Biomarker signatures of biological, chemical, or psychological stress

生物、化学或心理压力的生物标志物特征

• 批准号: 7882119
• 负责人: David A Lawrence
• 金额: $ 10.84万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882119
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Animals; Antibodies; Antigen-Presenting Cells; Antioxidants; Arsenic; Autoimmune Diseases; Benzene; Bioinformatics; Biological; Biological Assay; Biological Markers; Biosensor; Blood; Blood Clot; Blood Coagulation Factor; Blood coagulation; Cadmium; Cells; Characteristics; Chemicals; Communicable Diseases; Complex; Coupled; Dendritic Cells; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Disease susceptibility; Distress; Dose; Endocrine; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Evaluation; Exposure to; Genes; Genotype; Goals; HLA Antigens; Health; Heat shock proteins; Human; Image; Image Analysis; Imaging technology; Immune; Immune response; Immune system; Individual; Infection; Inflammation; Inflammatory; Investigation; Label; Leukocytes; Listeria monocytogenes; Lymphocyte; Malignant Neoplasms; Mercury; Metallothionein; Methodology; Microarray Analysis; Modification; Molecular; Mus; Nerve Degeneration; Nervous system structure; Neuropeptides; Oxidants; Oxidation-Reduction; Oxidative Stress; Pain; Parkinson Disease; Pathology; Pathway interactions; Patients; Pattern; Performance; Plasma; Plasma Proteins; Poison; Polychlorinated Biphenyls; Population; Predisposition; Procedures; Process; Proteins; Psychological Stress; Regulatory Pathway; Research; Research Activity; Research Personnel; Rheumatoid Arthritis; Sampling; Sepsis; Serum; Serum Proteins; Severities; Source; Stress; Sulfhydryl Compounds; Surface Plasmon Resonance; System; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Transgenes; Two-Dimensional Gel Electrophoresis; Vinyl Chloride; Work; base; biological adaptation to stress; biological systems; blood product; body system; comparative; cytokine; design; disease registry; environmental stressor; exposed human population; immune function; instrument; instrumentation; new technology; outcome forecast; oxidation; programs; protein expression; prototype; psychologic; psychological stressor; research study; response; restraint; restraint stress; sensor; septic; stress management; stress protein; stressor

We hypothesize that human exposures to environmental stresses (biological, chemical, physical and psychological) result in alterations to the neuro-endocrine-immune axis. These changes provoke shifts in molecular components of the blood that reflect changes in biomarker levels. Septic patients and rheumatoid arthritis patients will be used as prototype stressed individuals to identify and quantify the presence of serum proteins that have increased, decreased, or which display epitope-modified expression. These molecular features will form the basis of specific biomarker signatures that are characteristic of stressed human individuals. Preliminary experiments document that biological, chemical, and psychological stress alters plasma protein expression levels, which in part, are due to inflammation and/or oxidative processes. Since we suggest the different forms of stressors modulate the interactive pathways between the endocrine, immune, and nervous systems, we anticipate that immune, endocrine, and nervous system factors will be predictors of stress and that the profiles of these factors will provide prognosis for the degree of stress and the severity of the exposure. Individual biomarkers, which are predicted to relate to regulatory pathways associated with inflammation:anti-inflammation, oxidants:anti-oxidants, and innate immune processes, will then be quantified in humanized mice after exposure to three prototype stressors: cadmium, cold-restraint, and listerial infection. Our plan is to delineate and quantify the normal basal and responsive plasma concentrations of relevant biomarkers and to validate their analysis with a new biosensor employing grating- coupled surface plasmon resonance imaging (GCSPRI). GCSPRI is a microarray platform that will enable the multiplexed detection of these biomarker signatures with an automated diagnostic system in near real time. In addition to stressor-induced changes in plasma constituents, we will evaluate changes to blood leukocyte antigens; lymphocytes are especially sensitive to inflammatory products and oxidants. Blood products are obtained with minimal invasiveness, and they represent the best composite of the systemic response to a stressor. The GCSPRI technology will be parallel tested against the Luminex technology. The biomarkers to be evaluated include blood clotting factors, cytokines, stress proteins, neuropeptides, antioxidant enzymes, and normal plasma proteins with thiol-related modifications. Finally, we will evaluate the consequences of different stress response capabilities on the character of the biomarker signatures that have been identified in this work. At the conclusion of this work we will have identified specific biomarker signatures that are both diagnostic of specific signatures, and which will be invaluable in both the diagnosis of stress, and the characterization of therapeutic management of stressed individuals.

我们假设，人类暴露于环境压力（生物，化学，物理和 心理学）导致神经-内分泌-免疫轴的改变。这些变化引起了 血液中反映生物标志物水平变化的分子成分。脓毒症患者和类风湿 关节炎患者将被用作原型应激个体以鉴定和量化血清 增加、减少或显示表位修饰表达的蛋白质。这些分子 这些特征将形成特定生物标志物特征的基础， 个体初步实验证明，生物、化学和心理压力会改变 血浆蛋白表达水平，这部分是由于炎症和/或氧化过程。以来 我们认为不同形式的应激源调节内分泌， 免疫系统和神经系统，我们预计免疫，内分泌和神经系统因素将 压力的预测因素，这些因素的概况将提供压力程度的预后， 暴露的严重性。预测与调控途径相关的个体生物标志物 与炎症相关的：抗炎，氧化剂：抗氧化剂和先天免疫过程，将 然后在暴露于三种原型应激源（镉，冷束缚， 和尿道感染。我们的计划是描绘和量化正常的基础和反应性血浆 浓度的相关生物标志物，并验证他们的分析与一个新的生物传感器采用光栅- 偶联表面等离子体共振成像（GCSPRI）。GCSPRI是一个微阵列平台， 用自动诊断系统对这些生物标志物特征的多重检测接近真实的， 时间除了应激诱导的血浆成分变化外，我们还将评估血液中 白细胞抗原;淋巴细胞对炎症产物和氧化剂特别敏感。血液 产品是以最小的侵入性获得的，它们代表了系统性的最佳组合物。 对压力的反应。GCSPRI技术将与Luminex技术进行平行测试。的 待评价的生物标志物包括凝血因子、细胞因子、应激蛋白，神经肽， 抗氧化酶和具有巯基相关修饰的正常血浆蛋白。最后，我们将评估 不同的应激反应能力对生物标志物特征的影响， 在这项工作中得到了确认。在这项工作结束时，我们将确定特定的生物标志物 这些特征都是特定特征的诊断特征，并且在诊断中都是非常宝贵的。 的压力，并强调个人的治疗管理的特点。