請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99911完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林靖愉 | zh_TW |
| dc.contributor.advisor | Ching-Yu Lin | en |
| dc.contributor.author | 賴靖丰 | zh_TW |
| dc.contributor.author | Ching-Feng Lai | en |
| dc.date.accessioned | 2025-09-19T16:16:28Z | - |
| dc.date.available | 2025-09-20 | - |
| dc.date.copyright | 2025-09-19 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-06 | - |
| dc.identifier.citation | Akin, M., Demirbilek, S., Ay, S., Gurunluoglu, K., Turkmen, E., Tas, E., Aksoy, R. T., Baykarabulut, A., & Edali, M. N. (2007). Attenuation of ureteral obstruction-induced renal injury by polyenylphosphatidylcholine. Int J Urol, 14(4), 350-356. https://doi.org/10.1111/j.1442-2042.2006.01717.x
Alderete, T. L., Jin, R., Walker, D. I., Valvi, D., Chen, Z., Jones, D. P., Peng, C., Gilliland, F. D., Berhane, K., Conti, D. V., Goran, M. I., & Chatzi, L. (2019). Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis. Environ Int, 126, 445-453. https://doi.org/10.1016/j.envint.2019.02.047 Alijagic, A., Sinisalu, L., Duberg, D., Kotlyar, O., Scherbak, N., Engwall, M., Oresic, M., & Hyotylainen, T. (2024). Metabolic and phenotypic changes induced by PFAS exposure in two human hepatocyte cell models. Environ Int, 190, 108820. https://doi.org/10.1016/j.envint.2024.108820 Amstutz, V. H., Cengo, A., Gehres, F., Sijm, D., & Vrolijk, M. F. (2022). Investigating the cytotoxicity of per- and polyfluoroalkyl substances in HepG2 cells: A structure-activity relationship approach. Toxicology, 480, 153312. https://doi.org/10.1016/j.tox.2022.153312 Bagley, B. D., Chang, S.-C., Ehresman, D. J., Eveland, A., Zitzow, J. D., Parker, G. A., Peters, J. M., Wallace, K. B., & Butenhoff, J. L. (2017). Perfluorooctane sulfonate-induced hepatic steatosis in male Sprague Dawley rats is not attenuated by dietary choline supplementation. Toxicological sciences, 160(2), 284-298. Bonanini, F., Singh, M., Yang, H., Kurek, D., Harms, A. C., Mardinoglu, A., & Hankemeier, T. (2024). A comparison between different human hepatocyte models reveals profound differences in net glucose production, lipid composition and metabolism in vitro. Exp Cell Res, 437(1), 114008. https://doi.org/10.1016/j.yexcr.2024.114008 Brusseau, M. L., Anderson, R. H., & Guo, B. (2020). PFAS concentrations in soils: Background levels versus contaminated sites. Sci Total Environ, 740, 140017. https://doi.org/10.1016/j.scitotenv.2020.140017 Butenhoff, J. L., Chang, S.-C., Olsen, G. W., & Thomford, P. J. (2012). Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats. Toxicology, 293(1-3), 1-15. Chang, S.-C., Noker, P. E., Gorman, G. S., Gibson, S. J., Hart, J. A., Ehresman, D. J., & Butenhoff, J. L. (2012). Comparative pharmacokinetics of perfluorooctanesulfonate (PFOS) in rats, mice, and monkeys. Reproductive Toxicology, 33(4), 428-440. Chen, Y. Y., Chung, J. G., Wu, H. C., Bau, D. T., Wu, K. Y., Kao, S. T., Hsiang, C. Y., Ho, T. Y., & Chiang, S. Y. (2010). Aristolochic acid suppresses DNA repair and triggers oxidative DNA damage in human kidney proximal tubular cells. Oncol Rep, 24(1), 141-153. https://doi.org/10.3892/or_00000839 Chiang, S. Y., Lee, P. Y., Lai, M. T., Shen, L. C., Chung, W. S., Huang, H. F., Wu, K. Y., & Wu, H. C. (2011). Safrole-2',3'-oxide induces cytotoxic and genotoxic effects in HepG2 cells and in mice. Mutat Res, 726(2), 234-241. https://doi.org/10.1016/j.mrgentox.2011.09.014 Control, C. f. D., & Prevention. (2022). Biomonitoring data tables for environmental chemicals. In. Cui, Z., & Vance, D. E. (1996). Expression of phosphatidylethanolamine N-methyltransferase-2 is markedly enhanced in long term choline-deficient rats. J Biol Chem, 271(5), 2839-2843. https://doi.org/10.1074/jbc.271.5.2839 Darrow, L. A., Groth, A. C., Winquist, A., Shin, H.