CER on CAM Antioxidant Therapies (CERCAT)

CAM 抗氧化疗法的 CER (CERCAT)

• 批准号: 8294792
• 负责人: BALZ B FREI
• 金额: $ 118.8万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-26 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294792
• 关键词: Aging; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Antioxidants; Atherosclerosis; Biological; Cells; Centers of Research Excellence; Chronic Disease; Clinical; Complementary Medicine; Complementary and alternative medicine; Development; Diet; Education; Faculty; Fostering; Free Radical Scavenging; Functional disorder; Funding; Gene Expression; Goals; Grant; Health Sciences; Human; Individual; Institutes; International; Knowledge; Lead; Life; Life Style; Medical; Micronutrients; Modality; Molecular; National Center for Complementary and Alternative Medicine; Oregon; Oxidation-Reduction; Persons; Process; Program Research Project Grants; Public Health; Reporting; Research; Research Personnel; Resistance; Risk Factors; Safety; Signal Transduction; Supplementation; Testing; Therapeutic; Thioctic Acid; Tissues; Toxin; Universities; antioxidant therapy; improved; in vivo; macromolecule; oxidative damage; prevent; transcription factor

This competitive renewal of our Program Project Grant, "Center of Excellence for Research on Complementary and Alternative Medicine (CAM) Antioxidant Therapies (CERCAT)," which was one of the first two CERCs funded by NCCAM in 2003, combines the scientific and research expertise of many faculty from the Linus Pauling Institute at Oregon State University and the clinical and medical expertise from faculty at Oregon Health & Science University. The Linus Pauling Institute has established itself as a national and international leader in research and education on micronutrients and antioxidants, and is one of a few research centers in the U.S. to focus entirely on increasing human "healthspan" - the period of a person's life during which they are generally healthy and free from serious or chronic illness - by dietary, lifestyle, and complementary medicine means. The results from the current funding period of the grant have lead to a paradigm shift in our understanding of how natural antioxidants function in the body, viz., not only by scavenging free radicals and preventing oxidative damage to biological macromolecules, but also through more subtle, yet profound changes in reduction-oxidation (redox)-sensitive processes inside cells. This new knowledge is fostering the development of new CAM modalities that reverse cell and tissue dysfunctions by "re-setting" intracellular signal transduction, transcription factor activation, and gene expression to normal, healthy levels. Hence, the goals of this competitive renewal of CERCAT are to better understand the molecular and cellular mechanisms of action and to test the in vivo efficacy - both in experimental animals and humans - of redox-active CAM modalities that have the potential to substantially improve the body's resistance to chronic disease and aging. These goals will be accomplished through three highly interactive projects: 1) "Lipoic acid supplementation to reduce risk factors for atherosclerosis in humans" (Dr. Balz Frei, Project Leader); 2) "Lower vulnerability to toxins in aging by treatment with lipoic acid" (Dr. Tory Hagen); and 3) "CAM antioxidants in amyotrophic lateral sclerosis" (Dr. Joseph Beckman). Center Investigators will be aided by an Administrative Core, which handles budgetary, reporting, and external advisory needs. In summary, CERCAT will provide an integrated set of mechanistic studies for the redox-active compound, (R)- a-lipoic acid, and other CAM antioxidants at the cellular and molecular level, and develop the proof of concept of their therapeutic value in suitable animal models and humans. We expect to make significant advances in the identification of the molecular and cellular mechanisms and relevant biological targets of these CAM antioxidants and - by discovering both beneficial and potentially harmful effects in vivo - to establish their safety and efficacy. This knowledge will help identify and develop new CAM modalities that enhance individual and public health and increase healthspan through affordable, safe, and effective means.

