Triterpenoids in mitigation of radiation induced acute or delayed inflammation

三萜类化合物可减轻辐射引起的急性或迟发性炎症

基本信息

  • 批准号:
    10852214
  • 负责人:
  • 金额:
    $ 13.42万
  • 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
  • 起止时间:
    2022-07-21 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Currently, there is a need for strategies that mitigate acute and delayed radiation syndrome. The risk of large populations encountering radiation exposure is real and growing. Radiation induced inflammation plays significant role in inducing radiation toxicity. Chemokine signaling plays key role in systemic and local inflammation by modulating egress and recruitment inflammatory immune cells such as inflammatory monocytes and T cells. Radiation exposure induces recruitment of inflammatory cells and promotes systemic and local inflammation. We have observed that deletion of genes expressing chemokine receptor 2 in mice promotes resistance radiation induced acute and delayed inflammation. Triterprenoids are very potent anti-inflammatory agents. Recent findings suggest that synthetic derivatives of oleanolic acid that are more potent at suppressing production of the inflammatory mediator such as chemokine ligand 2. Under NIAID Chemical Countermeasures Research Program (CCRP) Triterprenoids such as CDDO- methyl ester (CDDO-Me) has been shown to mitigate chemical induced ocular injury by nrf2 dependent manner. In this proposal we will examine the effect of CDDO- Me against radiation induced acute and delayed inflammation using mice model of radiation induced gastrointestinal syndrome and radiation induced pulmonary syndrome respectively. We will also characterize the effect of CDDO-Me in modulation of bone marrow derived inflammatory immune cell recruitment in injured tissue. Determination of mechanism of action of will facilitate CDDO-Me as a medical countermeasure against radiation under the FDA’s Animal Rule.
项目摘要 目前,需要制定减轻急性和延迟辐射综合征的策略。风险很大, 遭遇辐射暴露的人口是真实存在的,而且还在不断增长。辐射致炎作用 在诱发辐射毒性方面的重要作用。趋化因子信号在全身和局部发挥关键作用 通过调节外流和募集炎性免疫细胞(如炎性单核细胞)来实现炎症 和T细胞。辐射可诱导炎性细胞募集,促进全身和局部 发炎。我们观察到,小鼠体内表达趋化因子受体2的基因的缺失促进了 抗辐射可引起急性和迟发性炎症。三烯类化合物具有很强的抗炎作用。 探员们。最近的发现表明,齐墩果酸的合成衍生物更能有效地抑制 趋化因子配体等炎症介质的产生2.化学对策 研究计划(CCRP)三烯类化合物,如CDDO-甲酯(CDDO-Me)已被证明可以缓解 Nrf2依赖的化学性眼损伤。在这项建议中,我们将研究CDDO的影响- 用小鼠辐射模型研究ME抗辐射所致急性和迟发性炎症 诱发胃肠综合征和放射性肺综合征。我们还将 CDDO-Me对骨髓炎性免疫细胞调节作用的研究 在受伤的组织中进行募集。Will促进CDDO-Me作为药物的作用机制的确定 根据FDA的动物规则,针对辐射的对策。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity.
  • DOI:
    10.3390/cells13010046
  • 发表时间:
    2023-12-25
  • 期刊:
  • 影响因子:
    6
  • 作者:
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Richard J DiPaolo其他文献

Richard J DiPaolo的其他文献

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{{ truncateString('Richard J DiPaolo', 18)}}的其他基金

The Role of Inflammation in Regulating Gastric Metaplasia
炎症在调节胃化生中的作用
  • 批准号:
    10567107
  • 财政年份:
    2023
  • 资助金额:
    $ 13.42万
  • 项目类别:
Modulation of chemokine signaling to mitigate radiation induced inflammation
调节趋化因子信号传导以减轻辐射引起的炎症
  • 批准号:
    10474889
  • 财政年份:
    2022
  • 资助金额:
    $ 13.42万
  • 项目类别:
Modulation of chemokine signaling to mitigate radiation induced inflammation
调节趋化因子信号传导以减轻辐射引起的炎症
  • 批准号:
    10669126
  • 财政年份:
    2022
  • 资助金额:
    $ 13.42万
  • 项目类别:
The Role of EBI3 in Regulating Gastritis and Gastric Carcinogenesis
EBI3在调节胃炎和胃癌发生中的作用
  • 批准号:
    9160090
  • 财政年份:
    2016
  • 资助金额:
    $ 13.42万
  • 项目类别:
The Role of EBI3 in Regulating Gastritis and Gastric Carcinogenesis
EBI3在调节胃炎和胃癌发生中的作用
  • 批准号:
    9750691
  • 财政年份:
    2016
  • 资助金额:
    $ 13.42万
  • 项目类别:
The Role of EBI3 in Regulating Gastritis and Gastric Carcinogenesis
EBI3在调节胃炎和胃癌发生中的作用
  • 批准号:
    9980387
  • 财政年份:
    2016
  • 资助金额:
    $ 13.42万
  • 项目类别:
The Role of EBI3 in Regulating Gastritis and Gastric Carcinogenesis
EBI3在调节胃炎和胃癌发生中的作用
  • 批准号:
    9316596
  • 财政年份:
    2016
  • 资助金额:
    $ 13.42万
  • 项目类别:

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