臺灣博碩士論文加值系統

石決明（Shijueming, SJM），是一種中國傳統中藥。於清朝時期，古籍上關於SJM的記載逐漸增加。記載SJM可用於治療皮膚損傷，特別是用於治療照料不善引起的潰瘍或外傷創口。但先前的研究仍沒有通過動物模式來驗證SJM對於促進傷口癒合的功效。另外在新穎的天然物活性研究中發現海螵蛸（Os Sepiae, OS）可以治療傷口。因此，本研究利用離體和活體模型、組織切片分析和西方點墨法來評估兩種天然物對於傷口癒合的效果。先用RAW264.7巨噬細胞（macrophages）測試抗發炎活性及吞噬作用。也利用雄性Wistar大鼠評估SJM跟OS對燒燙傷及割傷癒合的作用。最後利用蘇木精-伊紅（hematoxylin and eosin）染色、天狼星紅（picrosirius red）染色和西方點墨法（Western blotting）進行分析。結果顯示，在離體模式中SJM可以促進RAW264.7生長，而OS可以促進EA hy 926細胞移行（migration）。SJM和OS均可以降低誘導型一氧化氮合酶（inducible nitric oxide synthase, iNOS）蛋白質表現和增強巨噬細胞的吞噬作用（phagocytosis）。大鼠燒傷模型的結果顯示，相較於空白溶劑（vehicle）組，給予SJM以及OS都可以顯著促進燒燙傷老鼠之傷口癒合。SJM可以降低嗜中性粒細胞浸潤（neutrophil infiltratio），促進轉化生長因子（transforming growth factor-beta 1, TGF-β1）蛋白的表現，從而增加了Ⅰ型膠原蛋白（collagen I）含量。因此我們推測，SJM對於促進傷口癒合的機轉與巨噬細胞活化有關係，而OS促進傷口癒合的機轉則是與促血管新生有關。在發炎過程中，SJM透過抑制iNOS的表現，與促進巨噬細胞吞噬作用去除嗜中性粒細胞使發炎現象緩解。此外，SJM誘導TGF-1的分泌，在組織重塑階段可以轉換膠原蛋白促使增生。

Shijueming (SJM) is a traditional Chinese medicine. Records from 1757, in the Qing dynasty, detail the use of SJM for treating skin injuries, particularly poorly managed ulcers or traumatic wounds. However, no study has yet adopted an animal model to verify the phenomenon described in these records regarding the efficacy of SJM in promoting wound healing. In studies identifying novel bioactive materials in natural products that are useful for treating skin injuries, os sepiae (OS) extract has been reported to have a wound-healing effect. Therefore, this study used in vitro and in vivo models and performed tissue section analysis and Western blotting to evaluate the effect of SJM and OS on wound healing. RAW264.7 cells were used in antiinflammatory activity and phagocytic assays. Male Wistar rats were used to evaluate the effect of SJM and OS on burn and excision wound healing. The results were analyzed through hematoxylin and eosin staining, picrosirius red staining, and Western blotting. The results revealed that in the in vitro model, SJM promoted the phagocytic activity of RAW264.7 cells and OS promoted EA. hy 926 endothelial cell migration. Both SJM and OS reduced inducible nitric oxide synthase (iNOS) expression and enhanced macrophage phagocytosis in vitro. Compared with vehicle-treated rats, both SJM and OS significantly promoted wound healing in the rat burn injury model. Furthermore, SJM reduced neutrophil infiltration and promoted transforming growth factor-beta 1 (TGF-β1) protein expression, thus increasing the collagen I content. We suggest that the mechanism through which SJM and OS promote wound healing is related to macrophage activation and angiogenesis enhancement, respectively. In the inflammatory phase, both SJM and OS alleviate inflammation by inhibiting iNOS expression and removing neutrophils through phagocytosis. Furthermore, SJM induces TGF-β1 secretion, converting collagen during the tissue remodeling phase. These findings indicate that SJM is a promising therapeutic option for treating burn injury.

論文審定書 i
誌謝 ii
中文摘要 iii
Abstract iv
目錄 v
圖目錄 vii
縮寫表 x
一、前言 1
皮膚的組成 1
皮膚傷口癒合機制 2
臨床傷口藥物 4
傷口復原指標性反應 6
海洋中藥：石決明與海螵蛸 7
石決明 7
海螵蛸 10
石決明與海螵蛸之現代藥理機制研究進展 12
石決明 12
海螵蛸 12
傷口癒合研究之離體與活體模式 13
二、實驗材料與方法 15
(一)細胞部分 15
細胞培養 15
製備海螵蛸與石決明液 15
細胞存活率測試 15
傷口癒合細胞移動能力試驗（in vitro wound healing assay） 16
細胞樣品製備 16
西方點墨法（Western blot） 17
螢光細胞吞噬測試（phagocytic assay） 17
中性紅細胞吞噬試驗（neutral red phagocytic assay） 17
(二)動物部分 18
實驗動物準備 18
燒燙傷傷口製造 18
病理組織切片與HE染色 19
組織西方墨點法 19
實驗分組 20
數據分析 21
三、實驗結果 22
海螵蛸促進血管內皮細胞移動 22
石決明促進巨噬細胞增生 23
石決明與海螵蛸對燙傷傷口癒合速率之影響 25
石決明與海螵蛸對燙傷傷口病理組織之影響 26
石決明與海螵蛸促進燙傷傷口膠原蛋白含量之影響 27
石決明與海螵蛸對燙傷傷口蛋白質與生長因子表現量的影響 28
礦物油基質之石決明與海螵蛸促進割傷傷口癒合的效果 30
礦物油基質之石決明與海螵蛸對割傷傷口病理組織的影響 31
礦物油基質之石決明與海螵蛸促進割傷傷口膠原蛋白含量的影響 32
礦物油基質之石決明與海螵蛸對割傷傷口蛋白質與生長因子表現量的影響 32
凝膠基質之石決明與海螵蛸促進割傷傷口癒合的效果 33
凝膠基質之石決明與海螵蛸對割傷傷口病理組織的影響 33
凝膠基質之石決明與海螵蛸促進割傷傷口膠原蛋白含量的影響 34
凝膠基質之石決明與海螵蛸對割傷傷口蛋白質與生長因子表現量的影響 35
四、討論 98
五、結果總整 105
六、參考文獻 108
七、個人履歷 115
八、附錄 118

Akhoondinasab MR, Akhoondinasab M, Saberi M (2014) Comparison of healing effect of aloe vera extract and silver sulfadiazine in burn injuries in experimental rat model. World Journal of Plastic Surgery 3:29-34.
Ashkani-Esfahani S, Imanieh M, Khoshneviszadeh M, Meshksar A, Noorafshan A, Geramizadeh B, Ebrahimi S, Handjani F, Tanideh N (2012) The healing effect of arnebia euchroma in second degree burn wounds in rat as an animal model. Iranian Red Crescent Medical Journal 2012:70-74.
Atiyeh BS, Costagliola M, Hayek SN, Dibo SA (2007) Effect of silver on burn wound infection control and healing: review of the literature. Burns : journal of the International Society for Burn Injuries 33:139-148.
Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. The Journal of surgical research 153:347-358.
Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 16:585-601.
Baum CL, Arpey CJ (2005) Normal cutaneous wound healing: clinical correlation with cellular and molecular events. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al] 31:674-686; discussion 686.
Behm B, Babilas P, Landthaler M, Schreml S (2012) Cytokines, chemokines and growth factors in wound healing. J Eur Acad Dermatol Venereol 26:812-820.
Bielefeld KA, Amini-Nik S, Alman BA (2013) Cutaneous wound healing: recruiting developmental pathways for regeneration. Cellular and molecular life sciences : CMLS 70:2059-2081.
Browder W, Williams D, Lucore P, Pretus H, Jones E, McNamee R (1988) Effect of enhanced macrophage function on early wound healing. Surgery 104:224-230.
Campbell NA, Reece JB (2005) Biology. San Francisco: Pearson Education.
Chaby G, Viseux V, Poulain JF, De Cagny B, Denoeux JP, Lok C (2005) [Topical silver sulfadiazine-induced acute renal failure]. Annales de dermatologie et de venereologie 132:891-893.
Chen C, Zhao C, Wang X, Li W, Chen X (2013) Mechanism and effect of shijueming (Concha Haliotidis) on serum calcium in spontaneously hypertensive rats. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan / sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine 33:373-377.
Chen J-C, Lin B-B, Hu H-W, Lin C, Jin W-Y, Zhang F-B, Zhu Y-A, Lu C-J, Wei X-J, Chen R-J (2014) NGF accelerates cutaneous wound healing by promoting the migration of dermal fibroblasts via the PI3K/Akt-Rac1-JNK and ERK pathways. BioMed research international 2014.
Chen Q-Y, Wang G-G, Li W, Jiang Y-X, Lu X-H, Zhou P-P (2015) Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats. Journal of diabetes research 2016.
