Consequences of redox imbalance in preterm parturition
早产中氧化还原失衡的后果
基本信息
- 批准号:6875420
- 负责人:
- 金额:$ 7.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-07-01 至 2004-11-30
- 项目状态:已结题
- 来源:
- 关键词:birth cytokine disease /disorder etiology embryo /fetus death embryo /fetus membrane enzyme linked immunosorbent assay female free radical oxygen free radicals gene expression high performance liquid chromatography histology human subject inflammation laboratory mouse lipopolysaccharides oxidation reduction reaction oxidative stress patient oriented research pregnancy infection premature labor radioimmunoassay thiols western blottings women's health
项目摘要
Both intrauterine (e.g. chorioamnionitis) and various matemal systemic infections are proposed causes of preterm labor triggered by a protective inflammatory response (based on the finding of elevated cytokines) that becomes maladaptive for the pregnancy. A large amount of free radicals and reactive oxygen species (FR/ROS) are formed during all inflammatory processes. FR are highly reactive chemical species with half-filled orbitals. The potency to initiate one electron transfer reactions explains their oxidizing action as well as microorganism killing efficiency. Cellular FR/ROS concentration is carefully regulated by antioxidant defense mechanisms to prevent nonspecific damage against endogenous cell constituents. An alteration in the oxidant/antioxidant (redox) balance in favor of FRIROS leaves an imprint of their interaction with various morphological or signaling targets. Recently, it was suggested that the redox balance is an.important modulator of the inflammatory cascade, including cytokine levels. Our working hypothesis is that during maternal (systemic and/or intrauterine) infection and inflammation there is an outpouring of free radicals in both the maternal and fetal compartments. However, the consequences (and hence the clinical impact) of FR/ROS formation are varied and depend on the amount of FR/ROS formed as well as upon the fetal-maternal reducing abilities. A net shift in redox balance is an important modulator of events leading to adverse fetal/neonatal outcome and preterm birth. To test aspects of this working hypothesis the experiments performed under Specific Aim 1 are designed to correlate different levels of redox shift induced by inflammation with FR/ROS formation, fetal outcome and preterm birth in a mouse model. If linked as postulated, targeting free radical /reactive oxygen species (FR/ROS) formation by altering thiol levels will reduce both the direct damage and the indirect effects of FR/ROS by reducing cytokjne expression. Thus, therapeutic interventions that would limit the pathophysiological chain of events leading to adverse fetal outcome and /or preterm premature rupture of membranes (PPROM) and preterm birth are tested under experiments performed in Specific Aim 2. Finally, we document in Specific Aim 3 whether alterations in thiol levels occur in human fetuses in pregnancies complicated by chorioamnionitis. This proposal could initiate a new area of therapeutic intervention targeted to prevent prematurity and its impact on postnatal life.
子宫内(如绒毛膜炎)和各种母体系统性感染被认为是由保护性炎症反应(基于细胞因子升高的发现)触发的早产的原因,该炎症反应变得对妊娠不适应。在所有炎症过程中都会形成大量的自由基和活性氧(FR/ROS)。FR是具有半满轨道的高活性化学物种。引发一个电子转移反应的效力解释了它们的氧化作用以及微生物杀灭效率。细胞FR/ROS浓度受到抗氧化防御机制的仔细调节,以防止对内源性细胞成分的非特异性损伤。有利于FRIROS的氧化剂/抗氧化剂(氧化还原)平衡的改变留下了它们与各种形态学或信号传导靶标相互作用的印记。最近,有人提出氧化还原平衡是炎症级联反应的重要调节剂,包括细胞因子水平。我们的工作假设是,在母体(全身和/或子宫内)感染和炎症过程中,母体和胎儿室中都有自由基的溢出。然而,FR/ROS形成的后果(以及因此的临床影响)是不同的,并且取决于形成的FR/ROS的量以及胎儿-母体还原能力。氧化还原平衡的净变化是导致胎儿/新生儿不良结局和早产的事件的重要调节因素。为了测试这一工作假设的各个方面,在特定目标1下进行的实验被设计为在小鼠模型中将由炎症诱导的不同水平的氧化还原转变与FR/ROS形成、胎儿结局和早产相关联。如果如假设的那样连接,则通过改变硫醇水平来靶向自由基/活性氧物质(FR/ROS)形成将通过减少硫醇表达来减少FR/ROS的直接损伤和间接作用。因此,在特定目标2中进行的实验中,对限制导致不良胎儿结局和/或早产胎膜早破(PPROM)和早产的病理生理学事件链的治疗干预进行了检测。最后,我们在特定目标3中记录了在妊娠合并绒毛膜炎的人胎儿中是否发生巯基水平的改变。这一建议可以启动一个新的治疗干预领域,旨在预防早产及其对产后生活的影响。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
