Enterolactone and asthma

肠内酯与哮喘

• 批准号: 9529139
• 负责人: Juan Carlos Cardet
• 金额: $ 13.59万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9529139
• 关键词: A549; Adrenal Cortex Hormones; Adult; Affect; American; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Area; Asthma; Attenuated; Award; B-Lymphocytes; Basic Science; Biochemical; Biological Markers; Biometry; Bronchial Spasm; Bronchoscopy; Cell model; Cells; Chemicals; Clinical; Clinical Research; Data; Data Analyses; Data Set; Diet; Dietary Intervention; Dietary Lignans; Disease; Emergency department visit; Enrollment; Environment; Epithelial Cells; Exposure to; Extrinsic asthma; F2-Isoprostanes; Funding; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Healthcare; Histologic; Hospitalization; Human; In Vitro; Inbred BALB C Mice; Inflammation; Interleukin-6; Interleukin-8; Intervention Trial; Israel; Lead; Lignans; Longitudinal cohort; Measures; Mentors; Mentorship; Morbidity - disease rate; National Health and Nutrition Examination Survey; National Heart, Lung, and Blood Institute; Nature; Outcome; Oxidative Stress; Participant; Patients; Phenotype; Physicians; Physiological; Plants; Population; Positioning Attribute; Prevalence; Property; Public Health; Publishing; Reporting; Research; Research Design; Research Personnel; Role; Sampling; Scientist; Serum amyloid A protein; Severities; Structure; Techniques; Time; Training; Translational Research; Translations; United States National Institutes of Health; Urine; Work; airway epithelium; airway inflammation; bacterial metabolism; career; career development; cohort; cost; design; enterolactone; experience; experimental study; follow-up; gut microbiome; in vivo; laboratory experiment; mortality; mouse model; novel; nutrition; oxidation; patient oriented research; pediatric patients; programs; prospective; public health relevance; research and development; skills; translational scientist

Project Summary/Abstract 1  This proposal details a 5-yr plan to prepare the candidate, Juan C. Cardet MD, for a career as an 2  independent, translational investigator positioned to impact our understanding of asthma. The aim is to clarify 3  the relationship between enterolactone and asthma through complementary clinical and basic strategies. 4  Lignans are dietary, plant-derived chemicals with anti-inflammatory and antioxidant properties. Enterolactone 5  is the end product of human gut bacterial metabolism of lignans. Differences in gut microbiome composition 6  categorize patients into high- vs. low-enterolactone producers. This group reported concentration-dependent 7  inverse associations between enterolactone and asthma in a nationally-representative cohort (NHANES); but 8  this study is limited by its cross-sectional design and incomplete clinical characterization. We hypothesize 9  that enterolactone's inverse relationship with asthma is driven by its anti-inflammatory and anti- 10  oxidative properties. The candidate will clarify whether enterolactone has a clinically-evident relationship 11  with asthma by analyzing data from the NHLBI Severe Asthma Research Program's (SARP) prospective 12  study. As a founding partnership in SARP, our group has access to stored biospecimens and participants' 13  clinical, biochemical, and physiological data collected during 3 years of follow-up. Further, the candidate 14  will employ in vitro and in vivo approaches to determine enterolactone's effects on human airway structural 15  cells and murine models of asthma. Preliminary data by Cardet et al suggest that enterolactone may have 16  anti-inflammatory effects on A549 human airway epithelial cells, observations this group will extend through 17  this proposal. Clinical findings will steer the focus of laboratory experiments, and reversely, discoveries at the 18  bench will generate clinical questions. At this project's conclusion, the candidate will be skillful with (1) 19  sophisticated biostatistical analyses on clinical datasets such as SARP's; and with designing, conducting, and 20  interpreting experiments on (2) airway structural cells (3) and murine models of asthma. 21  During the award period, the candidate will leverage his clinical experience with asthma, regular exposure to 22  NIH research networks, and structured academics at the HSPH's MPH program. This training will allow him to 23  transition to independence during the 4-5th years of the award. Dr. Cardet will work under the 1° mentorship of 24  Dr. Elliot Israel, an expert in translation asthma research with an excellent mentoring record. He will have as 25  co-mentors Drs. Quan Lu and Stephanie Shore, who will train Dr. Cardet to master the basic experiments 26  described herein (see `Research Strategy, Aim 2'). Further, Dr. Cardet has assembled a team of 27  extraordinary physician-scientists (Drs. Joshua Boyce, Bruce Levy, and Wanda Phipatanakul), who have 28  committed their time and expertise to assist his career development and research goals. Their mentorship, the 29  scientific-clinical environment at BWH and HSPH, and the proposed research goals and career development 30  plan will position the candidate to establish himself as an independent translational asthma researcher.

项目摘要/摘要 1本提案详细介绍了一项5年计划，以准备候选人Juan Cardet MD，以作为一个职业 2独立的转化调查员定位，以影响我们对哮喘的理解。 3通过互补的临床和基本策略，肠甲酮与哮喘之间的关系。 4个木木是具有抗炎和抗氧化特性的植物衍生化学物质 5是人类肠道细菌代谢的最终产物。 6将患者分为高与低进入的患者。 7肠肠酮与哮喘之间的7逆关联 8这项研究受到IT横截面设计的限制和我们假设的临床表征 9肠甲酮与哮喘的逆关系是由其抗炎和抗促进的 10个氧化特性。 11与哮喘分析NHLBI严重哮喘研究计划（SARP）的数据 12研究。 13临床，生化和生理数据在3年的随访中收集 14将采用体外和体内方法来确定肠甲酮对人类气道结构的影响 15个细胞和哮喘的鼠模型。 16对A549人类气道上皮细胞的抗炎作用，观察结果将延伸 17临床发现。 18台将在候选人中产生临床问题。 19对SARP等临床数据集进行了19个复杂的生物统计分析； 20对（2）气道结构细胞（3）和哮喘的鼠模型进行解释实验。 21在奖励期间，候选人有利用哮喘的临床经验，定期接触 22个NIH研究网络，以及HSPH的MPH计划的构建学者。 23在第4-5届第4-5奖中过渡到独立。 24艾略特博士，以表现出色的指导记录进行翻译哮喘研究的经验。 25 Co-Mentors Drs。 26本文描述（请参阅“研究策略，AIM 2”）。 27个非凡的医师科学家（Joshua Boyce博士，Bruce Levy和Wanda Phipatanakul） 28投入了时间和专业知识，以帮助他的护理职业发展和研究目标 29 BWH和HSPH的科学临床环境以及支撑的研究目标和职业发展 30计划将把候选人定位为将自己确立为哮喘研究员。