固醇调节元件结合蛋白与脂代谢的基因调控

固醇调节元件结合蛋白(SREBPs)是脂肪合成基因重要的转录调节因子。SREBP-1a、-1c主要调节与脂肪酸代谢相关的酶，SREBP-2主要调控胆固醇代谢。SREBP-1c又称脂肪细胞定向和分化因子(ADD1)，在脂肪细胞的分化中发挥重要作用。SREBPs还参与脂肪合成基因的营养调控，并受胰岛素／葡萄糖和瘦素调控，而且是代谢综合征中重要的基因调控连结点。对其调控作用进行全面深入的研究，将对糖尿病、肥胖等代谢综合征的发病机理和临床治疗有更新、更全面的认识。     

固醇调节元件结合蛋白与脂质代谢的研究进展

固醇调节元件结合蛋白(SREBP)是重要的核转录因子之一,它能与脂质合酶基因的启动子/增强子的固醇调节元件结合,激活靶基因转录,特异性调控胆固醇和脂肪酸代谢.体内脂质代谢的稳定依赖于SREBP的调节.通过对SREBP作用和调控机制深入了解,将有助于提高对脂质代谢性疾病如糖尿病、高脂血症、脂肪肝、肥胖等的认识以及指导临床治疗.     

Survivin转录调节研究进展

Survivin是凋亡抑制蛋白(inhibitor of apoptosis protein,IAP)家族中结构独特的新成员,特异性高表达于大多数肿瘤组织中.Survivin表达调控主要在转录水平,多个转录因子(如P53、Sp1等)参与survivin转录调节,并有不同的信号转导分子参与.了解survivin表达的调控机制,对于肿瘤的靶向治疗有十分重要的意义.     

锌指蛋白36家族的研究进展

本文对锌指蛋白（ZFP）36家族成员的结构和功能的研究进展进行了综述。研究表明,ZFP36作为转录后调节因子,参与了多种生物学功能包括炎症、代谢综合征及肿瘤的发生发展,并证明ZFP36基因可作为肥胖相关的代谢综合征的重要候选基因。     

耶尔森氏菌属铁的摄取和转运

耶尔森氏菌属中有三种致病性的细菌：鼠疫菌、假结核菌和小肠结肠炎菌。这些致病菌引起感染的过程中，一种普遍而重要的因素是病原菌具有侵袭能力，并能在宿主组织内增殖，细菌需产生为病原性所必需的各种毒力决定体。众所周知在环境发生变化时，细菌能迅速改变它们的新陈...     

HCV NS5A反式调节蛋白13研究进展

HCV NS5A反式调节蛋白13(HCV NS5A trans-regulated protein13,NS5ATP13)又称核螺旋体磷酸化蛋白1(nucleolar and coiled-body phosphoprotein1,NOLC1)或核仁磷酸化蛋白140(nucleolar phosphoprotein140,Nopp140),     

高脂膳食对小鼠脑内铁调节蛋白-2基因表达的影响

目的 探讨高脂膳食对脑老化及脑铁代谢的影响,为合理膳食预防脑老化提供科学依据.方法 24只ICR小鼠分4组:脑老化模型组、高脂膳食组、脑老化+高脂膳食组和对照组.连续造模10 w后,以RT-PCR法检测各组脑内铁调节蛋白-2(IRP-2)表达水平.结果 脑老化组和高脂膳食组小鼠IRP-2表达水平均低于对照组且差异显著(P＜0.05);高脂膳食组与脑老化模型组、脑老化+高脂膳食组间IRP-2表达无显著差异(P＞0.05).结论 高脂膳食可降低小鼠脑内IRP-2表达,这可能是高脂膳食诱发脑老化及神经退行性变的机制之一.     

SRC家族蛋白通过自身修饰对基因表达的调节

最早认识SRC家族蛋白是将其作为一组与转录调控有关的蛋白辅助因子,它们发挥作用是通过与其它的核受体超家族成员的相互作用实现的.后来发现,SRC与其它转录因子的转录调控有关系,这些转录因子是不同的信号途径的重要组分,并在细胞过程的信号途径中发挥重要的作用.SRC家族成员能够和肌细胞生成素、MEF-2、转录增强子、NF-KB、AP-1、STAT、p53和E2F1等发生相互作用,这表明SRC共激活因子能参与到多个细胞代谢过程中.近来的研究表明,多种SRC蛋白的自身修饰在决定转录产物和招募特定的SRC共激活因子过程中发挥重要的作用.本文就SRC家族蛋白自身修饰的特点予以综述.     

