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研究mPEG-ALD修饰CPU-HM的反应条件并对修饰产物的体内药效进行初步筛选。采用正交试验法,利用HPLC的面积归一化法检测各修饰条件下的修饰率,确定不同PEG修饰CPU-HM的反应条件,其中,mPEG-ALD10k修饰CPU-HM的修饰率可达83.1%,mPEG-ALD20k修饰CPU-HM的修饰率可达91.4%。通过B16F10黑色素瘤C57Bl/6黑鼠移植瘤模型检测修饰产物的体内活性,给予不同频率和剂量的mPEG-ALD10k-CPUHM(42 mg/kg)和mPEG-ALD20k-CPU-HM(79.5 mg/kg),其中mPEG-ALD10k-CPU-HM(3 d给药一次)组和mPEGALD20k-CPU-HM(2 d给药一次)组抑瘤效果较好,瘤重抑瘤率与分别达到79.34%和78.76%,与阴性组相比有极显著差异,筛选出了体内活性高,半衰期延长的修饰产物。 相似文献
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Fatuma Felix Felician Rui-He Yu Meng-Zhen Li Chun-Jie Li Hui-Qin Chen Ying Jiang Tao Tang Wei-Yan Qi Han-Mei Xu 《中华创伤杂志(英文版)》2019,22(1):12-20
Purpose: Wound represents a major health challenge as they consume a large amount of healthcare resources to improve patient''s quality of life. Many scientific studies have been conducted in search of ideal biomaterials with wound-healing activity for clinical use and collagen has been proven to be a suitable candidate biomaterial. This study intended to investigate the wound healing activity of collagen peptides derived from jellyfish following oral administration.
Methods: In this study, collagen was extracted from the jellyfish–Rhopilema esculentum using 1% pepsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fourier transform infrared (FTIR) were used to identify and determine the molecular weight of the jellyfish collagen. Collagenase II, papain and alkaline proteinase were used to breakdown jellyfish collagen into collagen peptides. Wound scratch assay (in vitro) was done to determine migration potential of human umbilical vein endothelial cells (HUVEC) covering the artificial wound created on the cell monolayer following treatment with
collagen peptides. In vivo studies were conducted to determine the effects of collagen peptides on wound healing by examining wound contraction, re-epithelialization, tissue regeneration and collagen deposition on the wounded skin of mice. Confidence level (p < 0.05) was considered significant using GraphPad Prism software.
Results: The yield of collagen was 4.31%. The SDS-PAGE and FTIR showed that extracted collagen from jellyfish was type I. Enzymatic hydrolysis of this collagen using collagenase II produced collagen peptides (CP1) and hydrolysis with alkaline proteinase/papain resulted into collagen peptides (CP2). Tricine SDSPAGE revealed that collagen peptides consisted of protein fragments with molecular weight <25 kDa. Wound scratch assay showed that there were significant effects on the scratch closure on cells treated with collagen peptides at a concentration of 6.25 mg/mL for 48 h as compared to the vehicle treated cells.
Overall treatment with collagen peptide on mice with full thickness excised wounds had a positive result in wound contraction as compared with the control. Histological assessment of peptides treated mice models showed remarkable sign of re-epithelialization, tissue regeneration and increased collagen deposition. Immunohistochemistry of the skin sections showed a significant increase in b-fibroblast growth factor (b-FGF) and the transforming growth factor-b1 (TGF-b1) expression on collagen peptides treated group.
Conclusion: Collagen peptides derived from the jellyfisheRhopilema esculentum can accelerate the wound healing process thus could be a therapeutic potential product that may be beneficial in wound clinics in the future. 相似文献
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