人体特征的头发代谢组学及蛋白质组学研究进展

人类头发是以角蛋白和角蛋白相关蛋白为主要成分的天然纤维,是一种可表征一定时间内机体状态的良好生物学样本。头发易采集、低成本、易于运输和存储等优点使其在毒品、酒精及兴奋剂等的检测中具有独特优势。蛋白质组学是一种在整体水平上研究蛋白表达和调控的新兴技术,在生命科学领域应用广泛。蛋白质组学技术可用于不同人群头发蛋白组成及动态变化研究,在寻找疾病标志物、区分个人特质等方面具有巨大潜力。本文从头发的结构及组成、心理压力下头发的变化以及头发蛋白质组学分析技术的研究进展进行了全面综述,对理解头发蛋白质组学表征人体特征以及指导相关研究具有重要意义。     

蛋白质组学及其在肿瘤研究中的应用

简要介绍了蛋白质组学的概念、研究方法及其在肿瘤研究中的应用.蛋白质组学研究直接定位于蛋白质水平,从整体、动态、定量的角度去研究基因的功能,是后基因组计划的一个重要组成部分.恶性肿瘤是一种多基因参与的复杂疾病,从蛋白质整体水平上研究恶性肿瘤将有助于进一步揭示恶性肿瘤的发病机制,发现恶肿瘤特异性的标志物及其药物治疗的靶标.     

糖尿病肾病蛋白质组学研究进展

糖尿病肾病(diabetic kidney disease, DKD)是糖尿病的主要并发症之一,严重威胁人类健康与生命.截至目前, DKD的致病机制尚未阐释清楚,且临床常用诊断方法的灵敏性和准确性并不十分理想,从而导致DKD确诊后治疗方案的确定比一般性肾脏疾病更为棘手.蛋白质作为生命活动的主要承担者与体现者,直接参与和调控各种生命过程.从蛋白质组学水平开展DKD研究,能够从整体、动态、互作网络等视角探究该疾病相关分子机制.针对不同生理病理条件下的DKD临床样本开展蛋白质组学研究,可全面探查与DKD显著相关的关键蛋白质;通过对这些蛋白质进行深入分析和验证,能够更直观地理解DKD发生发展的分子机制,并获得DKD进程相关候选标志物和后续疾病的潜在治疗靶点,为DKD的早期诊断和治疗新方法的探究奠定基础.近年来,随着蛋白质组学技术的不断发展,在蛋白质分离、质谱鉴定、生物信息学分析等蛋白质组学核心技术基础上衍生出了许多新兴技术,进一步推动了蛋白质组学在疾病生物标志物筛选、致病分子机制揭示、药物作用蛋白质靶点等研究中的应用.本文基于蛋白质组学研究技术,主要从DKD致病机制研究、早期诊断潜在生物标志物筛选、治疗靶点及效果评估三个方面对蛋白质组学在DKD研究中的应用进展进行了系统性综述.尽管蛋白质组学在DKD研究中取得了长足的进步,但仍具有较大的发展空间,特别是现已识别的大量潜在DKD分子标志物的相关性分析、药物蛋白质作用靶点临床验证与应用将是DKD未来研究的重点.     

蛋白质组学及其在肿瘤研究中的应用

简要介绍了蛋白质组学的概念、研究方法及其在肿瘤研究中的应用.蛋白质组学研究直接定位于蛋白质水平，从整体、动态、定量的角度去研究基因的功能，是后基因组计划的一个重要组成部分.恶性肿瘤是一种多基因参与的复杂疾病，从蛋白质整体水平上研究恶性肿瘤将有助于进一步揭示恶性肿瘤的发病机制，发现恶性肿瘤特异性的标志物及其药物治疗的靶标.     