同醇调节元件结合蛋白1c激活大鼠Patatin样磷酯酶结构域蛋白3基因转录

目的探讨固醇调节元件结合蛋白1c（SREBP-1e）对Patatin样磷酯酶结构域蛋白3（PNPLA3）基因的转录调控作用。方法构建7周龄雄性体重匹配的禁食（24h）以及禁食后再喂食（48h）SD大鼠（自由饮食组3只,饥饿组3只,再喂食组4只）和高脂及小剂量链脲佐菌素诱导的2型糖尿病sD大鼠（正常对照组5只,2型糖尿病组6只）。用逆转录聚合酶链反应（RT—PCR）和Western blotting法检测各组大鼠肝脏组织中SREBP一1c和PAPM3的表达水平。将大鼠PⅣP翻3启动子5’端上游-1000bp序列分成3段,分别构建荧光素酶报告载体（R—PⅣPM3．1、R—PM似3—2、R—PNPL43—3）,转染人正常肝细胞株L02,比较3个载体基础荧光素酶活性以及SREBP-1e过表达诱导的荧光素酶活性。分析上述实验中荧光素酶活性最高的PNPLA3启动子片段可能的SREBP-1c结合位点（SRE）,分别构建野生型和SRE突变型报告载体,比较两个载体荧光素酶活性。多组定量资料比较用方差分析,两组定量资料比较用t检验。结果与自由饮食组相比,饥饿组大鼠肝脏SREBP—lc、PNPLA3和脂肪酸合成酶FAS基因表达均下降,再喂食组三者表达显著升高,差异均有统计学意义（F=114．14,334．11,754．20,均P〈0．05）。与正常对照组相比,2型糖尿病组SREBP-1e、PNPLA3基因（t=-18．39,-30．07,均P〈0．05）及蛋白表达（t=4．58,6．81,均P〈0．05）均显著增高。R—PNPLA3-1报告载体基础荧光素酶活性较对照升高51．13倍（t=-28．93,P〈0．05）,R一删PM3—2和R—PNPLA3—3无基础荧光素酶活性;在L02细胞中,转染SREBP-1c表达质粒的R—PⅣPL43—1组荧光比值较转染空质粒的组升高2．63倍（t=-7．64,P〈0．05）,而R—PⅣPM3．2组及R—PNPLA3—3组转染SREBP-1e表达质粒荧光比值较转染空质粒组均无变化;PNPLA3启动子-100～-911）p存在SRE,SRE突变的报告载体（MUT—R—PNPLA３—1）荧光比值较野生型（R—PNPLA３-1）降低40．80％（t=4．99,P〈0．05）。结论SREBP-1c通过PNPLA３基因启动子－100～－91bp激活大鼠PNPLA3基因转录。     

脑衰老相关转录调节因子NF-E2、YB-1、LRG47的研究进展

大量的基因调节蛋白(转录调节因子)通过直接影响基因启动子的调控序列,来调控特殊基因的转录率,起到了抗衰老的关键性作用.转录调节因子可以调节随衰老出现的机体生理功能的减退和衰老基因显性的增加[1].在前期工作中,我们应用cDNA Microarray技术,观察了588个基因在快速老化小鼠全脑、皮层、海马中的表达变化,发现快速老化小鼠有56个基因的表达不同,涉及氧化应激蛋白、DNA合成、重组、修复相关基因、神经营养因子及受体、凋亡相关蛋白、转录调节因子等十多类,说明了脑衰老机制的复杂性[2].本文就与脑衰老相关的转录调节因子红细胞系统转录因子(NF-E2)、YB-1、干扰素诱生蛋白[LRG47(Ifi1)]的结构功能加以阐述.     