Chen W, Zhang W, Shen W, Wang K (2010) Effects of the acid polysaccharide fraction isolated from a cultivated Cordyceps sinensis on macrophages in vitro. Cellular immunology 262:69-74.
Condé-Green A, Chung TL, Holton III LH, Hui-Chou HG, Zhu Y, Wang H, Zahiri H, Singh DP (2013) Incisional negative-pressure wound therapy versus conventional dressings following abdominal wall reconstruction: a comparative study. Annals of plastic surgery 71:394-397.
Cowin AJ, Brosnan MP, Holmes TM, Ferguson MW (1998) Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse. Dev Dyn 212:385-393.
Crane NJ, Elster EA (2012) Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing. Journal of biomedical optics 17:010902.
Deuel TF, Senior RM, Huang JS, Griffin GL (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. The Journal of clinical investigation 69:1046-1049.
Dipietro LA, Reintjes MG, Low QE, Levi B, Gamelli RL (2001) Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 9:28-33.
Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJ, Angel P, Heath JK (1987) Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. The EMBO journal 6:1899-1904.
Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. The Journal of investigative dermatology 127:514-525.
Eppley BL, Woodell JE, Higgins J (2004) Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 114:1502-1508.
Escamez MJ, Garcia M, Larcher F, Meana A, Munoz E, Jorcano JL, Del Rio M (2004) An in vivo model of wound healing in genetically modified skin-humanized mice. The Journal of investigative dermatology 123:1182-1191.
Gailit J, Welch MP, Clark RA (1994) TGF-beta 1 stimulates expression of keratinocyte integrins during re-epithelialization of cutaneous wounds. The Journal of investigative dermatology 103:221-227.
Gong C, Wu Q, Wang Y, Zhang D, Luo F, Zhao X, Wei Y, Qian Z (2013) A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials 34:6377-6387.
Goto F, Goto K, Weindel K, Folkman J (1993) Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Laboratory investigation; a journal of technical methods and pathology 69:508-517.
Gottrup F, Agren MS, Karlsmark T (2000) Models for use in wound healing research: a survey focusing on in vitro and in vivo adult soft tissue. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 8:83-96.
Gugerell A, Pasteiner W, Nürnberger S, Kober J, Meinl A, Pfeifer S, Hartinger J, Wolbank S, Goppelt A, Redl H (2014) Thrombin as important factor for cutaneous wound healing: comparison of fibrin biomatrices in vitro and in a rat excisional wound healing model. Wound Repair and Regeneration 22:740-748.
Guo Sa, DiPietro LA (2010) Factors affecting wound healing. Journal of dental research 89:219-229.
Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453:314-321.
Haase I, Evans R, Pofahl R, Watt FM (2003) Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways. Journal of cell science 116:3227-3238.
Huang C, Jacobson K, Schaller MD (2004) MAP kinases and cell migration. Journal of cell science 117:4619-4628.
Hunt TK, Knighton DR, Thakral KK, Goodson WH, 3rd, Andrews WS (1984) Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 96:48-54.
Jang HJ, Tsoyi K, Kim YM, Park EJ, Park SW, Kim HJ, Lee JH, Chang KC (2013a) (S)‐1‐α‐naphthylmethyl‐6, 7‐dihydroxy‐1, 2, 3, 4‐tetrahydroisoquinoline (CKD712), promotes wound closure by producing VEGF through HO‐1 induction in human dermal fibroblasts and mouse skin. British journal of pharmacology 168:1485-1496.
Jang JK, Lee OS, Kang TJ, Lim SC (2013b) Wound healing effect of cuttlebone extract in burn injury of rat. Food Sci Biotechnol 22:99-105.
Jarrett F, Ellerbe S, Demling R (1978) Acute leukopenia during topical burn therapy with silver sulfadiazine. American journal of surgery 135:818-819.
Jeong HW, Kim IS (2004) TGF-beta1 enhances betaig-h3-mediated keratinocyte cell migration through the alpha3beta1 integrin and PI3K. J Cell Biochem 92:770-780.
Jinnin M, Ihn H, Mimura Y, Asano Y, Yamane K, Tamaki K (2005) Regulation of fibrogenic/fibrolytic genes by platelet-derived growth factor C, a novel growth factor, in human dermal fibroblasts. J Cell Physiol 202:510-517.
Johnson KE, Wilgus TA (2014) Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Advances in wound care 3:647-661.
