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Cationic CAMKIIN nanoparticles that reduce chlorine-induced airway oxidative stress

Cationic CAMKIIN nanoparticles that reduce chlorine-induced airway oxidative stress
阳离子 CAMKIIN 纳米颗粒可减少氯诱导的气道氧化应激
批准号:
10408405
负责人:
Aliasger K Salem
金额:
$19.31万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-06 至 2024-08-31

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中文摘要
翻译
项目摘要 氯是一种对人体有害的化学物质。急性吸入高浓度氯 导致气道上皮细胞死亡并对呼吸系统健康产生不利影响, 包括气道重塑和高反应性。在小鼠氯暴露模型中,动物 在大气道中出现炎症和纤维化。这种炎症和纤维化 据报道与线粒体损伤和氧化应激的产生有关, 活性氧物质。我们的研究小组已经表明,钙/钙调素依赖性蛋白激酶 II(CaMKII)在气道中的ROS产生中起关键作用。在本提案中,我们将测试 假设,在应对氯气的挑战,CaMKII有助于诱导 气道炎症的标志性特征。利用一种新的药物输送系统,我们将揭示 小鼠对包封在PLGA NP中的CaMKII抑制剂肽(CaMKIIN)的耐受性。这些NP将 通过口咽滴注直接输送到肺部。此外,我们将包括壳聚糖 包被负载CaMKIIN的PLGA-NP以增加肺细胞中的摄取,从而减少 氧化应激和纤维化。该项目将通过首先评估CaMKII激活来完成 氯暴露后幼年小鼠肺中ROS的表达水平, 确定负载CaMKII转运蛋白的阳离子纳米颗粒是否可以减轻ROS表达, 氯暴露后的肺损伤
英文摘要
Project Summary Chlorine is a chemical agent that is harmful to humans. Acute inhalation of high levels of chlorine results in the death of airway epithelial cells and leads to adverse effects on respiratory health, including airway remodeling and hyperreactivity. In a mouse chlorine exposure model, animals developed inflammation and fibrosis in large airways. This inflammation and fibrosis has been reported to be linked to damage to mitochondria and the generation of oxidative stress and reactive oxygen species. Our group has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in ROS generation in the airways. In this proposal, we will test the hypothesis that, in response to chlorine gas challenge, CaMKII contributes to the induction of hallmark features of airway inflammation. Utilizing a novel drug delivery system, we will expose mice to a CaMKII inhibitor peptide (CaMKIIN) encapsulated in PLGA NPs. These NPs will be directly delivered to the lung via oropharyngeal instillation. Furthermore, we will include a chitosan coating of the CaMKIIN-loaded PLGA-NPs to increase uptake in lung cells thereby reducing oxidative stress and fibrosis. This project will be completed by first evaluating CaMKII activation and ROS expression levels in the lungs of juvenile mice following chlorine exposure and then determining if a CaMKII inhibitor-loaded cationic nanoparticle can mitigate ROS expression and lung damage following chlorine exposure.
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CST6-mRNA activated matrices for efficient bone regeneration
  • 批准号:
    10576944
  • 项目类别:
  • 资助金额:
    $23.18万
  • 财政年份:
    2022
  • 负责人:
    Aliasger K Salem
  • 依托单位:
CST6-mRNA activated matrices for efficient bone regeneration
  • 批准号:
    10456455
  • 项目类别:
  • 资助金额:
    $19.31万
  • 财政年份:
    2022
  • 负责人:
    Aliasger K Salem
  • 依托单位:
Cationic CAMKIIN nanoparticles that reduce chlorine-induced airway oxidative stress
  • 批准号:
    10698067
  • 项目类别:
  • 资助金额:
    $23.18万
  • 财政年份:
    2022
  • 负责人:
    Aliasger K Salem
  • 依托单位:
Engineered Optimal Adjuvant and Antigen Release from Biodegradable Nanoparticles
  • 批准号:
    7742670
  • 项目类别:
  • 资助金额:
    $13.2万
  • 财政年份:
    2009
  • 负责人:
    Aliasger K Salem
  • 依托单位:
海外基金