阴道加德纳菌感染与细菌性阴道病研究进展

阴道加德纳菌(GV)是细菌性阴道病(BV)的重要病原菌,经性接触传播,可引起输卵管异位妊娠、胎膜早破或新生儿早产等不良妊娠结局,同时也与男性尿道感染/男性不育有关。药敏试验显示GV对常用抗生素多已耐药。重视GV感染的细菌学诊断,根据药敏结果合理治疗GV感染性疾病具有重要的临床意义。本文对GV感染现状、致病机制及细菌学检验等研究进展进行了综述。     

噬菌体解聚酶及其与细菌荚膜间作用机制的研究进展

噬菌体疗法随着临床上耐药菌的种类与数量的增多而重新受到重视.细菌荚膜一方面是重要的毒力因子,另一方面也为噬菌体的识别和侵染宿主菌提供吸附位点.近年来研究表明部分噬菌体能产生降解细菌荚膜多糖的解聚酶,从而破坏细菌表面的保护结构,帮助噬菌体完成侵染,也利于血清或抗生素发挥作用.并且解聚酶具有化学性质和生物学效应稳定的特点,...     

Combinatorics of feedback in cellular uptake and metabolism of small molecules

We analyze the connection between structure and function for regulatory motifs associated with cellular uptake and usage of small molecules. Based on the boolean logic of the feedback we suggest four classes: the socialist, consumer, fashion, and collector motifs. We find that the socialist motif is good for homeostasis of a useful but potentially poisonous molecule, whereas the consumer motif is optimal for nutrition molecules. Accordingly, examples of these motifs are found in, respectively, the iron homeostasis system in various organisms and in the uptake of sugar molecules in bacteria. The remaining two motifs have no obvious analogs in small molecule regulation, but we illustrate their behavior using analogies to fashion and obesity. These extreme motifs could inspire construction of synthetic systems that exhibit bistable, history-dependent states, and homeostasis of flux (rather than concentration).     

Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice.METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe²⁺) iron salt or ferric (Fe³⁺) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated using quantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria.RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.     

蓝氏贾第鞭毛虫细胞骨架蛋白的分子生物学研究进展

蓝氏贾第鞭毛虫作为真核生物的模型,越来越受到广大生物学学者的重视,贾第虫借助细胞骨架蛋白附着于宿主肠上皮细胞,导致贾第虫病。将蓝氏贾第鞭毛虫细胞骨架蛋白成分作为新药物开发靶点的研究与日俱增。本文综述了蓝氏贾第鞭毛虫细胞骨架蛋白的分子生物学研究方法及最新进展,为新药物的开发及贾第虫骨架蛋白的进一步研究提供有价值的资料。     

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients: A systematic review and meta-analysis

Introduction:Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients.Methods:We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3.Results:We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], −0.07 to 015; I² = 0%; P = 0.48) and ferritin levels (MD, −0.42 ng/mL; 95% CI, −1.61 to 0.78; I² = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25–1.08; I² = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06–36.76; I² = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35–0.80; I² = 0%; P = 0.003). Serious adverse events were not reported in any group.Conclusion:FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity.Trial registration:The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).     

Heme uptake across the outer membrane as revealed by crystal structures of the receptor–hemophore complex

Gram-negative bacteria use specific heme uptake systems, relying on outer membrane receptors and excreted heme-binding proteins (hemophores) to scavenge and actively transport heme. To unravel the unknown molecular details involved, we present 3 structures of the Serratia marcescens receptor HasR in complex with its hemophore HasA. The transfer of heme over a distance of 9 Å from its high-affinity site in HasA into a site of lower affinity in HasR is coupled with the exergonic complex formation of the 2 proteins. Upon docking to the receptor, 1 of the 2 axial heme coordinations of the hemophore is initially broken, but the position and orientation of the heme is preserved. Subsequently, steric displacement of heme by a receptor residue ruptures the other axial coordination, leading to heme transfer into the receptor.     

我国蚊媒研究概况

蚊类不仅吸血骚扰,而且传播多种严重疾病。本文就我国疟疾媒介鉴定及基因特征,登革热媒介白纹伊蚊基因特征与易感性做了综述,并就淋巴丝虫病媒介与乙脑媒介做了概要。