ABSTRACT
Background@#We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. @*Objective@#To explore the role and mechanism of miR-1246 in severe AA. @*Methods@#Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. @*Results@#miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. @*Conclusion@#miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.
ABSTRACT
Objective To investigate the efficacy and tolerability of a recombinant human tumor necrosis factor:Fc fusion protein (rhTNFR:Fc,with a trade name of Yisaipu) in the treatment of moderate to severe psoriasis vulgaris.Methods A multicentre,randomized,double blind,and parallel-controlled trial was performed.One hundred and forty-four patients with moderate to severe psoriasis vulgaris from four centres were randomly assigned and treated with either once-weekly subcutaneous injection of rhTNFR:Fc (50 mg) or oral methotrexate (MTX)(7.5 mg) for 12 weeks.Patients were followed up at 2,4,8,12 weeks after the treatment.Results One hundred and twenty-four patients finished the 12-week course of treat- ment.At 12 weeks after the treatment,a 50%,75%,90% improvement in psoriasis area and severity index (PASI) was achieved by 86.11%,76.39%,52.78% respectively of rhTNFR:Fc-treated patients,and by 63.89%,44.44%,22.22% respectively in MTX-treated patients,and all the three improvement rates were of significant difference between the two groups of patients (all P0.05).Conclusion Compared with MTX,rhTNFR:Fc acts more quickly with a higher cure rate and less toxic reactions in the treatment of psoriasis vulgaris.