-M., Bartell, S. M., & Steenland, K. (2016). Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environmental health perspectives, 124(8), 1227-1233. Dehghani, M. H., Aghaei, M., Bashardoust, P., Rezvani Ghalhari, M., Nayeri, D., Malekpoor, M., Sheikhi, S., & Shi, Z. (2025). An insight into the environmental and human health impacts of per- and polyfluoroalkyl substances (PFAS): exploring exposure pathways and their implications. Environmental Sciences Europe, 37(1). https://doi.org/10.1186/s12302-025-01122-9 DeLong, C. J., Shen, Y. J., Thomas, M. J., & Cui, Z. (1999). Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. J Biol Chem, 274(42), 29683-29688. https://doi.org/10.1074/jbc.274.42.29683 Dennis, E. A. (2016). Liberating Chiral Lipid Mediators, Inflammatory Enzymes, and LIPID MAPS from Biological Grease. J Biol Chem, 291(47), 24431-24448. https://doi.org/10.1074/jbc.X116.723791 EPA, U. (2018). Strategic plan to promote the development and implementation of alternative test methods within the TSCA program. US Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention. Eriksen, K. T., Raaschou-Nielsen, O., McLaughlin, J. K., Lipworth, L., Tjonneland, A., Overvad, K., & Sorensen, M. (2013). Association between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population. PLoS One, 8(2), e56969. https://doi.org/10.1371/journal.pone.0056969 Eriksson, L., Byrne, T., Johansson, E., Trygg, J., & Vikström, C. (2013). Multi-and megavariate data analysis basic principles and applications (Vol. 1). Umetrics Academy. Evich, M. G., Davis, M. J. B., McCord, J. P., Acrey, B., Awkerman, J. A., Knappe, D. R. U., Lindstrom, A. B., Speth, T. F., Tebes-Stevens, C., Strynar, M. J., Wang, Z., Weber, E. J., Henderson, W. M., & Washington, J. W. (2022). Per- and polyfluoroalkyl substances in the environment. Science, 375(6580), eabg9065. https://doi.org/10.1126/science.abg9065 Fahy, E., Cotter, D., Sud, M., & Subramaniam, S. (2011). Lipid classification, structures and tools. Biochim Biophys Acta, 1811(11), 637-647. https://doi.org/10.1016/j.bbalip.2011.06.009 Fahy, E., Subramaniam, S., Brown, H. A., Glass, C. K., Merrill, A. H., Jr., Murphy, R. C., Raetz, C. R., Russell, D. W., Seyama, Y., Shaw, W., Shimizu, T., Spener, F., van Meer, G., VanNieuwenhze, M. S., White, S. H., Witztum, J. L., & Dennis, E. A. (2005). A comprehensive classification system for lipids. J Lipid Res, 46(5), 839-861. https://doi.org/10.1194/jlr.E400004-JLR200 Fasano, W., Kennedy, G., Szostek, B., Farrar, D., Ward, R., Haroun, L., & Hinderliter, P. (2005). Penetration of ammonium perfluorooctanoate through rat and human skin in vitro. Drug and Chemical Toxicology, 28(1), 79-90. Fenton, S. E., Ducatman, A., Boobis, A., DeWitt, J. C., Lau, C., Ng, C., Smith, J. S., & Roberts, S. M. (2021). Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research. Environ Toxicol Chem, 40(3), 606-630. https://doi.org/10.1002/etc.4890 Fiehn, O. (2001). Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comparative and functional genomics, 2(3), 155-168. Folch, J., Lees, M., & Stanley, G. H. S. (1957). A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues. Journal of Biological Chemistry, 226(1), 497-509. https://doi.org/10.1016/s0021-9258(18)64849-5 Fragki, S., Dirven, H., Fletcher, T., Grasl-Kraupp, B., Bjerve Gutzkow, K., Hoogenboom, R., Kersten, S., Lindeman, B., Louisse, J., Peijnenburg, A., Piersma, A. H., Princen, H. M. G., Uhl, M., Westerhout, J., Zeilmaker, M. J., & Luijten, M. (2021). Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not? Crit Rev Toxicol, 51(2), 141-164. https://doi.org/10.1080/10408444.2021.1888073 Gaines, L. G. T., Sinclair, G., & Williams, A. J. (2023). A proposed approach to defining per- and polyfluoroalkyl substances (PFAS) based on molecular structure and formula. Integr Environ Assess Manag, 19(5), 1333-1347. https://doi.org/10.1002/ieam.4735 Gao, Y., Fu, J., Cao, H., Wang, Y., Zhang, A., Liang, Y., Wang, T., Zhao, C., & Jiang, G. (2015). Differential accumulation and elimination behavior of perfluoroalkyl Acid isomers in occupational workers in a manufactory in China. Environ Sci Technol, 49(11), 6953-6962. https://doi.org/10.1021/acs.est.5b00778 Gathungu, R. M., Kautz, R., Kristal, B. S., Bird, S. S., & Vouros, P. (2020). The integration of LC-MS and NMR for the analysis of low molecular weight trace analytes in complex matrices. Mass Spectrom Rev, 39(1-2), 35-54. https://doi.org/10.1002/mas.21575 Gluge, J., Scheringer, M., Cousins, I. T., DeWitt, J. C., Goldenman, G., Herzke, D., Lohmann, R., Ng, C. A., Trier, X., & Wang, Z. (2020). An overview of the uses of per- and polyfluoroalkyl substances (PFAS). Environ Sci Process Impacts, 22(12), 2345-2373. https://doi.org/10.1039/d0em00291g Goodrum, P. E., Anderson, J. K., Luz, A. L., & Ansell, G. K. (2021). Application of a framework for grouping and mixtures toxicity assessment of PFAS: A closer examination of dose-additivity approaches. Toxicological sciences, 179(2), 262-278. Guo, J., Wu, P., Cao, J., Luo, Y., Chen, J., Wang, G., Guo, W., Wang, T., & He, X. (2019). The PFOS disturbed immunomodulatory functions via nuclear Factor-kappaB signaling in liver of zebrafish (Danio rerio). Fish Shellfish Immunol, 91, 87-98. https://doi.org/10.1016/j.fsi.2019.05.018 Jain, R. B. (2019). Concentration of selected liver enzymes across the stages of glomerular function: the associations with PFOA and PFOS. Heliyon, 5(7), e02168. https://doi.org/10.1016/j.heliyon.2019.e02168 Jane, L. E. L., Yamada, M., Ford, J., Owens, G., Prow, T., & Juhasz, A. (2022). Health-related toxicity of emerging per- and polyfluoroalkyl substances: Comparison to legacy PFOS and PFOA. Environ Res, 212(Pt C), 113431. https://doi.org/10.1016/j.envres.2022.113431 Jang, J. E., Park, H. S., Yoo, H. J., Baek, I. J., Yoon, J. E., Ko, M. S., Kim, A. R., Kim, H. S., Park, H. S., Lee, S. E., Kim, S. W., Kim, S. J., Leem, J., Kang, Y. M., Jung, M. K., Pack, C. G., Kim, C. J., Sung, C. O., Lee, I. K.,…Lee, K. U. (2017). Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice. Hepatology, 66(2), 416-431. https://doi.org/10.1002/hep.29039 Jian, J. M., Chen, D., Han, F. J., Guo, Y., Zeng, L., Lu, X., & Wang, F. (2018). A short review on human exposure to and tissue distribution of per- and polyfluoroalkyl substances (PFASs). Sci Total Environ, 636, 1058-1069. https://doi.org/10.1016/j.scitotenv.2018.04.380 Kannan, K., Corsolini, S., Falandysz, J., Fillmann, G., Kumar, K. S., Loganathan, B. G., Mohd, M. A., Olivero, J., Wouwe, N. V., & Yang, J. H. (2004). Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. Environmental Science & Technology, 38(17), 4489-4495. Kashobwe, L., Sadrabadi, F., Brunken, L., Coelho, A., Sandanger, T. M., Braeuning, A., Buhrke, T., Oberg, M., Hamers, T., & Leonards, P. E. G. (2024). Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells. Toxicology, 506, 153862. https://doi.org/10.1016/j.tox.2024.153862 Kersten, S., & Stienstra, R. (2017). The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie, 136, 75-84. https://doi.org/10.1016/j.biochi.2016.12.019 Khan, E. A., Gronnestad, R., Krokje, A., Bartosov, Z., Johanson, S. M., Muller, M. H. B., & Arukwe, A. (2023). Alteration of hepato-lipidomic homeostasis in A/J mice fed an environmentally relevant PFAS mixture. Environ Int, 173, 107838. https://doi.org/10.1016/j.envint.2023.107838 Khanna, R. K., Catanese, S., Emond, P., Corcia, P., Blasco, H., & Pisella, P.-J. (2022). Metabolomics and lipidomics approaches in human tears: A systematic review. Survey of ophthalmology, 67(4), 1229-1243. Kovrlija, I., Menshikh, K., Abreu, H., Cochis, A., Rimondini, L., Marsan, O., Rey, C., Combes, C., Locs, J., & Loca, D. (2024). Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment. Biomaterials Advances, 160, 213866. Lee, J. Y., Ye, J., Gao, Z., Youn, H. S., Lee, W. H., Zhao, L., Sizemore, N., & Hwang, D. H. (2003). Reciprocal Modulation of Toll-like Receptor-4 Signaling Pathways Involving MyD88 and Phosphatidylinositol 3-Kinase/AKT by Saturated and Polyunsaturated Fatty Acids. Journal of Biological Chemistry, 278(39), 37041-37051. https://doi.org/10.1074/jbc.M305213200 Li, X., Jing, K., He, L., Song, P., & Yu, J. (2025). Impact of per- and polyfluoroalkyl substances structure on oxidative stress and lipid metabolism disruption in HepG2 cells. Toxicology, 517, 154218. https://doi.org/10.1016/j.tox.2025.154218 Li, X., Li, T., Wang, Z., Wei, J., Liu, J., Zhang, Y., & Zhao, Z. (2021). Distribution of perfluorooctane sulfonate in mice and its effect on liver lipidomic. Talanta, 226, 122150. https://doi.org/10.1016/j.talanta.2021.122150 Li, Z., & Vance, D. E. (2008). Phosphatidylcholine and choline homeostasis. J Lipid Res, 49(6), 1187-1194. https://doi.org/10.1194/jlr.R700019-JLR200 Lin, C. Y., Chen, W. L., Chen, T. Z., Lee, S. H., Liang, H. J., Chou, C. C., Tang, C. H., & Cheng, T. J. (2021). Lipid changes in extrapulmonary organs and serum of rats after chronic exposure to ambient fine particulate matter. Sci Total Environ, 784, 147018. https://doi.org/10.1016/j.scitotenv.2021.147018 Ling, Y. S., Liang, H. J., Chung, M. H., Lin, M. H., & Lin, C. Y. (2014). NMR- and MS-based metabolomics: various organ responses following naphthalene intervention. Mol Biosyst, 10(7), 1918-1931. https://doi.org/10.1039/c4mb00090k Louisse, J., Rijkers, D., Stoopen, G., Janssen, A., Staats, M., Hoogenboom, R., Kersten, S., & Peijnenburg, A. (2020). Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells. Arch Toxicol, 94(9), 3137-3155. https://doi.org/10.1007/s00204-020-02808-0 Luo, Y. S., Ying, R. Y., Chen, X. T., Yeh, Y. J., Wei, C. C., & Chan, C. C. (2024). Integrating high-throughput phenotypic profiling and transcriptomic analyses to predict the hepatosteatosis effects induced by per- and polyfluoroalkyl substances. J Hazard Mater, 469, 133891. https://doi.org/10.1016/j.jhazmat.2024.133891 Malhotra, P., Gill, R. K., Saksena, S., & Alrefai, W. A. (2020). Disturbances in cholesterol homeostasis and non-alcoholic fatty liver diseases. Frontiers in Medicine, 7, 467. Martínez-Uña, M., Varela-Rey, M., Cano, A., Fernández-Ares, L., Beraza, N., Aurrekoetxea, I., Martínez-Arranz, I., García-Rodríguez, J. L., Buqué, X., Mestre, D., Luka, Z., Wagner, C., Alonso, C., Finnell, R. H., Lu, S. C., Martínez-Chantar, L. M., Aspichueta, P., & Mato, J. M. (2013). Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis. Hepatology, 58(4), 1296-1305. https://doi.org/10.1002/hep.26399 Masoodi, M., Gastaldelli, A., Hyötyläinen, T., Arretxe, E., Alonso, C., Gaggini, M., Brosnan, J., Anstee, Q. M., Millet, O., & Ortiz, P. (2021). Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests. Nature reviews Gastroenterology & hepatology, 18(12), 835-856. Matic, I. (2018). The major contribution of the DNA damage-triggered reactive oxygen species production to cell death: implications for antimicrobial and cancer therapy. Curr Genet, 64(3), 567-569. https://doi.org/10.1007/s00294-017-0787-3 Maximino, P., Horta, P. M., Santos, L. C. d., Oliveira, C. L. d., & Fisberg, M. (2015). Fatty acid intake and metabolic syndrome among overweight and obese women. Revista Brasileira de Epidemiologia, 18, 930-942. Mei, X., Xiang, W., Pan, W., Lin, Q., Jia, X., Zhang, X., Tang, X., Cheng, X., Weng, Y., Yang, K., & Lu, N. (2024). Plasmalogens Reversed Oxidative Stress and Inflammatory Response Exacerbated by Damage to Cell Membrane Properties in Acute Liver Injury. J Agric Food Chem, 72(51), 28280-28293. https://doi.org/10.1021/acs.jafc.4c06929 Ming, Y. N., Zhang, J. Y., Wang, X. L., Li, C. M., Ma, S. C., Wang, Z. Y., Liu, X. L., Li, X. B., & Mao, Y. M. (2017). Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice. Lipids Health Dis, 16(1), 153. https://doi.org/10.1186/s12944-017-0540-4 Norris, P. C., & Dennis, E. A. (2012). Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling. Proceedings of the National Academy of Sciences, 109(22), 8517-8522. OECD, H. (2021). Reconciling terminology of the universe of per-and polyfluoroalkyl substances: recommendations and practical guidance. In (Vol. 61, pp. 45): OECD Publishing Paris. Olsen, G. W., Burris, J. M., Ehresman, D. J., Froehlich, J. W., Seacat, A. M., Butenhoff, J. L., & Zobel, L. R. (2007). Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect, 115(9), 1298-1305. https://doi.org/10.1289/ehp.10009 Pizzurro, D. M., Seeley, M., Kerper, L. E., & Beck, B. D. (2019). Interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics and application to health-based criteria. Regul Toxicol Pharmacol, 106, 239-250. https://doi.org/10.1016/j.yrtph.2019.05.008 Post, G. B., Gleason, J. A., & Cooper, K. R. (2017). Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern. PLoS Biol, 15(12), e2002855. https://doi.org/10.1371/journal.pbio.2002855 Prentki, M., & Madiraju, S. R. M. (2008). Glycerolipid Metabolism and Signaling in Health and Disease. Endocrine Reviews, 29(6), 647-676. https://doi.org/10.1210/er.2008-0007 Qin, Y., Gu, T., Ling, J., Luo, J., Zhao, J., Hu, B., Hua, L., Wan, C., & Jiang, S. (2022). PFOS facilitates liver inflammation and steatosis: An involvement of NLRP3 inflammasome-mediated hepatocyte pyroptosis. J Appl Toxicol, 42(5), 806-817. https://doi.org/10.1002/jat.4258 Reiner, J. L., & Place, B. J. (2015). Perfluorinated alkyl acids in wildlife. Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances, 127-150. Riss, T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., & Minor, L. (2016). Cell viability assays. Assay guidance manual [Internet]. Roth, K., Yang, Z., Agarwal, M., Liu, W., Peng, Z., Long, Z., Birbeck, J., Westrick, J., Liu, W., & Petriello, M. C. (2021). Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury. Environ Int, 157, 106843. https://doi.org/10.1016/j.envint.2021.106843 Saher, G., Brügger, B., Lappe-Siefke, C., Möbius, W., Tozawa, R.