硒与HIV感染的关系研究进展

HIV感染及AIDS至今依然严重威胁着人类的生命,因而成为医学界研究的热点。本文着重从硒与细胞因子角度揭示硒与HIV和AIDS在发生、发展中的关系,证明其扮演的重要角色,提示了一种研究HIV和AIDS的新方向。     

新型稠环嘧啶类HIV-1 NNRTIs的 设计、合成、抗病毒活性与初步成药性研究

正艾滋病(AIDS)是由人类免疫缺陷病毒(HIV)感染引起的全球重大流行性传染病。据世界卫生组织(WHO)的数据报道,截至2018年底,因感染艾滋病毒而死亡的人数达到了3200万,全球现存约有3790万艾滋病毒感染者,其中2018年新增感染人数约170万人,77万人死于艾滋病引起的并发症。逆转录酶(RT)在HIV-1的生命周期起着必不可少的作用,是开发抗HIV新药的     

基于靶标结构及作用机制的抗艾滋病药物研究进展

人体免疫缺陷病毒(Human immunodeficiency virus,HIV)是一种主要以CD4~+T淋巴细胞和巨噬细胞等免疫细胞为靶点的感染性逆转录病毒,HIV感染的最终阶段为出现获得性免疫缺陷综合征(Acquired immunodeficiency syndrome,AIDS).HIV迄今为止已经夺去近3300万人生命,是全球最大的公共卫生挑战之一.自从抗逆转录病毒治疗(Antiretrovial therapy,ART)出现以后,抗逆转录药物的联合使用使艾滋病从致死性疾病变成慢性可控性疾病.为了开发新的抗艾滋病药物,基于病毒复制周期中的不同靶标将近年发展的抗艾滋病药物进行分类简述,重点关注于药物的作用机制研究、临床应用现状及未来发展方向.     

AZT磷酰胺类的ESI-MS研究

面对威胁人类健康的艾滋病,不少生物学家、化学家和药物学家都在积极的研究和开发新的、高疗效的抗AIDS的药物.AZT和d4T氢磷酸酯类与磷酰胺类衍生物以其毒性低和高活性可望成为-类新的抗HIV的前药[1-3].我们合成了一系列的AZT磷酰胺类,并对它们的电喷雾质谱进行了详细的研究.     

香豆素类衍生物的合成

由人免疫缺陷病毒 ( HIV)感染引起的免疫缺陷综合症 ( AIDS)——艾滋病 ,是人类致命疾病之一。世界各国都在致力于寻找抗艾滋病药物 ,其中一个研究热点是通过大规模筛选寻找生物活性较强的小分子非肽类抑制剂 ,然后进行结构优化 ,以期找到新一代的抗艾滋病药物。香豆素类衍生物是一类具有抗病毒等许多生物活性的化合物 ,一直被人们所重视。 1 992年 ,从马来西亚热带雨林植物 Calophllum L anigerum中分离出具有抗艾滋病病毒活性的香豆素类化合物 Calanolides[1] 。同时 ,由于香豆素类化合物合成相对简单 ,生物利用度高 ,促使人们在这个…     

毕赤酵母表达的HIV-2外膜糖蛋白的纯化与活性测定

人免疫缺陷病毒(Human immunodeficiency virus,HIV)是艾滋病（AIDS）的病原体,其外膜蛋白是HIV侵入人体靶细胞的物质基础,对其结构与功能的深入研究不但能为彻底揭示HIV致病机理奠定基础,而且有助于抗感染免疫研究和治疗物的设计^[1,2],HIV－2ROD外膜蛋白gp105是一种高度糖基化的糖蛋白,近年来发展迅速的毕赤酵母（Pichia Pastoris）真核表达系统对分泌蛋白的糖基化修饰形式与天然的gp105相同^[3]。为实现大量制备有活性的gp105,我们用PCR法去除了gp105基因5′端28个密码子的非功能片段,以提高gp105的表达水平,并成功地在毕赤酵母中实现了gp105的高效分泌表达。本文对这一表面产物的纯化、性质及活性进行了研究,为尽快研制出有效的疫苗奠定基础。     

