Team members:

Professor: Yan Qiu

Associate Professor: Jie Ren

Postgraduate students: Qi Chen, Ruihe Zheng, Pan Zhou, Yitian Li, Chunyan Ji

Email: yanqiu@xmu.edu.cn

Research Focus:

Endogenous lipid metabolism and ocular surface homeostasis

Dye eye disease is a multi-factor disease with unstable ocular surface. The continuous inflammation in the cornea, conjunctiva, lacrimal gland and other lacrimal systems can further aggravate the instability of the tear film and result in the vicious circle of dry eyes. Clinical practice believes that controlling inflammation is an effective means to break the vicious circle of dry eye, and restore the steady state of the ocular surface and tear system. Recent studies have shown that inflammation regression is a biosynthetic active process induced by a series of endogenous-specific lipids. The steady state of the above lipids is important for maintaining the health and integrity of the ocular surface.

Our group has been focusing on the regulation mechanisms of endogenous fatty acylethanolamine PEA and OEA under ocular surface disease. We established a variety of transgenic mouse animal models to elucidate the pathogenesis of dry eye disease characterized by inflammation and endogenous lipid metabolism imbalance. Based on the metabolic enzymes NAAA and FAAH, several series of small molecule chemical inhibitors were designed and synthesized to maintain the endogenous lipid metabolism homeostasis in the ocular surface microenvironment for development of novel small molecule drugs.

Analytic methodological study of endogenous lipids

Lipids are the basic substances of organic life. About 70% of the metabolites in plasma are lipid molecules. The diversity of lipid structures confers a variety of important biological functions. Abnormal lipid metabolism is closely related to the development of various diseases including ophthalmic diseases. Our group has established a series of lipidomics analytic methods, including: 1. Rapid analysis and identification of endogenous lipids based on UPLC-MSn and the relationship with major diseases; 2, the relationship between dynamic changes of cells lipid groups and abnormal cell function; 3. The metabolic pathways of endocannabinoids, ceramides and related drug development.

Recent publications:

1. Yuhang Li, Pan Zhou, Huixia Chen, Qi Chen, Xiaofei Kuang, Canzhong Lu*, Jie Ren, and Yan Qiu*, Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid amidase (NAAA) inhibitor F215, Pharmacological Research, 2018, 1323, 7-14.

2. Yuhang Li, Qi Chen, Longhe Yang, Yanting Li, Yang Zhang, Yan Qiu*, Jie Ren,  Canzhong Lu*, Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors: Optimization of the terminal phenyl moiety of oxazolidone derivatives, European Journal of Medicinal Chemistry, 2017, 139, 214-221.

3. Yan Qiu†, Jie Ren†, Hongwei Ke, Yang Zhang, Qi Gao, Longhe Yang, Canzhong Lu* and Yuhang Li*, Design and synthesis of uracil urea derivatives as potent and selective fatty acid amide hydrolase inhibitors, RSC Advances, 2017, 7, 22699-22705.

4. Jie Ren, Yuhang Li*, Hongwei Ke, Yanting Li, Longhe Yang, Helin Yu, Rui Huang, Canzhong Lu, and Yan Qiu*, Design, synthesis, and biological evaluation of oxazolidone derivatives as highly potent N-acylethanolamine acid amidase (NAAA) inhibitors, RSC Advances, 2017,7, 12455-12463.

5. Yan Qiu*, Yang Zhang, Yuhang Li, Jie Ren, Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase, Molecules, 2016, 21, 229; doi:10.3390/molecules21020229.

6. Ling Chen, Jie Ren, Longhe Yang, Yanting Li, Jin Fu, Yuhang Li, Yifeng Tian, Funan Qiu, Zuguo Liu*, Yan Qiu*, Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis, Scientific Reports, 2016, 6, 19665; doi: 10.1038/srep19665.

7. Longhe Yang†, Long Li†, Ling Chen, Yanting Li, Huixia Chen, Yuhang Li, Guangnian Ji, Donghai Lin, Zuguo Liu*, Yan Qiu*, Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α, Scientific Reports, 2015, 5, 13565; doi: 10.1038/srep13565.

8. Long Li, Lei Li, Ling Chen, Xiaoyu Lin, Yaping Xu, Jie Ren, Jin Fu, Yan Qiu*, Effect of Oleoylethanolamide on Diet-induced Nonalcoholic Fatty Liver in Rats, Journal of Pharmacological Sciences, 2015, 127, 244-250.

9. Longhe Yang, Yanting Li, Jie Ren, Chenggang Zhu, Jin Fu, Donghai Lin*, Yan Qiu*, Celastrol Attenuates Inflammatory and Neuropathic Pain Mediated by Cannabinoid Receptor Type 2, International Journal of Molecular Sciences, 2014, 15, 13637-13648.

10. Ling Chen†, Baoying Xie†, Lei Li, Weizhong Jiang, Yang Zhang, Jin Fu, Guoxian Guan, Yan Qiu*, Rapid and Sensitive LC-MS/MS Analysis of Fatty Acids in Clinical Samples, Chromatographia, 2014, 77, 1241-1247.

11. Xiyue Wu, Lijun Han, Xiaolin Zhang, Long Li, Changzhen Jiang, Yan Qiu, Rui Huang, Baoying Xie, ZhiXiong Lin, Jie Ren*, Jin Fu*, Alteration of endocannabinoid system in human gliomas, Journal of Neurochemistry, 2012，120 (5), 842-849.