蛋白质组学研究相关技术及进展

蛋白质组学以蛋白质组为研究对象,应用相关研究技术,从整体水平上来认识蛋白的存在及活动方式。随着人类基因组计划的完成,蛋白质组学的研究也得到了快速发展,与蛋白质组学研究相关的一些技术也日益得到完善和提高。简要综述了近年来蛋白质组学研究中最为重要的样品制备、蛋白质分离、蛋白质鉴定等技术及研究进展。     

蛋白质组学研究技术及其联合应用

蛋白质组学是研究细胞、组织和器官内所有蛋白质的组成及其动态变化的科学,是在蛋白质水平上定量的、动态的、整体的研究生物体。目前蛋白质组学技术分为样品制备、分离和鉴定3个方面,其新技术主要有激光捕捉显微解剖法、离心超滤法、双向凝胶电泳、同位素亲和标签技术、色谱技术以及质谱技术等。然而,任何一种蛋白质组学研究技术都有其缺陷。因此多种技术的联合应用能使蛋白质组研究更精确和完整,是蛋白质组学的发展趋势。     

蛋白质组学技术及其在心血管疾病研究中的应用

蛋白质组学是旨在研究蛋白质表达谱和蛋白质与蛋白质之间相互作用的新的领域。蛋白质组学的研究必须依赖高通量、自动化程度很高的技术。双向电泳、液相色谱和生物质谱技术的发展推动了蛋白质组学的研究。蛋白质组学为疾病发病机制的研究提供了新的思路和方法 ,本文重点介绍了蛋白质组学技术在心血管疾病研究中的应用     

蛋白质组学在神经退行性疾病中的研究进展

蛋白质组学是后基因组时代兴起的新型学科,是从整体水平对蛋白质的综合分析。阿尔茨海默病、帕金森病、肌萎缩侧索硬化症等是最常见的神经退行性疾病。应用蛋白质组学对它们进行研究,不仅可从蛋白质水平上揭示疾病的本质,还有助于全面探讨其病理机制,建立诊断标准,发现药物治疗靶点。     

果蝇蛋白质组学研究进展

蛋白质组学旨在阐明基因组所表达的真正执行生命活动的全部蛋白质的表达规律和生物功能。随着人类基因组学计划的逐渐成熟,分子水平的实验技术不断发展,蛋白质组学的研究被提高到了前所未有的高度。果蝇是生命科学领域最为常用的一种模式生物,长期的系统研究也使果蝇的基因组成为至今注释最好的基因组之一,为功能基因组研究奠定了基础。但由于技术的限制,迄今有关果蝇蛋白质组学研究的报道尚不多见。近年来果蝇蛋白质组学的研究主要包括表达谱、修饰谱、比较蛋白质组学和疾病模型蛋白质组等四个方向,为进一步开展人类疾病临床蛋白质组学研究奠定了基础。     

蛋白质组学在感染性疾病研究中的应用

蛋白质组学在人类疾病研究中的应用 ,主要是通过比较分析正常组织细胞与异常组织细胞、同一疾病在不同的发展时期细胞内整体蛋白质的表达差异 ,对差异表达的蛋白质进行鉴定、定量、表征 ,寻找与疾病相关的新的标志物 ,为人类疾病研究提供新的手段和依据 ,蛋白质组学在感染性疾病研究中的应用就是其中的一个方面。1 .蛋白质组学在感染性疾病研究中的应用蛋白质组学在人类感染性疾病研究中的应用主要是对引起感染性疾病的致病源的整体蛋白质进行研究 ,同时结合血清学 ,对其进行分析 ,鉴定出与疾病相关的新的标志物 ,为感染性疾病的诊断、治疗…     

