Carbon Monoxide: Novel Opportunities for Therapy

急性肺损伤（ALI）和多器官功能障碍综合征（MODS）的发病率和死亡率高 脓毒症中的多器官功能障碍综合征（MODS）反映了目前可用的诊断标志物和治疗方式的无效性。 我们的基础科学家和翻译/临床研究人员组成的多学科团队是该领域的领导者 血红素氧合酶-1（HO-1）/一氧化碳（CO）和炎症的解决方案， 高效协同地朝着一个共同的目标前进。推进气体分子CO的研究 这样我们就可以将临床前发现的一氧化碳细胞保护作用应用于人类疾病。这种平移 PPG将使我们能够实现三个主要目标，在我们的最终追求使用一种新的细胞保护剂， 分子，一氧化碳，在治疗一个可怕的疾病，如急性肺损伤：i）阐明新的生理和细胞 当以低生理剂量施用时，毒性分子可以提供有效的 ii）鉴定新的CO分子靶标，其本身可以是细胞保护的平台， ALI诊断和治疗模式的发展提供了关键的概念验证“第一次在 ALI”研究，为我们在下一个转换PPG周期II进行的ALI CO干预试验做准备 程序.达到这3个主要目标的影响将是重大的重症监护疾病， 我们希望通过这些研究来揭示新的诊断ALI的生物标志物和/或治疗方法。我们 将尝试通过解决以下项目和核心来实现我们的目标： 项目： 1.一氧化碳在脓毒症和肺损伤中的细胞保护作用 2.脓毒症肺损伤中一氧化碳和线粒体质量控制 3.一氧化碳预处理骨髓间充质干细胞 4.一氧化碳和专业的亲解决调解员 核心： 核心A：行政核心 核心B：临床研究协调核心 核心C：脂质介质代谢组学 核心D：脓毒症和急性肺损伤中的一氧化碳输送

The high morbidity and mortality of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS) in sepsis reflect the inefficacy of currently available diagnostic markers and therapeutic modalities. Our multi-disciplinary team of basic scientists and translational/clinical researchers are leaders in the field of heme oxygenase-1 (HO-1 )/carbon monoxide (CO) and resolution of inflammation who have worked efficiently and synergistically towards a common goal: that is. to advance the field of gaseous molecule CO so that we can translate the pre-clinical findings of CO cvtoprotection to human disease. This translational PPG will enable us to accomplish three major goals in our ultimate quest to use a novel cytoprotective molecule, CO, in the treatment of a dreadful disease such as ALI: i) elucidate novel physiologic and cellular mechanism(s) by which a toxic molecule when administered at low physiologic doses can provide potent cytoprotection ii) identify novel molecular targets of CO which can by themselves be a platform for the development of both diagnostic and therapeutic modalities in ALI Hi) provide critical proof-of-concept "first in ALI" studies to prepare us for a CO intervention trial in ALI at the next Cycle II of the translational PPG program. The impact of reaching these 3 major goals will be significant in the critical care illness and pulmonary community as we hope to unravel new diagnostic biomarkers and/or treatment(s) for ALI. We will attempt to reach our goals by the addressing the following projects and cores: Projects: 1. Cytoprotection by Carbon Monoxide in Sepsis and Lung Injury 2. Carbon Monoxide and Mitochondrial Quality Control in Sepsis-induced Lung Injury 3. Mesenchymal Stromal Cell Conditioning by Carbon Monoxide 4. Carbon Monoxide and Specialized Pro-Resolving Mediators Cores: Core A: Administrative Core Core B: Clinical Studies Coordination Core Core C: Lipid Mediator Metabolomics Core D: Carbon Monoxide Delivery in Sepsis and Acute Lung Injury