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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice
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作者 Zhengwei Hu Jing Yang +7 位作者 Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu 《Neural Regeneration Research》 SCIE CAS 2025年第1期253-264,共12页
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed... The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease. 展开更多
关键词 adeno-associated virus Alzheimer’s disease APP/Ps1 mice carboxyl terminus of Hsp70 interacting protein gene therapy
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Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用
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作者 高娜 梁平 +3 位作者 单彬 高亚乾 尹金妥 冯锐 《中国药业》 2024年第3期128-128,I0001-I0004,共5页
目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GP... 目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。 展开更多
关键词 Wilm′s tumor gene1肽疫苗 Galinpepimut-S 免疫治疗 新生抗原 肿瘤疫苗
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Molecular Characteristics of S1 Gene of Infectious Bronchitis Virus Isolated from Chicken Proventriculus
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作者 CHENG Li-qin, ZHOU Ji-yong, John Dikki, SHEN Xing-yan, CHEN Ji-gang and ZHANG De-yongInstitute of Preventive Veterinary Medicine , College of Animal Sciences , Zhejiang University , Hangzhou 310029 , P.R.China 《Agricultural Sciences in China》 CAS CSCD 2003年第1期107-112,共6页
Infectious bronchitis virus was isolated from swollen proventriculi of clinically ill chicken. The suspected virus samples (2/97, 3/97, 1/98) were adapted in SPF chicken embryos for virus isolation and identification.... Infectious bronchitis virus was isolated from swollen proventriculi of clinically ill chicken. The suspected virus samples (2/97, 3/97, 1/98) were adapted in SPF chicken embryos for virus isolation and identification. All the virus isolates were able to agglutinate chicken erythrocytes after treatment with trypsin, and interfer with the reproduction of Newcastle disease virus in chicken embryos, and have low antigenic relat-edness values with reference positive IBV. The isolates 2/97, 3/97, 1/98 RNAs extracted from the allantoic fluid of inoculated embryonated eggs were converted to cDNA by reverse transcription with 3'-primer of S1 gene of (IBV). Polymerase chain reaction (PCR) was performed with two primers which span the S1 gene. Amplified product of 1. 93 kb was subjected to EcoR I and BamH I digestion and the fragments obtained were the same as expected size. The PCR product was ligated to pBlueScript-SK ( + ) vector, and its nucleotide sequence was determined by the dideoxy-mediated chain termination method. Nucleotide sequence analysis showed 73. 6 - 99. 7% homology between the isolated IBV and the IBV strains in GenBank. The homology of amino acid was 71. 4 - 99.4%. 展开更多
关键词 CHICKEN Infectious bronchitis virus s1 gene Molecular characteristics
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Prokaryotic Expression of Infectious Bronchitis Virus S1 Gene and Analysis of Biological Activity of Recombinant Protein
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作者 WANG Chun-li WANG Hong-jun ZHAO Quan 《Animal Husbandry and Feed Science》 CAS 2010年第4期46-48,共3页
