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1.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3(APOBEC3)胞嘧啶脱氨酶通过脱氨和非脱氨机制抑制逆转录病毒复制.其通过脱氨作用使HBV负链cDNA胞嘧啶脱氨形成G→A超突变的前病毒;非脱氨机制,目前尚未完全清楚.APOBEC3B(A3B)、APOBEC3C(A3C)、APOBEC3G(A3G)和APOBEC3F(A3F)能通过脱氨机制抑制HBV复制,HBV感染患者血清可检测到G→A超突变的HBV基因组;A3B、A3F和A3G同时具有非脱氨的逆转录抑制作用.A3B、A3F和A3G在人类原代肝细胞呈低水平表达,IFN可诱导A3G表达上调并足够抑制HBV复制.APOBEC3胞嘧啶脱氨酶极可能参与非溶细胞HBV清除过程,发挥多大作用有待进一步明确.A3B和A3G更倾向于引起HBV X的基因突变,在HBV相关的肝癌患者可检测到截短型HBVX变异体,可能与肝癌形成有关.此文就APOBEC3通过脱氨和非脱氨机制抑制HBV复制及与HBV相关性肝癌的关系进行了综述. 相似文献
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Baraldi PG Tabrizi MA Bovero A Avitabile B Preti D Fruttarolo F Romagnoli R Varani K Borea PA 《European journal of medicinal chemistry》2003,38(4):367-382
In the last years adenosine receptors have been extensively studied, and mainly at present we understand the importance of A(2A) and A(3) adenosine receptors. A(2A) selective adenosine receptors antagonists are promising new drugs for the treatment of Parkinson's disease, while A(3) selective adenosine receptors antagonists have been postulated as novel anti-inflammatory and antiallergic agents; recent studies also indicated a possible employment of these derivatives as antitumour agents. Lately different classes of compounds have been identified as potent A(2A) and A(3) antagonists. In this article we report the past and present efforts which led to development of more potent and selective A(2A) and A(3) antagonists. Our group has mainly worked on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine nucleus both as A(2A) and A(3) antagonists, aiming to improve the affinity, selectivity and the hydrophilic profile. In fact, we have synthesised several compounds endowed with high affinity and selectivity versus A(2A) adenosine receptors, as 2, 2a-c (K(i)A(2A)=0.12-0.19 nM), or A(3) adenosine receptors, as 4p (K(i)A(3)=0.01 nM) and 4q (K(i)A(3)=0.04 nM). 相似文献
3.
大豆异黄酮联合叶酸对β淀粉样肽介导的神经毒性的影响—对大鼠学习记忆损伤的拮抗作用 总被引:2,自引:0,他引:2
目的探讨大豆异黄酮(SIF)单独或联合叶酸(FA)拮抗β淀粉样肽(Aβ)致大鼠学习记忆损伤的神经保护作用及其机制。方法(1)神经毒性研究Wistar大鼠随机分为4组,每组15只,分别于侧脑室注射生理盐水、Aβ25-35、Aβ31-35和Aβ1-40。于术后7d,Morris水迷宫试验检测大鼠学习记忆能力;术后14d,免疫组织化学法检测大脑Aβ阳性表达细胞数及脑组织中抗氧化相关指标,观察不同Aβ片段的神经毒性。(2)干预研究实验分为5组(对照、Aβ模型、SIF、FA、SIF与SIF+FA干预组),每组15只,分别灌胃0.5%羧甲基纤维素钠(CMC-Na)、0.5%的CMC-Na、SIF(160mg/kg bw·d)、FA(0.7mg/kg bw·d)和SIF(160mg/kg bw·d)+FA(0.7mg/kg bw·d),14d后,对照组于侧脑室注射生理盐水,Aβ模型、SIF、FA、SIF+FA干预组于侧脑室注射Aβ1-40,检测指标同毒性实验。结果(1)与对照组相比,Aβ25-35、Aβ1-40组大鼠平均逃避潜伏期和总路程显著延长;Aβ25-35、Aβ31-35和Aβ1-40组大鼠大脑皮质Aβ阳性表达细胞数显著增加,Aβ31-35和Aβ1-40组大鼠海马CA1区Aβ阳性表达细胞数显著增加;脑组织中AOC、GSH水平显著降低。(2)与模型组相比,SIF、FA和SIF+FA干预组大鼠平均逃避潜伏期显著缩短;大脑皮质和海马CA1区Aβ阳性表达细胞数显著减少;脑组织中AOC和GSH水平显著增高。结论三种Aβ片段均可引起大鼠学习能力障碍,其作用机制可能与Aβ介导的神经氧化损伤和脑内Aβ沉积直接神经毒作用有关;单独SIF或FA以及二者联合均可拮抗Aβ介导的大鼠神经毒性,发挥神经保护作用。 相似文献
