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Yue Shen,Matthew R. Zeglinski,Christopher T. Turner,Sheetal A. Raithatha,Zhenguo Wu,Valerio Russo,Cameron Oram,Sho Hiroyasu,Layla Nabai,Hongyan Zhao,Tatjana Bozin,Kathryn Westendorf,Irina Kopko,Rachel 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Granzyme B (GzmB) is a serine protease that has long been thought to function exclusively in lymphocyte-mediated apoptosis. In recent years, this paradigm has been revisited due to the recognition that GzmB accumulates in the extracellular milieu in many autoimmune and chronic inflammatory disorders, and contributes to impaired tissue remodeling due to the cleavage of extracellular matrix proteins. Knockout studies suggest that GzmB-mediated cleavage of decorin (DCN) contributes to impaired collagen fibrillogenesis and remodeling. As DCN is anti-fibrotic and contributes to reduced hypertrophic scarring, GzmB-induced DCN cleavage could play a role in wound healing following burn injury. In the present study, a novel, gel-formulated, first-in-class small-molecule inhibitor of GzmB, VTI- 1002, was assessed in a murine model of impaired, diabetic burn wound healing. VTI-1002 exhibited high specificity, potency, and target selectivity. Gel-formulated VTI-1002 was able to penetrate the stratum corneum and was retained in the skin with minimal systemic absorption. Daily topical administration of VTI-1002 gel for 30 days following thermal injury showed significantly accelerated wound closure, increased DCN protein levels, and collagen organization that was translated into significantly increased wound tensile strength compared to controls. Overall, VTI-1002 gel was well-tolerated in vivo and no adverse events were observed. Topical application of VTI-1002 represents a novel therapeutic approach for the treatment of cutaneous burn wounds.
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Yanli Liu,Yan Xia,Pan Guo,Guiping Wang,Zhenguo Shen,Yingchun Xu,Yahua Chen 한국원예학회 2013 Horticulture, Environment, and Biotechnology Vol.54 No.4
The effects of environmental factors on the paeonol accumulation in cortex moutan of herbal Paeonia suffruticosa cv. Fengdan were investigated. Cortex moutan of ‘Fengdan’ and the corresponding soil samples were collected from Tongling (Anhui Province, China). A pot experiment was also conducted to investigate the responses of plant growth and paeonol concentrations to copper (Cu) supply. The paeonol and Cu concentrations in cortex moutan samples, the basic soil properties and soil’s bacterial diversity were analyzed. The results showed that moderate levels of Cu in the soil enhanced the paeonol concentration in the cortex moutan. Moreover, the paeonol concentration was related significantly to soil bacterial diversity. The results of the pot experiment showed that increasing Cu supply from 63 to 263 mg·kg-1 did not produce any significant effect on the dry weight of ‘Fengdan’ cortex moutan,duramen, and total plant. Increasing Cu supply significantly increased the concentrations of paeonol in cortex moutan and duramen; but at 263 mg·kg-1 Cu there was a slight decline in their concentrations than those obtained at 156mg·kg-1 Cu. In all treatments, the concentrations of paeonol were much higher in the cortex moutan than those in the duramen. Due to its ecological benefits, ‘Fengdan’ can be planted in soil contaminated with moderate Cu.
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