1.
Watanabe, Y., and I. Tatsuno. 2020. Prevention of cardiovascular events with omega-3
polyunsaturated fatty acids and the mechanism involved. Journal of atherosclerosis and
thrombosis 27: 183-198.
2.
Hansen, T. V., and C. N. Serhan. 2022. Protectins: Their biosynthesis, metabolism and
structure-functions. Biochemical Pharmacology: 115330.
3.
Fierro, I., and C. Serhan. 2001. Mechanisms in anti-inflammation and resolution: the role
of lipoxins and aspirin-triggered lipoxins. Brazilian Journal of Medical and Biological
Research 34: 555-566.
4.
Tapiero, H., G. N. Ba, P. Couvreur, and K. Tew. 2002. Polyunsaturated fatty acids
(PUFA) and eicosanoids in human health and pathologies. Biomedicine & pharmacotherapy
56: 215-222.
5.
Serhan, C. N., and B. D. Levy. 2018. Resolvins in inflammation: emergence of the pro-
resolving superfamily of mediators. The Journal of clinical investigation 128: 2657-2669.
6.
Bento, A. F., R. F. Claudino, R. C. Dutra, R. Marcon, and J. B. Calixto. 2011. Omega-3
Fatty Acid-Derived Mediators 17(R)-Hydroxy Docosahexaenoic Acid, Aspirin-Triggered
Resolvin D1 and Resolvin D2 Prevent Experimental Colitis in Mice. The Journal of
Immunology 187: 1957-1969.
7.
Serhan, C. N. 2014. Pro-resolving lipid mediators are leads for resolution physiology.
Nature 510: 92-101.
8.
Serhan, C. N., J. Dalli, R. A. Colas, J. W. Winkler, and N. Chiang. 2015. Protectins and
maresins: New pro-resolving families of mediators in acute inflammation and resolution
bioactive metabolome. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of
Lipids 1851: 397-413.
9.
Gu, Z., G. J. Lamont, R. J. Lamont, S. M. Uriarte, H. Wang, and D. A. Scott. 2016.
Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4engaged human monocytes. Innate immunity 22: 186-195.
10. Lannan, K. L., S. L. Spinelli, N. Blumberg, and R. P. Phipps. 2017. Maresin 1 induces a
novel pro‐resolving phenotype in human platelets. Journal of Thrombosis and Haemostasis
45
15: 802-813.
11. Ledard, N., A. Liboz, B. Blondeau, M. Babiak, C. Moulin, B. Vallin, I. Guillas, V. Mateo,
C. Jumeau, and K. Blirando. 2020. Slug, a cancer‐related transcription factor, is involved in
vascular smooth muscle cell transdifferentiation induced by platelet‐derived growth factor‐BB
during atherosclerosis. Journal of the American Heart Association 9: e014276.
12. Panigrahy, D., M. M. Gilligan, C. N. Serhan, and K. Kashfi. 2021. Resolution of
inflammation: An organizing principle in biology and medicine. Pharmacology &
therapeutics 227: 107879.
13. Kain, V., K. A. Ingle, R. A. Colas, J. Dalli, S. D. Prabhu, C. N. Serhan, M. Joshi, and G.
V. Halade. 2015. Resolvin D1 activates the inflammation resolving response at splenic and
ventricular site following myocardial infarction leading to improved ventricular function.
Journal of molecular and cellular cardiology 84: 24-35.
14. Chiurchiù, V., A. Leuti, J. Dalli, A. Jacobsson, L. Battistini, M. Maccarrone, and C. N.
Serhan. 2016. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are
critical in modulating T cell responses. Science translational medicine 8: 353ra111-353ra111.
15. Minihane, A. M., and J. Lovegrove. 2006. Health benefits of polyunsaturated fatty acids
(PUFAs). In Improving the fat content of foods. Elsevier. 107-140.
16. Seppänen-Laakso, T., I. Laakso, and R. Hiltunen. 2002. Analysis of fatty acids by gas
chromatography, and its relevance to research on health and nutrition. Analytica Chimica Acta
465: 39-62.
17. Brondz, I. 2002. Development of fatty acid analysis by high-performance liquid
chromatography, gas chromatography, and related techniques. Analytica Chimica Acta 465: 137.
18. Chen, S.-H., and Y.-J. Chuang. 2002. Analysis of fatty acids by column liquid
chromatography. Analytica Chimica Acta 465: 145-155.
19. Li, G., J. You, Y. Suo, C. Song, Z. Sun, L. Xia, X. Zhao, and J. Shi. 2011. A developed
pre-column derivatization method for the determination of free fatty acids in edible oils by
reversed-phase HPLC with fluorescence detection and its application to Lycium barbarum
seed oil. Food Chemistry 125: 1365-1372.