[Objective] To study the prokaryotic expression and antigenicity identification of S1 gene from avian infectious bronchitis virus (IBV). [Method] The S1 gene was cloned into a pMD18-T vector to yield a recombinant p... [Objective] To study the prokaryotic expression and antigenicity identification of S1 gene from avian infectious bronchitis virus (IBV). [Method] The S1 gene was cloned into a pMD18-T vector to yield a recombinant plasmids pMD18-T-IBV-S1. Then S1 gene was inserted into the multiple cloning site of a prokaryotic expression vector pET-32a ( + ). The recombinant plasmid was transformed into E. coil BL21. The recombinant protein was induced by IPTG and measured by SDS-PAGE and western-blotting. [Result] The S1 gene was successfully expressed in E. coil BL21, the fusion proteins were about 66.0 kDa in a form of inclusion body. Western-blotting test showed that the recombinant proteins could be identified by IBV polyclonal antibody. [ Conclusion] The recombinant proteins of S1 gene have the antigenicity, which lays a good foundation for further research on new generation vaccine of IBV. 展开更多
关键词 Avian infectious bronchitis virus s1 gene Prokaryotic expression Western-blotting
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Alzheimer病患者APP及PS1基因的表达水平 被引量:1
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作者 张野 钱伊萍 +4 位作者 江开达 禹顺英 汪栋祥 张明园 江三多 《遗传》 CAS CSCD 北大核心 2006年第5期525-528,共4页
为了检测Alzheimer病(Alzheimer’s disease,AD)患者外周血中淀粉样前体蛋白(Amyloid Precursor Protein,APP)基因及早老素1(Presenilin 1,PS1)基因的表达情况,进而探讨APP及PS1基因的表达与AD的相关性,采用SYBRGreenⅠ的方法对45例AD... 为了检测Alzheimer病(Alzheimer’s disease,AD)患者外周血中淀粉样前体蛋白(Amyloid Precursor Protein,APP)基因及早老素1(Presenilin 1,PS1)基因的表达情况,进而探讨APP及PS1基因的表达与AD的相关性,采用SYBRGreenⅠ的方法对45例AD患者、25例血管性痴呆(vascular dementia,VD)患者及60名正常对照组样本的mRNA进行绝对定量,检测得到APP基因及PS1基因在对照组中的表达水平分别为0.026±0.005 amol/μg cDNA和0.026±0.004 amol/μg cDNA;在AD患者组中的表达量分别为0.044±0.006 amol/μg cDNA和0.051±0.011amol/μg cDNA;,在VD患者组中的表达水平分别为0.072±0.013 amol/μg cDNA和0.039±0.005 amol/μg cDNA。经显著性检验,AD患者组APP基因的表达水平上调,t=2.639,P<0.01;PS1基因的表达水平同样呈上调趋势,t=2.173,P<0.05,差异均具有统计学意义。VD患者组APP基因的表达水平上调,t=3.028,P<0.01;PS1基因的表达水平也同样呈上调趋势,t=2.012,P<0.05,均有显著性差异。因此,APP及PS1基因的表达水平的增高并不一定与AD发生特异性关联,而可能与多种导致痴呆的脑部病变发生关联。 展开更多
关键词 ALZHEIMER病 APP基因 Ps1基因 表达水平 关联
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Progress of CACNA1S Gene and Hypokalemic Periodic Paralysis
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作者 王雪 任守文 刘红林 《Animal Husbandry and Feed Science》 CAS 2009年第2期18-21,共4页
CACNA1 S gene is the gene encoding L-type calcium channel αa-subunit. CACNA1 S gene mutations can cause hypokalemic periodic pa- ralysis (HOKPP). The related research speculated that CACNA1 S gene was the candidate... CACNA1 S gene is the gene encoding L-type calcium channel αa-subunit. CACNA1 S gene mutations can cause hypokalemic periodic pa- ralysis (HOKPP). The related research speculated that CACNA1 S gene was the candidate genes which affect meat quality traits. In the present ar- ticle, the biological characteristics of CACNA1 S gene, structure, genetic diseases and the research development were respectively reviewed so as to provide a reference for further research. 展开更多
关键词 CACNA1 S gene L-type calcium channel α1-subunit Human hypokalemic periodic paralysis
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2株鸡传染性支气管炎病毒的分离鉴定与S1、M和N基因序列分析 被引量:3
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作者 何家辉 封柯宇 +3 位作者 李鸿鑫 宋才良 张钰坤 谢青梅 《中国兽医杂志》 CAS 北大核心 2021年第1期10-14,共5页
