Carbon Monoxide: Novel Opportunities for Therapy

急性肺损伤（ALI）和多器官功能障碍综合征的高发病率和死亡率 败血症（MODS）反映了目前可用的诊断标志物和治疗方式的无效性。 我们的多学科团队由基础科学家和转化/临床研究人员组成，是该领域的领导者 血红素加氧酶-1 (HO-1)/一氧化碳 (CO) 和炎症消退 高效、协同地实现一个共同目标：那就是。推进气态分子CO领域 这样我们就可以将 CO 细胞保护的临床前发现转化为人类疾病。这个翻译 PPG 将使我们能够实现三个主要目标，最终寻求使用新型细胞保护剂 CO 分子在治疗 ALI 等可怕疾病中的作用：i) 阐明新的生理和细胞机制 有毒分子以低生理剂量给药时可以提供有效作用的机制 ii) 识别 CO 的新分子靶点，其本身可以成为细胞保护的平台 ALI 诊断和治疗模式的开发 Hi) 提供了“首创”的关键概念验证 ALI”研究为我们在转化 PPG 的下一个周期 II 中进行 ALI 的 CO 干预试验做好准备 程序。实现这 3 个主要目标将对重症护理疾病和 肺部社区，我们希望揭示新的 ALI 诊断生物标志物和/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. 脓毒症引起的肺损伤中的一氧化碳和线粒体质量控制 3. 一氧化碳调理间充质基质细胞 4. 一氧化碳和专门的促分解介质 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