Kaneki M, Fukushima Y, Shinozaki S, Fukaya M, Habiro M, Shimizu N, Chang K, Yasuhara S, Martyn JJ (2013) iNOS inhibitor, L-NIL, reverses burn-induced glycogen synthase kinase-3β activation in skeletal muscle of rats. Metabolism 62:341-346.
Kanitakis J (2002) Anatomy, histology and immunohistochemistry of normal human skin. European journal of dermatology : EJD 12:390-399; quiz 400-391.
Kezic S, Jakasa I (2016) Filaggrin and Skin Barrier Function. In: Skin Barrier Function, vol. 49, pp 1-7: Karger Publishers.
Kezic S, Novak N, Jakasa I, Jungersted JM, Simon M, Brandner JM, Middelkamp-Hup MA, Weidinger S (2013) Skin barrier in atopic dermatitis. Frontiers in bioscience (Landmark edition) 19:542-556.
Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, Bhasker V, Gordillo GM, Sen CK, Roy S (2010) Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One 5:e9539.
Komorowski J, Jerczyńska H, Siejka A, Barańska P, Ławnicka H, Pawłowska Z, Stępień H (2006) Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA. hy 926 cells. Life sciences 78:2558-2563.
Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA (2013) The effects of topical treatment with curcumin on burn wound healing in rats. Journal of molecular histology 44:83-90.
Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circulation research 100:782-794.
Lee DE, Ayoub N, Agrawal DK (2016) Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem cell research & therapy 7:1.
Lee HS, Kooshesh F, Sauder DN, Kondo S (1997) Modulation of TGF-beta 1 production from human keratinocytes by UVB. Exp Dermatol 6:105-110.
Lee KM, Shim H, Lee GS, Park IH, Lee OS, Lim SC, Kang TJ (2013) Chitin from the Extract of Cuttlebone Induces Acute Inflammation and Enhances MMP1 Expression. Biomol Ther 21:246-250.
Leibovich SJ, Ross R (1975) The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol 78:71-100.
Leitch IO, Kucukcelebi A, Robson MC (1993) Inhibition of wound contraction by topical antimicrobials. The Australian and New Zealand journal of surgery 63:289-293.
Li J, Chen J, Kirsner R (2007) Pathophysiology of acute wound healing. Clinics in dermatology 25:9-18.
Li X, Wu Z, Gao Y, Ho Y, Fu H (1997) [Comparision on the effects of ALI aeute liver injury of three species of concha haliotidis in mice]. Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 20:521-523.
Liang J, Kang D, Wang Y, Yu Y, Fan J, Takashi E (2015) Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats. PloS one 10:e0117106.
Lynch SE, Nixon JC, Colvin RB, Antoniades HN (1987) Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proceedings of the National Academy of Sciences of the United States of America 84:7696-7700.
Macri LK, Clark RAF (2012) An Introduction to Biomaterials. Boca Raton, US: Taylor & Fransic Group.
Mahdavian Delavary B, van der Veer WM, van Egmond M, Niessen FB, Beelen RH (2011) Macrophages in skin injury and repair. Immunobiology 216:753-762.
Martin P, Leibovich SJ (2005) Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15:599-607.
Meszaros AJ, Reichner JS, Albina JE (1999) Macrophage phagocytosis of wound neutrophils. J Leukoc Biol 65:35-42.
Meszaros AJ, Reichner JS, Albina JE (2000) Macrophage-induced neutrophil apoptosis. Journal of immunology 165:435-441.
Min LJ, Cui TX, Yahata Y, Yamasaki K, Shiuchi T, Liu HW, Chen R, Li JM, Okumura M, Jinno T, Wu L, Iwai M, Nahmias C, Hashimoto K, Horiuchi M (2004) Regulation of collagen synthesis in mouse skin fibroblasts by distinct angiotensin II receptor subtypes. Endocrinology 145:253-260.
Mirza R, DiPietro LA, Koh TJ (2009) Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol 175:2454-2462.
Nain PS, Uppal SK, Garg R, Bajaj K, Garg S (2011) Role of negative pressure wound therapy in healing of diabetic foot ulcers. Journal of surgical technique and case report 3.
Nicks BA, Ayello EA, Woo K, Nitzki-George D, Sibbald RG (2010) Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations. International journal of emergency medicine 3:399-407.
O''Kane S, Ferguson MW (1997) Transforming growth factor beta s and wound healing. Int J Biochem Cell Biol 29:63-78.
Oliveira GV, Hawkins HK, Chinkes D, Burke A, Tavares AL, Ramos-e-Silva M, Albrecht TB, Kitten GT, Herndon DN (2009) Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: type I and III collagens. International wound journal 6:445-452.
