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旋毛虫5′-nucleotidase基因特征与克隆表达 被引量:1
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作者 廖成水 王晓利 +7 位作者 杜付玉 郁川 余祖华 张春杰 李银聚 吴庭才 刘明远 程相朝 《中国人兽共患病学报》 CAS CSCD 北大核心 2018年第11期971-976,共6页
目的研究旋毛虫5′-nucleotidase基因的序列结构特征及其蛋白克隆表达。方法从旋毛虫获得5′-nucleotidase基因的序列,利用生物信息学方法进行系统性分析,并进行原核表达。结果旋毛虫5′-nucleotidase基因大小为1 653bp,编码550个氨基酸... 目的研究旋毛虫5′-nucleotidase基因的序列结构特征及其蛋白克隆表达。方法从旋毛虫获得5′-nucleotidase基因的序列,利用生物信息学方法进行系统性分析,并进行原核表达。结果旋毛虫5′-nucleotidase基因大小为1 653bp,编码550个氨基酸,119个氨基酸残基组成,理论相对分子质量(Mr)为62kD,分子式为C_(2800)H_(4358)N_(742)O_(803)S_(23),等电点为6.13,属于稳定存在的亲水蛋白质。该蛋白含有21个氨基酸组成的信号肽,同时具有跨膜区域,此外还含有3个N-糖基化位点、2个O-糖基化位点、20个磷酸化位点、28个B细胞线性结合位点和13个T细胞结合位点。二级结构中,α-螺旋占43.27%(238个),伸展链占22.73%(125个),β-折叠占7.82%(43个),无规则卷曲占26.18%(144个)。SDS-PAGE显示,5′-nucleotidase基因在原核表达系统中呈可溶性形式表达,重组蛋白大小约为74kD。结论成功克隆了旋毛虫5′-nucleotidase基因,对其进行序列分析和原核表达,为进一步探究5′-nucleotidase蛋白在旋毛虫感染过程中的作用奠定基础。 展开更多
关键词 旋毛虫 5′-nucleotidase 克隆 原核表达 生物信息学
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Study the effect of kidney stones on serum xanthine oxidase, ecto-5'-nucleotidase activity and E3 SUMO-protein ligase NSE2(NSMCE2) in Malaysian individuals
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作者 Faridah Yusof Atheer Awad Mehde +2 位作者 Wesen Adel Mehdi Hamid Ghazali Azlina Abd Rahman 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2015年第8期665-668,共4页
Objective: To verify possible relations between 5'-nucleotidase, xanthine oxidase to E3 small ubiquitin-like modifier-protein ligase non structural maintenance of chromosomes elements 2 in sera patients with kidne... Objective: To verify possible relations between 5'-nucleotidase, xanthine oxidase to E3 small ubiquitin-like modifier-protein ligase non structural maintenance of chromosomes elements 2 in sera patients with kidney stones and to evaluate the possibility of a new biomarker for the evaluation of kidney damage. Methods: A sixty patients with known kidney stones who appeared the government health clinics in Kuantan–Pahang and fifty apparently healthy were taken as control group. The 5'-nucleotidase,xanthine oxidase and other biochemical parameters were measured by colorimetric tests. The serum NSMCE2 were measured by enzyme linked immunosorbent assay.Results: The mean serum xanthine oxidase [(39.98±19.70) IU/L] and ecto-5'-nucleotidase activity(40.03±9.53 IU/L) were significantly higher than the controls' levels of(18.04 ±6.26) and(16.06 ±4.61) IU/L respectively. There were 85.00% and 83.33%, of patients with kidney stones who had abnormal ecto-5'-nucleotidase activity and