IRINA A BUHIMSCHI其他文献
IRINA A BUHIMSCHI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('IRINA A BUHIMSCHI', 18)}}的其他基金
UIC Building Interdisciplinary Research Careers in Women's Health Program
UIC在女性健康项目中建立跨学科研究职业
- 批准号:
10159299 - 财政年份:2020
- 资助金额:
$ 7.45万 - 项目类别:
UIC Building Interdisciplinary Research Careers in Women's Health Program
UIC在女性健康项目中建立跨学科研究职业
- 批准号:
10887253 - 财政年份:2020
- 资助金额:
$ 7.45万 - 项目类别:
UIC Building Interdisciplinary Research Careers in Women's Health Program
UIC在女性健康项目中建立跨学科研究职业
- 批准号:
10681107 - 财政年份:2020
- 资助金额:
$ 7.45万 - 项目类别:
UIC Building Interdisciplinary Research Careers in Women's Health Program
UIC在女性健康项目中建立跨学科研究职业
- 批准号:
10640959 - 财政年份:2020
- 资助金额:
$ 7.45万 - 项目类别:
UIC Building Interdisciplinary Research Careers in Women's Health Program
UIC在女性健康项目中建立跨学科研究职业
- 批准号:
10434722 - 财政年份:2020
- 资助金额:
$ 7.45万 - 项目类别:
Misfoldome-centered multiOMICS approach to unravel preeclampsia subphenotypes
以错误折叠组为中心的多组学方法揭示先兆子痫亚表型
- 批准号:
9933617 - 财政年份:2019
- 资助金额:
$ 7.45万 - 项目类别:
Misfoldome-centered multiOMICS approach to unravel preeclampsia subphenotypes.
以错误折叠组为中心的多组学方法揭示先兆子痫亚表型。
- 批准号:
9269245 - 财政年份:2015
- 资助金额:
$ 7.45万 - 项目类别:
Misfoldome-centered multiOMICS approach to unravel preeclampsia subphenotypes.
以错误折叠组为中心的多组学方法揭示先兆子痫亚表型。
- 批准号:
8947210 - 财政年份:2015
- 资助金额:
$ 7.45万 - 项目类别:
DAMP-RAGE Signaling and Fetal Injury in Inflammation-Induced Preterm Birth
炎症引起的早产中的 DAMP-RAGE 信号传导和胎儿损伤
- 批准号:
8727308 - 财政年份:2010
- 资助金额:
$ 7.45万 - 项目类别:
DAMP-RAGE Signaling and Fetal Injury in Inflammation-Induced Preterm Birth
炎症引起的早产中的 DAMP-RAGE 信号传导和胎儿损伤
- 批准号:
8698867 - 财政年份:2010
- 资助金额:
$ 7.45万 - 项目类别:
相似海外基金
Development of platform for non-invasive, rapid, and simple analysis of cytokine secretion from single cells
开发非侵入、快速、简单分析单细胞细胞因子分泌的平台
- 批准号:
23H01824 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Therapeutic approach to confer an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine in effector T cells
赋予效应T细胞中促肿瘤细胞因子IL-6抗肿瘤作用的治疗方法
- 批准号:
23K06723 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Diversity of haematopoietic cytokine receptor activation exploring with marine probes
用海洋探针探索造血细胞因子受体激活的多样性
- 批准号:
23K14019 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
A point-of-care salivary cytokine test for early detection of oral cancer
用于早期发现口腔癌的即时唾液细胞因子检测
- 批准号:
10760626 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Development of Coccidioides Cytokine Release Assay
球孢子菌细胞因子释放测定的发展
- 批准号:
10760131 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Combinatorial cytokine-coated macrophages for targeted immunomodulation in acute lung injury
组合细胞因子包被的巨噬细胞用于急性肺损伤的靶向免疫调节
- 批准号:
10648387 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
FOXA1 regulates cytokine signaling and immune landscape in prostate cancer through ARID1A
FOXA1 通过 ARID1A 调节前列腺癌中的细胞因子信号传导和免疫景观
- 批准号:
10681898 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Cytokine Regulation of Secondary Neural Progenitors
次级神经祖细胞的细胞因子调节
- 批准号:
10752901 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Generating a novel conditional knockout mouse for a super-enhancer that controls cytokine responsiveness
生成一种新型条件敲除小鼠,用于控制细胞因子反应的超级增强子
- 批准号:
10740932 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Cytokine receptor common beta chain alterations in mediastinal lymphomas
纵隔淋巴瘤细胞因子受体常见β链改变
- 批准号:
489197 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Operating Grants