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Frazer LT O'Brien-Simpson NM Slakeski N Walsh KA Veith PD Chen CG Barr IG Reynolds EC 《Vaccine》2006,24(42-43):6542-6554
Porphyromonas gingivalis is a pathogen associated with chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. A major virulence factor for P. gingivalis is the RgpA-Kgp proteinase-adhesin complex. We have prepared the following recombinant proteins corresponding to domains/regions of the RgpA-Kgp complex; rRgpA(cat), rRgpA(A1), rRgpA(A2), rRgpA(A4), rRgpA(A1)(784-1009), rRgpA(A1)(911-1009), rKgp(A1) and rKgp(A1)(759-989). The ability of each recombinant protein to attenuate P. gingivalis infection, when used as a vaccine, in the murine lesion model was determined. All of the recombinant adhesin domains were found to significantly attenuate P. gingivalis infection with the most effective being rKgp(A1) and rKgp(A1)(759-989) followed by rRgpA(A1), rRgpA(A1)(784-1009) and rRgpA(A1)(911-1009). The predominant antibody isotype was IgG1. The A1 adhesins, which gave the best protection, contain specific motifs implicated in binding to host tissue. Immunisation with rRgpA(cat) had no effect on P. gingivalis infection. As well as detecting the Kgp(A1) adhesin in a Western blot, the rKgp(A1) and rKgp(A1)(759-989) antisera were also immunoreactive with the A1 and A3 adhesins of RgpA and HagA. Flow cytometric analysis indicated that rKgp(A1) and rRgpA(A1) antisera recognised native antigen on P. gingivalis whole cells. Furthermore, the rKgp(A1) and rKgp(A1)(759-989) antisera exhibited a similar immunoreactive profile with outer membrane preparations of all P. gingivalis serotypes and clinical isolates tested. The recombinant A1 adhesin therefore has potential in the development of a P. gingivalis vaccine. 相似文献
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Holschbach MH Bier D Wutz W Sihver W Schüller M Olsson RA 《European journal of medicinal chemistry》2005,40(5):421-437
The importance of the brain A2A adenosine receptor (A(2A)AR) in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently generated analogs 10b-s for pharmacological evaluation. Radioligand binding experiments showed affinities for the rat brain A(2A)AR in the low nanomolar range but similar affinities for the A1AR and substantial unspecific binding. Autoradiography employing [3H]10a, showing that high unspecific binding obscured specific binding to both the A1AR and A(2A)AR. Thus, compounds 10b-s are unsuitable as ligands for imaging brain A(2A)ARs by PET. 相似文献
6.
