Molecular mechanisms and novel therapeutic approaches to combined radiation and b

描述（由申请人提供）：我们将在一项两阶段研究中研究两种模型中中等剂量辐射的联合损伤。在第一阶段，我们将使用匿名手术样本照射和烧伤离体研究基因和蛋白质的表达差异，开发一种非侵入性测定来预测成功的伤口愈合，并测试β肾上腺素能受体拮抗剂作为改善伤口愈合的潜在疗法。在第二阶段，我们将在小鼠模型中研究类似的问题。因此，整个研究将结合联合收割机的人体数据（但不是体内数据）和完整动物的数据（体内数据），以获得相关信息，从而更好地了解辐射损伤情况下伤口愈合的机制，并开发可在临床上进行测试的潜在疗法。在核战争或恐怖事件中，辐射和烧伤的复合损伤是可能的。我们将提供一个更好的机制理解复合损伤伤口愈合背后的分子生物学，并将测试伤口愈合成功的非侵入性测定和潜在的治疗，以改善愈合。在这种情况下，所有这一切都将对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): We will investigate combined injury by moderate dose radiation in two models in a two-phase study. In the first phase, we will use anonymized surgical samples irradiated and wounded ex vivo by burning to study gene and protein expression differences, develop a non-invasive assay to predict successful wound healing, and test a beta adrenergic receptor antagonist as potential therapy to improve wound healing. In the second phase, we will investigate similar issues in a mouse model. Thus, the total study will combine human data (which is, however, not in vivo) and data from intact animals (which is in vivo) to obtain relevant information that can inform the development of a better mechanistic understanding of the mechanisms of wound healing in the presence of radiation damage, and to develop potential therapies that can later be tested in the clinic. Public Health Relevance In a nuclear warfare or terrorist incident, combined injury by radiation and burn wounding is likely. We will provide a better mechanistic understanding of the molecular biology behind healing of combined injury wounds, and will test a non-invasive assay for wound healing success and a potential therapy to improve healing. All of this would be of considerable public health benefit in such a scenario.