Hypertrophic scars (HS) are skin disorders which occur after wounding and thermal injury. Our previous studies have suggested that secreted frizzled-related protein 2 (SFRP2) is involved in HS formation and that the suppression of SFRP2 promotes apoptosis of hypertrophic scar fibroblasts (HSFBs). However, the mechanisms have not been clarified. Previous studies revealed that Slug expression inhibits cell apoptosis, in vitro and in vivo, and SFRP2 regulates the expression of Slug in cervical cancer cells. In the present study, we quantified differential expression levels of expression of SFRP2 and Slug in HS and normal skin tissues by immunohistochemistry, both of which have important anti-apoptosis roles. Furthermore, a short hairpin RNA approach was adopted to investigate the potential function of SFRP2 and Slug in HSFB apoptosis. Cell apoptosis was detected using fluorescence-activated cell sorting and Caspase-3 activity was assayed by spectrophotometry. This study demonstrates that SFRP2 expression, as well as Slug, is dramatically up-regulated in HS relative to normal skin tissues, and the Slug expression is positively correlated with SFRP2. Slug expression was down-regulated in SFRP2-deficient cells, and the down-regulation of Slug expression increased sensitivity to apoptosis which was induced through a caspase-3-dependent pathway. The infected cells with reduced levels of Slug were tested for the expression of apoptosis-related genes (Bcl-2, Bax and PUMA) which were previously identified as Slug targets. Bcl-2 expression was down-regulated in Slug-deficient cells. In conclusion, SFRP2 appears to interact with Slug to affect the apoptosis of hypertrophic scar fibroblasts.

Xanthine oxidase (XO) is an important target for the treatment of hyperuricemia (HUA), which mediates the production of uric acid (UA). The mechanism of action between flavonoids and XO in cell biology and structural bioinformatics has not been fully explored. In this study, 160 flavonoids were extensively screened and evaluated for their XO inhibitory activity in vitro. Molecular docking and molecular dynamics (MD) simulation were further used to explore the interaction mechanism between flavonoids and XO. The diosmetin, luteolin, and kaempferol were innovatively found to inhibit the UA production of AML12 cells in a time-and dose-dependent manner, in which the IC 50 is 6.56, 8.92, and 10.46 μM, respectively. Combined with the MD simulations of the complexes of flavonoids and XO, results showed that flavonoids bind the Mo-molybdopterin domain of XO mainly through hydrogen bonding and hydrophobicity. Lys772 and Thr1011 were the key sites to enhance the inhibitory activity of XO.

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