Clinical proteomics: present and future prospects

Advances in proteomics technology offer great promise in the understanding and treatment of the molecular basis of disease. The past decade of proteomics research, the study of dynamic protein expression, post-translational modifications, cellular and sub-cellular protein distribution, and protein-protein interactions, has culminated in the identification of many disease-related biomarkers and potential new drug targets. While proteomics remains the tool of choice for discovery research, new innovations in proteomic technology now offer the potential for proteomic profiling to become standard practice in the clinical laboratory. Indeed, protein profiles can serve as powerful diagnostic markers, and can predict treatment outcome in many diseases, in particular cancer. A number of technical obstacles remain before routine proteomic analysis can be achieved in the clinic; however the standardisation of methodologies and dissemination of proteomic data into publicly available databases is starting to overcome these hurdles. At present the most promising application for proteomics is in the screening of specific subsets of protein biomarkers for certain diseases, rather than large scale full protein profiling. Armed with these technologies the impending era of individualised patient-tailored therapy is imminent. This review summarises the advances in proteomics that has propelled us to this exciting age of clinical proteomics, and highlights the future work that is required for this to become a reality.     

Recent progress in mass spectrometry proteomics for biomedical research

Proteins are the key players in many cellular processes. Their composition, trafficking, and interactions underlie the dynamic processes of life. Furthermore, diseases are frequently accompanied by malfunction of proteins at multiple levels. Understanding how biological processes are regulated at the protein level is critically important to understanding the molecular basis for diseases and often shed light on disease prevention, diagnosis, and treatment. With rapid advances in mass spectrometry (MS) instruments and experimental methodologies, MS-based proteomics has become a reliable and essential tool for elucidating biological processes at the protein level. Over the past decade, we have witnessed great expansion of knowledge of human diseases with the application of MS-based proteomic technologies, which has led to many exciting discoveries. Herein we review the recent progress in MS-based proteomics in biomedical research, including that in establishing disease-related proteomes and interactomes. We also discuss how this progress will benefit biomedical research and clinical diagnosis and treatment of disease.     

Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics

Modern pathology is an amalgam of many disciplines, such as microbiology, biochemistry and immunology, which historically have been intermingled with the practice of clinical medicine. For centuries, the pre-eminent pathological tool, at least in the context of patients, was a post-mortem examination. With the advent of optical microscopes, morphology became a predominant means of developing tissue classification. A further paradigm shift occurred in the attempt to understand the nature and origin of disease; the recognition that, ultimately, it is the derangement in the structure and function of genes and proteins that causes human disease. More recent progress in pathology has led to the use of genomics and molecular technologies, including DNA sequencing, microarray analysis, PCR, in situ hybridization and proteomics. Today, the newest frontier appears to be histopathology proteomics, which adds the mass spectrometer to the arsenal of tools for the direct analysis of tissue biopsies and molecular diagnosis. Typically called MALDI imaging, this technique takes mass spectral snapshots of intact tissue slices, revealing how proteins and peptides are spatially distributed within a given sample. In this review, MALDI imaging technology is presented as well as applications of such technology in cancer or neurodegenerative diseases.     

Asthma, the ugly duckling of lung disease proteomics?

The human respiratory system represents a vital but vulnerable system. It is a major target for many diseases such as cancer and asthma. The incidence of these diseases has increased dramatically in the last 40-50 years. In the search for possible new therapies, many experimental tools and methods have been developed to study these diseases, ranging from animal models to in vitro studies. In the last decades, genomic and proteomic approaches have gained a lot of attention. After the major scientific breakthroughs in the field of genomics, it is now widely accepted that to understand biological processes, large-scale protein studies through proteomics techniques are required. In the battle against lung cancer, the proteomics approach has already been successfully implemented. Surprisingly, only a few proteomics studies on the ever-increasing global asthma problem have been published so far. And although proteomics also has its limitations and experimental difficulties, in our opinion, proteomics can definitely contribute to the understanding of a complex disease such as asthma. Therefore, the additional values and possibilities of proteomics in asthma research should be thoroughly investigated. A close collaboration between the different scientific disciplines may eventually lead to the development of new therapeutic strategies against asthma.     

