水通道蛋白与自身免疫性疾病关系的研究进展

水通道蛋白(aquaporins,AQPs)是广泛存在于微生物、动植物和人体内的一组小分子蛋白质,是与水通透有关的细胞膜上转运水的特异孔道。迄今已知在哺乳动物体内至少存在13种AQPs分子(AQP0～AQP12),它们介导着不同类型细胞膜上跨膜水转运,对水有选择性通透作用[1],并与某些疾病的发生密切相关。自身免疫性疾病是指机体免疫系统针对自身组织成分产     

肾脏水通道蛋白-1(AQP-1)的研究进展

水通道蛋白(AQP)是一种分子量约28 kD的四聚体结构膜通道蛋白。哺乳动物中有13种不同的AQP,表达于不同的组织器官,调节水以及甘油和尿素等小分子跨膜转运。AQP-1主要表达于肾近曲小管和髓袢降支细段上皮细胞顶膜和基底膜,负责肾小管水分子的重吸收。当肾脏发生病变或者损伤时,AQP-1的表达也会随之改变,所以研究AQP-1对于了解水代谢疾病的发生机制以及指导临床水代谢疾病的治疗具有十分重要的意义。     

水通道蛋白与脑组织内水转运

水通道蛋白(aquaporins,AQP)是一组构成水通道与水通透有关的细胞膜转运蛋白,该通道是由一系列具有同源性的内在膜蛋白家庭成员所形成,广泛存在于动物、植物及微生物界,介导着不同类型细胞膜的跨膜水转运。水的跨膜转运对维持细胞正常代谢具有重要作用,所有组织细胞都允许水以简单扩散方式通过细胞膜,但某些细胞如红细胞、肾近曲小管上皮细胞等对水的通透性很高,不能以水穿越脂质双分子层弥散来解释。1991年,Preston等[1] 完成了对第一个水通道的cDNA的分子克隆和功能鉴定,才证明了在哺乳动物的细胞膜上存在特异转运水的孔道———AQP。…     

水通道蛋白成像技术及其在脑胶质瘤中的应用进展

<正>水是生命基础。水分子在人体组织细胞扩散、转运和代谢的过程及机制备受重视。长期以来,一直认为水和一些小分子物质以自由扩散方式通过细胞膜。自Agre等[2]在1992年发现了水通道蛋白(water channel protein,WCP),即水通道蛋白(aquaporin,AQP)后彻底改变了传统的水在细胞膜上扩散的观念,从而创立了水分子在细胞膜转运的全新理论基础[1-3]。迄今,在哺乳动物体内发现至     

AQP磁共振分子成像在肿瘤中的研究进展

水通道蛋白(aquaporins,AQPs)是细胞膜上选择性转运水分子的膜内在蛋白,广泛存在于生物体内各组织器官,其生理状态的改变与许多疾病的发生发展密切相关,特别是恶性肿瘤的生长、浸润和转移。早期准确检测肿瘤细胞AQPs分布和表达水平能为肿瘤的术前诊断及分期、术后疗效评估提供更为精准的信息。近年来,以AQPs理论为基础的多b值扩散加权成像(diffusion weighted imaging,DWI)技术已展现出巨大的发展潜力,其通过表观扩散系数(apparent diffusion coefficient,ADC)的变化来反映细胞膜AQPs的分布和功能,开辟了MR分子成像的新领域。笔者对AQPs的基本结构、生理功能、肿瘤中的表达及其意义进行简要概述,同时就AQP磁共振分子成像的基本原理以及在肿瘤中的应用进行综述。     

水通道蛋白9与消化系统疾病

水通道蛋白是一组对水有高选择性的跨膜转运蛋白,广泛分布在机体各组织,在水的分泌吸收、细胞内外水平衡等过程中起着重要作用。水通道蛋白9(AQP9)是水通道蛋白家族成员之一,是1998年发现的一种新的水通道蛋白亚型,现就AQP9的基本特点,在消化道的分布、表达,与疾病的关系作一     

细菌水通道蛋白研究展望

根据通透特异性,现已证实和命名了三类细菌的水通道蛋白,它们以四聚体形式存在于特定细菌的细胞膜上,共同完成水、甘油、小分子物质转运,在细菌各个生长期有着不同的分布和表达,对细菌的生长、繁殖、变异和死亡有着重要的生理作用,可能是杀灭细菌的切入点之一。     