-i., Wehr, M. C., Wieland, F., Ishibashi, S., & Nave, K.-A. (2005). High cholesterol level is essential for myelin membrane growth. Nature neuroscience, 8(4), 468-475. Sala, A., Proschak, E., Steinhilber, D., & Rovati, G. E. (2018). Two-pronged approach to anti-inflammatory therapy through the modulation of the arachidonic acid cascade. Biochem Pharmacol, 158, 161-173. https://doi.org/10.1016/j.bcp.2018.10.007 Salihovic, S., Stubleski, J., Karrman, A., Larsson, A., Fall, T., Lind, L., & Lind, P. M. (2018). Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study. Environ Int, 117, 196-203. https://doi.org/10.1016/j.envint.2018.04.052 Schmid, R., Heuckeroth, S., Korf, A., Smirnov, A., Myers, O., Dyrlund, T. S., Bushuiev, R., Murray, K. J., Hoffmann, N., Lu, M., Sarvepalli, A., Zhang, Z., Fleischauer, M., Duhrkop, K., Wesner, M., Hoogstra, S. J., Rudt, E., Mokshyna, O., Brungs, C.,…Pluskal, T. (2023). Integrative analysis of multimodal mass spectrometry data in MZmine 3. Nat Biotechnol, 41(4), 447-449. https://doi.org/10.1038/s41587-023-01690-2 Serhan, C. N. (2014). Pro-resolving lipid mediators are leads for resolution physiology. Nature, 510(7503), 92-101. Shankar, A., Xiao, J., & Ducatman, A. (2011). Perfluoroalkyl chemicals and chronic kidney disease in US adults. Am J Epidemiol, 174(8), 893-900. https://doi.org/10.1093/aje/kwr171 Stratakis, N., D, V. C., Jin, R., Margetaki, K., Valvi, D., Siskos, A. P., Maitre, L., Garcia, E., Varo, N., Zhao, Y., Roumeliotaki, T., Vafeiadi, M., Urquiza, J., Fernandez-Barres, S., Heude, B., Basagana, X., Casas, M., Fossati, S., Grazuleviciene, R.,…Chatzi, L. (2020). Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children. Hepatology, 72(5), 1758-1770. https://doi.org/10.1002/hep.31483 Sud, M., Fahy, E., Cotter, D., Brown, A., Dennis, E. A., Glass, C. K., Merrill Jr, A. H., Murphy, R. C., Raetz, C. R., & Russell, D. W. (2007). Lmsd: Lipid maps structure database. Nucleic acids research, 35(suppl_1), D527-D532. Svegliati-Baroni, G., Pierantonelli, I., Torquato, P., Marinelli, R., Ferreri, C., Chatgilialoglu, C., Bartolini, D., & Galli, F. (2019). Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease. Free Radic Biol Med, 144, 293-309. https://doi.org/10.1016/j.freeradbiomed.2019.05.029 Tang, C. H., Tsao, P. N., Chen, C. Y., Shiao, M. S., Wang, W. H., & Lin, C. Y. (2011). Glycerophosphocholine molecular species profiling in the biological tissue using UPLC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci, 879(22), 2095-2106. https://doi.org/10.1016/j.jchromb.2011.05.044 van der Veen, J. N., Kennelly, J. P., Wan, S., Vance, J. E., Vance, D. E., & Jacobs, R. L. (2017). The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim Biophys Acta Biomembr, 1859(9 Pt B), 1558-1572. https://doi.org/10.1016/j.bbamem.2017.04.006 Vance, D. E. (2014). Phospholipid methylation in mammals: from biochemistry to physiological function. Biochim Biophys Acta, 1838(6), 1477-1487. https://doi.org/10.1016/j.bbamem.2013.10.018 Villas-Boas, S. G., Nielsen, J., Smedsgaard, J., Hansen, M. A., & Roessner-Tunali, U. (2007). Metabolome analysis: an introduction. John Wiley & Sons. Wan, H., Zhao, Y., Wei, X., Hui, K., Giesy, J., & Wong, C. K. (2012). PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport. Biochimica et Biophysica Acta (BBA)-General Subjects, 1820(7), 1092-1101. Wang, J., He, W., Tsai, P. J., Chen, P. H., Ye, M., Guo, J., & Su, Z. (2020). Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease. Lipids Health Dis, 19(1), 72. https://doi.org/10.1186/s12944-020-01210-0 Wang, J., Wang, C., & Han, X. (2019). Tutorial on lipidomics. Anal Chim Acta, 1061, 28-41. https://doi.org/10.1016/j.aca.2019.01.043 Wang, L. Q., Liu, T., Yang, S., Sun, L., Zhao, Z. Y., Li, L. Y., She, Y. C., Zheng, Y. Y., Ye, X. Y., Bao, Q., Dong, G. H., Li, C. W., & Cui, J. (2021). Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome. Nat Commun, 12(1), 2915. https://doi.org/10.1038/s41467-021-23201-0 Wee, S. Y., & Aris, A. Z. (2023). Environmental impacts, exposure pathways, and health effects of PFOA and PFOS. Ecotoxicol Environ Saf, 267, 115663. https://doi.org/10.1016/j.ecoenv.2023.115663 Wilkening, S., Stahl, F., & Bader, A. (2003). Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos, 31(8), 1035-1042. https://doi.org/10.1124/dmd.31.8.1035 Yao, Z. M., & Vance, D. E. (1988). The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. Journal of Biological Chemistry, 263(6), 2998-3004. https://doi.org/10.1016/s0021-9258(18)69166-5 Yen, T. H., Lee, S. H., Tang, C. H., Liang, H. J., & Lin, C. Y. (2024). Lipid responses to perfluorooctane sulfonate exposure for multiple rat organs. Ecotoxicol Environ Saf, 277, 116368. https://doi.org/10.1016/j.ecoenv.2024.116368 Zhang, L., Krishnan, P., Ehresman, D. J., Smith, P. B., Dutta, M., Bagley, B. D., Chang, S. C., Butenhoff, J. L., Patterson, A. D., & Peters, J. M. (2016). Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice. Toxicol Sci, 153(1), 186-197. https://doi.org/10.1093/toxsci/kfw120 Zhu, L., Yang, X., Feng, J., Mao, J., Zhang, Q., He, M., Mi, Y., Mei, Y., Jin, G., & Zhang, H. (2022). CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/beta-catenin signaling. J Transl Med, 20(1), 194. https://doi.org/10.1186/s12967-022-03396-6 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99911 | - |
| dc.description.abstract | 全氟與多氟烷基物質（per- and polyfluoroalkyl substances; PFAS）是一類廣泛應用於產品中的化學物質。其中，全氟辛烷磺酸（perfluorooctanesulfonic acid; PFOS）是最常在人體血清與環境樣本中檢測到的化合物之一。由於其對蛋白質具有高度結合親和力，PFOS 容易在肝臟中累積。PFOS 會引發多種有害健康效應，包括干擾脂質代謝、肝臟脂肪累積，以及肝臟發炎。本研究旨在透過脂質體學方法，分析PFOS暴露對人類肝癌細胞株 HepG2 中含磷酸膽鹼的脂質（phosphorylcholine-containing lipids; PC-CL）的變化，以探討其可能毒性機制。
本研究分別以對照組、1/10 IC₁₀、IC₁₀與IC₂₀ PFOS濃度處理HepG2細胞48 小時。細胞收集後，脂質經由改良的Folch法萃取，並以超高效液相層析串聯三重四極桿質譜儀分析HepG2細胞的PC-CL組成。經圖譜處理後，透過主成分分析與偏最小平方區別分析等多變量統計方法，辨識各暴露劑量組別間脂質體的差異；同時使用Kruskal–Wallis檢定以篩選在不同處理組之間具顯著差異的脂質種類。 在高劑量PFOS暴露組中，單元與雙元不飽和二酰基PC（DPC）下降，而多元不飽和DPC（polyunsaturated-DPC; PUFA-DPC）上升。這些結果顯示PFOS可能干擾肝臟中磷脂醯膽鹼的生合成路徑，包括CDP-膽鹼(CDP-choline)路徑與磷脂醯乙醇胺N-甲基轉移酶(phosphatidylethanolamine N-methyltransferase; PEMT)路徑。此外，PUFA-DPC與P-PC的上升可能反映細胞為了對抗PFOS引發的發炎與氧化壓力而產生的肝保護性反應。 總結而言，本研究運用了質譜為基礎的脂質體學方法，探討PFOS暴露對 HepG2 細胞 PC-CL 脂質組成的影響。研究結果指出，在不引起細胞毒性的PFOS暴露濃度下，細胞可能透過肝保護機制來應對PFOS所造成的發炎與氧化壓力反應。本研究的結果展現出體外實驗在脂質體學研究中作為動物實驗替代方案的潛力，特別是在相對低劑量 PFOS 暴露的情況下。 | zh_TW |
| dc.description.abstract | Per- and polyfluoroalkyl substances (PFASs) are a group of synthetic chemicals widely used in consumer products. Among them, perfluorooctanesulfonic acid (PFOS) is one of the most commonly detected compounds in human serum and environmental samples. Due to its high binding affinity to proteins, PFOS accumulates in the liver. PFOS induces several adverse health effects, including the disruption of lipid metabolism, liver steatosis, and liver inflammation. The aims of this study are to understand the possible mechanisms of PFOS-induced cytotoxicity by analyzing changes of phosphorylcholine-containing lipids (PC-CL) in human hepatoma HepG2 cells exposed to a series dose of PFOS using lipidomic approach.