为跟踪了解广东地区鸡传染性支气管炎病流行情况,2019年从广东省清远、惠州两地疑似鸡传染性支气管炎发病鸡群中采集分离到2株传染性支气管炎病毒,并对其进行了鉴定和分析。结果显示,在鸡胚上盲传3代后均出现鸡胚的典型病变,死亡鸡胚全... 为跟踪了解广东地区鸡传染性支气管炎病流行情况,2019年从广东省清远、惠州两地疑似鸡传染性支气管炎发病鸡群中采集分离到2株传染性支气管炎病毒,并对其进行了鉴定和分析。结果显示,在鸡胚上盲传3代后均出现鸡胚的典型病变,死亡鸡胚全身出血明显,未死亡鸡胚发育受阻,呈明显的侏儒胚、蜷缩。将2个分离株分别命名为CK/CH/GD/QY1119和CK/CH/GD/HZ1225,分别测定其半数感染量(EID 50),扩增其S 1、M和N基因核苷酸序列,获得相应的推导氨基酸序列并对其分析。分离株CK/CH/GD/QY1119和CK/CH/GD/HZ1225的EID 50分别为10-7.5/0.1 mL和10-6.75/0.1 mL,2个分离株S 1基因与Mass型等疫苗株同源性为76.2%~82.1%,同源性均较低。与H120疫苗株相比,2个分离株的S 1、M和N基因存在若干氨基酸的差异,2个分离株S 1基因均存在氨基酸的插入,分离株CK/CH/GD/QY1119的M基因存在氨基酸的缺失,分离株CK/CH/GD/HZ1225的M基因存在氨基酸的插入。进化树分析显示,2个分离株分别属于LDT3型分支和QX型分支,均在S 1、M和N基因进化树上的分属上存在差异。结果表明本次分离得到的2个分离株的S 1、M和N基因均存在不同程度变异,在临床防控中应引起重视。本试验为鸡传染性支气管炎的有效防控提供了参考依据。 展开更多
关键词 鸡传染性支气管炎病毒 LDT3型 QX型 S 1基因 M基因 N基因 序列分析
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小分子RNA干扰鞘氨醇激酶1表达对APP/PS1小鼠海马神经元的影响 被引量:2
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作者 张远 黎钢 +1 位作者 孙圣刚 乔娴 《中风与神经疾病杂志》 CAS CSCD 北大核心 2013年第10期880-883,共4页
目的观察腺病毒介导的鞘氨醇激酶1(sphingosine kinase 1,sphk1)低表达对APP/PS1双转基因AD模型鼠海马超微结构的影响。方法立体定位法将携带sphk1-siRNA的腺病毒载体注射至APP/PS1双转基因AD模型鼠海马齿状回(dentate gyrus,DG)区,以1&... 目的观察腺病毒介导的鞘氨醇激酶1(sphingosine kinase 1,sphk1)低表达对APP/PS1双转基因AD模型鼠海马超微结构的影响。方法立体定位法将携带sphk1-siRNA的腺病毒载体注射至APP/PS1双转基因AD模型鼠海马齿状回(dentate gyrus,DG)区,以1×1011pfu/ml的病毒总量分2点注射,对照组海马内注射等量生理盐水,30d后观察海马组织DG区新生神经元及超微结构的改变,检测SNAP-25蛋白表达含量及转染后1-磷酸鞘氨醇(sphingosine1-phospate,s1p)受体的改变。结果注射sphk1-siRNA的小鼠30d后海马DG区转染后电镜结果显示:与生理盐水组相比,siRNA组小鼠有髓神经纤维减少,细胞空泡变性,核质边缘化明显加重。且共聚焦结果显示阴性对照尚有部分新生神经元形成,Western-blot结果显示siRNA组SNAP-25蛋白表达含量明显低于对照组。Real-time PCR结果显示转染后siRNA组s1pr1表达明显低于其他两组,而s1pr3表达则明显高于其他两组。结论上述结果表明,sphk1-siRNA转染后,促进了APP/PS1双转基因AD模型鼠海马DG区的神经元的脱髓鞘变性,抑制了新生神经元的形成。 展开更多
关键词 鞘氨醇激酶1 基因治疗 阿尔茨海默病 小分子干扰
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2019年冬季江苏部分地区鸡传染性支气管炎病毒S1基因遗传进化分析 被引量:3
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作者 冷梅 唐爽 +3 位作者 练家敏 邵冠明 谢青梅 蔺文成 《中国兽医杂志》 CAS 北大核心 2021年第12期7-11,18,共6页
为了解2019年冬季江苏省部分地区鸡传染性支气管炎病毒(IBV)的流行情况,本试验对江苏省内3个地区分离的23株IBV的S 1基因进行了遗传进化分析,首先对采集的病料进行毒株分离并进行病毒核酸测序,然后采用MEGA 5.2、Simplot、Megalign、RD... 为了解2019年冬季江苏省部分地区鸡传染性支气管炎病毒(IBV)的流行情况,本试验对江苏省内3个地区分离的23株IBV的S 1基因进行了遗传进化分析,首先对采集的病料进行毒株分离并进行病毒核酸测序,然后采用MEGA 5.2、Simplot、Megalign、RDP 4等分析软件对IBV的S 1基因序列进行分析。结果显示:23株分离毒株中有7株为HN08型(占30.4%),另外16株为QX型(占69.6%),其中分离毒株CKCHJSCZ1912-5的S 1基因发生了重组,其假定亲本分别为QX型QXL87毒株与HN08型SAIBK毒株,说明连云港地区减毒活疫苗的使用是IBV发生重组的关键因素,但因重组片段不大,所以该毒株没有单独形成进化分支。通过Megalign软件分析分离毒株之间的一致性,得出23株IBV分离毒株间核苷酸序列和氨基酸序列一致性分别为82.9%~99.9%和79.2%~99.8%。通过对江苏省IBV分离毒株与参考株进行遗传进化分析,发现23株分离毒株S 1基因发生较大程度变异,分离毒株与参考株间的一致性差异大,推测S 1基因的多样性可能是目前导致免疫失败的一个重要原因。毒株变异为鸡传染性支气管炎的防控工作带来了难题,也为研制新型疫苗提供指导。 展开更多
关键词 鸡传染性支气管炎病毒 s1基因 遗传进化分析 重组
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Inhibiting effect of antisense oligonucleotides phosphorthioate on gene expression of TIMP-1 in rat liver fibrosis 被引量:73
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作者 Qing He Nie Yong Qian Cheng Yu Mei Xie Yong Xing Zhou Yi Zhan Cao The Center of Infectious Disease Diagnosis and Treatment of PLA,Tangdu Hospital,Forth Military Medical University,Xi’an 710038,Shaanxi Province,ChinaDr,Qing He Nie graduated from Qinghai Medical College as a doctor in 1983,got master degree at Beijing 302 Army Hospital in 1993,got doctor degree at the Third Military Medical University in 1998,engaged in postdoctoral research at the Fourth Military Medical University from 1998 to 2000,now an associate professor,specialized in clinical and experimental research of infectious diseases,had more than 90 papers published,coauthor of ten books,first author of one book. 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期363-369,共7页
