使用ROBOKOP知识图解明过氧酶增殖器激活受体和肝纤维化之间的机制关系
Karamarie Fecho1,2, Nyssa Tucker3, Jon-Michael Beasley4
1Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Frontiers in toxicology
|May 7, 2025
概括
罗伯科普知识图表系统将PPARA激活剂克洛菲布拉特与肝纤维化联系起来. 它表明PPARA通过细胞脂质反应和CCL2调解这种联系,帮助环境暴露和肝毒性研究.
科学领域:
- 生物医学信息学 生物医学信息学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 在知识导向路径 (ROBOKOP) 中链接的生物医学对象的推理是一个开源的知识图.
- 它支持基于证据的生物医学发现和假设生成.
- 了解将环境暴露与肝脏毒性联系在一起的机制至关重要.
研究的目的:
- 应用ROBOKOP来研究将克洛菲布拉特暴露与肝纤维化相关联的生物机制.
- 为了验证ROBOKOP能够证明已知的关系 (clofibrate-PPARA) 的能力.
- 确定将PPARA激活与肝纤维化联系起来的中间途径.
主要方法:
- 使用ROBOKOP知识图表系统进行查询.
- 执行查询以验证克洛纤维酸-PPARA关系.
- 确定了将PPARA激活与肝纤维化联系起来的中间基因和生物过程.
主要成果:
- 罗博科普成功地证明了克洛菲布拉特,PPARA和肝纤维化之间的关系.
- 确定了一个关键途径:克洛菲布拉特会影响PPARA,这与细胞脂质反应有关,涉及CCL2,这是一种与肝纤维化相关的基因.
- 这表明,克洛菲布拉特的PPARA激活有助于肝纤维化.
结论:
- 机器人可以有效地获得对复杂关系的生物学见解.
- 该系统有助于理解环境暴露和肝脏毒性之间的机制.
- 这项研究突出了通过PPARA和CCL2.2引起的纤维化肝纤维化的潜在机制.
相关概念视频
Peroxisomes
8.1K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
8.1K
Protein Import into the Peroxisomes
3.3K
Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
3.3K
Liver Regeneration
3.2K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.2K
Peroxisomes and Mitochondria
85.5K
Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
85.5K
Phase I Oxidative Reactions: Overview
212
Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
212
Introduction to Fibroblasts
3.0K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.0K