水通道蛋白与脑水肿

水能道蛋白(AQPs)是一组具有高度选择性的水通道特异蛋白家族,其中分布于脑部的主要为AQP4,AQP4是胶质细胞与细胞间液、脑脊液以及血管之间的水调节和运输的重要结构基础,参与了各种原因如创伤、中风、脑肿瘤等所致的脑水肿的形成以及癫痫的发生,对AQP4在脑水肿中的形成机制的作用研究有望为临床脑水肿的治疗开辟新的途径。     

AQP水通道蛋白和脑水肿

头颅创伤、脑卒中及各种原因所致呼吸循环骤停均可引起脑水肿而危及生命。目前治疗主要局限于渗透性利尿或外科减压 ,尚少针对脑水肿形成机制方面的治疗。新近有研究显示 ,AQP水通道蛋白是大脑水转运的一个重要途径 ,它可能参与多种神经系统疾病中脑水肿的形成。现对大脑AQP水通道蛋白的表达与脑水肿形成的联系进行综述。1　AQP水通道蛋白家族生理学家很早就发现水分子通过多种细胞膜 (红细胞、肾小管 )的速度不能单用简单扩散来解释。过去几年中人们发现了水转运蛋白 -AQPs家族 ,它属于庞大的主体内在结构蛋白 (majorintrinsicprotein…     

水通道蛋白1与内皮细胞功能

水通道蛋白（AQP）是与转运水有关的一系列具有同源性的内在膜蛋白家族,广泛存在于动植物和微生物中,迄今为止哺乳动物已发现13种AQP（AQP0-AQP12）,其在机体的不同组织和部位也执行着不同的生物学功能。大量研究证实,许多疾病可能与AQP功能异常或调节失控有关。     

Unique adverse effects of molecular targeted drugs

Molecular targeted drugs have been developed to act principally on specific molecules expressed on either cancer cells or normal surrounding cells in cancerous tissues. Ideally, expressions of these targeted molecules are markedly increased in cancerous tissues as compared with normal tissue. This class of drugs has been expected to have superior antitumor effects without any toxicities. Over the last decade, however, the introduction of molecular targeted drugs into clinical setting revealed unexpected, occasionally lethal, "off-targeted" adverse effects which were different from the toxic profiles of cytotoxic drugs. In this review, the adverse effects of molecular targeted drugs, the managements of these toxicities and the molecular mechanism underlying of these toxicities are reviewed.     

分子影像在EGFR靶向治疗的研究进展

表皮生长因子受体的靶向治疗癌症需要准确估计肿瘤中的EGFR表达，以识别反应患者，评估疗效和预后。分子影像技术是分子探针与细胞特定靶分子结合，通过PET/CT检测技术获取图像，无创、重复、实时评价靶分子表达情况。分子成像是一种准确和无创评估体内EGFR表达的最佳方法。本文就PET的各类EGFR分子探针研究进展进行综述。     

Cellular and molecular imaging with targeted contrast ultrasound

There is growing interest in the availability of methods for imaging disease at the level of the cellular and/or molecular mediators. Techniques for imaging molecular alterations have been develop for essentially all non-invasive cardiac imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on the detection of novel site-targeted contrast agents. These microbubbles or nanoparticles are retained within regions of a specific disease process, thereby allowing phenotypic characterization of tissue. Since most of these tracers remain within the intravascular space, the disease processes assessed must be characterized by antigens that are expressed within the vascular compartment. Accordingly, the pathologic states that have been targeted include inflammation, ischemia-and tumor-related angiogenesis, and thrombus formation; all of which are mediated in part by molecular events within the vascular space. This review describes: 10 different strategies that have been employed to target ultrasound contrast agents to regions of disease, 2) the unique challenges for imaging targeted ultrasound contrast agents, and 3) some of the early experience imaging molecular events in animal models of disease.     