AIM: To observe the inhibition of antisense oligonucleotides (asON) phosphorthioate to the tissue inhibitors metalloproteinase-1 (TIMP-1) gene and protein expression in the liver tissue of immunologically induced hepa... AIM: To observe the inhibition of antisense oligonucleotides (asON) phosphorthioate to the tissue inhibitors metalloproteinase-1 (TIMP-1) gene and protein expression in the liver tissue of immunologically induced hepatic fibrosis rats. The possibility of reversing hepatic fibrosis through gene therapy was observed. METHODS: Human serum albumin (HSA) was used to attack rats, as hepatic fibrosis model, in which asONs were used to block the gene and protein expressing TIMP-1. According to the analysis of modulator, structure protein, coding series of TIMP-1 genome, we designed four different asONs. These asONs were injected into the hepatic fibrosis models through coccygeal vein. The results was observed by RT-PCR for measuring TIMP-1 mRNA expression, immunohistochemistry and in situ hybridization for collagen I, II, special staining of collagen fiber, and electron microscopic examination. RESULTS: Hepatic fibrosis could last within 363 days in our modified model. The expressing level of TIMP-1 was high during hepatic fibrosis process. It has been proved by the immunohistochemical and the electron microscopic examination that the asON phosphorthioate of TIMP-1 could exactly express in vivo. The effect of colchicine was demonstrated to inhibit the expressing level of mRNA and the content of collagen I, III in the liver of experimental hepatic fibrosis rats. However, the electron microscopy research and the pathologic grading of hepatic fibrosis showed that there was no significant difference between the treatment group and the model group (P】 0.05). CONCLUSION: The experimental rat model of hepatic fibrosis is one of the preferable models to estimate the curative effect of anti-hepatic fibrosis drugs. The asON phosphorthioate of TIMP-1 could block the gene and protein expression of TIMP-1 in the liver of experimental hepatic fibrosis rats at the mRNA level. It is possible to reverse hepatic fibrosis, and it is expected to study a new drug of antihepatic fibrosis on the genetic level. Colchicine has very limited therapeutic effect on hepatic fibrosis, furthermore, its toxicity and side effects are obvious. 展开更多
关键词 gene Therapy Animals Collagen Type I Collagen Type III Disease Models Animal Female gene Expression Hepatocytes Immunohistochemistry Liver Liver Cirrhosis Microscopy Electron Oligonucleotides Antisense PROCOLLAGEN RNA Messenger RATS Rats Wistar Research Support Non-U.S. Gov't Tissue Inhibitor of Metalloproteinase-1
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Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province 被引量:26
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作者 Lin Cai~1 Shun-Zhang Yu~2 Zuo-Feng Zhang~3 1 Department of Epidemiology,Fujian Medical University,Fuzhou 350004,Fujian Province,China2 Department of Epidemiology,Shanghai Medical University,Shanghai 200032,China3 Department of Epidemiology,UCLA School of Public Health,Los Angeles California,USA 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第6期792-795,共4页
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic... AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province. 展开更多
关键词 Polymorphism genetic Aged Asian Continental Ancestry Group Case-Control Studies China Cytochrome P-450 CYP2E1 Female gene Frequency genetic Predisposition to Disease Humans Male Middle Aged Research Support Non-U.S. Gov't Stomach Neoplasms