HepG2 cells were treated with vehicle control, 1/10 IC10, IC10 and IC20 of PFOS for 48 hours. PC-CL were extracted with modified Folch method and analyzed by ultra-performance liquid chromatography–triple quadrupole mass spectrometry. After spectral processing, multivariate analysis, including principal component analysis and partial least squares discriminant analysis, were conducted to identify different patterns of lipid across the various treatment groups. The Kruskal–Wallis test was applied to identify lipids that significantly differed among treatment groups. The decreased levels of mono- and di-unsaturated diacyl-PC (DPC) and increased levels of polyunsaturated-DPC (PUFA-DPC) were observed in the high dose group. These findings suggest that PFOS may disrupt the hepatic PC biosynthesis pathway by binding to bioavailable choline, thereby reducing PC production via the CDP-choline pathway and upregulating PEMT activity. This compensatory mechanism may enhance PC biosynthesis through the PEMT pathway. In conclusion, this study applied MS-based lipidomic approach to identify the changes of PC-CL profile in PFOS-treated HepG2 cells. The results suggested that at sublethal doses of PFOS, the hepatoprotective effects may occur due to the inflammation and oxidative stress caused by PFOS. The results of this study demonstrate the potential of in vitro models as alternatives to animal testing in lipidomic research, particularly under conditions of sublethal doses of PFOS exposure. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-19T16:16:28Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-19T16:16:28Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II Abstract IV Content VI List of figures VIII List of tables IX Chapter 1 Introduction 1 1.1 Per- and polyfluoroalkyl substances PFAS 1 1.2 Perfluorooctanesulfonic acid (PFOS) 5 1.3 Possible mechanism of PFOS-induced hepatotoxicity 9 1.4 Lipidomics 10 1.5 Application of focus lipidomic approach to phosphorylcholine-containing lipids profiling in hepatotoxicity study 13 1.6 Challenge in PFAS induced-hepatotoxicity studies 14 1.7 Study aims 15 Chapter 2 Materials and methods 17 2.1 The study framework 17 2.2 HepG2 cells treated with PFOS 18 2.2.1 Chemicals 18 2.2.2 HepG2 cells culture 18 2.2.3 Cytotoxicity assessment 19 2.2.4 PFOS exposure for lipidomic analysis 21 2.3 LC-MS based lipidomic analysis 21 2.3.1 Sample preparation 21 2.3.2 Lipid measurement through UPLC-MS/MS 22 2.3.3 Lipid identification 23 2.3.4 Data preprocessing 24 2.3.5 Statistical analysis 25 Chapter 3 Results 26 3.1 The MTS cytotoxicity assay for PFOS treatment 26 3.2 PC-CL in HepG2 cells 27 3.3 Multivariate analysis of PC-CL in response to PFOS treatments in HepG2 cells 27 3.4 Univariate analysis of PC-CL in response to PFOS treatments in HepG2 cells 28 Chapter 4 Discussion 30 4.1 Imbalance PC biosynthesis and lipid metabolism of HepG2 cells treated with various doses of PFOS 30 4.2 PFOS-induced hepatotoxicity through inflammatory response 32 4.3 PFOS-induced hepatotoxicity through oxidative stress and membrane damage 34 4.4 Comparison of the results with previous PFOS in vitro studies 36 4.5 Comparison of the lipid results with previous PFOS studies using animal models 38 Chapter 5 Conclusion 41 References 43 | - |
| dc.language.iso | en | - |
| dc.subject | 肝毒性 | zh_TW |
| dc.subject | 全氟與多氟烷基物質 | zh_TW |
| dc.subject | 全氟辛烷磺酸 | zh_TW |
| dc.subject | 體外研究 | zh_TW |
| dc.subject | 脂質代謝 | zh_TW |
| dc.subject | hepatotoxicity | en |
| dc.subject | lipid metabolism | en |
| dc.subject | in vitro study | en |
| dc.subject | perfluorooctanesulfonic acid | en |
| dc.subject | per- and polyfluoroalkyl substances | en |
| dc.title | 應用質譜儀為基礎的脂質體學探討全氟辛烷磺酸暴露對人類肝癌細胞脂質影響 | zh_TW |
| dc.title | Lipid Alterations in HepG2 Cells Exposed to Perfluorooctanesulfonic Acid: A Mass Spectrometry-based Lipidomic Approach | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 江素瑛;羅宇軒;魏嘉徵 | zh_TW |
| dc.contributor.oralexamcommittee | Su-Yin Chiang;Yu-Syuan Luo;Chia-Cheng Wei | en |
| dc.subject.keyword | 全氟與多氟烷基物質,全氟辛烷磺酸,體外研究,脂質代謝,肝毒性, | zh_TW |
| dc.subject.keyword | per- and polyfluoroalkyl substances,perfluorooctanesulfonic acid,lipid metabolism,in vitro study,hepatotoxicity, | en |
| dc.relation.page | 65 | - |
| dc.identifier.doi | 10.6342/NTU202503955 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-08-06 | - |
| dc.contributor.author-college | 公共衛生學院 | - |
| dc.contributor.author-dept | 環境與職業健康科學研究所 | - |
| dc.date.embargo-lift | 2025-09-20 | - |
| 顯示於系所單位： | 環境與職業健康科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-113-2.pdf | 1.74 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。