转录因子AP-2的研究进展

转录因子 AP- 2家族是一类 DNA结合蛋白 ,以二聚体形式结合到 DNA丰富 GC的元件上 ,调控基因表达。本文综述了近年来对 AP- 2的分子结构、活性调控以及对细胞增殖、分化、胚胎发育和肿瘤发生过程的作用的研究进展     

真核基因转录因子研究进展

转录因子(TFs)是一类能特异性地结合到基因启动子区,并且对靶基因的转录起到调控作用的蛋白质,又称为反式作用因子.作为基因调控网络的一个重要角色,准确地认识转录因子的结构与功能,是研究基因转录调控机制的关键.本文对转录因子的结构、普遍转录因子与激活转录因子的功能以及目前转录因子相关的研究方法进行了综述.     

蚓激酶对哮喘小鼠免疫相关转录因子T-bet、GATA-3、RORγt、Foxp3的影响北大核心CSCD

目的:观察蚓激酶对哮喘小鼠炎症因子IL-6、TGF-β、IL-1β、TNF-α水平和免疫相关转录因子T-bet、GATA-3、RORγt、Foxp3 mRNA及蛋白表达的影响。方法:40只BALB/c雄性小鼠随机分为4组:空白对照组(空白组)、哮喘模型组(模型组)、地塞米松组(地米组)和蚓激酶组,每组10只。第1、14天模型组、地米组和蚓激酶组腹腔注射OVA+Al(OH)3致敏,21~27 d雾化吸入5%OVA建立哮喘模型,每次雾化激发1 h后,地米组、蚓激酶组分别灌胃给予地塞米松溶液、蚓激酶溶液治疗7 d,空白组、模型组灌胃等量生理盐水。末次给药24 h后处死取材,HE染色观察肺组织病理学改变,ELISA检测支气管肺泡灌洗液(BALF)中IL-6、IL-1β、TGF-β、TNF-α水平,RT-PCR检测肺组织T-bet、GATA-3、RORγt、Foxp3 mRNA水平,Western blot检测肺组织T-bet、GATA-3、RORγt、Foxp3蛋白表达。结果:肺组织病理观察显示,模型组小鼠管腔及周围炎症细胞浸润明显,黏膜水肿增厚,地米组和蚓激酶组小鼠肺部炎症浸润及黏膜增厚水肿均较模型组好转。与空白组相比,模型组IL-6、TGF-β、IL-1β、TNF-α水平显著升高,GATA-3、RORγt mRNA及蛋白表达增加(P<0.01),T-bet、Foxp3 mRNA及蛋白表达降低(P<0.01)。与模型组相比,地米组和蚓激酶组IL-6、TGF-β、IL-1β、TNF-α水平降低(P<0.05,P<0.01),T-bet、Foxp3 mRNA表达升高(P<0.01),GATA-3、RORγt mRNA及蛋白表达降低(P<0.01)。结论:蚓激酶可降低炎症因子IL-6、TGF-β、IL-1β及TNF-α水平,抑制GATA-3、RORγt mRNA及蛋白表达,诱导T-bet、Foxp3 mRNA及其蛋白表达,且可能通过降低相关前炎症因子水平调节免疫细胞转录因子表达。     

ZHX2的研究进展

新型转录抑制因子ZHX2（zinc-fingers and homeoboxes 2,ZHX2）属于锌指和同源框（zinc-fingers and homeoboxes,ZHX）家族,广泛存在于各种组织细胞核内,发挥转录抑制作用。ZHX2与多发性骨髓瘤（multiple mye-loma,MM）和肝细胞癌（hepatocellular carcinoma,HCC）的发生发展密切相关。此外,ZHX2对肾脏疾病发展过程中基因表达的转录调控有重要作用。ZHX2亦参与大脑皮层发育过程中神经前体细胞维持的调控。     

转录因子AP-2与肿瘤的研究进展

激活蛋白AP-2是一种序列特异性的转录因子,由AP-2α,AP-2β,AP-2γ,AP-2δ和AP-2ε等几个关系密切、结构保守的成员组成,参与细胞增殖分化、凋亡和癌变的调控.在多种不同类型肿瘤的发生、发展过程中,AP-2都存在异常表达,且与肿瘤预后有着密切的关系.同时,AP-2对肿瘤的调节具有抑癌或促癌的双向效应,这...     

转录因子GATA-2的研究进展

转录因子GATA-2是具有锌指结构的GATA家族中的一员，它在造血系统中广泛表达。且与造血细胞的分化、发育关系密切．GATA-2主要调控造血干／祖细胞的增殖和分化，亦可调控其他造血相关因子的表达，并与白血病等血液病的发生有一定的相关．     

转录抑制因子ZHX2对AFP启动子的抑制作用

目的：探讨转录抑制因子ZHX2对人甲胎蛋白（AFP）启动子的抑制作用。方法PCR扩增人ZHX2基因，构建ZHX2与绿色荧光蛋白和HA-tag融合表达载体pEGFP-ZHX2、pcDNA-ZHX2-HA，共转染后通过荧光显微镜及Western blot检测融合基因的表达。扩增人AFP核心启动子269bp插入pGl3-Basic，构建报告质粒phAF269。将pcDNA-ZHX2-HA和phAF269共转染HepG2细胞。48h后裂解细胞，双荧光检测分析ZHX2对AFP启动子的抑制作用。结果荧光显微镜及westem blot检测证实pEGFP-ZHX2和pcDNA-ZHX2-HA可在体外有效表达ZHX2融合蛋白，双荧光实验表明报告质粒phAF269具有AFP启动子活性，且pcDNA-ZHX2-HA与phAF269共转染HepG2后可显著抑制AFP启动子的转录作用，此抑制作用具有剂量依赖性。结论：成功构建两种新型转录抑制因子ZHX2融合表达载体，并证实其对人AFP启动子的抑制作用，为进一步探讨肝癌发生中AFP表达调控机制及提高AFP介导的靶向肿瘤基因治疗提供基础资料。     