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EFFECT OF INTERLEUKIN-1β ON GROWTH HORMONE GENE EXPRESSION AND ITS POSSIBLE MOLECULAR MECHANISM IN RAT MtT/S SOMATOTROPH CELLS 被引量:3
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作者 Feng-ying Gong Jie-ying Deng Yi-fan Shi 《Chinese Medical Sciences Journal》 CAS CSCD 2008年第4期193-201,共9页
Objective To elucidate the effect of interleukin-1β (IL- 1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly es... Objective To elucidate the effect of interleukin-1β (IL- 1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to +30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 μmol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μmol/L) completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein. 展开更多
关键词 INTERLEUKIN-1Β growth hormone gene promoter MtT/S cells Pit-1 protein mitogen-activated protein kinase
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Association of Nurr1 gene mutations with Parkinson's disease in the Han population living in the Hubei province of China 被引量:1
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作者 Xiaoliang Lou Weijing Liao 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第23期1791-1796,共6页
Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to co... Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to compare the DNA sequences of eight exons of Nurr1 among 200 sporadic Parkinson’s disease patients and 200 healthy controls in the Han population in the Hubei province,China.One allele amplified from exon 3 of Nurr1 was polymorphic in five Parkinson’s disease patients(2.5%,5/200),and two individuals had a polymorphic allele amplified from exon 2 (1%,2/200).The anomalous electrophoresis fragment in exon 3 of Nurr1 gene contained a 709C/A missense mutation,and a polymorphic single nucleotide polymorphism at 388G/A was identified in exon 2.Compared with the control group,the Nurr1 gene expression level in the Parkinson’s disease group was decreased,and the Nurr1 gene expression levels in Parkinson’s disease patients carrying the polymorphisms at exons 2 and 3 were significantly decreased.Our data indicate that the single nucleotide polymorphism 388G/A in exon 2 and the 709C/A missense mutation in exon 3 of the Nurr1 gene in the Chinese population might affect the pathogenesis of Parkinson’s disease. 展开更多
关键词 Nurr1 gene Parkinson’s disease gene mutations gene polymorphism PATHOgeneSIS neurode-generative disease neural regeneration
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SEPS1——新发现的炎症相关基因(英文) 被引量:1
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作者 王健民 《中南大学学报(医学版)》 CAS CSCD 北大核心 2007年第5期723-725,共3页
Selenoprotein S1(SEPS1) ,一种新发现的对内质网的应激反应和炎症控制起作用的基因。近来的研究结果显示SEPS1与炎症细胞因子的产生存在直接的联系,可能在炎症介导的IDDM以及一些其他的免疫异常中起主要作用。
关键词 SELENOPROTEIN s1 基因 炎症 糖尿病
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PDRG1 at the interface between intermediary metabolism and oncogenesis 被引量:3
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作者 Maríaángeles Pajares 《World Journal of Biological Chemistry》 CAS 2017年第4期175-186,共12页
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expr... PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored. 展开更多
关键词 Epigenetic modifications GLUTATHIONE Methylation ONCOgeneS Intermediary metabolism p53 and DNA damage-regulated gene 1 Protein complexes R2TP/prefoldin complex S-adenosylmethionine synthesis Redox stress
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PARK1 gene mutation of autosomal dominant Parkinson's disease family