Papakonstantinou E, Aletras AJ, Roth M, Tamm M, Karakiulakis G (2003) Hypoxia modulates the effects of transforming growth factor-beta isoforms on matrix-formation by primary human lung fibroblasts. Cytokine 24:25-35.
Pasiyappazham Ramasamy, Aruldhason Barwin Vino, Ramachandran Saravanan, Namasivayam Subhapradha, Vairamani, Shanmugam, Shanmugam* A (2011) Screening of antimicrobial potential of polysaccharide from cuttlebone and methanolic extract from body tissue of Sepia prashadi Winkworth,1936. Asian Pacific Journal of Tropical Biomedicine.
Polverini PJ, Cotran PS, Gimbrone MA, Jr., Unanue ER (1977) Activated macrophages induce vascular proliferation. Nature 269:804-806.
Poon VK, Burd A (2004) In vitro cytotoxity of silver: implication for clinical wound care. Burns : journal of the International Society for Burn Injuries 30:140-147.
Ramasamy P, Subhapradha N, Shanmugam V, Shanmugam A (2014) Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury. International journal of biological macromolecules 65:559-563.
Ramasastry SS (2005) Acute wounds. Clin Plast Surg 32:195-208.
Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al. (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proceedings of the National Academy of Sciences of the United States of America 83:4167-4171.
Rodriguez LG, Wu X, Guan J-L (2005) Wound-healing assay. Cell Migration: Developmental Methods and Protocols 23-29.
Rolfe KJ, Richardson J, Vigor C, Irvine LM, Grobbelaar AO, Linge C (2007) A role for TGF-beta1-induced cellular responses during wound healing of the non-scarring early human fetus? The Journal of investigative dermatology 127:2656-2667.
Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. Journal of cellular and molecular medicine 9:267-285.
Salo T, Mäkelä M, Kylmäniemi M, Autio-Harmainen H, Larjava H (1994) Expression of matrix metalloproteinase-2 and-9 during early human wound healing. Laboratory investigation; a journal of technical methods and pathology 70:176-182.
Santoro MM, Gaudino G (2005) Cellular and molecular facets of keratinocyte reepithelization during wound healing. Experimental cell research 304:274-286.
Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738-746.
Soares MP, Seldon MP, Gregoire IP, Vassilevskaia T, Berberat PO, Yu J, Tsui TY, Bach FH (2004) Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. Journal of immunology 172:3553-3563.
Tsay T-B, Yang M-C, Chen P-H, Lin C-T, Hsu C-M, Chen L-W (2013) TNF-alpha decreases infection-induced lung injury in burn through negative regulation of TLR4/iNOS. journal of surgical research 179:106-114.
Velnar T, Bailey T, Smrkolj V (2009) The wound healing process: an overview of the cellular and molecular mechanisms. The Journal of international medical research 37:1528-1542.
Walter M, Wright KT, Fuller H, MacNeil S, Johnson WEB (2010) Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Experimental cell research 316:1271-1281.
White LA, Mitchell TI, Brinckerhoff CE (2000) Transforming growth factor beta inhibitory element in the rabbit matrix metalloproteinase-1 (collagenase-1) gene functions as a repressor of constitutive transcription. Biochim Biophys Acta 1490:259-268.
Wu L, Yu YL, Galiano RD, Roth SI, Mustoe TA (1997) Macrophage colony-stimulating factor accelerates wound healing and upregulates TGF-beta1 mRNA levels through tissue macrophages. The Journal of surgical research 72:162-169.
Xu GX, Cui LJ, Lin Y, Wu YB (2013) [Protective effect of haliotidis on the oxidative damage in the human lens epithelial cells]. [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 49:817-821.
Yamaguchi Y, Yoshikawa K (2001) Cutaneous wound healing: an update. The Journal of dermatology 28:521-534.
Zaja-Milatovic S, Richmond A (2008) CXC chemokines and their receptors: a case for a significant biological role in cutaneous wound healing. Histol Histopathol 23:1399-1407.
Zeng G, McCue HM, Mastrangelo L, Millis AJ (1996) Endogenous TGF-beta activity is modified during cellular aging: effects on metalloproteinase and TIMP-1 expression. Experimental cell research 228:271-276.
Zhao B, Liu J-Q, Zheng Z, Zhang J, Wang S-Y, Han S-C, Zhou Q, Guan H, Li C, Su L-L (2016) Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways. Cell and tissue research 1-15.