UNDERSTANDING MOLECULAR AND PHENOTYPIC EFFECTS OF CYCLO-OXYGENASE IN ZEBRAFISH
了解环加氧酶对斑马鱼的分子和表型影响
基本信息
- 批准号:1863062
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The aim of this project is to elucidate the effects of COX inhibitors on immune and gastro-intestinal system of zebrafish and to explore the interplay between the two responses. Using NSAIDs that differ in their ability to inhibit the two COX enzymes, the student will seek molecular and phenotypic signatures that define action in zebrafish larvae. Particular attention will be given to the dynamics of activation and migration of immune cells and their relationship with the manifestation of tissue damage.Exposure to COX-inhibitors will be carried out using healthy fish as well as fish undergoing inflammatory responses. The latter will be triggered by pre-treatment with lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria. The comparison of the drug-induced responses in healthy versus "inflamed" fish will help to elucidate the role played by the physiological state of the organism in determining effect type and magnitude. The effects on immune and gastro-intestinal systems will be quantified using a diverse set of imaging, flow cytometry, and molecular techniques. Zebrafish is an excellent model for inflammation biology as many aspects of its biology closely resemble the human system. Due to the high relevance of the modulation of COX-mediated pathways for both human, animal and environmental health, the use of zebrafish will also maximise the translational values of the data generated in this project across fields. This high translational potential is fully in line with the rapidly emerging "One Health" vision, which recognizes the inextricable link between human and environmental health. Project background Non-steroidal anti-inflammatory drugs (NSAIDs) are used by millions of people worldwide every day to treat a wide variety of conditions that involve pain, fever and inflammation. These compounds act by inhibiting one or both isoforms of the enzyme cyclo-oxygenase (COX1, COX2), which catalyse the synthesis of prostanoids. In healthy humans, low levels of prostanoids play important homeostatic functions; however, their biosynthesis increases dramatically during inflammation, leading, among other things, to pain and poor thermoregulation. The inhibition of prostanoids biosynthesis via COX inhibitors is therefore a highly effective therapeutic strategy in pain and fever management. However, long-term therapeutic use of NSAIDs can adversely affect the gastro-intestinal tract (e.g. dyspepsia, gastric ulcer, bleeding), but also kidney, liver and cardiovascular system. Significant efforts have been allocated to understand the mechanisms of toxicity of NSAIDs and to mitigate these risks. For example, many NSAIDs modulate both COX1 and COX2. It has been hypothesised that whereas the inhibition of COX2 in the gastrointestinal tract is beneficial, the inhibition of COX1 contributes significantly to the drug-induced toxicity. This mechanistic perspective represented the rationale for the development of selective-COX2 inhibitors that minimise the risk of gastro-intestinal toxicity. Despite the great advancements achieved in the understanding of NSAIDs pharmacology and toxicology, many aspects of the mechanisms of action of COX inhibitors and of their biological significance still remain to be elucidated. The importance of understanding these mechanisms is not only limited to human health, but it has also critical importance for environmental health and for the protection of animal health.
本研究旨在阐明考克斯抑制剂对斑马鱼免疫和胃肠系统的影响,并探讨两者之间的相互作用。使用不同的非甾体抗炎药,在他们的能力,以抑制这两种考克斯酶,学生将寻求分子和表型的签名,定义在斑马鱼幼虫的行动。将特别注意免疫细胞的激活和迁移的动力学及其与组织损伤表现的关系。将使用健康鱼以及发生炎症反应的鱼进行COX抑制剂暴露。后者将通过用脂多糖(LPS)(革兰氏阴性菌外膜的主要组分)预处理来触发。在健康与“发炎”鱼的药物诱导的反应的比较将有助于阐明生物体的生理状态在确定效果类型和幅度所发挥的作用。对免疫和胃肠道系统的影响将使用不同的成像,流式细胞术和分子技术进行量化。斑马鱼是炎症生物学的一个很好的模型,因为它的生物学的许多方面与人类系统非常相似。由于COX介导的途径的调节与人类、动物和环境健康的高度相关性,斑马鱼的使用也将最大限度地提高该项目在各个领域产生的数据的转化价值。这种高转化潜力完全符合迅速出现的“一个健康”愿景,该愿景认识到人类与环境健康之间不可分割的联系。非甾体抗炎药(NSAID)每天被全世界数百万人用于治疗各种各样的疾病,包括疼痛、发热和炎症。这些化合物通过抑制催化前列腺素类合成的酶环加氧酶(COX 1、COX 2)的一种或两种同工型起作用。在健康的人类中,低水平的前列腺素类发挥重要的稳态功能;然而,它们的生物合成在炎症期间急剧增加,导致疼痛和体温调节不良等。因此,通过考克斯抑制剂抑制前列腺素类生物合成是疼痛和发热管理中的高效治疗策略。然而,NSAID的长期治疗性使用可对胃肠道(例如消化不良、胃溃疡、出血)以及肾、肝和心血管系统产生不利影响。已分配了大量工作来了解NSAID的毒性机制并减轻这些风险。例如,许多NSAID调节COX 1和COX 2。已经假设,尽管胃肠道中COX 2的抑制是有益的,但是COX 1的抑制显著地有助于药物诱导的毒性。这种机制的观点代表了选择性COX 2抑制剂的发展,最大限度地减少胃肠道毒性的风险的基本原理。尽管在理解NSAID药理学和毒理学方面取得了很大进展,但考克斯抑制剂的作用机制及其生物学意义的许多方面仍有待阐明。了解这些机制的重要性不仅限于人类健康,而且对环境健康和保护动物健康也至关重要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('', 18)}}的其他基金
An implantable biosensor microsystem for real-time measurement of circulating biomarkers
用于实时测量循环生物标志物的植入式生物传感器微系统
- 批准号:
2901954 - 财政年份:2028
- 资助金额:
-- - 项目类别:
Studentship
Exploiting the polysaccharide breakdown capacity of the human gut microbiome to develop environmentally sustainable dishwashing solutions
利用人类肠道微生物群的多糖分解能力来开发环境可持续的洗碗解决方案
- 批准号:
2896097 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
A Robot that Swims Through Granular Materials
可以在颗粒材料中游动的机器人
- 批准号:
2780268 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Likelihood and impact of severe space weather events on the resilience of nuclear power and safeguards monitoring.