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作者 Ligang Jiang Qiuhui Chen +7 位作者 Ying Zhang Xinyu Hu Jia Fan Lifeng Liu Rui Guo Yajuan Sun Yizhi Zhang Guohua Hu 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第5期330-334,共5页
Studies have shown that PARK1 gene is associated with the autosomal dominant inheritance of Parkinson's disease. PARK1 gene contains two mutation sites, namely Ala30Pro and Ala53Thr, which are located on exons 3 and ... Studies have shown that PARK1 gene is associated with the autosomal dominant inheritance of Parkinson's disease. PARK1 gene contains two mutation sites, namely Ala30Pro and Ala53Thr, which are located on exons 3 and 4, respectively. However, the genetic loci of the pathogenic genes remain unclear. In this study, blood samples were collected from 11 members of a family with high prevalence of Parkinson's disease, including four affected cases, five suspected cases and two non-affected cases. Point mutation screening of common mutation sites on PARK1 gene exon 4 was conducted using PCR, to determine the genetic loci of the causative gene for Parkinson's disease. Gene identification and sequencing results showed that a T base deletion mutation was observed in the PARK1 gene exon 4 of all 11 collected samples. It was confirmed that the PARK1 gene exon 4 gene mutation is an important pathogenic mutation for Parkinson's disease. 展开更多
关键词 Parkinson's disease FAMILY geneTIC PARK1 gene MUTATION neurodegenerative disease
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Marek’s disease virus challenge induced immune-related gene expression and chicken repeat 1 (CR1) methylation alterations in chickens
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作者 Fei Tian Juan Luo +2 位作者 Huanmin Zhang Shuang Chang Jiuzhou Song 《American Journal of Molecular Biology》 2012年第3期232-241,共10页
Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene tr... Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future. 展开更多
关键词 Marek’s Disease CHICKEN REPEAT 1 DNA METHYLATION gene Expression
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Characterization of Ppd-D1 alleles on the developmental traits and rhythmic expression of photoperiod genes in common wheat
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作者 ZHAO Yong-ying WANG Xiang +2 位作者 WEI Li WANG Jing-xuan YIN Jun 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2016年第3期502-511,共10页
Photoperiodic response is an important characteristic that plays an important role in plant adaptability for various environments. Wheat cultivars grow widely and have high yield potential for the strong photoperiod a... Photoperiodic response is an important characteristic that plays an important role in plant adaptability for various environments. Wheat cultivars grow widely and have high yield potential for the strong photoperiod adaptibility. To assess the photoperiodic response of different genotypes in wheat cultivars, the photoperiodic effects of the Ppd-D1 alleles and the expressions of the related TaGI, TaCO and Ta FT genes in Liaochun 10 and Ningchun 36 were investigated under the short-day(6 h light, SD), moderate-day(12 h light, MD) and long-day(24 h light, LD) conditions. Amplicon length comparison indicated that the promoter of Ppd-D1 in Ningchun 36 is intact, while Liaochun 10 presented the partial sequence deletion of Ppd-D1 promoter. The durations of all developmental stages of the two cultivars were reduced by subjection to an extended photoperiod, except