請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95664完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 侯詠德 | zh_TW |
| dc.contributor.advisor | Yung-Te Hou | en |
| dc.contributor.author | 林泳亨 | zh_TW |
| dc.contributor.author | Yong-Heng Lin | en |
| dc.date.accessioned | 2024-09-15T16:41:21Z | - |
| dc.date.available | 2024-09-16 | - |
| dc.date.copyright | 2024-09-14 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-12 | - |
| dc.identifier.citation | [1] F. Nassir, R. S. Rector, G. M. Hammoud, and J. A. Ibdah, "Pathogenesis and prevention of hepatic steatosis," Gastroenterology & hepatology, vol. 11, no. 3, p. 167, 2015.
[2] G. R. Lichtenstein, "Shifting Our Focus From NASH to MASH," Gastroenterology & Hepatology, vol. 19, no. 9, p. 511, 2023. [3] M. Barbara, A. Scott, and N. Alkhouri, "New insights into genetic predisposition and novel therapeutic targets for nonalcoholic fatty liver disease," Hepatobiliary surgery and nutrition, vol. 7, no. 5, p. 372, 2018. [4] G. Targher, C. P. Day, and E. Bonora, "Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease," New England Journal of Medicine, vol. 363, no. 14, pp. 1341-1350, 2010. [5] O. E. Hegazi et al., "NAFLD and nutraceuticals: A review of completed phase III and IV clinical trials," Frontiers in Medicine, vol. 10, 2023. [6] R. R. Nathani and M. B. Bansal, "Update on clinical trials for nonalcoholic steatohepatitis," Gastroenterology & Hepatology, vol. 19, no. 7, p. 371, 2023. [7] S. Pottanam Chali and B. J. Ravoo, "Polymer nanocontainers for intracellular delivery," Angewandte Chemie International Edition, vol. 59, no. 8, pp. 2962-2972, 2020. [8] F. Chen and G. Huang, "Application of glycosylation in targeted drug delivery," European Journal of Medicinal Chemistry, vol. 182, p. 111612, 2019. [9] A. Mahapatro and D. K. Singh, "Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines," Journal of nanobiotechnology, vol. 9, pp. 1-11, 2011. [10] X. Huang, M. Li, D. C. Green, D. S. Williams, A. J. Patil, and S. Mann, "Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells," Nature communications, vol. 4, no. 1, p. 2239, 2013. [11] G. Sahay, D. Y. Alakhova, and A. V. Kabanov, "Endocytosis of nanomedicines," Journal of controlled release, vol. 145, no. 3, pp. 182-195, 2010. [12] B. E. Uygun et al., "Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix," Nature medicine, vol. 16, no. 7, pp. 814-820, 2010. [13] H. Shimoda et al., "Decellularized liver scaffolds promote liver regeneration after partial hepatectomy," Scientific reports, vol. 9, no. 1, p. 12543, 2019. [14] C. Quint, Y. Kondo, R. J. Manson, J. H. Lawson, A. Dardik, and L. E. Niklason, "Decellularized tissue-engineered blood vessel as an arterial conduit," Proceedings of the National Academy of Sciences, vol. 108, no. 22, pp. 9214-9219, 2011. [15] T. H. Petersen et al., "Tissue-engineered lungs for in vivo implantation," Science, vol. 329, no. 5991, pp. 538-541, 2010. [16] S. B. Seif-Naraghi et al., "Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction," Science translational medicine, vol. 5, no. 173, pp. 173ra25-173ra25, 2013. [17] S. Nakamura and H. Ijima, "Solubilized matrix derived from decellularized liver as a growth factor-immobilizable scaffold for hepatocyte culture," Journal of bioscience and bioengineering, vol. 116, no. 6, pp. 746-753, 2013. [18] A. Baldwin and B. W. Booth, "Biomedical applications of tannic acid," Journal of Biomaterials Applications, vol. 36, no. 8, pp. 1503-1523, 2022. [19] R. A. Youness, R. Kamel, N. A. Elkasabgy, P. Shao, and M. A. Farag, "Recent advances in tannic acid (gallotannin) anticancer activities and drug delivery systems for efficacy improvement; a comprehensive review," Molecules, vol. 26, no. 5, p. 1486, 2021. [20] J. Castro, "Mechanistical studies and prevention of free radical cell injury," in IUPHAR 9th International Congress of Pharmacology: Proceedings Volume 2, 1984: Springer, pp. 243-250. [21] H. Hapidin, N. A. A. Romli, and H. Abdullah, "Proliferation study and microscopy evaluation on the effects of tannic acid in human fetal osteoblast cell line (hFOB 1.19)," Microscopy research and technique, vol. 82, no. 11, pp. 1928-1940, 2019. [22] P.-Y. Chen, Y.-H. Liao, W.-T. Huang, Y.-C. Lin, and Y.-T. Hou, "Effects of tannic acid on liver function in a small hepatocyte–based detachable microfluidic platform," Biochemical Engineering Journal, vol. 190, p. 108757, 2023. [23] Y.-H. Lin, Y.-C. Lin, and Y.-T. Hou, "Prospective Application of Tannic Acid in Acetaminophen (APAP)-Induced Acute Liver Failure," International Journal of Molecular Sciences, vol. 25, no. 1, p. 317, 2024. [Online]. Available: https://www.mdpi.com/1422-0067/25/1/317. [24] G. Mazza et al., "Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation," Scientific reports, vol. 5, no. 1, p. 13079, 2015. [25] R. O. Hynes and A. Naba, "Overview of the matrisome—an inventory of extracellular matrix constituents and functions," Cold Spring Harbor perspectives in biology, vol. 4, no. 1, p. a004903, 2012. [26] M. Sharma, M. Premkumar, A. V. Kulkarni, P. Kumar, D. N. Reddy, and N. P. Rao, "Drugs for non-alcoholic steatohepatitis (NASH): quest for the holy grail," Journal of Clinical and Translational Hepatology, vol. 9, no. 1, p. 40, 2021. [27] Y. Sumida, A. Nakajima, and Y. Itoh, "Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis," World journal of gastroenterology: WJG, vol. 20, no. 2, p. 475, 2014. [28] R. Loomba et al., "Expert panel review to compare FDA and EMA guidance on drug development and endpoints in nonalcoholic steatohepatitis," Gastroenterology, vol. 162, no. 3, pp. 680-688, 2022. [29] J. J. Connolly, K. Ooka, and J. K. Lim, "Future pharmacotherapy for non-alcoholic steatohepatitis (NASH): review of phase 2 and 3 trials," Journal of clinical and translational hepatology, vol. 6, no. 3, p. 264, 2018. [30] S. A. Harrison et al., "Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: results from randomized phase III STELLAR trials," Journal of hepatology, vol. 73, no. 1, pp. 26-39, 2020. [31] V. Ratziu et al., "Cenicriviroc treatment for adults with nonalcoholic steatohepatitis and fibrosis: final analysis of the phase 2b CENTAUR study," Hepatology, vol. 72, no. 3, pp. 892-905, 2020. [32] Q. M. Anstee et al., "Cenicriviroc Lacked Efficacy to Treat Liver Fibrosis in Nonalcoholic Steatohepatitis: AURORA Phase III Randomized Study," Clinical Gastroenterology and Hepatology, 2023. [33] V. Ratziu et al., "Elafibranor, an agonist of the peroxisome proliferator− activated receptor− α and− δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening," Gastroenterology, vol. 150, no. 5, pp. 1147-1159. e5, 2016. [34] H.-C. Tsai et al., "Elafibranor inhibits chronic kidney disease progression in NASH mice," BioMed Research International, vol. 2019, 2019. [35] C. Keshvani, J. Kopel, and H. Goyal, "Obeticholic Acid—A Pharmacological and Clinical Review," Future Pharmacology, vol. 3, no. 1, pp. 238-251, 2023. [36] Z. M. Younossi et al., "Obeticholic acid impact on quality of life in patients with nonalcoholic steatohepatitis: REGENERATE 18-month interim analysis," Clinical Gastroenterology and Hepatology, vol. 20, no. 9, pp. 2050-2058. e12, 2022. [37] S.-W. Cho et al., "Small-diameter blood vessels engineered with bone marrow–derived cells," Annals of surgery, vol. 241, no. 3, pp. 506-515, 2005. [38] S.-W. Cho et al., "Evidence for in vivo growth potential and vascular remodeling of tissue-engineered artery," Tissue Engineering Part A, vol. 15, no. 4, pp. 901-912, 2009. [39] J. M. Ladowski, H. Hara, and D. K. Cooper, "The role of SLAs in xenotransplantation," Transplantation, vol. 105, no. 2, pp. 300-307, 2021. [40] A. Kandamachira, S. Selvam, N. Marimuthu, S. Janardhanan Kalarical, and N. Fathima Nishter, "Collagen-nanoparticle interactions: type I collagen stabilization using functionalized nanoparticles," Soft Materials, vol. 13, no. 1, pp. 59-65, 2015. [41] R. Zhao and C. W. Macosko, "Slip at polymer–polymer interfaces: Rheological measurements on coextruded multilayers," Journal of rheology, vol. 46, no. 1, pp. 145-167, 2002. [42] S. Zalba, T. L. Ten Hagen, C. Burgui, and M. J. Garrido, "Stealth nanoparticles in oncology: Facing the PEG dilemma," Journal of Controlled Release, vol. 351, pp. 22-36, 2022. [43] Y. Zhang, C. B. Higgins, B. A. Van Tine, J. S. Bomalaski, and B. J. DeBosch, "Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism," Cell Reports Medicine, vol. 3, no. 1, 2022. [44] J. K. Jackson and K. Letchford, "The effective solubilization of hydrophobic drugs using epigallocatechin gallate or tannic acid-based formulations," Journal of pharmaceutical sciences, vol. 105, no. 10, pp. 3143-3152, 2016. [45] P. Chowdhury et al., "Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in breast cancer cells," Journal of colloid and interface science, vol. 535, pp. 133-148, 2019. [46] P. Darvin et al., "Tannic acid inhibits the Jak2/STAT3 pathway and induces G1/S arrest and mitochondrial apoptosis in YD-38 gingival cancer cells," International journal of oncology, vol. 47, no. 3, pp. 1111-1120, 2015. [47] X. Chu et al., "Ameliorative effects of tannic acid on carbon tetrachloride-induced liver fibrosis in vivo and in vitro," Journal of pharmacological sciences, vol. 130, no. 1, pp. 15-23, 2016. [48] H. Rafiei, K. Omidian, and B. Bandy, "Dietary polyphenols protect against oleic acid-induced steatosis in an in vitro model of NAFLD by modulating lipid metabolism and improving mitochondrial function," Nutrients, vol. 11, no. 3, p. 541, 2019. [49] M.-Y. Chung et al., "Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model," Molecular metabolism, vol. 19, pp. 34-48, 2019. [50] A. E. Hagerman and L. G. Butler, "Condensed tannin purification and characterization of tannin-associated proteins," Journal of Agricultural and Food Chemistry, vol. 28, no. 5, pp. 947-952, 1980. [51] A. E. Hagerman and L. G. Butler, "Determination of protein in tannin-protein precipitates," Journal of agricultural and food chemistry, vol. 28, no. 5, pp. 944-947, 1980. [52] A. E. Hagerman and L. G. Butler, "The specificity of proanthocyanidin-protein interactions," Journal of Biological Chemistry, vol. 256, no. 9, pp. 4494-4497, 1981. [53] G. Luck et al., "Polyphenols, astringency and proline-rich proteins," Phytochemistry, vol. 37, no. 2, pp. 357-371, 1994. [54] A. J. Charlton et al., "Polyphenol/peptide binding and precipitation," Journal of agricultural and food chemistry, vol. 50, no. 6, pp. 1593-1601, 2002. [55] G. Agorastos, O. van Nielen, E. van Halsema, E. Scholten, A. Bast, and P. Klosse, "Lubrication behavior of ex-vivo salivary pellicle influenced by tannins, gallic acid and mannoproteins," Heliyon, vol. 8, no. 12, 2022. [56] N. Borgese, S. Colombo, and E. Pedrazzini, "The tale of tail-anchored proteins: coming from the cytosol and looking for a membrane," The Journal of cell biology, vol. 161, no. 6, pp. 1013-1019, 2003. [57] N. Ahmad et al., "A comparative brain Toxico-Pharmacokinetics study of a developed tannic acid nanoparticles in the treatment of epilepsy," Journal of Drug Delivery Science and Technology, vol. 76, p. 103772, 2022. [58] L. Wu et al., "Effects of tannic acid and its related compounds on food mutagens or hydrogen peroxide-induced DNA strands breaks in human lymphocytes," Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 556, no. 1-2, pp. 75-82, 2004. [59] V. C. Cogger et al., "Three-dimensional structured illumination microscopy of liver sinusoidal endothelial cell fenestrations," Journal of structural biology, vol. 171, no. 3, pp. 382-388, 2010. [60] A. Sanden, S. Suhm, M. Rüdt, and J. Hubbuch, "Fourier-transform infrared spectroscopy as a process analytical technology for near real time in-line estimation of the degree of PEGylation in chromatography," Journal of Chromatography A, vol. 1608, p. 460410, 2019. [61] C. R. Henry, "Morphology of supported nanoparticles," Progress in surface science, vol. 80, no. 3-4, pp. 92-116, 2005. [62] M. Musci and S. Yao, "Optimization and validation of Folin–Ciocalteu method for the determination of total polyphenol content of Pu-erh tea," International journal of food sciences and nutrition, vol. 68, no. 8, pp. 913-918, 2017. [63] M. Kajiwara et al., "Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells," Proceedings of the National Academy of Sciences, vol. 109, no. 31, pp. 12538-12543, 2012. [64] P. O. Seglen, "Hepatocyte suspensions and cultures as tools in experimental carcinogenesis," Journal of Toxicology and Environmental Health, Part A Current Issues, vol. 5, no. 2-3, pp. 551-560, 1979. [65] A. Moravcová, Z. Červinková, O. Kučera, V. Mezera, D. Rychtrmoc, and H. Lotkova, "The effect of oleic and palmitic acid on induction of steatosis and cytotoxicity on rat hepatocytes in primary culture," Physiological research, vol. 64, 2015. [66] C. J. Vorland et al., "Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats," Scientific reports, vol. 9, no. 1, p. 7936, 2019. [67] O. Huttala, J.-R. Sarkanen, M. Mannerström, T. Toimela, T. Heinonen, and T. Ylikomi, "Development of novel human in vitro vascularized adipose tissue model with functional macrophages," Cytotechnology, vol. 72, pp. 665-683, 2020. [68] X. Han et al., "Validation of an LDH assay for assessing nanoparticle toxicity," Toxicology, vol. 287, no. 1-3, pp. 99-104, 2011. [69] S. Kalgaonkar, H. Nishioka, H. B. Gross, H. Fujii, C. L. Keen, and R. M. Hackman, "Bioactivity of a flavanol‐rich lychee fruit extract in adipocytes and its effects on oxidant defense and indices of metabolic syndrome in animal models," Phytotherapy Research, vol. 24, no. 8, pp. 1223-1228, 2010. [70] P. M. Aja et al., "Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-ĸB signaling in rats," Life Sciences, vol. 259, p. 118268, 2020. [71] W. Kang et al., "Development and application of a transcriptomic signature of bioactivation in an advanced in vitro liver model to reduce drug-induced liver injury risk early in the pharmaceutical pipeline," Toxicological Sciences, vol. 177, no. 1, pp. 121-139, 2020. [72] J. Chao et al., "Gallic acid ameliorated impaired lipid homeostasis in a mouse model of high-fat diet—and streptozotocin-induced NAFLD and diabetes through Improvement of β-oxidation and Ketogenesis," Frontiers in pharmacology, vol. 11, p. 606759, 2021. [73] A. Sclafani, S. Zukerman, and K. Ackroff, "Fructose-and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition," American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, vol. 307, no. 12, pp. R1448-R1457, 2014. [74] M. Botros and K. A. Sikaris, "The de ritis ratio: the test of time," The Clinical Biochemist Reviews, vol. 34, no. 3, p. 117, 2013. [75] X. Han, J. Kong, H. Zhang, Y. Zhao, Y. Zheng, and C. Wei, "Triglycerides Mediate the Influence of Body Mass Index on Non-Alcoholic Fatty Liver Disease in a Non-Obese Chinese Population with Normal Low-Density Lipoprotein Cholesterol Levels," Obesity Facts, 2024. [76] D. Zou, L. Liu, Y. Zeng, H. Wang, D. Dai, and M. Xu, "LncRNA MEG3 up-regulates SIRT6 by ubiquitinating EZH2 and alleviates nonalcoholic fatty liver disease," Cell Death Discovery, vol. 8, no. 1, p. 103, 2022. [77] M. Jaramillo, H. Yeh, M. L. Yarmush, and B. E. Uygun, "Decellularized human liver extracellular matrix (hDLM)‐mediated hepatic differentiation of human induced pluripotent stem cells (hIPSCs)," Journal of tissue engineering and regenerative medicine, vol. 12, no. 4, pp. e1962-e1973, 2018. [78] D. Koley and A. J. Bard, "Triton X-100 concentration effects on membrane permeability of a single HeLa cell by scanning electrochemical microscopy (SECM)," Proceedings of the National Academy of Sciences, vol. 107, no. 39, pp. 16783-16787, 2010. [79] A. K. Bhuyan, "On the mechanism of SDS‐induced protein denaturation," Biopolymers: Original Research on Biomolecules, vol. 93, no. 2, pp. 186-199, 2010. [80] S. Geerts, S. Ozer, M. Jaramillo, M. L. Yarmush, and B. E. Uygun, "Nondestructive methods for monitoring cell removal during rat liver decellularization," Tissue Engineering Part C: Methods, vol. 22, no. 7, pp. 671-678, 2016. [81] N. E. M. Bühler, K. Schulze-Osthoff, A. Königsrainer, and M. Schenk, "Controlled processing of a full-sized porcine liver to a decellularized matrix in 24 h," Journal of bioscience and bioengineering, vol. 119, no. 5, pp. 609-613, 2015. [82] F. Tavakoli et al., "Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model," Artificial cells, nanomedicine, and biotechnology, vol. 46, no. sup2, pp. 75-86, 2018. [83] B. Adamczyk, J. P. Salminen, A. Smolander, and V. Kitunen, "Precipitation of proteins by tannins: effects of concentration, protein/tannin ratio and pH," International journal of food science & technology, vol. 47, no. 4, pp. 875-878, 2012. [84] Y.-C. Hsieh, W.-R. Yin, Y.-Y. Xu, and Y.-T. Hou, "HGF/heparin-immobilized decellularized liver matrices as novel hepatic patches for hepatocyte regeneration in an acute liver injury model," Biochemical Engineering Journal, vol. 180, p. 108354, 2022. [85] M. Parafati, R. J. Kirby, S. Khorasanizadeh, F. Rastinejad, and S. Malany, "A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis," Disease models & mechanisms, vol. 11, no. 9, p. dmm033530, 2018. [86] W. Liu et al., "Effects of linoleic acid and eicosapentaenoic acid on cell proliferation and lipid-metabolism gene expression in primary duck hepatocytes," Molecular and cellular biochemistry, vol. 352, pp. 19-24, 2011. [87] J. Fang, L. Zeng, Y. He, X. Liu, T. Zhang, and Q. Wang, "Effects of dietary tannic acid on obesity and gut microbiota in C57BL/6J mice fed with high-fat diet," Foods, vol. 11, no. 21, p. 3325, 2022. [88] X.-L. Chen et al., "Effects of interleukin-6 and IL-6/AMPK signaling pathway on mitochondrial biogenesis and astrocytes viability under experimental septic condition," International immunopharmacology, vol. 59, pp. 287-294, 2018. [89] E. Adeghate et al., "Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations," Experimental and clinical endocrinology & diabetes, pp. 699-707, 2010. [90] S. Yang et al., "Ginsenoside Rh4 improves hepatic lipid metabolism and inflammation in a model of NAFLD by targeting the gut liver axis and modulating the FXR signaling pathway," Foods, vol. 12, no. 13, p. 2492, 2023. [91] J. Ventura-Sobrevilla et al., "Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice," in Proc West Pharmacol Soc, 2011, vol. 54, no. 5, p. 9. [92] H. Vural, F. Armutcu, O. Akyol, and R. Weiskirchen, "The potential pathophysiological role of altered lipid metabolism and electronegative low-density lipoprotein (LDL) in non-alcoholic fatty liver disease and cardiovascular diseases," Clinica Chimica Acta, vol. 523, pp. 374-379, 2021. [93] C. L. Gentile, M. A. Frye, and M. J. Pagliassotti, "Fatty acids and the endoplasmic reticulum in nonalcoholic fatty liver disease," Biofactors, vol. 37, no. 1, pp. 8-16, 2011. [94] S. Li, H. Y. Tan, N. Wang, F. Cheung, M. Hong, and Y. Feng, "The potential and action mechanism of polyphenols in the treatment of liver diseases," Oxidative medicine and cellular longevity, vol. 2018, no. 1, p. 8394818, 2018. [95] J. Han and R. J. Kaufman, "The role of ER stress in lipid metabolism and lipotoxicity," Journal of lipid research, vol. 57, no. 8, pp. 1329-1338, 2016. [96] Y.-C. Chiu, K.-W. Huang, Y.-H. Lin, W.-R. Yin, and Y.-T. Hou, "Development of a decellularized liver matrix-based nanocarrier for liver regeneration after partial hepatectomy," Journal of Materials Science, vol. 58, no. 38, pp. 15162-15180, 2023. [97] P. Lertpatipanpong et al., "The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice," Scientific reports, vol. 11, no. 1, p. 15027, 2021. [98] A. Sonmez et al., "Low-and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease," Journal of clinical lipidology, vol. 9, no. 4, pp. 576-582, 2015. [99] S. K. Bansal and M. B. Bansal, "Pathogenesis of MASLD and MASH–role of insulin resistance and lipotoxicity," Alimentary Pharmacology & Therapeutics, vol. 59, pp. S10-S22, 2024. [100] Y. Cai, Y. Xu, H. F. Chan, X. Fang, C. He, and M. Chen, "Glycyrrhetinic acid mediated drug delivery carriers for hepatocellular carcinoma therapy," Molecular pharmaceutics, vol. 13, no. 3, pp. 699-709, 2016. [101] H. NISHINO et al., "Glycyrrhetic acid inhibits tumor-promoting activity of teleocidin and 12-O-tetradecanoylphorbol-13-acetate in two-stage mouse skin carcinogenesis," Japanese Journal of Cancer Research GANN, vol. 77, no. 1, pp. 33-38, 1986. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95664 | - |
| dc.description.abstract | 近年來人們在營養攝取過剩以及缺乏運動下，罹患非酒精性脂肪肝病 (Nonalcoholic fatty liver disease; NAFLD) 的比例逐年攀升。而在最近的研究中也發現其對身體的傷害不僅僅限於肝臟且有可能擴展至全身性的代謝功能失常，因此近來更將 NAFLD 進一步定義為代謝失能相關脂肪肝病 (Metabolic dysfunction-associated steatotic liver disease; MASLD)。然而目前在臨床測試藥物的結果仍無法證明其有效性。為了能更有效的解決 MASLD，本研究擬嘗試開發一套能對 MASLD 有顯著回復效果的奈米藥物。
本研究旨在開發一種新穎的奈米藥物，進入肝臟後並促進病患之脂肪肝回復成健康肝臟。研究分為兩個部分：第一部分是奈米藥物的開發：利用脫細胞化肝臟間質 (Decellularized liver matrix; DLM) 與單寧酸 (Tannic acid; TA) 形成奈米藥物，並對其進行性質檢測；第二部分則是對該奈米藥物進行體外和體內試驗。在體外實驗中分別使用誘導性多能幹細胞 (induced pluripotent stem cells; iPSC) 所誘導而成之肝細胞以及大鼠初代成熟肝細胞與該奈米藥物進行共培養，並檢測其細胞活性和肝細胞機能。此外，本研究亦建立小鼠 MASLD 模型，並評估該奈米藥物對於 MASLD 小鼠代謝機能回復的能力。 在本研究的結果中可以發現 TA 與 DLM 確實具備合成奈米粒子的能力；且在投入到 MASLD 體外模型時，除了由於 TA 活化了 AMPK pathway 而展現了降低脂質堆積以及提升肝細胞機能的能力外、TA-DLM 奈米藥物也展現了相較於只投入 TA 有著更為有效的表現。最後再將 TA-DLM 奈米藥物投入到 MASLD 體內模型時，該奈米藥物也展現了改善肝內脂質堆積以及全身性的脂質代謝的潛力。本研究的成果有望為 MASLD 的治療提供新的方法和展望，並為 MASLD 治療領域帶來重要的突破。 | zh_TW |
| dc.description.abstract | In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD) has been increasing due to excessive nutritional intake and lack of exercise. Recent studies show that NAFLD can cause systemic metabolic dysfunction, leading to its redefinition as metabolic dysfunction-associated steatotic liver disease (MASLD). However, current clinical trials have not proven effective. This study aims to develop a nanomedicine with significant recovery effects on MASLD.
This study aims to develop a novel nanomedicine that enters the liver and promotes the recovery of fatty liver to a healthy liver in patients. The research is divided into two parts: the first part involves the development of the nanomedicine by forming nanoparticles using decellularized liver matrix (DLM) and tannic acid (TA) and characterizing their properties. The second part involves in vitro and in vivo experiments with the nanomedicine. In the in vitro experiments, hepatocytes derived from induced pluripotent stem cells (iPSC) and primary mature rat hepatocytes are co-cultured with the nanomedicine, and their cell viability and liver functions are detected. Additionally, a mouse MASLD model is established to evaluate the ability of the nanomedicine to restore metabolic function in MASLD mice. The results indicate that TA and DLM can synthesize nanoparticles. In the in vitro MASLD model, TA activates the AMPK pathway, reducing lipid accumulation and enhancing hepatocyte function. The TA-DLM nanomedicine outperformed TA alone. In the in vivo MASLD model, TA-DLM nanomedicine improved intrahepatic lipid accumulation and systemic lipid metabolism. Therefore, this study offers new methods and prospects for MASLD treatment, potentially leading to significant breakthroughs in the field. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-09-15T16:41:21Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-09-15T16:41:21Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 i
中文摘要 iii 英文摘要 v 目次 vii 圖次 x 第一章 緒論 1 1.1 前言 1 1.2 研究目的 4 第二章 文獻探討 6 2.1 MASLD/MASH 治療發展現況 6 2.2 蛋白質奈米藥物 8 2.2.1 脫細胞化肝臟間質 8 2.2.2 單寧酸 (Tannic acid; TA) 11 2.2.3 蛋白質與單寧酸之間的交互作用 12 2.3 明確的目標 (Specific Aims) 13 第三章 研究方法 15 3.1 實驗藥品、耗材、儀器設備與實驗動物 15 3.1.1 實驗藥品 15 3.1.2 實驗耗材 18 3.1.3 實驗儀器設備 19 3.1.4 實驗動物 20 3.2 脫細胞化肝臟間質 (DLM) 之製備 21 3.2.1 大鼠肝 DLM 之製作流程 21 3.2.2 豬肝 DLM 之製作流程 21 3.2.3 豬肝 DLM 之萃取流程 23 3.3 奈米藥物之製作流程與分析 24 3.3.1 奈米藥物之合成 24 3.3.2 FT-IR 之圖譜分析 25 3.3.3 奈米載體的粒徑分析 25 3.3.4 TEM拍攝並觀察奈米藥物型態 26 3.3.5 TA-DLM 奈米藥物單寧酸釋放量檢測 27 3.4 誘導型多功能幹細胞誘導成肝細胞後之體外培養 28 3.4.1 健康人類與非酒精性脂肪肝病患之誘導型多功能幹細胞之繼代培養 28 3.4.2 誘導型多功能幹細胞分化成肝細胞之二維培養方式 29 3.5 大鼠初代肝細胞培養 31 3.5.1 大鼠初代成熟肝細胞採取與培養 31 3.6 體外毒化與奈米藥物回復 33 3.6.1 油酸毒化 33 3.6.2 體外毒化恢復試驗 34 3.7 體外實驗相關檢測方法 36 3.7.1 尿素分泌量檢測 36 3.7.2 細胞核、白蛋白免疫螢光染色 37 3.7.3 AdipoRed 細胞內脂質定量分析 38 3.7.4 乳酸脫氫酶 (LDH) 活性檢測 39 3.7.5 DNA 含量檢測 40 3.7.6 Interleukin 6 (IL-6) 表現量檢測 41 3.7.7 白蛋白 (Albumin) 表現量檢測 42 3.8 小鼠體內實驗 43 3.8.1 小鼠體內脂肪肝模型預試驗流程 43 3.8.2 小鼠體內脂肪肝模型主試驗流程 45 3.9 體內實驗相關檢測方法 47 3.9.1 血液分析 47 3.9.2 病理切片染色 48 3.9.3 肝內三酸甘油酯含量檢測 48 3.10 統計結果分析方法 49 第四章 實驗結果 50 4.1 脫細胞肝臟間質 (DLM) 之製備 50 4.1.1 大鼠肝臟 DLM (rDLM) 之製作 50 4.1.2 豬肝 DLM (pDLM) 之製作與萃取 51 4.1.3 rDLM 以及 pDLM DNA 含量檢測 52 4.2 奈米藥物之自組裝成果 54 4.2.1 FT-IR 圖譜分析聚乙二醇修飾成果 54 4.2.2 DLS 粒徑分析 55 4.2.3 TEM 觀察 TA-DLM 奈米藥物型態 56 4.2.4 TA-DLM 奈米藥物的單寧酸釋放曲線 57 4.3 TA-DLM 奈米藥物對 iPS 細胞誘導之肝細胞的影響 59 4.3.1 iPS 細胞誘導之肝細胞生長型態觀察 59 4.3.2 iPS 細胞誘導之肝細胞之 LDH 活性檢測 62 4.3.3 iPS 細胞誘導之肝細胞之尿素分泌量檢測 65 4.3.4 iPS 細胞誘導之肝細胞之白蛋白免疫螢光檢測 68 4.3.5 iPS 細胞誘導之肝細胞之白蛋白分泌量檢測 70 4.4 TA-DLM 奈米藥物對大鼠初代成熟肝細胞的影響 73 4.4.1 大鼠初代成熟肝細胞生長型態觀察 73 4.4.2 大鼠初代成熟肝細胞之 DNA 含量檢測 76 4.4.3 大鼠初代成熟肝細胞之 LDH 活性檢測 78 4.4.4 大鼠初代成熟肝細胞之尿素分泌量檢測 80 4.4.5 大鼠初代成熟肝細胞之白蛋白分泌量檢測 82 4.4.6 大鼠初代成熟肝細胞之 IL-6 分泌量檢測 84 4.4.7 大鼠初代成熟肝細胞之脂質累積量檢測 86 4.5 TA-DLM 奈米藥物對小鼠 MASLD 模型的影響 88 4.5.1 小鼠 MASLD 模型預試驗體重、肝臟重量結果 88 4.5.2 小鼠 MASLD 模型預試驗組織切片結果 92 4.5.3 小鼠 MASLD 模型預試驗血液分析結果 95 4.6 TA-DLM 奈米藥物對小鼠 MASLD 模型主試驗的影響 101 4.6.1 小鼠 MASLD 模型主試驗外型、體重、肝臟重量以及肝重/體重比例結果 101 4.6.2 小鼠 MASLD 模型主試驗肝內三酸甘油酯檢測 106 4.6.3 小鼠 MASLD 模型主試驗組織切片分析結果 108 4.6.4 小鼠 MASLD 模型主試驗血液分析結果 111 第五章 結果討論、結論與未來展望 116 5.1 結果討論 116 5.2 結論 123 5.3 未來展望 124 參考文獻 126 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 代謝失能脂肪肝病 | zh_TW |
| dc.subject | 肝臟回復 | zh_TW |
| dc.subject | 單寧酸 | zh_TW |
| dc.subject | 奈米藥物 | zh_TW |
| dc.subject | 脫細胞化肝臟間質 (Decellularied liver matrix; DLM) | zh_TW |
| dc.subject | Liver regeneration | en |
| dc.subject | Decellularized liver matrix (DLM) | en |
| dc.subject | Nanomedicine | en |
| dc.subject | Metabolic dysfunction-associated steatotic liver disease (MASLD) | en |
| dc.title | 以脫細胞化肝臟間質為基底之奈米藥物應用於代謝失能脂肪肝病 | zh_TW |
| dc.title | Development of Decellularized Liver Matrix-based Nanomedicine for MASLD Application | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 倪衍玄;黃凱文;鄭蕙芬 | zh_TW |
| dc.contributor.oralexamcommittee | Yen-Hsuan Ni;Kai-Wen Huang;Huei-Fen Jheng | en |
| dc.subject.keyword | 脫細胞化肝臟間質 (Decellularied liver matrix; DLM),奈米藥物,單寧酸,代謝失能脂肪肝病,肝臟回復, | zh_TW |
| dc.subject.keyword | Decellularized liver matrix (DLM),Nanomedicine,Metabolic dysfunction-associated steatotic liver disease (MASLD),Liver regeneration, | en |
| dc.relation.page | 147 | - |
| dc.identifier.doi | 10.6342/NTU202403205 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2024-08-13 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 生物機電工程學系 | - |
| 顯示於系所單位： | 生物機電工程學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf | 6.93 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。