNA稳定性及翻译效率的调节等多种生命活动中发挥重要作用,并且与人类癌症、Hutchinson-Gilford早衰综合症(Hutchinson-Gilford premature aging syndrome,HGPS)的发生、发展和预后密切相关。然而,关于NAT10的研究仍存在一些局限性,例如NAT10完整的结构以及这些结构对其功能的影响仍未知,由NAT10调控的细胞基本功能也尚不清楚,并且NAT10对人类癌症和HGPS发展的具体影响机制也待阐明。本文从NAT10的结构、酶活性、生物学功能及其在疾病中的作用进行了综述,并提出了目前研究的局限性,展望了未来的研究方向,以期为NAT10的相关研究提供参考。 展开更多
关键词 N-乙酰基转移酶10 乙酰化修饰 rRNA生物学合成 mRNA稳定性及翻译效率调节 Hutchinson-Gilford早衰综合症
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Effect of Nao Yikang on choline acetyltransferase and caspase-3 brain expression in a rat model of Alzheimer's disease 被引量:3
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作者 Jinsong Geng Hengjian Ni +3 位作者 Jiancheng Dong Kui Jiang Ailing Zhou Yae Hu 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第12期1073-1077,共5页
BACKGROUND: The main components of the traditional Chinese medicine compound Nao Yikang have been shown to possibly alleviate neural damage. OBJECTIVE: To observe the effects of Nao Yikang on expression of choline a... BACKGROUND: The main components of the traditional Chinese medicine compound Nao Yikang have been shown to possibly alleviate neural damage. OBJECTIVE: To observe the effects of Nao Yikang on expression of choline acetyltransferase (CHAT) and caspase-3 in the rat brains of an experimental Alzheimer's disease (AD) model, and to investigate the mechanisms of potential neuroprotective effects. DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Department of Pathophysiology, Medical School of Nantong University between November 2006 and December 2007. MATERIALS: The main active components of Nao Yikang were as follows: prepared polygonum multiflorum, Rhizoma anemarrhenae, and Rhizoma acori tatarinowii. Nao Yikang granules were prepared by Nantong Hospital of Traditional Chinese Medicine. Ibotenic acid (IBO) was purchased from Sigma-Aldrich, USA, ChAT goat anti-rat antibody from Chemicon, USA, and cleaved caspase-3 rabbit anti-rat (Asp175) (5A1) antibody from Cell Signaling, USA. METHODS: A total of 60 male, Sprague Dawley rats (2 months old) were randomly assigned to 6 groups: sham-surgery, model, Nao Yikang 1.73, 3.45, 6.90 g/kg per day, and piracetam, with 10 rats in each group. Bilateral infusions of 5 pg IBO into the nucleus basalis of Meynert were performed with Hamilton syringe and stereotaxic apparatus for AD model establishment. For the sham-surgery group, rats received 1 μL saline in the identical stereotaxic position. From the second day, Nao Yikang groups were administrated 1.73, 3.45, and 6.90 g/kg per day Nao Yikang, respectively, while the piracetam group received 0.04 g/mL piracetam, the model group received 0.5% sodium carboxymethyl cellulose, and the sham-surgery group received normal saline. Rats were intragastrically administered 1 mL/100 g daily for 28 consecutive days. MAIN OUTCOME MEASURES: Following treatment of the various solutions for 28 days, Western blot was utilized to observe ChAT expression in the frontal cortex of AD rats, and immunohistochemistry was applied to quantify caspase-3-positive cells in the frontal cortex. RESULTS: ChAT protein expression significantly decreased in the model group (P 〈 0.01), however caspase-3 expression was significantly elevated (P 〈 0.01) compared with the sham-surgery group. Compared with the model group, ChAT protein expression increased in the Nao Yikang 1.73 g/kg per day, 3.45 g/kg per day, 6.90 g/kg per day groups, and the piracetam group (P 〈 0.05 or P 〈 0.01) and the number of caspase-3-positive cells decreased in the Nao Yikang 3.45 g/kg per day and 6.90 g/kg per day groups (P 〈 0.01). However, there was no change in the number of caspase-3-positive cells in the 3.45 g/kg per day group. CONCLUSION: The traditional Chinese medicine compound Nao Yikang increased ChAT protein expression and suppressed caspase-3 expression in the frontal cortex in a dose-dependent manner. 展开更多