uric acid respectively while xanthine oxidase activity was less sensitive 58.33%.Conclusions: The present study suggests that the increase in serum of xanthine oxidase,ecto-5'-nucleotidase activities E3 small ubiquitin-like modifier-protein ligase NSE2 concentration can be used as biomarkers for diagnosis of kidney damage in patients with kidney stone,also in developments of change DNA damage and inflammation disorders in these patients. 展开更多
关键词 Kidney stones XANTHINE OXIDASE Ecto-5-nucleotidase E3 SUMO-protein LIGASE NSE2
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Effect of Fertilizer Diammonium Phosphate on Liver,Kidney and Muscle 5-Nucleotidase Activity of Fresh Water Teleost Fish Clarias batrachus
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作者 T.S.NAQVI M.S.NAQVI R.K.SINGH 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1993年第4期385-388,共4页
The toxic effect of fertilizer Diammonium phosphate resulted in alterations of 5'-Nucleotidase activity of tissues liver, kidney and muscles offish C. batrachus at varying intervals and exposures. Alterations in 5... The toxic effect of fertilizer Diammonium phosphate resulted in alterations of 5'-Nucleotidase activity of tissues liver, kidney and muscles offish C. batrachus at varying intervals and exposures. Alterations in 5'-Nuclcotidase activity of body organs gave an idea of the toxicity caused by the fertilizer. Thus the enzyme 5'-Nucleotidase can be used to monitor the pollution in aquatic ecosystem. 展开更多
关键词 Effect of Fertilizer Diammonium Phosphate on Liver Kidney and Muscle 5-nucleotidase Activity of Fresh Water Teleost Fish Clarias batrachus
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Changes in Adenosine Metabolism in Asthma. A Study on Adenosine, 5&#39-NT, Adenosine Deaminase and Its Isoenzyme Levels in Serum, Lymphocytes and Erythrocytes
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作者 Jitender Sharma Bala K. Menon +1 位作者 Vannan K. Vijayan Surendra K. Bansal 《Open Journal of Respiratory Diseases》 2015年第2期33-49,共17页
Background: Adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) play a crucial role in adenosine metabolism in healthy individuals. Adenosine is an inflammatory mediator of asthma. Changes in adenosine metab... Background: Adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) play a crucial role in adenosine metabolism in healthy individuals. Adenosine is an inflammatory mediator of asthma. Changes in adenosine metabolism and role of ADA and 5'-NT in regulating adenosine level in asthmatics and correlation of these changes with severity of asthma are not clearly understood. Methods: In this study, we screened 5217 patients, of which 2416 were diagnosed with asthma. Further, of 2416 asthmatics, only 45 patients who strictly fulfilled the selection criteria were enrolled in the study. The patients were classified into mild, moderate and severe persistent groups;each group consisted of fifteen patients. Fifteen healthy subjects served as controls. Adenosine levels and activities of 5'-NT, total ADA, ADA1 and ADA2 in serum, lymphocytes and erythrocytes were determined. The data were analysed statistically and p vice versa. 展开更多
关键词 ASTHMA ADENOSINE metabOLISM ADENOSINE DEAMINASE 5'-nucleotidase
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手性流动相添加剂法测定5-(对-羟基苯基)-5-苯基乙内酰脲的体外代谢的立体选择性 被引量:4
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作者 姚彤炜 曾苏 丁海青 《浙江医科大学学报》 CSCD 1996年第5期197-200,共4页
作者研究了5-(对-羟基苯基)-5-苯基乙内酰脲(p-HPPH)体外形成葡萄糖醛酸甙的立体选择性。以β-环糊精为手性流动相添加剂,反相高效液相法测定底物S-和R-p-HPPH的消失量。结果显示,在苯巴比妥(PB)和β... 作者研究了5-(对-羟基苯基)-5-苯基乙内酰脲(p-HPPH)体外形成葡萄糖醛酸甙的立体选择性。以β-环糊精为手性流动相添加剂,反相高效液相法测定底物S-和R-p-HPPH的消失量。结果显示,在苯巴比妥(PB)和β-萘黄酮(β-NF)诱导的鼠肝微粒体中,R-p-HPPH形成葡萄糖醛酸甙较S-p-HPPH快,尤其是β-NF诱导的微粒体,反应液中S-/R-浓度比值由起始时1.0,经反应50min后上升到1.85;而PB诱导的微粒体,经50min反应后,S-/R-浓度比值为1.09。这一结果表明,β-NF诱导的鼠肝微粒体对R-p-HPPH葡萄糖醛酸甙的形成,具有显著的立体选择性。 展开更多
关键词 羟基苯基 苯基乙内酰脲 代谢 高效液相色谱
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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease
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作者 Milica Zeljkovic Jovanovic Jelena Stanojevic +4 位作者 Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic 《Neural Regeneration Research》 SCIE CAS 2025年第7期2053-2067,共15页
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog... An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control. 展开更多
关键词 A_(1)R A_(2A)R adenosine receptors ADENOSINE ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling
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鼠伤寒沙门菌5'-nucleotidase基因缺失株的构建及其生物学特性的研究 被引量:1
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作者 张梦珂 廖成水 +5 位作者 毛福超 王晓利 张春杰 李银聚 吴庭才 程相朝 《中国兽医科学》 CAS CSCD 北大核心 2019年第5期589-597,共9页
为了探究5'-nucleotidase基因的功能及其在鼠伤寒沙门菌感染中的作用,本研究首先构建缺失1 112 bp的5'-nucleotidase基因的重组自杀性质粒pR E 112Δ5'-nucleotidase,利用重组自杀性质粒介导的等位基因交换技术,两步法筛选... 为了探究5'-nucleotidase基因的功能及其在鼠伤寒沙门菌感染中的作用,本研究首先构建缺失1 112 bp的5'-nucleotidase基因的重组自杀性质粒pR E 112Δ5'-nucleotidase,利用重组自杀性质粒介导的等位基因交换技术,两步法筛选出SL1344Δ5'-nucleotidase缺失株,并对其生物学特性进行初步研究。PCR及测序结果表明,SL1344Δ5'-nucleotidase构建成功,且回复株SL1344CΔ5'-nucleotidase构建成功。进一步研究表明,缺失株SL1344Δ5'-nucleotidase保留了亲本菌株SL1344的血清型1,4,5,12∶i∶1,2,且能够稳定遗传缺失1 112 bp的5'-nucleotidase基因,生长速度没有发生明显改变。但是,缺失株SL1344Δ5'-nucleotidase口服感染6周龄BALB/c小鼠的LD50为4.30×10~7CF U,毒力降低至亲本株SL1344的1.96%。免疫保护率试验结果显示,对6周龄BALB/c小鼠免疫后第17天,鼠伤寒沙门菌野生株攻毒有50%的保护率。缺失株免疫小鼠后第21天,血清抗体IgG水平达到最高。回复菌株与亲本亲株之间生物学特性无显著性差异,基本恢复到野生型水平。上述结果表明,SL1344Δ5'-nucleotidase基因缺失株构建成功,遗传稳定,毒力明显降低,且具有较好的免疫原性,为研究鼠伤寒沙门菌5'-nucleotidase基因与其致病力之间的关系提供了依据,并为研究它在鼠伤寒沙门菌感染中的作用奠定了基础。 展开更多
