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Mengjiao Wang,1 Liqing Chen,2 Wei Huang,2 Mingji Jin,2 Qiming Wang,2 Zhonggao Gao,2 Zhehu Jin1 1Klebs Research Center, Department of Dermatology, Yanbian University Hospital, Yanji 133000, China; 2State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China Background: Keloids represent benign fibroproliferative tumors which result from elevated expression of inflammation. Paclitaxel (PTX) was an effective chemotherapeutic agent and has been reported to have anti-fibrotic effects, but the strong hydrophobicity brings a challenge for its clinical application. Purpose: The objective of this study was to improve the water solubility of PTX and investigate its anti-keloid effects. Methods: We prepared a PTX-cholesterol-loaded liposomes (PTXL) by thin film evaporation fashion and characterized their physicochemical properties. We also investigated the effects of PTX on proliferation, invasion and fibrosis of keloid fibroblasts in vitro and in vivo. Results: The prepared PTXL have a spherical appearance, a particle size of 101.43 nm and a zeta potential of -41.63 mV. PTXL possessed a high drug entrapment efficiency of 95.63% and exhibited a good stability within 30 days. The drugs in PTXL were released in a slow and sustained mode. The PTXL could be effectively uptaken into human keloids fibroblast (HKFs) in a time-dependent manner. In vitro, PTXL showed better ability on inhibiting cell proliferation, migration and invasion, and effectively on promoting apoptosis and arresting cell cycle in G2/M phase compared to PTX. Meanwhile, in vivo studies indicated that the PTXL had better performance on inhibiting the keloids growth compared to the PTX in keloid-bearing BALB/c nude mice model. Finally, we found PTX treatment suppressed the production of tumor necrosis factor alpah (TNF-α), interleukin 6 (IL-6) and transforming growth factor beta (TGF-β) and inhibited the expression of alpha smooth muscle actin (β-SMA) and collagen I in HKFs. The activation of protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) signaling pathway also blocked by PTX in cultured HKFs and keloid tissues. LY294002, a PI3K (phosphatidylinositol 3-kinase)/AKT inhibitor, also suppressed the expression of TNF-α, IL-6 and TGF-β, and simultaneously, reduced the production of α-SMA and collagen I in HKFs. The inhibition of AKT/GSK3β signaling pathway contribute to inhibit the generation of fibrogenic cytokines by PTXL on ameliorating fibrosis progress in keloids. Conclusion: Our results suggested that the developed PTXL would become a promising therapeutic agent in the field of anti-keloid therapy. Keywords: keloids, paclitaxel, liposomes, AKT, GSK3β, fibrosis

Zhouna Li, Zhehu Jin Department of Dermatology, Yanbian University Affiliated hospital, Yanji, Jilin, People’s Republic of China Background: Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars.Methods: Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis.Results: Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions.Conclusion: There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to confirm our conclusion. Keywords: keloids, hypertrophic scars, verapamil, steroids, IPL