20. Fahy, E., S. Subramaniam, H. A. Brown, C. K. Glass, A. H. Merrill, R. C. Murphy, C. R.
Raetz, D. W. Russell, Y. Seyama, and W. Shaw. 2005. A comprehensive classification system
for lipids1. Journal of lipid research 46: 839-861.
21. Liebisch, G., E. Fahy, J. Aoki, E. A. Dennis, T. Durand, C. S. Ejsing, M. Fedorova, I.
Feussner, W. J. Griffiths, and H. Köfeler. 2020. Update on LIPID MAPS classification,
nomenclature, and shorthand notation for MS-derived lipid structures. Journal of lipid
research 61: 1539-1555.
22. Xu, F., L. Zou, Y. Liu, Z. Zhang, and C. N. Ong. 2011. Enhancement of the capabilities
46
of liquid chromatography–mass spectrometry with derivatization: general principles and
applications. Mass spectrometry reviews 30: 1143-1172.
23. Higashi, T., and S. Ogawa. 2016. Isotope-coded ESI-enhancing derivatization reagents
for differential analysis, quantification and profiling of metabolites in biological samples by
LC/MS: A review. Journal of pharmaceutical and biomedical analysis 130: 181-193.
24. Zhu, Q.-F., Z. Zhang, P. Liu, S.-J. Zheng, K. Peng, Q.-Y. Deng, F. Zheng, B.-F. Yuan, and
Y.-Q. Feng. 2016. Analysis of liposoluble carboxylic acids metabolome in human serum by
stable isotope labeling coupled with liquid chromatography–mass spectrometry. Journal of
Chromatography A 1460: 100-109.
25. Xiong, C.-F., Q.-F. Zhu, Y.-Y. Chen, D.-X. He, and Y.-Q. Feng. 2021. Screening and
identification of epoxy/dihydroxy-oxylipins by chemical labeling-assisted ultrahighperformance liquid chromatography coupled with high-resolution mass spectrometry.
Analytical Chemistry 93: 9904-9911.
26. Thomas, D., M. Morris, J. M. Curtis, and R. K. Boyd. 1995. Fragmentation mechanisms
of protonated actinomycins and their use in structural determination of unknown analogues.
Journal of Mass Spectrometry 30: 1111-1125.
27. Skolnik, J. M., J. S. Barrett, H. Shi, and P. C. Adamson. 2006. A liquid chromatographytandem mass spectrometry method for the simultaneous quantification of actinomycin-D and
vincristine in children with cancer. Cancer chemotherapy and pharmacology 57: 458-464.
28. Wheelan, P., J. A. Zirrolli, and R. C. Murphy. 1996. Electrospray ionization and low
energy tandem mass spectrometry of polyhydroxy unsaturated fatty acids. J Am Soc Mass
Spectrom 7: 140-149.
29. Kerwin, J. L., A. M. Wiens, and L. H. Ericsson. 1996. Identification of fatty acids by
electrospray mass spectrometry and tandem mass spectrometry. Journal of mass spectrometry
31: 184-192.
30. Griffiths, W. J., Y. Yang, J. Sjövall, and J. Å. Lindgren. 1996. Electrospray/collision‐
induced dissociation mass spectrometry of mono‐, di‐and tri‐hydroxylated lipoxygenase
products, including leukotrienes of the B‐series and lipoxins. Rapid communications in mass
spectrometry 10: 183-196.
31. Le Faouder, P., V. Baillif, I. Spreadbury, J.-P. Motta, P. Rousset, G. Chêne, C. Guigné, F.
Tercé, S. Vanner, and N. Vergnolle. 2013. LC–MS/MS method for rapid and concomitant
quantification of pro-inflammatory and pro-resolving polyunsaturated fatty acid metabolites.
Journal of Chromatography B 932: 123-133.
32. Hong, S., Y. Lu, R. Yang, K. H. Gotlinger, N. A. Petasis, and C. N. Serhan. 2007.
Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: analysis via
electrospray/low energy tandem mass spectrometry based on spectra and fragmentation
mechanisms. Journal of the American Society for Mass Spectrometry 18: 128-144.
47
33. Hu, T., C. Tie, Z. Wang, and J. L. Zhang. 2017. Highly sensitive and specific
derivatization strategy to profile and quantitate eicosanoids by UPLC-MS/MS. Anal Chim
Acta 950: 108-118.
