Harnessing the Power of p53 with Panaxynol from American Ginseng to Suppress Colitis and Prevent Colon Cancer - admin supp

利用 p53 与西洋参中的人参醇的功效来抑制结肠炎和预防结肠癌 - admin support

• 批准号: 10380268
• 负责人: ELIZABETH ANGELA MURPHY
• 金额: $ 2.65万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380268
• 关键词: American; Anti-Inflammatory Agents; Area; Award; Cancer Model; Carrots - dietary; Celery; Chronic; Colitis; Colon Carcinoma; Complement; Development; Ensure; Etiology; Exhibits; Fennel - dietary; Financial Hardship; Genetic; Ginseng Preparation; Goals; Immune Targeting; Immunologics; Inflammation; Inflammatory Bowel Diseases; Intestines; Lead; Link; Literature; Mentors; Methods; Modeling; Neuroimmune; Neurologic; Neurons; Neuroprotective Agents; Neurosciences Research; Paper; Positioning Attribute; Postdoctoral Fellow; Property; Protocols documentation; Public Health; Publishing; Relapse; Research; Research Institute; Research Training; Resources; Sensory; TP53 gene; Techniques; Testing; Training; Work; afferent nerve; base; career; career development; colon cancer prevention; cost effective; design; gastrointestinal system; high risk; immune function; interest; macrophage; notch protein; parent grant; preservation; research and development; tumor immunology

PROJECT SUMMARY Inflammatory Bowel Disease (IBD) is a chronic condition with a high risk for development of colon cancer. This illness has a high financial burden due to its relapsing and remitting features. Emerging evidence links the intestinal neuro-immune axis to the development and progression of IBD. Both macrophages and sensory afferent nerves are in close proximity in the gastrointestinal system, and they have the machinery necessary to communicate with one another. Thus, we are interested in targeting the immunological and neurological components of IBD and associated colon cancer. Specifically, we want to study the neuro-immune interactions between macrophages and sensory afferent nerves. Panaxynol is a bioactive component of American Ginseng, carrots, celery, and fennel. Panaxynol has been shown to exhibit anti-inflammatory properties and neuroprotective effects, which make it an ideal compound to test our hypothesis that panaxynol can modulate neuro-immune interactions in colitis and colitis-associated colon cancer. Two aims are proposed: 1) To determine the impact of panaxynol on sensory afferent nerves in the gastrointestinal system, and 2) To examine whether panaxynol influences macrophage interactions with sensory nerves. Based on the current literature and our previous work using methodical and scientifically rigorous protocols, we hypothesize that panaxynol can be developed as a safe, cost-effective anti-inflammatory and neuro-protective agent to be used for IBD and associated colon cancer. The studies in this proposal were designed by Gustavo and his Mentors (Drs. Murphy and Velazquez) taking into consideration: 1) previous research and training, 2) need for additional training, 3) research potential, 4) mentors’ commitment to training, 5) available resources, 6) career goals and objectives, and 7) the public health importance of the proposed research. Drs. Murphy (MPI on parent grant and Mentor) and Dr. Velazquez (Mentor) will guide Gustavo through each aspect of the research and training plan. Specifically, Dr. Murphy will provide training in aspects that involve immune function including macrophages and Dr. Velazquez will provide training in aspects involving neuro-protective properties of panaxynol. Both mentors will provide guidance in natural compound (panaxynol) research, and in colitis/cancer models. It also is important to point out that Drs. Murphy and Velazquez are at different stages of their careers so not only will their research areas complement each other but so will their training in professional development. Under this award it is expected that Gustavo will: 1) achieve new training in cutting edge techniques in cancer, immunology, and neuroscience research, 2) publish at least 6 papers with a minimum of 2 as first author, and 3) be successful in attaining a post-doctoral fellow position at a top-notch research institute. The elaborate research and career development training plan that is proposed will ensure that these goals are reached.

项目摘要 炎症性肠病（IBD）是一种慢性疾病，具有患结肠癌的高风险。这 由于疾病具有反复发作和缓解的特点，因此其经济负担很高。新出现的证据表明 肠道神经免疫轴参与IBD的发生和发展。巨噬细胞和感觉神经 传入神经在胃肠道系统中非常接近，并且它们具有必要的机械， 彼此沟通。因此，我们感兴趣的是靶向免疫和神经 IBD和相关结肠癌的组成部分。具体来说，我们想研究神经免疫相互作用 巨噬细胞和感觉传入神经之间的联系人参炔醇是一种活性成分， 人参，胡萝卜，芹菜，茴香。人参炔醇已被证明具有抗炎特性， 神经保护作用，这使其成为一个理想的化合物来测试我们的假设，人参炔醇可以调节 结肠炎和结肠炎相关结肠癌中的神经免疫相互作用。提出了两个目标：1） 确定人参炔醇对胃肠系统中感觉传入神经的影响，以及2） 检查人参炔醇是否影响巨噬细胞与感觉神经的相互作用。基于当前 文献和我们以前的工作使用有条不紊和科学严谨的协议，我们假设， 人参炔醇可以被开发为一种安全、经济有效的抗炎和神经保护剂， 治疗炎症性肠病和相关的结肠癌 本提案中的研究由Gustavo及其导师（Murphy和Velazquez博士）设计， 考虑：1）以前的研究和培训，2）额外培训的需要，3）研究潜力，4） 导师对培训的承诺，5）可用资源，6）职业目标和目的，以及7）公众 健康研究的重要性。Murphy博士（父母补助金和导师MPI）和Velazquez博士 （导师）将指导古斯塔沃通过研究和培训计划的各个方面。具体来说，墨菲医生将 提供涉及免疫功能（包括巨噬细胞）方面的培训，Velazquez博士将提供 在涉及人参炔醇的神经保护特性方面的培训。两位导师将提供指导， 天然化合物（人参炔醇）的研究，并在结肠炎/癌症模型。同样重要的是要指出，博士。 墨菲和贝拉斯克斯处于职业生涯的不同阶段，因此他们的研究领域不仅可以互补， 彼此，但他们在专业发展方面的培训也是如此。在这个奖项下，预计古斯塔沃 将：1）实现癌症，免疫学和神经科学研究前沿技术的新培训，2） 发表论文至少6篇，其中至少2篇为第一作者，3）成功获得博士后 顶尖研究机构的研究员精心设计的研究和职业发展培训计划 这将确保实现这些目标。