Enterolactone and asthma

肠内酯与哮喘

• 批准号: 10091388
• 负责人: Juan Carlos Cardet
• 金额: $ 19.28万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091388
• 关键词: A549; Adrenal Cortex Hormones; Adult; Affect; American; Anti-Inflammatory Agents; Antiinflammatory Effect; Antioxidants; Area; Asthma; Attenuated; Award; B-Lymphocytes; Basic Science; Biochemical; Biological; Biological Markers; Biometry; Bronchial Spasm; Bronchoscopy; Cell model; Cells; Cellular Structures; Chemicals; Clinical; Clinical Research; Data; Data Analyses; Data Set; 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; Oxidants; 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; asthma model; bacterial metabolism; career; career development; cohort; cost; design; dietary; enterolactone; experience; experimental study; follow-up; gut microbiome; in vivo; laboratory experiment; microbiome composition; mortality; mouse model; novel; nutrition; oxidation; patient oriented research; pediatric patients; programs; prospective; public health relevance; research and development; skills; systemic inflammatory response; 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个5年计划，以准备候选人Juan C. Cardet MD，以作为一个职业 2独立翻译的研究者定位，以影响我们对哮喘的理解。目的是澄清 3通过完整的临床和基本策略，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饮食，植物衍生的化学物质。肠肠酮 5是人类肠道细菌代谢的最终产物。肠道微生物组组成的差异 6年将患者分类为高与低肠乳酮生产者。该组报告浓度依赖性 7在全国代表性的队列（NHANES）中，肠甲酮与哮喘之间的逆关联； 8这项研究受其横截面设计和不完整的临床表征的限制。我们假设 9肠甲酮与哮喘的逆关系是由其抗炎和抗炎驱动的 10个氧化特性。候选人将阐明肠甲酮是否具有临床上的关系 11通过分析NHLBI严重哮喘研究计划（SARP）的哮喘的哮喘 12研究。作为在SARP的创始伙伴关系，我们的小组可以使用存储的生物测量和参与者的访问权限 13随访3年期间收集的临床，生化和物理数据。此外，候选人 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。 Cardet等人的初步数据表明，肠甲酮可能具有 16对A549人类气道上皮细胞的抗炎作用，观察结果将延伸 17这个建议。临床发现将引导实验室实验的焦点，并在 18台将产生临床问题。在这个项目的结论中，候选人将熟练（1） 19对SARP等临床数据集进行了19个复杂的生物统计分析；以及设计，指挥和 20对（2）气道结构细胞（3）和哮喘的鼠模型进行解释实验。 21在奖励期内，候选人将利用他的哮喘临床经验，定期接触 22 NIH研究网络以及HSPH的MPH计划的结构化学者。这项培训将使他能够 23在奖励的第4-5年中向独立过渡。 Cardet博士将以1°的心态工作 24 Elliot博士以色列，是翻译哮喘研究专家，具有出色的心理记录。他会 25个联合官员。 Quan Lu和Stephanie Shore，他们将训练Cardet博士掌握基本实验 26本文描述（请参阅“研究策略，目标2”）。此外，Cardet博士组建了一个团队 27个非凡的医师科学家（Joshua Boyce博士，Bruce Levy和Wanda Phipatanakul） 28花了时间和专业知识来协助他的职业发展和研究目标。他们的精神训练 29 BWH和HSPH的科学临床环境以及拟议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独立的翻译哮喘研究员。

项目成果

Hormonal Effects on Asthma, Rhinitis, and Eczema.

• DOI: 10.1016/j.jaip.2022.04.002
• 发表时间: 2022-08
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
• 影响因子: 9.4
• 作者: Weare-Regales, Natalia;Chiarella, Sergio E.;Cardet, Juan Carlos;Prakash, Y. S.;Lockey, Richard F.
• 通讯作者: Lockey, Richard F.

Socioeconomic impact of COVID-19 and willingness to be vaccinated in African American/Black and Hispanic/Latinx adults.

• DOI: 10.1016/j.jnma.2021.12.010
• 发表时间: 2022-04
• 期刊: Journal of the National Medical Association
• 影响因子: 3.3
• 作者: Carroll JK;Arias Hernandez P;Brooks-Greisen A;Carlos Cardet J;Cui J;Ericson B;Fagan M;Fajt ML;Forth VE;Fuhlbrigge AL;Lorenzi M;Rodriguez-Louis J;Maher NE;Manning BK;Pace WD;Shields JB;Israel E
• 通讯作者: Israel E

Reply.

回复。

• DOI: 10.1002/art.40923
• 发表时间: 2019
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Kim,AlfredHJ;Strand,Vibeke;Atkinson,JohnP
• 通讯作者: Atkinson,JohnP

A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial.

• DOI: 10.1016/j.cct.2020.106246
• 发表时间: 2021-03
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Israel E;Cardet JC;Carroll JK;Fuhlbrigge AL;Pace WD;Maher NE;She L;Rockhold FW;Fagan M;Forth VE;Hernandez PA;Manning BK;Rodriguez-Louis J;Shields JB;Coyne-Beasley T;Kaplan BM;Rand CS;Morales-Cosme W;Wechsler ME;Wisnivesky JP;White M;Yawn BP;McKee MD;Busse PJ;Kaelber DC;Nazario S;Hernandez ML;Apter AJ;Chang KL;Pinto-Plata V;Stranges PM;Hurley LP;Trevor J;Casale TB;Chupp G;Riley IL;Shenoy K;Pasarica M;Calderon-Candelario RA;Tapp H;Baydur A
• 通讯作者: Baydur A

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

• DOI: 10.1056/nejmoa2118813
• 发表时间: 2022-04-21
• 期刊: The New England journal of medicine