34. Matuszewski, B. K., M. Constanzer, and C. Chavez-Eng. 2003. Strategies for the
assessment of matrix effect in quantitative bioanalytical methods based on HPLC− MS/MS.
Analytical chemistry 75: 3019-3030.
35. Zhu, Q. F., Y. H. Hao, M. Z. Liu, J. Yue, J. Ni, B. F. Yuan, and Y. Q. Feng. 2015. Analysis
of cytochrome P450 metabolites of arachidonic acid by stable isotope probe labeling coupled
with ultra high-performance liquid chromatography/mass spectrometry. J Chromatogr A
1410: 154-163.
36. Bollinger, J. G., W. Thompson, Y. Lai, R. C. Oslund, T. S. Hallstrand, M. Sadilek, F.
Turecek, and M. H. Gelb. 2010. Improved sensitivity mass spectrometric detection of
eicosanoids by charge reversal derivatization. Analytical chemistry 82: 6790-6796.
37. Wang, M., R. H. Han, and X. Han. 2013. Fatty acidomics: global analysis of lipid species
containing a carboxyl group with a charge-remote fragmentation-assisted approach.
Analytical chemistry 85: 9312-9320.
38. Urabe, D., H. Todoroki, K. Masuda, and M. Inoue. 2012. Total syntheses of four possible
stereoisomers of resolvin E3. Tetrahedron 68: 3210-3219.
39. Isobe, Y., M. Arita, R. Iwamoto, D. Urabe, H. Todoroki, K. Masuda, M. Inoue, and H.
Arai. 2013. Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid
mediator resolvin E3. The Journal of Biochemistry 153: 355-360.
40. Colas, R. A., M. Shinohara, J. Dalli, N. Chiang, and C. N. Serhan. 2014. Identification
and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue.
American Journal of Physiology-Cell Physiology 307: C39-C54.
41. Zhang, J., Q. Yang, J. Li, Y. Zhong, L. Zhang, Q. Huang, B. Chen, M. Mo, S. Shen, and
Q. Zhong. 2018. Distinct differences in serum eicosanoids in healthy, enteritis and colorectal
cancer individuals. Metabolomics 14: 1-12.
42. Ferreiro-Vera, C., F. Priego-Capote, and M. L. de Castro. 2012. Comparison of sample
preparation approaches for phospholipids profiling in human serum by liquid
chromatography–tandem mass spectrometry. Journal of Chromatography A 1240: 21-28.
43. Murphy, R. C., R. M. Barkley, K. Zemski Berry, J. Hankin, K. Harrison, C. Johnson, J.
Krank, A. McAnoy, C. Uhlson, and S. Zarini. 2005. Electrospray ionization and tandem mass
spectrometry of eicosanoids. Anal Biochem 346: 1-42.
44. Parkinson, J. F. 2006. Lipoxin and synthetic lipoxin analogs: an overview of antiinflammatory functions and new concepts in immunomodulation. Inflammation & AllergyDrug Targets (Formerly Current Drug Targets-Inflammation & Allergy)(Discontinued) 5: 91106.
48
Acknowledgements
I would like to express my sincerest gratitude to Professor Toshifumi Takao, who
always gives me not only a great number of invaluable suggestions and feedback
through this work, but also huge unwavering support and heartfelt encouragement
throughout my academic journey. I am genuinely grateful for the knowledge and skills
I have gained under his mentorship. The whole work was carried out under his
supervision in Laboratory of Protein profiling and functional proteomics at Institute for
Protein Research, Osaka University.
I would like to express my gratitude to Professor Masayuki Inoue from Laboratory
of Synthetic Natural Products Chemistry at Graduate School of Pharmaceutical
Sciences, The University of Tokyo for providing the precious Resolvin E3 standards.
I would like to express my gratitude to Professor Michio Murata from Laboratory
for Biomolecular Chemistry at Graduate School of Science, Osaka University for the
valuable suggestions and fruitful discussions.
I would like to also express my gratitude to Professor Takayoshi Suzuki from
Department of Complex Molecular Chemistry at Institute of Scientific and Industrial
Research, Osaka University for the valuable suggestions and discussions.
I would like to express my special thanks to Mone Kurokawa and Mengyao Chen,
the members of Takao Lab who gave me so many helps on this work.
I am grateful to the financial support from Protein Research Foundation.
I am grateful to Hiroto Akiya and Ko Kanegae, the artists whose stages encouraged
me throughout my academic life.
Finally, I am grateful to my parents for their understanding, encouragement and
support on this study, especially my mother Caiqin Gu, who is not only a great woman
but also a respectable professor from The School of Chemistry and Chemical
Engineering, Guangzhou University.
49
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