Biomarker signatures of biological, chemical, or psychological stress

我们假设人类暴露在环境压力下(生物、化学、物理和 心理)导致神经-内分泌-免疫轴的改变。这些变化引发了 血液中反映生物标志物水平变化的分子成分。脓毒症患者与类风湿 关节炎患者将作为原型应激个体来识别和量化血清的存在。 增加、减少或表现出表位修饰的表达的蛋白质。这些分子 特征将形成特定生物标志物特征的基础，这些特征是应激状态下人类的特征 个人。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，部分原因是炎症和/或氧化过程。自.以来 我们认为，不同形式的应激源调节内分泌、 免疫和神经系统，我们预计免疫、内分泌和神经系统因素将是 压力的预测因素，这些因素的概况将为压力的程度和 暴露的严重程度。单个生物标记物，被预测与调控途径有关 与炎症有关：抗炎、氧化剂：抗氧化剂和先天免疫过程 然后在人源化小鼠暴露于三种原型应激源后进行量化：镉，冷束缚， 和李斯特菌感染。我们的计划是描绘和量化正常的基础和反应性血浆 相关生物标志物的浓度，并用一种使用光栅的新型生物传感器来验证它们的分析- 耦合表面等离子体共振成像(GCSPRI)。GCSPRI是一个微阵列平台，将使 利用近乎实时的自动诊断系统对这些生物标记物特征进行多路检测 时间到了。除了应激源引起的血浆成分变化外，我们还将评估血液的变化 白细胞抗原；淋巴细胞对炎症产物和氧化剂特别敏感。血样 产品是以最小的侵入性获得的，它们代表了系统的最佳组合 对压力源的反应。GCSPRI技术将与Luminex技术进行平行测试。这个 待评估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，以及与硫醇相关的正常血浆蛋白。最后，我们将评估 不同的应激反应能力对生物标记物特征的影响 已经在这项工作中被发现。在这项工作结束时，我们将识别出特定的生物标记物 签名既是特定签名的诊断，也是对两种诊断都有价值的签名 应激的特点，以及对应激个体的治疗管理的特征。

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.