目的初步探讨卡马西平所致药疹与CYP3A4*18B基因型的关系,以寻找预测药疹的分子学手段。方法用PCR-RFLP法检测65例卡马西平所致药疹组患者(重型药疹患者11名,轻型药疹患者54名)、100例卡马西平耐受组患者及100例健康对照组患者的CYP3A4*18B(intron10,G20338→A)基因多态性。结果卡马西平所致药疹组CYP3A4*1/CYP3A4*1(G/G)基因型30例,CYP3A4*1/CYP3A4*18B(G/A)基因型30例,CYP3A4*18B/CYP3A4*18B(A/A)基因型5例,等位基因A频率为30.8%;卡马西平耐受组G/G基因型51例,G/A基因型42例,A/A基因型7例,等位基因A频率为28%;健康对照组G/G基因型44例,G/A基因型49例,A/A基因型7例,等位基因A频率为31.5%。各组间基因型与等位基因频率差异均无统计学意义。结论由于病例数较少,目前尚没有发现卡马西平药疹与CYP3A4*18B相关联。 相似文献
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目的:探讨钙结合蛋白S100A2、S100A4和ER、PR在子宫肉瘤中的表达及其相关性研究的临床意义。方法:采用免疫组织化学,过氧化物酶标记的链霉素抗生物素-过氧化酶连接法(Streptavidin-peroxidase-biotin,SP),SP法检测69例子宫肉瘤组织中S100A2、S100A4、ER、PR的表达情况。结果:S100A2和S100A4的表达与子宫肉瘤发生及预后有密切关系。S100A4阳性患者5年无病生存率显著低于阴性者(P<001)。S100A2和S100A4在子宫肉瘤中的表达有明显相关性。结论:S100A2和S100A4可以作为预测子宫肉瘤早期诊断和预后的独立分子指标。 相似文献
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目的:探讨肿瘤坏死因子启动子TNFα-238G/A、-308G/A基因多态性与子宫内膜异位症的相关性。方法:运用PCR-RFLP技术检测100例内异症组及100例对照组肿瘤坏死因子启动子TNFα-238G/A、-308G/A基因多态性。结果:内异症组TNFα-238G/G、G/A、A/A表型频率(%)分别为0.93、0.07、0,TNFα-238G、TNFα-238A基因频率(%)分别为0.965、0.035;内异症组TNFα-308G/G、G/A、A/A表型频率(%)分别为0.87、0.12、0.01,TNFα-308G、TNFα-308A基因频率(%)分别为0.93、0.07。TNFα-238G/A和TNFα-308G/A各种基因型频率和基因频率在两组间差异无统计学意义(P>0.05)。结论:TNFα-238G/A、-308G/A基因多态性与子宫内膜异位症无明显相关。 相似文献
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目的探讨维生素A对SD大鼠食欲和下丘脑神经肽Y基因表达的影响,初步探讨维生素A影响大鼠食欲的机制。方法将雄性SD大鼠随机分为2组:A组(维生素A缺乏组)和B组(对照组)。喂养74d,A组随机取出16只,分为2组:A1组(维生素A缺乏组)和A2组(维生素A皮下补充组);B组随机取出8只,为B1组(对照组)。实验79d,将这3组大鼠全部处死,取血和组织进行相关指标测定。A组剩余的动物按体重随机分为2组:A3组(维生素A缺乏组)和A4组(维生素A食物补充组)。B组剩余的8只动物为B2组(对照组)。30d后将其全部处死,取血和组织进行相关指标测定。结果维生素A缺乏组进食量显著低于正常对照组,给予缺乏组大鼠维生素A皮下和食物补充后,大鼠进食量显著增多。维生素A缺乏组下丘脑神经肽YmRNA表现为低表达,皮下补充维生素A后大鼠下丘脑神经肽YmRNA的表达水平明显升高。结论维生素A影响大鼠食欲的可能机制是改变了下丘脑有关控制食欲的基因表达。 相似文献
10.
