荧光分子成像的探针技术及其应用

近几年,随着生物和基因技术的发展,荧光探针的获取手段越来越丰富.荧光探针的发展使得荧光分子成像技术及其应用备受关注.借助于荧光探针,可以对目标分子、蛋白质、基因等特异性成像,从而实现分子、蛋白、基因等的精确定位与分析,进一步实现疾病的早期诊断与治疗.主要对荧光分子成像技术中用到的荧光探针技术以及在生物医学领域的应用进行概述.     

动态荧光分子成像技术研究进展

动态荧光分子成像技术能够描述荧光分子探针在生物体内吸收、分布以及排出的完整过程,是一种可以对生物体的生理、病理过程进行连续监测的动态成像技术.这项技术具有无电离辐射、成像速度快、灵敏度及特异度高、费用低廉等优点,在基础医学及临床医学研究中具有广阔的应用前景.从系统、算法和应用3个方面对动态荧光分子成像技术的研究进展进行了综述.     

基于FRET荧光蛋白探针的活体定量分子影像方法探究

目的荧光共振能量转移(fluorescent resonance energy transfer,FRET)探针由于自身仍存在诸多局限,其在活体成像领域尚未得到广泛应用。本文旨在解决FRET探针在活体定量分子影像应用中所存在的瓶颈问题,即如何利用FRET探针精准计算目标物浓度,以及如何基于FRET探针实现三维成像。方法基于探针和目标物结合时的化学反应平衡关系,提出一种新型分析方法,以精确定量待测物[钙调素(calmodulin,Ca M)]的浓度。同时对于FRET探针的活体分子成像,结合荧光透射成像(3DFMT)方法,建立了可进行三维时空动态FRET检测的平台系统,对FRET探针的测量结果(即待测物浓度)进行实时定量的三维重建。结果准确地定量了待测物Ca M浓度,并得到了高质量的3D-FRET分布影像。结论提出FRET探针在活体成像应用领域两个关键问题的解决方案,为基因编码FRET探针向活体分子影像领域的推广奠定了重要的技术基础。     

基于MR分子成像的分子探针及其研究进展

MR分子成像可以利用MRI技术并借助对比剂的生化特征来直接或间接地反映目的基因的情况,其核心任务的关键在于分子探针的选用。本文介绍了分子探针在MRI技术中的重要性及MR分子成像对分子探针的要求,且着重阐述了MR分子成像中分子探针的种类及其应用进展情况。     

PCR分子信标法及其应用

PCR分子信标法是近几年发展起来的一种全新的核酸定量检测技术 ,它具有 PCR技术的高效核酸扩增特性 ,核酸探针杂交的高特异性 ,以及光谱技术的高灵敏性和可计量性。目前 ,PCR分子信标法已被广泛应用于病原微生物的检测、肿瘤研究、基因突变研究等多个领域     

荧光分子断层成像系统的研究进展与比较

荧光分子断层成像（FMT）利用具有特异性的荧光分子探针,在体成像、观测生物体内细胞和分子水平的变化。介绍FMT系统的国内外研究进展,从系统的复杂性、投影数目、光源-探测器（S-D）数据对集大小、重构图像的质量等方面,分析5种S-D几何结构的特点。着重从实现方面,分析、比较已报道的几种FMT系统的特点,并对其多模态成像的可扩展性、临床应用的可能性等进行了总结与展望。     

肺癌靶向多肽荧光分子探针的研制及其应用

目的:选择能与整合素α3受体结合的小分子多肽cNGQGEQc-L作为靶向载体，将羧基荧光素（FAM）与cNGQGEQc-L连接构建荧光分子探针，通过荧光成像探讨荧光多肽分子探针用于肺腺癌显像的可行性。方法:利用倒置荧光显微镜观察FAM-cNGQGEQc-L与肺腺癌A549细胞结合部位，流式细胞仪检测荧光多肽与A549细胞的竞争抑制实验，观察FAM-cNGQGEQc-L随浓度的增加与肺腺癌A549细胞结合能力的变化情况。通过小动物活体成像仪，观察荧光多肽在荷瘤裸鼠体内的生物分布特点。结果:倒置荧光显微镜显示荧光多肽cNGQGEQc-L能与A549细胞结合，结合部位在细胞膜和细胞质中。流式细胞仪测试结果证明荧光多肽与A549细胞的结合具有特异性和饱和性，当FAM-cNGQGEQc-L浓度为0.125 mmol/L时，荧光多肽与A549细胞的结合趋近饱和。荷瘤裸鼠活体成像显示移植瘤能够摄取荧光多肽，且荧光多肽通过泌尿系统和胆道系统排泄。结论:体外、体内荧光实验结果显示，荧光多肽分子探针FAM-cNGQGEQc-L可与肺腺癌A549细胞、肺癌移植瘤结合，能够特异性靶向肺腺癌。     

