权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Non-Invasive Probing Cellular Oxidative Stress and Antioxidants Therapeutic Effectiveness

非侵入性探测细胞氧化应激和抗氧化剂的治疗效果

基本信息

批准号：
10652764
负责人：
Anhong Zhou
金额：
$ 41.47万
依托单位：
UTAH STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10652764
关键词：
Acceleration Air Pollutants Air Pollution Animals Antioxidants Biochemical Biological Biological Assay Biological Markers Biological Models Biomedical Engineering Biomedical Research Carbohydrates Carcinogens Cardiovascular Diseases Cells Collaborations Cytoprotection DNA Data Development Diesel Exhaust Dietary Intervention Dietetics Disease Docosahexaenoic Acids Engine Exhaust Epithelial Cells Exposure to Fingerprint Fluorescence Fluorescent Dyes Generations Goals Health Human In Situ In Vitro Inflammatory Inhalation Inhalation Exposure Injury International Agency for Research on Cancer Knowledge Label Learning Link Lipid Peroxidation Lipids Lung Lung diseases Machine Learning Malignant Neoplasms Malignant neoplasm of lung Mathematics Measurement Measures Mediating Methodology Methods Molecular Mus Nucleic Acids Oxidative Stress Oxidative Stress Induction Particulate Particulate Matter Peer Review Photobleaching Polyunsaturated Fatty Acids Process Production Proteins Public Health Publications Pulmonary Heart Disease Raman Spectrum Analysis Reactive Oxygen Species Research Research Personnel Research Project Grants Resolution Respiratory System Resveratrol Role Specificity Structure of parenchyma of lung Students System Techniques Technology Testing Therapeutic Therapeutic Agents Tissues Toxic effect Toxicology Validation Work World Health Organization biological adaptation to stress cancer classification carcinogenicity cell injury cell type effectiveness evaluation experimental study food science in vivo machine learning algorithm multidisciplinary nanoprobe new technology novel therapeutics nutrition oxidative damage particle particle exposure peroxidation programs respiratory response screening skills training statistics symposium therapeutic effectiveness training opportunity undergraduate student

项目摘要

PROJECT SUMMARY. Particulate matter (PMs) that induces oxidative stress have prominent impacts and adverse health effects including increased cardiovascular and pulmonary diseases. The World Health Organization recognizes diesel engine particles (DEPs) as mutagenic and carcinogenic to humans and the International Agency for Research on Cancer (IARC) classified diesel engine exhaust as a human group I carcinogen. It has been established that generation of reactive oxygen species (ROS) and oxidative stress is an important toxicological mechanism of particulate air pollution-induced lung cancer and disorders. However, the pathophysiological mechanism of air pollutant mediated pulmonary toxicity still remains unclear. This is primarily due to the lack of efficient test systems, mimicking human air pollutant inhalation exposure scenarios. Furthermore, it is unclear, but important, to understand whether epithelial cells from different respiratory tract regions respond to PMs similarly or differently and how to develop measurement technology to assess responses in both in vitro and in vivo. Dietary interventions with antioxidants (e.g., resveratrol), polyunsaturated fatty acids (PUFA, such as docosahexaenoic acid or DHA) are an attractive therapeutic approach to ameliorate air pollution-induced respiratory toxicity. Current methods to detect cellular ROS are fluorescence-based, suffering several drawbacks: each fluorescent dye is limited to a couple of ROS species, not detecting the overall ROS production; single-cell resolution is not achievable; lack of both molecule-level details and temporal specificity; and the photobleaching problem. The primary goal of this proposal is to test the application of a non-invasive, non-destructive, label-free Raman spectroscopy technique in combination with machine learning analysis to assess cellular oxidative stress and cytoprotection by antioxidants. Our central hypothesis is that subcellular and biochemical composition alterations induced by oxidative stress and intracellular ROS production can be quantitatively detected in the cell by Raman spectroscopy using the combinational analysis of respective spectral markers of the fingerprint and the silent regions. To accomplish this goal, we propose the following specific aims: 1) In vitro toxicity assessment of epithelial cells exposed to DEP and the effects of antioxidants; 2) Identification of oxidative stress-associated spectral markers in the fingerprint region and development of intracellular ROS sensing nanoprobes in the silent region; and 3) Pre-validation of Raman-derived spectral markers and ROS quantitation on the lung tissues isolated from DEP exposed mice. We expect that successful completion of these aims will yield a wealth of new knowledge regarding the mechanistic link(s) between cellular oxidative stress biomarkers and non-physiological spectral markers. Further, we expect that these experiments will establish a new technical platform for screening antioxidant activities that can benefit the discovery of new therapeutic agents to battle PM-induced lung disease and other oxidative stress induced inflammatory diseases.

项目总结。