关键词 鼠伤寒沙门菌SL1344 5-nucleotidase基因 缺失株 回复株 生物学特性
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过敏性疾病患者血清Th1/Th2细胞因子和趋化因子测定及其意义 被引量:12
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作者 韩睿 林爱华 +2 位作者 朱可建 程浩 吴善东 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2009年第4期352-356,共5页
目的:检测过敏性疾病患者血清Th1细胞因子IFN-γ和Th2细胞因子IL-4、IL-5、IL-13以及趋化因子Eotaxin、RANTES、LTB4的水平,探讨其临床意义。方法:过敏性疾病患者64例,正常对照21例。采用双抗体夹心酶联免疫吸附实验(ELISA)检测血清IL-4... 目的:检测过敏性疾病患者血清Th1细胞因子IFN-γ和Th2细胞因子IL-4、IL-5、IL-13以及趋化因子Eotaxin、RANTES、LTB4的水平,探讨其临床意义。方法:过敏性疾病患者64例,正常对照21例。采用双抗体夹心酶联免疫吸附实验(ELISA)检测血清IL-4、IL-5、IL-13、IFN-γ、LTB4、RANTES和Eotaxin水平。结果:1过敏性疾病患者血清IL-4、IL-5、IL-13和Eotaxin、LTB4水平较对照组明显增高,差异有统计学意义(P<0.05)。2IFN-γ和RANTES在过敏性疾病患者血清中的水平低于对照组,但无统计学差异(P>0.05)。3IL-4、IL-5、IL-13和LTB4彼此之间呈显著正相关(P<0.01)。4Eotaxin、RANTES和IFN-γ彼此之间呈显著正相关(P<0.05)。5LTB4和Eotaxin之间呈显著正相关(P<0.01)。结论:过敏性疾病的发生存在多种细胞因子和趋化因子复杂的相互作用。 展开更多
关键词 细胞因子类 Th1细胞/代谢 Th2细胞/代谢 白细胞介素4/代谢 白细胞介素5/代谢 白细胞介素13/代谢 干扰素Ⅱ型/代谢 趋化因子类 RANTES/代谢 过敏反应/病理生理学
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mthfr基因第1298位核苷酸多态性与酶活性的关系 被引量:21
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作者 朱慧萍 刘明珠 +1 位作者 刀京晶 李竹 《北京医科大学学报》 CSCD 2000年第3期262-264,共3页
探讨mthfr基因第 12 98位核苷酸的多态性对酶活性及热稳定性的影响。方法 :用PCR RFLP方法检测 6 4例中国女性mthfr基因第 12 98位核苷酸 ,并检测外周血淋巴细胞MTHFR酶活性和 46℃灭活 5min后的残余酶活性 ,比较不同基因型其酶活性和... 探讨mthfr基因第 12 98位核苷酸的多态性对酶活性及热稳定性的影响。方法 :用PCR RFLP方法检测 6 4例中国女性mthfr基因第 12 98位核苷酸 ,并检测外周血淋巴细胞MTHFR酶活性和 46℃灭活 5min后的残余酶活性 ,比较不同基因型其酶活性和热稳定性的差别。结果 :第 6 77位核苷酸基因型为 6 77CC时 ,正常型12 98AA平均酶活性最高 ,为每毫克蛋白每小时 12 .2 6 3nmolCH2 O ,杂合型 12 98AC平均酶活性为每毫克蛋白每小时 9.5 2 4nmolCH2 O ,纯合突变型 12 98CC酶活性最低 ,仅为每毫克蛋白每小时 7.830nmolCH2 O ;第 12 98位核苷酸不同基因型的残余酶活性无明显差别。结论 :mthfr基因第 12 98位核苷酸由A→C的变异可引起酶活性降低 ,但与热稳定性无关。 展开更多
关键词 亚甲基四氢叶酸 脱氢酶 代谢 基因多态性
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预处理对大鼠肝脏缺血再灌注损伤的影响 被引量:12
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作者 刘秀华 庞永政 +2 位作者 陈魁 苏静怡 唐朝枢 《北京医科大学学报》 CSCD 1996年第3期208-210,共3页
目的:探讨预处理(PC)对大鼠肝脏I/R损伤的影响及其机制。方法:采用原位灌流肝脏I/R模型,观察肝脏组织损伤、血管床功能、肝脏5′-核苷酸酶活性及分布的改变。结果:PC减少肝组织MDA产生及LDH漏出(均P<0.0... 目的:探讨预处理(PC)对大鼠肝脏I/R损伤的影响及其机制。方法:采用原位灌流肝脏I/R模型,观察肝脏组织损伤、血管床功能、肝脏5′-核苷酸酶活性及分布的改变。结果:PC减少肝组织MDA产生及LDH漏出(均P<0.0l),并抑制I/R引起的5′-核苷酸酶活性下降。结论:PC对肝脏I/R损伤有保护作用,5′-核苷酸酶参与了该保护机制。 展开更多