关键词 Alzheimer's disease Nao Yikang choline acetyltransferase CASPASE-3
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Estrogen intervention in microvascular morphology and choline acetyltransferase expression in rat hippocampal neurons in chronic cerebral ischemia 被引量:1
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作者 Zhenjun Yang Hongwei Yan +2 位作者 Guomin Zhang Zhihong Chen Jingfeng xue 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第17期1285-1290,共6页
We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and... We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia. 展开更多
关键词 ESTROGEN chronic cerebral ischemia HIPPOCAMPUS MICROVASCULATURE Bcl-2 BAX choline acetyltransferase neural regeneration
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N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer 被引量:4
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作者 Tiago Donizetti da Silva Aledson Vitor Felipe +2 位作者 Jacqueline Miranda de Lima Celina Tizuko Fujiyama Oshima Nora Manoukian Forones 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第6期760-765,共6页
AIM:To investigate the possible association between meat intake,cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.METHODS:Patients with CRC were matched for gende... AIM:To investigate the possible association between meat intake,cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.METHODS:Patients with CRC were matched for gender and age to healthy controls.Meat intake and cigarette smoking were assessed using a specific frequency questionnaire.DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism.Five NAT2 alleles were studied (WT,M1,M2,M3 and M4) using specific digestion enzymes.RESULTS:A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied.The mean age of the two groups was 62 years.More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators.The odds ratio for colorectal cancer was 1.38 (95% CI:0.90-2.12) in slow acetylators.Although the number of women was small (n=76 in the case group),the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR):0.55,95% confidence interval (95% CI):0.29-1.02].This difference was not observed in men (OR:0.56,95% CI:0.16-2.00).Among NAT2 fast acetylators (W/W or W/Mx),meat consumption more than 3 times a week increased the risk of colorectal cancer (OR:2.05,95% CI:1.01-4.16).In contrast,cigarette smoking increased the risk of CRC among slow acetylators (OR:1.97,95% CI:1.02-3.79).CONCLUSION:The risk of CRC was higher among fast acetylators who reported a higher meat intake.Slow NAT2 acetylation was associated with an increased risk of CRC. 展开更多
关键词 乙酰基转移酶 基因多态性 大肠癌 危险 限制性片段长度多态性 聚合酶链反应 平均年龄 遗传多态性
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Histone acetyltransferase GCN5 interferes with the miRNA pathway in Arabidopsis 被引量:11
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作者 Wanhui Kim Moussa Benhamed Caroline Servet David Latrasse Wei Zhang Marianne Delarue Dao-Xiu Zhou 《Cell Research》 SCIE CAS CSCD 2009年第7期899-909,共11页