for the stamen and pistil differentiation stage in the Liaochun 10 cultivar. The expression levels of the Ppd-D1 alleles and the TaGI, TaCO and TaFT genes associated with the photoperiod pathway were examined over a 24-h period under SD and MD conditions. The relationships of different photoperiodic responses of the two cultivars and the expression of photoperiod pathway genes were analyzed accordingly. The photoperiod insensitive(PI) genotype plants flower early under SD; meanwhile, the abnormal expression of the Ppd-D1 a allele is accompanied with an increase in Ta FT1 expression and the TaCO expression variation. The results would facilitate molecular breeding in wheat. 展开更多
关键词 wheat photoperiod spike differentiation heading gene expression Ppd-D1
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Expression of GST-IL-1 fusion gene
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作者 陈梅红 王字玲 +3 位作者 邓健蓓 赵忠良 陈南春 苏成芝 《Journal of Medical Colleges of PLA(China)》 CAS 1996年第2期79-83,共5页
Two GST-IL-1 fusion genes were constructed by inserting different cDNA fragments of human interleukin1 (IL-1) into the 3'-terminus of GST gene in the fusion protein expression vector pGEX-4T. After IPTG induction ... Two GST-IL-1 fusion genes were constructed by inserting different cDNA fragments of human interleukin1 (IL-1) into the 3'-terminus of GST gene in the fusion protein expression vector pGEX-4T. After IPTG induction ,SDS-PAGE was employed to detect the gene expression. No corresponding protein encoded by GST gene fused with the whole-length 816 bp IL-1 cDNA was observed, nor was free GST protein. However, the fusion protein of GST and IL-1 cDNA without the 189 bp at the 5'- terminus was detected, amounting to 30% of the total bacterial protein expressed. This might suggest that the sequence of 1-189 bp of IL-1 cDNA affected the expression of the fusion gene. That is to say, the downstream sequence distant from the translation start codon AUG in the target gene could significantly affect the expression of the fusion gene. 展开更多
关键词 gene EXPRESSION fusion PROTEIN INTERLEUKIN-1 GLUTATHIONE-S-TRANSFERASE
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谷胱甘肽S转移酶P1和X线修复交错互补基因1基因多态性与前列腺癌化疗敏感性及预后关系研究
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作者 薛松 张祥 +2 位作者 潘鑫 易晓明 商学军 《中华男科学杂志》 CAS CSCD 2024年第9期803-808,共6页
目的:探究前列腺癌患者谷胱甘肽S转移酶P1(GSTP1)和X线修复交错互补基因1(XRCC1)基因多态性与化疗敏感性及预后的关系。方法:选取2018年5月至2021年5月行雄激素剥夺治疗+双药化疗的前列腺癌患者103例,收集患者临床资料,采用PCR-PFLP方... 目的:探究前列腺癌患者谷胱甘肽S转移酶P1(GSTP1)和X线修复交错互补基因1(XRCC1)基因多态性与化疗敏感性及预后的关系。方法:选取2018年5月至2021年5月行雄激素剥夺治疗+双药化疗的前列腺癌患者103例,收集患者临床资料,采用PCR-PFLP方法对患者行基因分型,并分析其GSTP1-rs1695位点和XRCC1-rs25487位点的多态性,分析其与化疗敏感性的关系,并探究GSTP1和XRCC1基因多态性与患者3年生存率的相关性。结果:103例前列腺癌化疗患者GSTP1-rs1695位点和XRCC1-rs25487位点分布均符合Hardy-Weinberg平衡(χ2=9.794,P>0.05)。GSTP1-rs1695位点中AA基因型占比为65.05%(67/103),AG基因型占比为23.30%(24/103),GG基因型占比为11.65%(12/103);XRCC1-rs25487位点中AA基因型占比为29.13%(30/103),AG基因型占比为50.49%(52/103),GG基因型占比为20.39%(21/103)。GSTP1-rs1695 AA型化疗敏感性为35.82%,低于AG/GG型58.33%(P<0.05)。XRCC1-rs25487 AA型化疗敏感性为40.00%,AG/GG型45.21%,两者差异无统计学意义(P>0.05)。GSTP1-rs1695、XRCC1-rs25487不同表型患者3年无进展生存率之间无明显差异(P>0.05)。GSTP1-rs1695 AA型3年总生存率低于AG/GG型;XRCC1-rs25487 AA型低于AG/GG型(P<0.05)。多因素COX回归分析结果显示,GSTP1-rs1695 AA型、XRCC1-rs25487 AA型均为前列腺癌患者化疗后3年总生存期的独立影响因素。结论:GSTP1-rs1695、XRCC1-rs25487基因多态性对前列腺癌患者化疗敏感性和预后均有一定影响,GSTP1-rs1695和XRCC1-rs25487 A等位基因突变均可导致更短的3年生存率,G等位基因突变可带来更好的化疗敏感性和生存期。 展开更多
关键词 前列腺癌 谷胱甘肽S转移酶P1 X线修复交错互补基因1 基因多态性 化疗敏感性
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