关键词 肝缺血 再灌流损伤 预处理
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淋巴管生成因子与大肠癌转移的相关性研究 被引量:1
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作者 吕媛芳 贺建宇 《临床肿瘤学杂志》 CAS 2009年第4期309-313,共5页
目的:探讨淋巴管生成因子的定量表达与大肠癌转移的相关性。方法:本文通过收集已有淋巴结转移的大肠腺癌手术标本37例,运用荧光实时定量PCR技术对淋巴管生成因子LYVE-1、Prox-1、podoplanin及5’-nucleotidase分子表达进行定量分析,分... 目的:探讨淋巴管生成因子的定量表达与大肠癌转移的相关性。方法:本文通过收集已有淋巴结转移的大肠腺癌手术标本37例,运用荧光实时定量PCR技术对淋巴管生成因子LYVE-1、Prox-1、podoplanin及5’-nucleotidase分子表达进行定量分析,分别比较这些因子在切除标本的肿瘤、癌旁正常组织中表达的差异。结果:Prox-1及podoplanin在肿瘤及癌旁正常组织分别为:Prox-1表达量为0.96±0.25和0.52±0.22(P=0.003 8),podoplanin表达量为0.87±0.26和0.78±0.22(P=0.028 8),并与肿瘤的淋巴结转移有关。LYVE-1在肿瘤及癌旁正常组织中表达都明显增加,分别为0.90±0.28和0.87±0.26(P=0.365),未检出5’-nucleotidase在肿瘤及癌旁正常组织中的表达。结论:Prox-1及podoplanin与大肠癌发生及淋巴结转移可能有一定关系,联合检测Prox-1和podoplanin的表达,对了解大肠癌的侵袭转移及判定预后具有一定价值。 展开更多
关键词 大肠癌 淋巴管内皮标记物 PROX-1 PODOPLANIN 5′-nucleotidase LYVE-1
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HL-60细胞降钙素基因高甲基化的发生机制
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作者 赵明明 白志勇 +2 位作者 白晓川 徐国宾 武淑兰 《北京医科大学学报》 CSCD 2000年第6期530-532,共3页
目的 :探讨HL 6 0细胞降钙素基因高甲基化的发生机制。方法 :采用HL 6 0细胞 ,以正常骨髓单个核细胞为对照 ,应用甲基化敏感的限制性内切酶消化 ,结合设有内外参照的PCR技术 ,检测CT基因甲基化状态 ;应用同位素微量分析法检测DNA 胞嘧... 目的 :探讨HL 6 0细胞降钙素基因高甲基化的发生机制。方法 :采用HL 6 0细胞 ,以正常骨髓单个核细胞为对照 ,应用甲基化敏感的限制性内切酶消化 ,结合设有内外参照的PCR技术 ,检测CT基因甲基化状态 ;应用同位素微量分析法检测DNA 胞嘧啶 甲基转移酶 (DNA cytosin methyltransferase,MTase)活性 ;应用RT PCR技术检测MTase基因表达水平。结果 :HL 6 0细胞经甲基化敏感的内切酶HpaⅡ消化后仍可扩增出清晰的CT基因特异条带 ,提示CT基因 5′端呈高甲基化状态 ;HL 6 0细胞MTase活性平均测定值为 5 39.9Bq ,是正常骨髓单个核细胞 (平均 2 1 8Bq)的 2 9.8倍 ;MTase基因的mRNA表达水平以MTase与β actin内参照RT PCR产物的比值表示 ,HL 6 0细胞 (0 .72 )为正常对照 (0 .0 2 )的 36倍。结论 :HL 6 0细胞CT基因呈高甲基化状态 。 展开更多
关键词 HL-60细胞 隆钙素 甲基化 白血病 发生机制
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The Biochemical and Cytochemical Study of 5'-nucleotldase Activity in Chilling-sensitive and Chilling-tolerant Rice Plasmalemma
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作者 潘杰 孙龙华 简令成 《Chinese Science Bulletin》 SCIE EI CAS 1993年第1期81-85,共5页
5′-nucleotidase (EC 3.1.3.5) can catalyze the hydrolysis of most ribonucleoside 5′-monophosphates and deoxynucleoside 5′-monophosphates to the corresponding nucleosides and orthophosphates. It is localized predomin... 5′-nucleotidase (EC 3.1.3.5) can catalyze the hydrolysis of most ribonucleoside 5′-monophosphates and deoxynucleoside 5′-monophosphates to the corresponding nucleosides and orthophosphates. It is localized predominantly in the plasma membranes of human and animal tissues,and often used as a marker enzyme for plasma membranes 展开更多
关键词 5-nucleotidase RICE chilling-tolerance.
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PQBP1:A New Player in Metabotropic Glutamate Receptor Signaling and Synaptic Plasticity
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作者 Li-Da Su Ying Shen 《Neuroscience Bulletin》 SCIE CAS CSCD 2021年第11期1637-1638,共2页
Group 1 metabotropic glutamate receptors(Gp1 mGluRs),comprising mGluR1 and mGluR5,are predominantly located at postsynaptic terminals.Gp1 mGluRs induce the activation of phospholipase C-γ.
关键词 MGLUR5 metab RECEPTOR
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少些完美,多些自由——临床及科研工作中胰岛β细胞功能评估的困难与对策 被引量:45
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作者 李光伟 《中华内分泌代谢杂志》 CAS CSCD 北大核心 2003年第1期5-7,共3页
胰岛素的分泌既有分泌量和时限的变化 ,又受糖负荷刺激和胰岛素敏感性的双重调节 ,这使得临床和科研工作中对β细胞功能评估十分困难。目前国内外文献中尚无可称为完美的评估方法。只有清楚地了解现行各种评估方式的优点及局限性 ,扬长... 胰岛素的分泌既有分泌量和时限的变化 ,又受糖负荷刺激和胰岛素敏感性的双重调节 ,这使得临床和科研工作中对β细胞功能评估十分困难。目前国内外文献中尚无可称为完美的评估方法。只有清楚地了解现行各种评估方式的优点及局限性 ,扬长避短 ,合理运用 ,才能在 β细胞功能研究中少犯错误。 展开更多
关键词 胰岛 Β细胞功能 评估 葡糖耐量试验
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Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B 被引量:1
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作者 Shuang-Nan Zhou Ning Zhang +8 位作者 Hong-Hong Liu Peng Xia Chao Zhang Jin-Wen Song Xing Fan Ming Shi Lei Jin Ji-Yuan Zhang Fu-Sheng Wang 《Gastroenterology Report》 SCIE EI 2021年第1期49-58,I0002,共11页
Background:The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus(HBV)infection remain largely undefined.The present study assessed the clinical characteristics of the CD39/CD73/ad... Background:The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus(HBV)infection remain largely undefined.The present study assessed the clinical characteristics of the CD39/CD73/adenosine pathway in patients with chronic hepatitis B(CHB).Methods:We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients.B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine pathway.Results:CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA,HBeAg positivity,high HBsAg levels,and active liver inflammation,and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg reduction.However,CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral treatments.Furthermore,CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory livers.In vitro,B-cells from CHB patients showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production blockade.Contrastingly,metformin significantly reduced activation-marker expression via regulating AMP-activated protein kinase.Conclusions:The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden,liver inflammation,and antiviral efficacy in CHB patients,and the skewed CD39/CD73/adenosine pathway contributed to B-cell hyperactivation.Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBVinduced immune pathogenesis. 展开更多
关键词 hepatitis B virus B-LYMPHOCYTE CD39 5-nucleotidase lymphocyte activation
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