Wei-Gang Hu Amanda L. Phelps Scott Jager Damon Chau Charles C. Hu Lyn M. O’Brien Stuart D. Perkins Amanda J. Gates Robert J. Phillpotts Les P. Nagata 《Vaccine》2010
A recombinant humanized antibody to Venezuelan equine encephalitis virus (VEEV) was constructed in a monocistronic adenoviral expression vector with a foot-and-mouth-disease virus-derived 2A self-cleavage oligopeptide inserted between the antibody heavy and light chains. After expression in mammalian cells, the heavy and light chains of the humanized antibody (hu1A4A1IgG1-2A) were completely cleaved and properly dimerized. The purified hu1A4A1IgG1-2A retained VEEV binding affinity and neutralizing activity similar to its parental murine antibody. The half-life of hu1A4A1IgG1-2A in mice was approximately 2 days. Passive immunization of hu1A4A1IgG1-2A in mice (50 μg/mouse) 24 h before or after virulent VEEV challenge provided complete protection, indicating that hu1A4A1IgG1-2A has potent prophylactic and therapeutic effects against VEEV infection. 相似文献
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Rowland M Mohammed N Rehman H Hewitt S Mendis C Ahmad M Kamal M Wirtz R 《Transactions of the Royal Society of Tropical Medicine and Hygiene》2002,96(6):620-626
Anopheline vectors and malaria transmission were studied in 2 river-irrigated, rice-growing districts of eastern Afghanistan from May 1995 to December 1996. Clinical malaria was monitored in 12 rural villages (population 14,538) by passive case detection at local clinics. Adult mosquitoes were collected by space-spraying of living quarters and stables and by cattle bait catches. Mosquito head-thoraces (17,255 specimens) were tested for Plasmodium falciparum and P. vivax circumsporozoite protein (CSP) using enzyme-linked immunosorbent assay. The recorded incidence of P. vivax and P. falciparum was 199 and 41 episodes per 1000 person years, respectively. Twelve species of anopheline were recorded; Anopheles stephensi comprised 82% and A. culicifacies 5%. Eight species tested positive for CSP: A. stephensi, A. culicifacies, A. fluviatilus, A. annularis, A. pulcherrimus, A. maculatus, A. splendidus and A. superpictus. Among infected mosquitoes 46% were positive for P. falciparum, 45% for P. vivax VK-247, and 9% for P. vivax PV-210. Estimates of the feeding rates of infective vectors on humans indicated that A. stephensi would contribute 76% of infective bites, A. fluviatilis and A. pulcherrimus 7% each, and A. culicifacies and A. superpictus 3% each. The overall infective vector feeding rate correlated with the P. vivax incidence rate in the human population. The conventional view of A. culicifacies being the main rural vector and A. stephensi important only in urban settings needs to be reconsidered in western outreaches of the Indo-Pakistan subcontinent. 相似文献
13.
《Vaccine》2020,38(4):779-789
BackgroundThis phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.MethodsWe enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime – MVA85A boost) or Group C (n = 12; ChAdOx1 85A – ChAdOx1 85A prime – MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.ResultsAEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.ConclusionA ChAdOx1 85A prime – MVA85A boost is well tolerated and immunogenic in healthy UK adults. 相似文献
14.
目的:探讨抑制素A、激活素A在胎儿生长受限(FGR)发病中的作用。方法:选择2008年10月—2009年12月在苏州大学附属第一医院分娩的产妇46例,其中分娩FGR新生儿者23例(FGR组),同期住院分娩正常出生体质量新生儿者23例(对照组)。用酶联免疫吸附法测定母血及脐血抑制素A、激活素A的水平。对2组胎盘组织进行HE染色;用免疫组织化学法分析胎盘组织抑制素α、βA亚基表达部位及水平。结果:FGR组孕妇血清及脐血抑制素A、激活素A水平均高于正常对照组(P<0.05);所有孕妇血清抑制素A、激活素A均与新生儿出生体质量、皮下脂肪厚度呈负相关(均P<0.05)。FGR组胎盘绒毛发育欠佳,绒毛血管扩张不良;抑制素α、βA亚基表达较正常对照组高(均P<0.05)。母儿血清抑制素A、激活素A之间均无相关性。胎盘组织抑制素α、βA亚基分别与孕妇血清抑制素A、激活素A水平呈正相关(均P<0.05)。孕妇血清抑制素A、激活素A的ROC曲线下面积分别为0.862和0.782。结论:抑制素A、激活素A在胎儿宫内生长发育过程中起重要的调节作用,可通过检测母血抑制素A、激活素A来间接评价胎儿生长发育或胎盘功能状态。 相似文献
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P E Caldwell 《Social work in health care》1999,28(4):45-61