转录因子FOXA2与肺发育相关研究

在肺发育过程中，需要多种转录因子、生长因子以及其他的信号分子协调作用，共同促进细胞的增殖和分化，实现肺正常发育，其中翼螺旋转录因子Foxa2可参与促进肺上皮细胞增殖分化、表面活性物质合成等过程，在建立正常肺形态和功能上发挥重要作用，其表达异常可致肺发育异常。     

红系NFE2反式作用因子

NFE2是碱性亮氨酸拉链家族成员之一,由一个广泛表达的18kD亚基和一个组织限制表达的45kD亚基组成。NFE2是生血组织特异的反式作用因子。它通过α和β珠蛋白基因簇的位点控制区调节珠蛋白基因转录。而且对正常血小板的生成是必须的。     

Random and block 2-alkyl-2-oxazolines telechelic macromonomers

Ring-opening polymerization of 2-methyl-2-oxazoline initiated by 2-(p-nitrobenzenesulfonato)ethyl methacrylate follows the so-called “living mechanism”, i.e. fast initiation compared to slow propagation and no chain transfer. Accordingly, methacryl macromonomers having homopolymers, block or random copolymers of 2-methyl and 2-pentyl-2-oxazoline backbones with narrow molecular weight distribution were obtained. Termination of the propagating species by ion-exchange or aminolysis with triethylamine yielded hydroxyl and quaternary ammonium terminated macromonomers, respectively.     

In vitro anti-mycobacterial activities of various 2'-deoxyuridine, 2'-arabinouridine and 2'-arabinofluoro-2'-deoxyuridine analogues: synthesis and biological studies

M. tuberculosis, M. bovis and M. avium infections cause the most important mycobacterioses leading to increased mortality in patients with AIDS. Various 5-substituted 2'-deoxyuridines, arabinouridines, arabinocytidines and 2'-arabinofluoro-2'-deoxyuridines were synthesized and evaluated for their in vitro inhibitory activity against M. bovis, M. tuberculosis and M. avium. 5-(C-1 Substituted)-2'-deoxyuridine derivatives emerged as potent inhibitors of M. avium (MIC50 = 1-10 microg/mL range); 5-(1-azidovinyl)-2'-deoxyuridine being the most active (MIC50 = 1-5 microg/mL range). The nature of C-5 substituents appeared to be a determinant of anti-mycobacterial activity.     

Lack of association between schizophrenia and the phospholipase-A(2) genes cPLA2 and sPLA2

The well-established role of genetic factors in the etiology of schizophrenia together with reports of allelic association with cPLA2, a phospholipase-A(2) gene, a reported increase of phospholipase-A(2) activity, and the phospholipase-A(2) hypothesis of Horrobin et al. [1995: Med Hypotheses 45:605-613] strongly support cPLA2 (PLA2G4A) and sPLA2 (PLA2G1B) as candidate genes for schizophrenia. In search for allelic association between these phospholipase-A(2) genes and schizophrenia, two samples of Chinese and European origins, in total 328 unrelated schizophrenic patients and their parents, were investigated using Falk and Rubinstein's haplotype relative risk method. Both genes showed marginally significant evidence for association in the total sample (P 相似文献   

Synthesis and polymerization of 2-cyano-2-methyltrimethylene carbonate

2-Cyano -methyltrimethylene carbonate (CMTC, 2 ) was synthesized starting from 2-methylacrolein (6), propionaldehyde (8) or 2-hydroxymethyl-2-methyl-1,3-propanediol (9). A key position in this synthesis is held by 2,2-bis(hydroxymethyl)propionitrile ( 3 ), which in a first step, is reacted — in conjunction with 2,2-dimethyl-1,3-propanediol ( 20 0) — with diphenyl carbonate ( 17 ) to result in a statistical copolycarbonate. Ring-closing depolymerization of this polymer, with a catalyst based on tin, yields in a second step the title monomer, CMTC (2), along with 2,2-dimethyltrimethylene carbonate (DTC, 1b ). Separation of the two monomers can be achieved by selective solubilization of the latter in toluene. Polymerization of CMTC is performed preferentially by using weak nucleophiles as initiators, such as Et₂AlOEt, Al(O-secBu)₃ or MgBu₂, since strong nucleophiles such as BuLi or ZnEt₂ tend to give side reactions with the cyano group. Copolymerization of CMTC with DTC results in statistical copolymers. With Et₂AlOEt as initiator copolymers with Bernoulli statistics are obtained, with a ratio of diads DTC/DTC : (DTC/CMTC + CMTC/DTC) : CMTC/CMTC equal to 1:2:1 for equimolar feed composition. With MgBu₂ as initiator and the same feed composition, a copolymer with the diad ratio 1:5:1 is obtained. Poly(CMTC) is a crystalline polymer with a melting point of 132.9°C and a glass transition temperature of 68.8 °C.     

Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 treatment should be explored.