MicroRNAs (miRNA ) 指导在基因表示的一个重要角色在植物为到环境条件的发展进程和回答要求了的顺序特定的 posttranscriptional 基因 silencing 玩。然而,很少对 transcriptional 和 miRNA 表示的 posttranscriptional 规定被知道。H... MicroRNAs (miRNA ) 指导在基因表示的一个重要角色在植物为到环境条件的发展进程和回答要求了的顺序特定的 posttranscriptional 基因 silencing 玩。然而,很少对 transcriptional 和 miRNA 表示的 posttranscriptional 规定被知道。Histone acetylation 在染色质改变起一个重要作用并且为基因激活被要求。由在 Arabidopsis 的异种分析 miRNAs 和相应主要 miRNAs 的子集的累积,我们显示出那 histone acetyltransferase GCN5 (一般控制非镇压的 protein5 )在 miRNA 上有一般压抑的效果生产,当它为一个子集的表示被要求时(例如压力可诱导) MIRNA 基因。在 miRNA 生产的 GCN5 的一般否定功能多半通过象 DICER LIKE1 (DCL1 ) 那样的 miRNA 机械基因的间接压抑被完成,有锯齿(SE ) ,偏下性的 LEAVES1 (HYL1 ) 和 ARGONAUTE1 (AGO1 ) 。染色质 immunoprecipitation 试金表明 GCN5 指向到 MIRNA 基因的一个子集并且为在这些 loci 的 histone H3 离氨酸 14 的 acetylation 被要求。而且,由 trichostatin 的 histone deacetylation 的抑制一个处理或在 histone deacetylase,基因异种损害了某些 miRNAs 的累积。这些数据一起建议 Arabidopsis GCN5 在 transcriptional 和 posttranscriptional 层次防碍 miRNA 小径, histone acetylation/deacetylation 是涉及 miRNA 的规定的 epigenetic 机制生产。 展开更多
关键词 组蛋白乙酰转移酶 MIRNA 拟南芥 通路 干扰
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Polymorphism of N-acetyltransferase 2 (NAT2) Gene Polymorphism in Shanghai population: Occupational and Non-occupational Bladder Cancer Patient Groups 被引量:13
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作者 QING-WENMA GUO-FANGLIN +4 位作者 JI-GANGCHEN CUI-QINGXIANG WEI-CHAOGUO KLAUSGOLKA JIAN-HUASHEN 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2004年第3期291-298,共8页
Objective Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzi... Objective Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism. Methods NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A. Results The wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P<0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients. Conclusion The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups. 展开更多
关键词 BENZIDINE Occupational exposure N-acetyltransferase 2 POLYMORPHISM Bladder cancer Dyestuff industry
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Are polymorphisms of N-acetyltransferase genes susceptible to primary liver cancer in Luoyang, China? 被引量:3
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作者 Xiu-FengZhang Jian-ChaoBian +6 位作者 Xiao-YanZhang Zhu-MeiZhang FengJiang Qi-MinWang Qi-JunWang Yan-YanCao Bo-MingTang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第10期1457-1462,共6页
AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 P... AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 PLC cases and 173 controls were determined by PCR-RFLP.Both interaction between NAT1 or NAT2 and environmental risk factors were analyzed based on case control study.RESULTS: Compared to the control group, the frequencies of alleles NAT1*3, NAT1*4, NAT1*10, NAT1*14B and alleles NAT2*4, NAT2*6, NAT2*7 in PLC group showed no statistically significant difference (x2 = 2.61 and 4.16,respectively, both P>0.05). The frequencies of NAT1 genotypes NAT1*3/*3, NAT1*3/*4, NAT1*3/*10,NAT1*3/*14B, NAT1*4/*4, NAT1*4/*10, NAT1*4/*14B,NAT1*10/*10, NAT1*10/*14B, and NAT2 genotypes NAT2*4/*4, NAT2*4/*6, NAT2*4/*7, NAT2*6/*6,NAT2*6/*7 and NAT2*7/*7 also had no statistically significant difference between the two groups (x2 = 11.86 and 2.94respectively both, P>0.05). Neither the frequencies of rapid and slow NAT1 acetylators nor the frequencies of rapid and slow NAT2 acetylators were significantly different between the two groups (x2 = 0.598 and 0.44,respectively, both P>0.05). The interaction betweenNAT1*10 and occupational exposures was found significant with an odds ratio of 3.40 (x2 = 8.42, P = 0.004,OR 95%CI:1.03-11.22). But no interaction was found between NAT2 and any environmental risk factors.CONCLUSION: The polymorphisms of NAT1 and NAT2are not susceptible to PLC in Luoyang. Allele NAT1*10interacts with occupational exposures. 展开更多
关键词 N-乙酰转移酶 基因表达 原发型肝癌 洛阳市
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