我们的计划项目拨款的竞争性更新，“卓越研究中心” 补充和替代医学 (CAM) 抗氧化疗法 (CERCAT)”，这是其中之一 2003 年由 NCCAM 资助的前两个 CERC 结合了许多教师的科学研究专业知识 来自俄勒冈州立大学莱纳斯鲍林研究所的教授以及教师的临床和医学专业知识 在俄勒冈健康与科学大学。莱纳斯·鲍林研究所已成为国家级和 微量营养素和抗氧化剂研究和教育领域的国际领导者，是少数几个之一 美国的研究中心完全专注于延长人类的“健康寿命”——一个人的生命周期 他们通常健康且没有严重或慢性疾病的生活 - 通过饮食、生活方式和 补充医学手段。当前资助期的结果导致 我们对天然抗氧化剂如何在体内发挥作用的理解发生了范式转变，即不仅通过 清除自由基，防止生物大分子氧化损伤，还可以通过 细胞内还原氧化（氧化还原）敏感过程发生更微妙但深刻的变化。这个新的 知识正在促进新 CAM 模式的发展，通过以下方式逆转细胞和组织功能障碍： “重置”细胞内信号转导、转录因子激活和基因表达至正常状态， 健康水平。因此，CERCAT 竞争性更新的目标是更好地了解 分子和细胞作用机制并测试体内功效 - 均在实验动物中进行 和人类 - 氧化还原活性 CAM 模式有可能大幅改善身体的 抵抗慢性疾病和衰老。这些目标将通过三个高度互动的项目来实现 项目：1）“补充硫辛酸以减少人类动脉粥样硬化的危险因素”（Balz Frei 博士， 项目负责人）； 2) “通过硫辛酸治疗降低衰老过程中毒素的脆弱性”（Tory Hagen 博士）；和 3) “肌萎缩侧索硬化症中的 CAM 抗氧化剂”（Joseph Beckman 博士）。中心调查员将 由管理核心协助，处理预算、报告和外部咨询需求。在 总之，CERCAT 将为氧化还原活性化合物 (R)- 提供一套完整的机理研究 a-硫辛酸和其他 CAM 抗氧化剂在细胞和分子水平上的作用，并开发了以下证据： 它们在合适的动物模型和人类中的治疗价值的概念。我们期望做出重大贡献 分子和细胞机制及相关生物学靶点鉴定方面的进展 这些 CAM 抗氧化剂 - 通过发现体内有益和潜在有害的影响 - 确定其安全性和有效性。这些知识将有助于识别和开发新的 CAM 模式 通过负担得起、安全和有效的手段增强个人和公共健康并延长健康寿命。

项目成果

Authors' perspective: What is the optimum intake of vitamin C in humans?

作者观点：人体维生素 C 的最佳摄入量是多少？

• 发表时间: 2012
• 影响因子: 10.2
• 作者: Frei, Balz;Birlouez;Lykkesfeldt, Jens
• 通讯作者: Lykkesfeldt, Jens

Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure-function relationships and activity after first pass metabolism.

• DOI: 10.1074/jbc.m606804200
• 发表时间: 2006-12-01
• 期刊: The Journal of biological chemistry
• 作者: S. Lotito;B. Frei
• 通讯作者: B. Frei

Vitamin E revisited: do new data validate benefits for chronic disease prevention?

重新审视维生素 E：新数据是否验证了对慢性病预防的益处？

• 发表时间: 2008-02
• 影响因子: 4.4
• 作者: Traber, Maret G;Frei, Balz;Beckman, Joseph S
• 通讯作者: Beckman, Joseph S

Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity.

α-硫辛酸是体内活性氧的清除剂吗？

• 发表时间: 2008-06
• 影响因子: 4.6
• 作者: Petersen Shay, Kate;Moreau, Régis F;Smith, Eric J;Hagen, Tory M
• 通讯作者: Hagen, Tory M

Lead exposure stimulates VEGF expression in the spinal cord and extends survival in a mouse model of ALS.

铅暴露刺激脊髓中 VEGF 的表达并延长 ALS 小鼠模型的生存期。

• 发表时间: 2010-03
• 影响因子: 6.1
• 作者: Barbeito, Ana G;Martinez;Vargas, Marcelo R;Pehar, Mariana;Mañay, Nelly;Beckman, Joseph S;Barbeito, Luis;Cassina, Patricia
• 通讯作者: Cassina, Patricia