量子点探针辅助的近红外荧光成像技术在肿瘤显影中的应用

肿瘤早期检测是精准并高效诊疗癌症的关键因素。荧光成像技术凭借其高灵敏度、高时空分辨率、无电离辐射和无创实时成像等优点,在生物医学领域,尤其在肿瘤检测方面展现出了广泛的应用前景。近红外光穿过生物组织时,受到的吸收和散射较少,因此在生物成像方面体现了高信噪比和强组织穿透能力。在众多荧光探针中,近红外发光的量子点探针因其量子产率高、抗光漂白性强、发射光可调和稳定性良好等特点在荧光成像方面显示出突出的优势。本文基于量子点探针的近红外荧光成像技术在肿瘤显影中的应用,介绍了量子点优异的光学性能,并重点讨论了硫化铅（PbS）和硫化银（Ag2S）近红外发光量子点探针在肿瘤成像方面的研究进展,并对近红外发光量子点探针的应用前景进行了展望。     

基于磁共振图像的乳腺癌分子分型研究进展

在基因表达水平上,乳腺癌分子亚型的分析对评价乳腺癌的恶性程度及制定个体化治疗方案具有重要的临床应用价值。除免疫组织化学染色和基因芯片技术外,影像组学的兴起也为乳腺癌分子分型提供新的预测方式。综述基于磁共振成像的乳腺癌分子分型的研究现状。在概述乳腺磁共振成像原理和特点的基础上,分别从统计学分析及机器学习方法的角度,阐述乳腺癌的磁共振影像学表现与各分子亚型之间的关联性研究成果及预测算法,最后对乳腺癌分子分型研究做出总结并对未来的研究进行展望。基于磁共振成像(MRI)的乳腺癌分子分型的研究已取得了一些实质性进展,未来可借助更高阶的算法进一步深入挖掘乳腺癌MRI的形态学、背景实质增强、统计量及纹理等成像特征,使影像学特征作为潜在生物标记物,为乳腺癌的精准医疗提供帮助。     

核酸分子探针制备技术新进展

目前各种非同位素核酸分子杂交检测技术发展很快,而这些进展的关键在非同位素探针的制备。本文综述了最近几年各种非同位素核酸探针的制备技术,主要为生物素探针的制备技术、蛋白质标记探针及半抗原标记探针的制备技术。并对各种非同位素核酸探针的制备技术的新进展及其优缺点进行了初步比较。     

Evolutionary molecular medicine

Evolution has long provided a foundation for population genetics, but some major advances in evolutionary biology from the twentieth century that provide foundations for evolutionary medicine are only now being applied in molecular medicine. They include the need for both proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, competition between alleles, co-evolution, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are transforming evolutionary biology in ways that create even more opportunities for progress at its interfaces with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine.     

分子标记在生物材料分子生物相容性中的应用现状

对生物材料进行生物相容性的评价是进入临床实验前的关键环节.随着分子生物学的迅速发展,研究者已经深入到分子水平对生物材料进行生物相容性的评价,并提出了分子生物相容性的概念.当前,主要任务是借助分子生物学技术,确定更多的分子标记物,以便建立分子生物相容性评价标准,并藉此指导设计出相容性更好的生物材料.     

Pitfalls in molecular diagnostics

Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis, tumorigenesis, and immune function contribute to the development of these assays. However, each technique, if applied incorrectly or in ignorance, can lead to difficulties in execution or errors in interpretation. In this review of commonly used molecular diagnostic tests, including immunohistochemistry, microsatellite instability testing, chromosomal microarray testing, and conventional and next-generation sequencing, the emphasis will be on potential pitfalls and considerations for each platform. Emerging technologies that may be used in clinical applications in the near future will also be discussed. An understanding of the methodologies, advantages, and drawbacks of molecular assays will help pathologists aid in diagnostic and therapeutic decisions.     

Low molecular weight immunopotentiators

It has long been recognized that modulation of the immune system by various agents may have potential for the management of certain infectious and neoplastic diseases. Both natural products as well as chemically synthesized compounds have been investigated for immunotherapeutic potential. Over the years, conflicting reports on the clinical efficacy of these agents have left the early promise of immunotherapy unfulfilled. However, the manipulation of the immune system to generate a desired effect is becoming feasible as the mechanisms which regulate the immune network are better understood. Much of the early work on immunotherapy concentrated on the development of immunopotentiators, agents which enhance the host's own immune system against cancer cells or infectious pathogens. Furthermore, with the development of subunit and/or synthetic vaccines, which are often weakly immunogenic, the importance of developing agents capable of acting as adjuvants became apparent. As a result, the utility of immunopotentiators has now extended to the area of vaccines. There are a number of reviews available on immunomodulators [see Fenichel, R. L. and Chirigos, M. A. (eds) (1984), Immune Modulation Agents and Their Mechanisms, Marcel Dekker, New York]. The purpose of this article is to provide an update on low molecular weight agents capable of potentiating the immunological network. Attention will be given to those agents which have undergone significant clinical development in the areas of cancer, infectious diseases and vaccination over the past several years. These agents will be categorized as to whether they are naturally occurring or chemically synthesized.