微量元素与艾滋病相关标志物

人类免疫缺陷病毒（HIV）感染病程监督是防治艾滋病的重要措施和手段。阐述了微量元素在HIV病变进程中的变化及与其它相关标志物的关系,内容包括：微量元素与HIV病变、微量元素与CD4淋巴细胞、微量元素与谷胱甘肽、微量元素与HIV消瘦综合征,以及微量元素与炎性反应标志等5个方面。迄今的研究表明,微量元素可以作为反映HIV感染疾病进展的一种新的替代标志物。     

基于微流控芯片的CD4+T淋巴细胞计数检测

CD4 +T淋巴细胞是人体免疫缺陷病毒(HIV)的主要感染细胞,慢性HIV感染者逐渐耗尽CD4 +T淋巴细胞,使免疫系统变弱,导致获得性免疫缺陷综合症(AIDS),因此,CD4 +T淋巴细胞的数量对HIV/AIDS的诊断和治疗至关重要。全球范围内HIV/AIDS正处于快速增长期,现有的CD4 +T淋巴细胞计数检测方法由于仪器昂贵、操作复杂、检测成本高,不利于疾病诊疗的普及与推广。为实现低成本、方便、快捷的临床检测,基于微流控芯片的CD4 +T淋巴细胞计数检测方法与技术的研究正日益受到人们的重视。本文在回顾传统CD4 +T淋巴细胞检测方法的基础上,综述、归纳了基于微流控芯片的CD4 +T淋巴细胞计数方法,在全面分析其技术特点的基础上,进一步评述了其综合性能、适用范围、及典型优缺点。最后,本文针对基于微流控芯片的CD4 +T淋巴细胞计数检测技术的发展趋势及商业化应用前景进行了讨论和展望。     

抗氧化能力评价方法

生物体系中的氧化与抗氧化系统失衡会导致氧化应激,被认为同诸多疾病的发病机理密切相关,具有抗氧化能力的物质能有效抵御氧化应激的有害损伤。本文介绍了氧化应激的有关概念,包括活性氧物种、抗氧化剂、氧化损伤等,并重点针对生物体内和体外的各种活性氧、活性氮物种清除能力检测方法以及本研究小组最新发展的利用金纳米壳复合材料和其他小组基于纳米材料的评价方法进行了综述与比较,包括化学原理、优缺点及实际应用等。简要分析了目前检测方法存在的问题并对未来标准化检测方法进行了展望。     

艾滋病与微量元素

从艾滋病的病理特征与微量元素缺乏症的类似性，艾滋病患者的微量元素含量变化，艾洋患者微量元素补充等方面综述了艾滋病与微量元素的联系，讨论了微量元素在防治艾滋病中的可能作用，附３１篇参考文献。     

硒补充：防治艾滋病的有效新策略

从以下四方面：（1）低硒——引发艾滋病的基础性因素,（2）病毒复制——进一步消耗体内的硒,（3）硒水平——艾滋病结局的独立预测指标,（4）硒补充——防治艾滋病的有效新策略,详细论述了硒在艾滋病发生、发展和结局中的作用,列举了硒剂防艾滋病干预试验的某些初步结果。如能采用理想的“硒”,并在随机化、大样本量的对照试验中得到进一步证实,则硒补充作为一种简单易行、消费得起的干预措施,可能具有公共健康效益。     

TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts

Apoptosis has an important role in maintaining tissue homeostasis in cellular stress responses such as inflammation, endoplasmic reticulum stress, and oxidative stress. T-cell death-associated gene 51 (TDAG51) is a member of the pleckstrin homology-like domain family and was first identified as a pro-apoptotic gene in T-cell receptor-mediated cell death. However, its pro-apoptotic function remains controversial. In this study, we investigated the role of TDAG51 in oxidative stress-induced apoptotic cell death in mouse embryonic fibroblasts (MEFs). TDAG51 expression was highly increased by oxidative stress responses. In response to oxidative stress, the production of intracellular reactive oxygen species was significantly enhanced in TDAG51-deficient MEFs, resulting in the activation of caspase-3. Thus, TDAG51 deficiency promotes apoptotic cell death in MEFs, and these results indicate that TDAG51 has a protective role in oxidative stress-induced cell death in MEFs.     

Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions**

Human telomeric DNA, in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.     

Oxidative Stress in Down and Williams-Beuren Syndromes: An Overview

Oxidative stress is the result of an imbalance in the redox state in a cell or a tissue. When the production of free radicals, which are physiologically essential for signaling, exceeds the antioxidant capability, pathological outcomes including oxidative damage to macromolecules, aberrant signaling, and inflammation can occur. Down syndrome (DS) and Williams-Beuren syndrome (WBS) are well-known and common genetic conditions with multi-systemic involvement. Their etiology is linked to oxidative stress with important causative genes, such as SOD-1 and NCF-1, respectively, of the diseases being primarily involved in the regulation of the redox state. Early aging, dementia, autoimmunity, and chronic inflammation are some of the main characteristics of these conditions that can be associated with oxidative stress. In recent decades, there has been a growing interest in the possible role of oxidative stress and inflammation in the pathology of these conditions. However, at present, few studies have investigated these correlations. We provide an overview of the current literature concerning the role of oxidative stress and oxidative damage in genetic syndromes with a focus on Down syndrome and WBS. We hope to provide new insights to improve the management of complications related to these diseases.     

The energy-chemistry nexus: A vision of the future from sustainability perspective

The changing energy-chemistry nexus is discussed in this perspective paper about the future of sustainable energy and chemical production to identify the priorities and open issues on which focus research and development. Topics discussed regard(i) the new sustainable energy scenario,(ii) the role of energy storage(from smart grids to chemical storage of energy),(iii) the outlooks and role of solar(bio)refineries and solar fuels,(iv) how to integrate bio- and solar-refineries to move to new economy,(v) the role of methanol at the crossover of new energy-chemistry nexus,(vi) the role of chemistry in this new scenario,(vii) the role of nanomaterials for a sustainable energy,(viii) the use of nanocarbons to design advanced energy conversion and storage devices, and(ix) possibilities and routes to exploit solar energy and methane(shale gas). The contribution provides a glimpse of the emerging directions and routes with some elements about their possible role in the future scenario, but does not provide a detailed analysis of the state of the art in these directions.     

Effects of glutamate on dehydroascorbate uptake and its enhanced vulnerability to the peroxidation in cerebral cortical slices

Pro-oxidant properties of ascorbate have been studied with uses of brain tissues and neuronal cells. Here we address potential mechanism of ascorbate coupling with glutamate to generate oxidative stress, and the role which oxidized ascorbate (dehydroascorbate) transport plays in oxidative neuronal injury. Ascorbate in neurones can be depleted by adding glutamate in culture medium since endogenous ascorbate can be exchanged with glutamate, which enhances ascorbate/dehydroascorbate transport by depleting ascorbate in the neurons with the glutamate- heteroexchange. However, ascorbate is known readily being oxidized to dehydroascorbate in the medium. Glutamate enhanced the dehydroascorbate uptake by cells via a glucose transporter (GLUT) from extracellular region, and cytosolic dehydroascorbate enhanced lipid peroxide production and reduced glutathione (GSH) concentrations. Iso-ascorbate, the epimer of ascorbate was ineffective in generating the oxidative stress. These observations support the current concept that the high rates of dehydroascorbate transport via a GLUT after the release of ascorbate by glutamate leads to peroxidation, the role of glutamate on ascorbate/dehydroascorbate recycling being critical to induce neuronal death via an oxidative stress in the brain injury.