ABSTRACT
According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
Subject(s)
Humans , Carboxylesterase/metabolism , Hydrogen Bonding , Hydrophobic and Hydrophilic InteractionsABSTRACT
<p><b>OBJECTIVE</b>To investigate the possibility of placenta mesenchymal stem cells (PMSCs) differentiation into dermal fibroblast, and the potency of PMSCs used in cutaneous wound healing and stored as seed cells.</p><p><b>METHODS</b>Enzyme digestion method was used to obtain PMSCs, and PMSCs were amplified after culture in vitro. Flow cytometry assay, osteogenic and adipogenic differentiation were done for MSCs identification. The induction medium composed of DMEM/F12 + 50 microg/ml VC + 100 ng/ml connective tissue growth factor (CTGF) was added into the 24-well plate for 16 days induction period. Pictures were taken to record morphologic change. Immunofluorescence tests were performed to detect Vimentin, FSP-1, collagen I , collagen III, desmin and laminin expression before and after induction. At the same time osteogenic and adipogenic differentiation were used to assay the differentiation ability change after induction. The induced dermal fibroblasts were frozen in liquid nitrogen and recovery and trypan blue was used to detect cell viability.</p><p><b>RESULTS</b>After CTGF induction, PMSCs got obvious fibroblasts morphology, the protein level of Vimentin, FSP-1, collagen I, collagen III and Laminin increased, PMSCs started to express Desmin, the dermal fibroblasts specific proteins, and osteogenic and adipogenic differentiation ability was diminished. PMSCs were successfully induced into dermal fibroblasts, and these induced cells could get a high cell viability ( more than 90% ) after recovery.</p><p><b>CONCLUSIONS</b>PMSCs could be induced into dermal fibroblasts by CTGF in vitro. PMSCs have the potential application in skin wound healing, and can be used as seed cells of dermal fibroblasts.</p>