CORE C: Biorepository and Tissue Material Characterization Core

核心摘要 该计划项目拨款(PPG)的首要假设是关注无序的角色 食管壁力学在食道疾病发病机制中的作用鉴于的主要目的是 食道是输送丸剂，对流体动力学和应变/应力有更深入的了解 食管壁的关系是认识食道疾病的关键。团注运输 异常是大多数食道症状和并发症的原因，这一过程高度 取决于食管壁的力学性能。食道蠕动只是食道蠕动的一小部分 团注在食道中的运输机制及团注调节之间的相互作用 通过不收缩的食道推进可能比减少蠕动活力更重要。这个 吞咽过程中从口咽部输送的药丸必须适应，即使是轻微的干扰也是如此 在机械状态下的食管壁可以对应变/应力关系产生显著影响。因此， 我们已经提出了一个PPG，专注于开发对墙的膨胀性如何 改变药丸的运输和症状。项目1将重点确定IKKβ/NFκB在促进 嗜酸性食管炎(EoE)的扩张性降低及STAT3在促进萎缩中的作用 硬皮病的纤维化。人体研究将在明确定义的EoE和EoE表型中进行 硬皮病以及生物库和组织材料表征核心(核心C)将是#年的关键。 为这些研究收集和准备标本。此外，我们还将确定是否 在组织材料表征亚核中测量的材料特性与 在项目1的动物研究期间定义的目标。核心C也将在 为数学模型和虚拟疾病景观提供关键信息作为素材 正常受试者和各种疾病状态的特性将是模型的重要输入。这个 用于模型的标本将由微观和宏观尺度测量组成，组织将 通过内窥镜活检和术后患者丢弃的组织获得。尽管主要角色是 对于核心C，将通过在生物生理学中开发的模型来支持项目1和项目3 建模核心(核心B)，项目2和4将间接受益于核心C，因为收集的数据将 生成并提炼模型中的机械生物标记物，以预测团注运输和症状严重程度。

CORE SUMMARY The overarching hypothesis of this program project grant (PPG) is focused on the role of disordered esophageal wall mechanics in the pathogenesis of esophageal diseases. Given that the primary purpose of the esophagus is to transport bolus, a more in depth understanding of fluid dynamics and the strain/stress relationship of the esophageal wall is crucial to understanding esophageal diseases. Bolus transport abnormalities are the cause of most esophageal symptoms and complications and this process is highly dependent on the mechanics of the esophageal wall. Esophageal peristalsis is only a small component of the bolus transport mechanism in the esophagus and the interplay between bolus accommodation and how it is propelled through the non-contracting esophagus is likely more important than reduced peristaltic vigor. The bolus delivered from the oropharynx during swallowing must be accommodated and even minor perturbations in the mechanical state of the esophageal wall can have dramatic effects on strain/stress relationship. Thus, we have proposed a PPG focused on developing a comprehensive understanding of how wall distensibility can alter bolus transport and symptoms. Project 1 will focus on determining the role of IKKβ/NFκB in promoting reduced distensibility in eosinophilic esophagitis (EoE) and assessing the role of STAT 3 in promoting atrophy and fibrosis in scleroderma. Human studies will be performed in well-defined phenotypes of EoE and scleroderma and the Biorepository and Tissue Material Characterization CORE (CORE C) will be crucial in collecting and preparing the specimens for these studies. Additionally, we will also determine whether the material properties measured in the Tissue Material Characterization sub-CORE are correlated with activity of the targets defined during the animal studies in Project 1. CORE C will also be extremely important in providing crucial information for the mathematical models and Virtual Disease Landscape as the material properties in normal subjects and various disease states will be important inputs into the models. The specimens used for the model will be comprised of micro- and macros-scale measurements and tissue will be obtained through endoscopic biopsies and discarded tissue in post-surgery patients. Although the primary role for CORE C will be to support Project 1 and Project 3 through the models developed within the Biophysiologic Modeling Core (CORE B), Projects 2 and 4 will benefit indirectly from CORE C as the data collected will generate and refine the mechanical biomarkers in the models to predict bolus transport and symptom severity.