严重空间天气事件对核电和保障监督的恢复力的可能性和影响。
- 批准号:
2908918 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Proton, alpha and gamma irradiation assisted stress corrosion cracking: understanding the fuel-stainless steel interface
质子、α 和 γ 辐照辅助应力腐蚀开裂:了解燃料-不锈钢界面
- 批准号:
2908693 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Field Assisted Sintering of Nuclear Fuel Simulants
核燃料模拟物的现场辅助烧结
- 批准号:
2908917 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Assessment of new fatigue capable titanium alloys for aerospace applications
评估用于航空航天应用的新型抗疲劳钛合金
- 批准号:
2879438 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
使用右旋糖酐-胶原蛋白水凝胶开发 3D 打印皮肤模型,以分析白细胞介素 17 抑制剂的细胞和表观遗传效应
- 批准号:
2890513 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
- 批准号:
2876993 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
相似国自然基金
Kidney injury molecular(KIM-1)介导肾小管上皮细胞自噬在糖尿病肾病肾间质纤维化中的作用
- 批准号:81300605
- 批准年份:2013
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
Molecular Plant
- 批准号:31224801
- 批准年份:2012
- 资助金额:20.0 万元
- 项目类别:专项基金项目
Molecular Interaction Reconstruction of Rheumatoid Arthritis Therapies Using Clinical Data
- 批准号:31070748
- 批准年份:2010
- 资助金额:34.0 万元
- 项目类别:面上项目
Molecular Plant
- 批准号:31024802
- 批准年份:2010
- 资助金额:20.0 万元
- 项目类别:专项基金项目
Cellular & Molecular Immunology
- 批准号:30824806
- 批准年份:2008
- 资助金额:20.0 万元
- 项目类别:专项基金项目
相似海外基金
Conference: 2023 Molecular Mechanisms in Evolutions GRC and GRS: Genetic and Phenotypic Evolution at the Organismal, Cellular and Molecular Levels
会议:2023进化中的分子机制GRC和GRS:有机体、细胞和分子水平的遗传和表型进化
- 批准号:
2328755 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Standard Grant
Molecular Mechanisms and Evolution of Phenotypic Plasticity
表型可塑性的分子机制和进化
- 批准号:
10326657 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Molecular Origins of Phenotypic Changes in the Obese Microvascular Endothelium
肥胖微血管内皮表型变化的分子起源
- 批准号:
10538224 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Molecular Mechanisms and Evolution of Phenotypic Plasticity
表型可塑性的分子机制和进化
- 批准号:
10540401 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Molecular Mechanisms and Evolution of Phenotypic Plasticity
表型可塑性的分子机制和进化
- 批准号:
10790490 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Molecular Origins of Phenotypic Changes in the Obese Microvascular Endothelium
肥胖微血管内皮表型变化的分子起源
- 批准号:
10761699 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Molecular mechanisms and phenotypic change during the process toward drug resistance
耐药过程中的分子机制和表型变化
- 批准号:
21K20716 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Research Activity Start-up
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory code
通过顺式调控密码的视角预测遗传变异的特定背景分子和表型效应
- 批准号:
10659170 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory code
通过顺式调控密码的视角预测遗传变异的特定背景分子和表型效应
- 批准号:
10297562 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Mass Spectrometry-based Global Molecular Approaches and Computational Tools to Determine Phenotypic and Environmental Signatures of Endometriosis
基于质谱的全局分子方法和计算工具来确定子宫内膜异位症的表型和环境特征
- 批准号:
10699969 - 财政年份:2021
- 资助金额:
-- - 项目类别: