請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80335完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林峯輝(Feng-Hui Lin) | |
| dc.contributor.author | Ya-Jyun Liang | en |
| dc.contributor.author | 梁雅鈞 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:04:41Z | - |
| dc.date.available | 2026-06-25 | |
| dc.date.available | 2022-11-24T03:04:41Z | - |
| dc.date.copyright | 2021-07-09 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-06-25 | |
| dc.identifier.citation | 1. Kim, T.N. and K.M. Choi, Sarcopenia: definition, epidemiology, and pathophysiology. J Bone Metab, 2013. 20(1): p. 1-10. 2. Argiles, J.M., et al., Cachexia and sarcopenia: mechanisms and potential targets for intervention. Curr Opin Pharmacol, 2015. 22: p. 100-6. 3. Cruz-Jentoft, A.J., et al., Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing, 2014. 43(6): p. 748-59. 4. Bowen, T.S., G. Schuler, and V. Adams, Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle, 2015. 6(3): p. 197-207. 5. Yu, J., The etiology and exercise implications of sarcopenia in the elderly. International Journal of Nursing Sciences, 2015. 2(2): p. 199-203. 6. McNeil, C.J., et al., Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men. Muscle Nerve, 2005. 31(4): p. 461-7. 7. Balagopal, P., et al., Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. Am J Physiol, 1997. 273(4 Pt 1): p. E790-800. 8. van Geel, T.A., et al., Measures of bioavailable serum testosterone and estradiol and their relationships with muscle mass, muscle strength and bone mineral density in postmenopausal women: a cross-sectional study. Eur J Endocrinol, 2009. 160(4): p. 681-7. 9. Greenlund, L.J. and K.S. Nair, Sarcopenia--consequences, mechanisms, and potential therapies. Mech Ageing Dev, 2003. 124(3): p. 287-99. 10. Churchward-Venne, T.A., L. Breen, and S.M. Phillips, Alterations in human muscle protein metabolism with aging: Protein and exercise as countermeasures to offset sarcopenia. Biofactors, 2014. 40(2): p. 199-205. 11. Dalle, S., L. Rossmeislova, and K. Koppo, The Role of Inflammation in Age-Related Sarcopenia. Front Physiol, 2017. 8: p. 1045. 12. Wang, J., et al., Inflammation and age-associated skeletal muscle deterioration (sarcopaenia). J Orthop Translat, 2017. 10: p. 94-101. 13. Hall, D.T., et al., Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY), 2011. 3(8): p. 702-15. 14. Bian, A.L., et al., A study on relationship between elderly sarcopenia and inflammatory factors IL-6 and TNF-alpha. European Journal of Medical Research, 2017. 22. 15. Schaap, L.A., et al., Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med, 2006. 119(6): p. 526 e9-17. 16. Zhu, Y., et al., Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care, 2014. 17(4): p. 324-8. 17. Dionyssiotis, Y., et al., Sarcopenia: From definition to treatment. Hormones (Athens), 2017. 16(4): p. 429-439. 18. Gonzalez, M.C. and S.B. Heymsfield, Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating? J Cachexia Sarcopenia Muscle, 2017. 8(2): p. 187-189. 19. Cruz-Jentoft, A.J., et al., Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing, 2019. 48(4): p. 601. 20. Brown, W.J. and M.S. McCarthy, Sarcopenia: What Every NP Needs to Know. Jnp-Journal for Nurse Practitioners, 2015. 11(8): p. 753-760. 21. Delmonico, M.J. and D.T. Beck, The Current Understanding of Sarcopenia: Emerging Tools and Interventional Possibilities. American Journal of Lifestyle Medicine, 2017. 11(2): p. 167-181. 22. El Hajj, C., et al., Vitamin D supplementation and muscle strength in pre-sarcopenic elderly Lebanese people: a randomized controlled trial. Archives of Osteoporosis, 2018. 14(1). 23. Remelli, F., et al., Vitamin D Deficiency and Sarcopenia in Older Persons. Nutrients, 2019. 11(12). 24. Khor, S.C., et al., Vitamin E in sarcopenia: current evidences on its role in prevention and treatment. Oxid Med Cell Longev, 2014. 2014: p. 914853. 25. Moon, J.J., et al., New Skeletal Muscle Mass Index in Diagnosis of Sarcopenia. J Bone Metab, 2018. 25(1): p. 15-21. 26. Kurita, T. and Y. Makino, Novel curcumin oral delivery systems. Anticancer Res, 2013. 33(7): p. 2807-21. 27. McFarlin, B.K., et al., Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin. BBA Clin, 2016. 5: p. 72-8. 28. Berger, F., I. Buchsler, and B. Munz, The effect of the NF-kappa B inhibitors curcumin and lactacystin on myogenic differentiation of rhabdomyosarcoma cells. Differentiation, 2012. 83(5): p. 271-81. 29. Sahebkar, A., et al., Curcumin: An effective adjunct in patients with statin-associated muscle symptoms? J Cachexia Sarcopenia Muscle, 2017. 8(1): p. 19-24. 30. Franceschi, F., et al., A novel phospholipid delivery system of curcumin (Meriva(R)) preserves muscular mass in healthy aging subjects. Eur Rev Med Pharmacol Sci, 2016. 20(4): p. 762-6. 31. Fu, Y. and W.J. Kao, Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opinion on Drug Delivery, 2010. 7(4): p. 429-444. 32. Shyong, Y.J., et al., Mesoporous Hydroxyapatite as Olanzapine Carrier Provides a Long-Acting Effect in Antidepression Treatment. Journal of Medicinal Chemistry, 2015. 58(21): p. 8463-8474. 33. Jogiya, B., et al., Synthesis and characterization of novel bio-material: Nano composites of hydroxyapatite and curcumin. International Journal of Applied Ceramic Technology, 2018. 15(1): p. 148-160. 34. Oledzka, E., et al., Selenium-Substituted Hydroxyapatite/Biodegradable Polymer/Pamidronate Combined Scaffold for the Therapy of Bone Tumour. Int J Mol Sci, 2015. 16(9): p. 22205-22. 35. Yanhua, W., et al., Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma. Colloids Surf B Biointerfaces, 2016. 140: p. 297-306. 36. Holecek, M., Muscle wasting in animal models of severe illness. Int J Exp Pathol, 2012. 93(3): p. 157-71. 37. Peter, J.C., et al., Protective effects of an anti-melanocortin-4 receptor scFv derivative in lipopolysaccharide-induced cachexia in rats. J Cachexia Sarcopenia Muscle, 2013. 4(1): p. 79-88. 38. Peng, H., et al., Synthesis and characterization of hydroxyapatite nanoparticles prepared by a high-gravity precipitation method. Ceramics International, 2015. 41(10): p. 14340-14349. 39. Hsiao, M.Y., et al., Oxidized Hyaluronic Acid/Adipic Acid Dihydrazide Hydrogel as Drug-Carrier for Cytoprotective Medications - Preliminary Results. Biomedical Engineering-Applications Basis Communications, 2019. 31(5). 40. Yang, I.H., et al., The development of laminin-alginate microspheres encapsulated with Ginsenoside Rg1 and ADSCs for breast reconstruction after lumpectomy. Bioact Mater, 2021. 6(6): p. 1699-1710. 41. Ko, I.G., et al., Aerobic Exercise Affects Myostatin Expression in Aged Rat Skeletal Muscles: A Possibility of Antiaging Effects of Aerobic Exercise Related With Pelvic Floor Muscle and Urethral Rhabdosphincter. International Neurourology Journal, 2014. 18(2): p. 77-85. 42. Kemmochi, Y., et al., Pathophysiological analyses of skeletal muscle in obese type 2 diabetes SDT fatty rats. Journal of Toxicologic Pathology, 2018. 31(2): p. 113-123. 43. Callegari, G.A., et al., Creatine Kinase and Lactate Dehydrogenase Responses After Different Resistance and Aerobic Exercise Protocols. Journal of Human Kinetics, 2017. 58(1): p. 65-72. 44. Fang, C.H., et al., Biomimetic Synthesis of Nanocrystalline Hydroxyapatite Composites: Therapeutic Potential and Effects on Bone Regeneration. International Journal of Molecular Sciences, 2019. 20(23). 45. Romanick, M., L.V. Thompson, and H.M. Brown-Borg, Murine models of atrophy, cachexia, and sarcopenia in skeletal muscle. Biochimica Et Biophysica Acta-Molecular Basis of Disease, 2013. 1832(9): p. 1410-1420. 46. Wilson, D., et al., Frailty and sarcopenia: The potential role of an aged immune system. Ageing Research Reviews, 2017. 36: p. 1-10. 47. Cesari, M., et al., Biomarkers of sarcopenia in clinical trials-recommendations from the International Working Group on Sarcopenia. Journal of Cachexia Sarcopenia and Muscle, 2012. 3(3): p. 181-190. 48. Scharf, G. and J. Heineke, Finding good biomarkers for sarcopenia. Journal of Cachexia Sarcopenia and Muscle, 2012. 3(3): p. 145-148. 49. Candow, D.G., et al., Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation. Journal of Clinical Medicine, 2019. 8(4). 50. Sumien, N., R.A. Shetty, and E.B. Gonzales, Creatine, Creatine Kinase, and Aging. Subcell Biochem, 2018. 90: p. 145-168. 51. Shibata, M., et al., High Concentration of Serum Aspartate Aminotransferase in Older Underweight People: Results of the Kanagawa Investigation of the Total Check-Up Data from the National Database-2 (KITCHEN-2). Journal of Clinical Medicine, 2019. 8(9). 52. Agrawal, A., G. Suryakumar, and R. Rathor, Role of defective Ca2+ signaling in skeletal muscle weakness: Pharmacological implications. Journal of Cell Communication and Signaling, 2018. 12(4): p. 645-659. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80335 | - |
| dc.description.abstract | 肌少症是一個會隨著年齡老化而伴隨肌肉量減少以及肌肉功能衰退之疾病。有鑑於目前治療肌少症的方式有許多副作用及效果不明顯之問題，希望能經由藥物釋放之系統來預防或治療早期肌少症的產生。薑黃素能降低肌肉發炎反應，對人體的毒性低，且副作用小。但薑黃素的口服利用率低，因此需要發展一個能乘載薑黃素的藥物載體。而氫氧基磷灰石有著良好的生物相容性，能透過控制藥物釋放的方式減少所需施打藥物的次數及頻率。因此本研究利用表面改質後之氫氧基磷灰石作為藥物載體乘載薑黃素來治療及預防早期肌少症。 在本研究中，使用共沉澱法合成氫氧基磷灰石，再利用硬脂酸進行表面改質，最後利用物理吸附乘載薑黃素(Cur-SHAP)。經由材料分析結果顯示，氫氧基磷灰石能有效乘載薑黃素，乘載量達 17.6%。合成的 Cur-SHAP 顆粒的大小為 500 到 1500 nm，這是細胞吞噬的適合大小。此外經由薑黃素釋放曲線能證明薑黃素能完全釋放並從endosome/lysosome複合物中逸出。細胞實驗中，證實Cur-SHAP 具有良好的生物相容性、抗氧化作用與抗發炎作用。動物研究的結果表明，利用LPS 誘導產生肌少症之大鼠，經由Cur-SHAP 治療後大鼠的肌肉耐力、握力和脂肪/瘦肉質量比均得到改善。綜合上述結果，我們成功合成疏水表面改質之氫氧基磷灰石，能有效乘載薑黃素並且藉由 IM 途徑給藥後，能有效減緩肌少症，在肌少症之早期治療與預防中具有應用潛力。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:04:41Z (GMT). No. of bitstreams: 1 U0001-2106202114481700.pdf: 3796145 bytes, checksum: b63a765418dbf937944ce776b236cd71 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員會審定書 # 中文摘要 i ABSTRACT ii CONTENTS iii List of Charts vi List of Tables vii Chapter 1 Introduction 1 1.1 Sarcopenia 1 1.1.1 Etiology of sarcopenia 2 1.1.2 Pathogenesis and Inflammation of Sarcopenia 3 1.1.3 Diagnostic strategy 4 1.1.4 Current Preventions and Treatment 5 1.1.5 Classification of stages of sarcopenia 7 1.2 Curcumin 7 1.2.1 Disadvantage of curcumin 9 1.3 Hydroxyapatite as drug carrier for curcumin 10 1.4 Purpose of Study 11 Chapter 2 Theoretical Basis 13 2.1 Hydroxyapatite as drug carrier 13 2.2 HAP drug release mechanism 13 2.3 Lipopolysaccharide (LPS) induced model of Sarcopenia 14 Chapter 3 Materials and methods 16 3.1 Reagents, drugs, cells and animals 16 3.2 Experiment Design 17 3.3 Synthesized of Cur-HAP 18 3.3.1 Synthesis of HAP 18 3.3.2 Surface modification of HAP (SHAP) for hydrophobicity and curcumin loading (Cur-SHAP) 19 3.4 Materials characterization and analysis 19 3.4.1 Efficiency of curcumin loading 20 3.4.2 Curcumin release profile 21 3.4.3 Internalization of Cur-SHAP by RAW-264.7 Macrophages 22 3.5 Cell viability and cytotoxicity of Cur-SHAP 22 3.5.1 Cell viability assay by WST-1 22 3.5.2 Cell cytotoxicity assay by LIVE /DEAD 23 3.6 Antioxidant activity of Cur-SHAP 24 3.6.1 Detection of Cellular ROS Generation 24 3.6.2 RNA Extraction and Gene Expression of C2C12 25 3.7 LPS-induced sarconpenia animal studies of Cur-SHAP 26 3.7.1 Animal model of rats with induced sarcopenia 26 3.7.2 Treatmail 27 3.7.3 Grip Strength Tests 27 3.7.4 MRI 28 3.7.5 Histological analysis 28 3.7.6 Blood analysis 28 3.8 Statistical Analysis 29 Chapter 4 Results and Discussion 30 4.1 Crystal Structure Identification 30 4.2 Functional Groups Identification 31 4.3 Chemical Composition and Morphology of Cur-SHAP 32 4.4 Particle Size, and Surface Area of Cur-SHAP 33 4.5 Determination of the Loading Efficiency of Curcumin 35 4.6 Release Profile of Curcumin from Cur-SHAP 35 4.7 Examination of Cur-SHAP Particles in RAW-264.7 Macrophages 37 4.8 Cytotoxicity and Cell Viability Assays 38 4.9 Antioxidant Effect of Cur-SHAP 39 4.10 Effect of Cur-SHAP on LPS-Induced Gene Expression 40 4.11 Muscle Endurance Analysis Using the Treadmill Test and Grip Strength Measurement 41 4.12 The Ratio of Fat to Lean Mass in Rat Muscle in Terms of MRI 42 4.13 Histological analysis 43 4.14 Serological analysis safety of Cur-SHAP in Vivo 44 4.15 Safety of Cur-SHAP in vivo by blood element analysis 45 Chapter 5 Discussion 47 Chapter 6 Conclusions 51 Chapter 7 References 52 " | |
| dc.language.iso | en | |
| dc.subject | 藥物遞送 | zh_TW |
| dc.subject | 薑黃素 | zh_TW |
| dc.subject | 肌少症 | zh_TW |
| dc.subject | 藥物載體 | zh_TW |
| dc.subject | 氫氧基磷灰石 | zh_TW |
| dc.subject | drug carrier | en |
| dc.subject | sarcopenia | en |
| dc.subject | curcumin | en |
| dc.subject | hydroxyapatite | en |
| dc.subject | drug delivery | en |
| dc.title | 利用氫氧基磷灰石為藥物載體長效釋放薑黃素來預防肌少症 | zh_TW |
| dc.title | Curcumin-Loaded Hydrophobic Surface-Modified Hydroxyapatite as an Antioxidant for Sarcopenia Prevention | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.author-orcid | 0000-0002-3353-1524 | |
| dc.contributor.oralexamcommittee | 黃義侑(Hsin-Tsai Liu),郭士民(Chih-Yang Tseng),劉華昌,王至弘 | |
| dc.subject.keyword | 肌少症,氫氧基磷灰石,薑黃素,藥物遞送,藥物載體, | zh_TW |
| dc.subject.keyword | sarcopenia,curcumin,hydroxyapatite,drug delivery,drug carrier, | en |
| dc.relation.page | 54 | |
| dc.identifier.doi | 10.6342/NTU202101077 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-06-25 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-06-25 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2106202114481700.pdf 未授權公開取用 | 3.71 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。