分子靶向药物治疗毒副作用的护理

肿瘤分子靶向治疗是利用肿瘤组织或细胞所具有的特异性（或相对特异）的结构分子作为靶点,使用某些能与这些靶分子特异结合的抗体、配体等达到直接治疗或导向治疗目的的生物治疗模式。分子靶向治疗有较好的选择性,能减少对正常组织的损伤,具有较少的远、近期毒副作用和良好的疗效,能够延长患者的无瘤生存期、提高患者的生活质量。它已经成为肿瘤内科治疗的重要手段之一。     

Applying molecular networking for targeted isolation of depsipeptides

LC-HRMS/MS molecular networking enabled the targeted isolation of three new neoantimycin analogs (1, 3, 5) and two known ones (2, 4) from the culture broth of Streptomyces conglobatus RJ8. After derivatization into C1-hydroxyl form compounds (6–10) respectively, the absolute structures of 1–5 were clearly determined by analyzing the hydrolyzed components from 6–10. Compounds 2 and 3 were confirmed to be a pair of epimers with different stereochemistry at C-2, and so were 4 and 5. This is the first report of the isolation and characterization of epimers of NATs. The most abundant eight compounds we obtained were subjected to a cytotoxicity assay, 1 and 6 exhibited excellent cytotoxicity with the lowest IC₅₀ value in the picomolar range against six human carcinoma cell lines while 7 and 8 showed potent cytotoxicity against PC-9 and PC-9/GR cell lines.

LC-HRMS/MS molecular networking enabled the targeted isolation of three new neoantimycin analogs (1, 3, 5) and two known ones (2, 4) from the culture broth of Streptomyces conglobatus RJ8.     

宫颈癌分子靶向治疗的研究新进展

宫颈癌作为女性最常见的恶性肿瘤,发病率在全球女性肿瘤中占第二位,并且具有年轻化的趋势.传统手术和放化疗在治疗宫颈癌方面非常局限,随着分子生物学和免疫学技术的发展,宫颈癌治疗逐渐向微观方向发展,其中备受关注的是宫颈癌分子靶向治疗,现已进入临床研究阶段.     

一例晚期肺癌患者应用新型分子靶向药物治疗的护理

大多数非小细胞肺癌患者就诊时已属晚期,需行姑息治疗,尤其是年龄较大或功能评分较差的患者,不能耐受肿瘤的一线和二线治疗方案来控制肿瘤（阻止或延迟肿瘤持续生长和进展）和提高生活质量。随着人们对肿瘤生物学、转移因子及细胞机制的深入研究,产生了新一代化疗药物新型分子靶向药物。盐酸厄洛替尼是其中的一种。     

Multiplex photoacoustic molecular imaging using targeted silica-coated gold nanorods

The establishment of multiplex photoacoustic molecular imaging to characterize heterogeneous tissues requires the use of a tunable, thermally stable contrast agent targeted to specific cell types. We have developed a multiplex photoacoustic imaging technique which uses targeted silica-coated gold nanorods to distinguish cell inclusions in vitro. This paper describes the use of tunable targeted silica-coated gold nanorods (SiO(2)-AuNRs) as contrast agents for photoacoustic molecular imaging. SiO(2)-AuNRs with peak absorption wavelengths of 780 nm and 830 nm were targeted to cells expressing different cell receptors. Cells were incubated with the targeted SiO(2)-AuNRs, incorporated in a tissue phantom, and imaged using multiwavelength photoacoustic imaging. We used photoacoustic imaging and statistical correlation analysis to distinguish between the unique cell inclusions within the tissue phantom.     

骨髓增殖性肿瘤分子靶向治疗策略

骨髓增殖性肿瘤以一系或多系髓系细胞增殖为特点,近年来发现的活化酪氨酸激酶突变JAK2V617F在某些类型骨髓增殖性肿瘤的分子发病机制中可能发挥关键作用,该发现极大地推动了选择性JAK2抑制剂用于治疗骨髓增值性肿瘤的研究发展。该文总结了JAK2抑制剂在骨髓增殖性肿瘤靶向治疗中的地位,并分析了其可能带来的益处和面临的挑战。     

Emergence of targeted molecular imaging in atherosclerotic cardiovascular disease

Atherosclerosis, a systemic disease, remains one of the leading causes of morbidity and mortality in the world. Our improved understanding of the molecular mechanisms underlying atherosclerotic lesion progression and sudden transformation into unstable plaques, indicate complex interactions of lipid metabolism, inflammatory processes and genetic predisposition. Currently, novel imaging approaches to visualize the process of atherosclerosis, particularly at the molecular level, are actively being developed. Important targets include inflammatory and endothelial cells, as well as apoptosis and angiogenesis. The next decade should solidify the role of targeted molecular imaging in all aspects of cardiovascular medicine.