Molecular mechanisms and novel therapeutic approaches to combined radiation and b

描述(由申请人提供)：在两个阶段的研究中，我们将在两个模型中研究中等剂量辐射的复合损伤。在第一阶段，我们将使用匿名的手术样本，研究体外照射和烧伤后的基因和蛋白表达的差异，开发一种非侵入性的方法来预测伤口是否成功愈合，并测试一种β肾上腺素能受体拮抗剂作为促进伤口愈合的潜在治疗方法。在第二阶段，我们将在小鼠模型中研究类似的问题。因此，整个研究将结合人类数据(然而，不是在体内)和来自完整动物(在体内)的数据，以获得相关信息，以便更好地从机制上理解在存在辐射损伤的情况下伤口愈合的机制，并开发潜在的治疗方法，稍后可以在临床上进行测试。与公共卫生相关在核战争或恐怖事件中，辐射和烧伤很可能造成复合伤害。我们将对复合伤伤口愈合背后的分子生物学提供更好的机制理解，并将测试伤口愈合成功的非侵入性测试和促进愈合的潜在治疗方法。在这种情况下，所有这些都将对公众健康产生相当大的好处。

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.