Proteomics in clinical trials and practice: present uses and future promise

The study of clinical proteomics is a promising new field that has the potential to have many applications, including the identification of biomarkers and monitoring of disease, especially in the field of oncology. Expression proteomics evaluates the cellular production of proteins encoded by a particular gene and exploits the differential expression and post-translational modifications of proteins between healthy and diseased states. These biomarkers may be applied towards early diagnosis, prognosis, and prediction of response to therapy. Functional proteomics seeks to decipher protein-protein interactions and biochemical pathways involved in disease biology and targeted by newer molecular therapeutics. Advanced spectrometry technologies and new protein array formats have improved these analyses and are now being applied prospectively in clinical trials. Further advancement of proteomics technology could usher in an era of personalized molecular medicine, where diseases are diagnosed at earlier stages and where therapies are more effective because they are tailored to the protein expression of a patient's malignancy.     

Decreased striatal levels of PEP-19 following MPTP lesion in the mouse

PEP-19 is a neuronal calmodulin-binding protein, and as such, a putative modulator of calcium regulated processes. In the present study, we used proteomics technology approaches such as peptidomics and imaging MALDI mass spectrometry, as well as traditional techniques (immunoblotting and in situ hybridization) to identify PEP-19 and, specifically, to measure PEP-19 mRNA and protein levels in an animal model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice resulted in a significant decrease in striatal PEP-19 mRNA. Capillary nano-flow liquid chromatography electrospray mass spectrometry analysis of striatal tissue revealed a significant decrease of the PEP-19 protein level. Moreover, imaging MALDI mass spectrometry also showed that PEP-19 protein was predominantly localized to the striatum of the brain tissue cross sections. After MPTP administration, PEP-19 levels were significantly reduced by 30%. We conclude that PEP-19 mRNA and protein expression are decreased in the striatum of a common animal model of Parkinson's disease. Further studies are needed to show the specific involvement of PEP-19 in the neurodegeneration seen in MPTP lesioned animals. Finally, this study has shown that the combination of traditional molecular biology techniques with novel, highly specific and sensitive mass spectrometry methods is advantageous in characterizing molecular events of many diseases, including Parkinson's disease.     

Proteomics technologies and challenges

Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.     

Imaging aspects of cardiovascular disease at the cell and molecular level

Cell and molecular imaging has a long and distinguished history. Erythrocytes were visualized microscopically by van Leeuwenhoek in 1674, and microscope technology has evolved mightily since the first single-lens instruments, and now incorporates many types that do not use photons of light for image formation. The combination of these instruments with preparations stained with histochemical and immunohistochemical markers has revolutionized imaging by allowing the biochemical identification of components at subcellular resolution. The field of cardiovascular disease has benefited greatly from these advances for the characterization of disease etiologies. In this review, we will highlight and summarize the use of microscopy imaging systems, including light microscopy, electron microscopy, confocal scanning laser microscopy, laser scanning cytometry, laser microdissection, and atomic force microscopy in conjunction with a variety of histochemical techniques in studies aimed at understanding mechanisms underlying cardiovascular diseases at the cell and molecular level.     

Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases. Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs. The study of blood stasis syndrome (BSS) and activated blood circulation of traditional Chinese medicine (TCM) is one of the most active fields where the integration of TCM and western medicine in China has been successful. Activated blood circulation herbs (ABC herbs) of Chinese medicine are often used in the treatment of BSS. Most ABC herbs have antiplatelet and anti-atherosclerosis activity, but knowledge about their targets is lacking. Coronary heart disease (CHD), BSS, and platelet activation are closely related. By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD, platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs. In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.     

Urinary proteomics: a tool to discover biomarkers of kidney diseases

There is intense interest in applying proteomics to urine analysis in order to promote a better understanding of kidney disease processes, develop new biomarkers for diagnosis and detect early factors that contribute to end–stage renal diseases. This interest creates numerous opportunities as well as challenges. To fulfill this task, proteomics requires, in its different stages of realization, various technological platforms with high sensitivity, high throughput and large automation ability. In this review, we will give an overview of promising proteomic methods that can be used for analyzing urinary proteome and detecting biomarkers for different kidney diseases. Furthermore, we will focus on the current status and future directions in investigating kidney diseases using urinary proteomics.