Alcohol abuse is common among clients in human service agencies, but most never seek help for their drinking problems, either in professional treatment or self-help (mutual aid) groups such as Alcoholics Anonymous (A.A.). A.A. is a widely-available resource, but it is not always introduced to clients in a manner that fosters acceptance of A.A. Social workers in various practice settings can facilitate A.A. affiliation by working collaboratively with clients, seeking a goodness-of-fit between client needs and the resources available within A.A. This article offers a pragmatic approach to initial A.A. involvement, intended to help professionals utilize barriers to affiliation as opportunities for furthering both counseling goals and the connection to A.A. 相似文献
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The effects of a 21-week exposure to Aroclor 1242 (1mg per day in feed) on plasma concentrations of vitamins A(1) (retinol) and A(2) (3,4-didehydroretinol) and their principal fatty acyl esters (A(1)-16:0, A(2)-16:0 (palmitates), A(1)-18:1n-9; A(2)-18:1n-9 (oleates), and A(1)-18:0; A(2)-18:0 (stearates)) were studied in young female mink (Mustela vison) fed a diet based on freshwater smelt. These vitamin levels were also examined in mink fed diets containing Baltic herring or fatty marine fish. In the Aroclor-exposed smelt-fed mink, the plasma concentrations of A(1) and A(2) esters were significantly lower than the levels in controls fed the uncontaminated smelt diet. In addition, the A(2) esters reacted more sensitively to the polychlorinated biphenyls than did A(1) esters. In contrast, in the plasma of the exposed mink the level of alcoholic A(1) was normal, and transport of thyroxine (T(4)) and nonspecific lipoprotein transport of major lipids were not impaired. Despite the large dietary supply of vitamin A(2) and high levels of plasma A(2) esters, the mink fed freshwater smelt had only trace amounts of alcoholic vitamin A(2) in their plasma. The concentrations of A(1) and A(2) esters in the plasma of all the mink studied correlated with the hepatic total concentrations of the vitamins. Thus, in carnivores that have nonspecific lipoprotein transport of vitamin A esters, determination of plasma levels of the esterified vitamins may be a useful nondestructive way to estimate stores of the vitamin A analogs in the body and to assess the organochlorine-induced decrease in the vitamin stores. 相似文献
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Olga V. Masalova Ekaterina I. Lesnova Alexei V. Pichugin Tatiana M. Melnikova Vadim V. Grabovetsky Natalia V. Petrakova Olga A. Smirnova Alexander V. Ivanov Alexei D. Zaberezhny Ravshan I. Ataullakhanov Maria G. Isaguliants Alla A. Kushch 《Vaccine》2010
The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax®. The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-γ. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4+ and CD8+ T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials. 相似文献
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BACKGROUND/OBJECTIVESIt has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats.MATERIALS/METHODSForty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope.RESULTSLipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation.CONCLUSIONSThese results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats. 相似文献
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《The Journal of school health》1940,10(8):256-256
Book reviewed in this article:
A College Textbook of Hygiene , Dean Franklin Smiley, A.B., M.D., and Adrian Gordon Gould, Ph.B., M.D.
Handbook of Hearing Aids . A. F. Niemoeller, A.B., M.A., B.S.
Complete Guide for the Deafened . A. F. Niemoeller, A.B., M.A., B.S. 相似文献
A College Textbook of Hygiene , Dean Franklin Smiley, A.B., M.D., and Adrian Gordon Gould, Ph.B., M.D.
Handbook of Hearing Aids . A. F. Niemoeller, A.B., M.A., B.S.
Complete Guide for the Deafened . A. F. Niemoeller, A.B., M.A., B.S. 相似文献