Therapeutic targeting of mechanical stretch-induced FAK/ERK signaling by fisetin in hypertrophic scars.

Hypertrophic scarring is a complex fibrotic disease with few treatment options. Mechanical stress has been proven to be crucial for hypertrophic scar (HS) formation. Here, we showed that the flavonoid small molecule fisetin, could dramatically ameliorate HS formation in a mechanical stretch-induced mouse model. In addition, in vitro and in vivo studies demonstrated that fisetin inhibited the stretch-induced profibrotic effects by suppressing the proliferation, activation, and collagen production of fibroblasts. Mechanistically, we revealed that fisetin obviously downregulated mechanical stretch-induced the phosphorylation of FAK and ERK, and reduced nuclear localization of ERK. This bioactivity of fisetin may result from its selective binding to the catalytic region of FAK, which was suggested by the molecular docking study and kinase binding assay. Taken together, these findings suggest that fisetin is a promising agent for the treatment of hypertrophic scars and other excessive fibrotic diseases.

IL-21 Induces an Imbalance of Th17/Treg Cells in Moderate-to-Severe Plaque Psoriasis Patients.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood. Methods: IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4+ T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis. Results: IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients. Conclusion: Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.

Effects of recombinant human parathyroid hormone (1-34)on cell proliferation, chemokine expression and the Hedgehog pathway in keratinocytes.

Psoriasis is an autoimmune disease involving the excessive proliferation of keratinocytes mediated by T­cells. Parathyroid hormone (PTH) has been identified as an essential factor in the treatment of psoriasis. In the present study, the mechanism underlying the effect of recombinant human parathyroid hormone (rhPTH) (1­34) in keratinocytes was investigated. The effects of rhPTH (1­34) on cell proliferation, cell cycle, and the secretion and expression of C­X­C motif chemokine 11 (CXCL11) and components of the Hedgehog signaling pathway were examined in HaCaT cells by MTT assay, flow cytometric analysis, ELISA and gene chip analysis. The data showed that rhPTH (1­34) significantly inhibited keratinocyte proliferation at concentrations >8x10­7 mol/l. rhPTH (1­34) induced G1 phase arrest of the cell cycle in the keratinocytes. The secretion of CXCL11 in tumor necrosis factor (TNF)­α­induced keratinocytes was downregulated by rhPTH (1­34) in a dose­dependent manner, compared with that in keratinocytes treated with TNF­α alone. It was also found that rhPTH (1­34) inhibited the expression of CXCL11 in the HaCaT cells. rhPTH (1­34) also affected the Hedgehog signaling pathway specifically by regulating the expression of associated genes. In conclusion, these data suggested that rhPTH (1­34) inhibited cell proliferation, and the secretion and expression of CXCL11 in HaCaTs. rhPTH (1­34) also altered the expression of associated genes in the Hedgehog pathway. Therefore, rhPTH (1­34) can be considered as a novel therapeutic agent for the treatment of psoriasis.

Norwegian scabies in a patient treated with Tripterygium glycoside for rheumatoid arthritis.

We report an 80-year-old male patient with severe rheumatoid arthritis who was treated with tripterygium glycoside, an immunosuppressive agent made from the extract of a Chinese medicinal herb called Tripterygium wilfordii Hook F. The patient had no apparent skin lesions before the treatment, but he developed aggressive hyperkeratotic lesions with rapid progression after using tripterygium glycoside. He was repeatedly diagnosed with eczema, but treatment failed to achieve efficacy. Interestingly, a microscopic examination of the lesions revealed numerous scabies mites and eggs. Thus, we confirmed the diagnosis of Norwegian scabies infection. Treated with crotamiton 10% cream and 10% sulfur ointment for one month, the patient's clinical symptoms disappeared.

Norwegian scabies in a patient treated with Tripterygium glycoside for rheumatoid arthritis

Abstract: We report an 80-year-old male patient with severe rheumatoid arthritis who was treated with tripterygium glycoside, an immunosuppressive agent made from the extract of a Chinese medicinal herb called Tripterygium wilfordii Hook F. The patient had no apparent skin lesions before the treatment, but he developed aggressive hyperkeratotic lesions with rapid progression after using tripterygium glycoside. He was repeatedly diagnosed with eczema, but treatment failed to achieve efficacy. Interestingly, a microscopic examination of the lesions revealed numerous scabies mites and eggs. Thus, we confirmed the diagnosis of Norwegian scabies infection. Treated with crotamiton 10% cream and 10% sulfur ointment for one month, the patient's clinical symptoms disappeared.