Clinical and pathological study of 328 cases of actinic keratosis in eastern chinese patients.

BACKGROUND: Actinic keratosis (AK) is prevalent and has been widely studied in fair-skinned populations. However, this is not the case in eastern countries. AK in Asians has not been so thoroughly investigated. OBJECTIVES: To analyse the clinical and pathological features of a relatively large number of cases of AK diagnosed in older Chinese patients. METHODS: Case histories of 328 patients with pathologically diagnosed AK were analysed retrospectively. Their demographic, clinical, pathological and treatment data were collected for analysis of associated factors. RESULTS: Lesions were usually distributed on the face, especially the cheeks and temples. The most frequent pathological type was hypertrophic. Only 34% of the cases had been diagnosed correctly as AK before biopsy; many were mistaken for seborrhoeic keratosis. CONCLUSIONS: Most patients were elderly females and there was a higher incidence of lesions on the face, and a lower incidence on the extremities and trunk; this finding contrasts with previous investigations in fair-skinned people.

MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata.

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.

Low-concentration hydrogen peroxide can upregulate keratinocyte intracellular calcium and PAR-2 expression in a human keratinocyte-melanocyte co-culture system.

Hydrogen peroxide (H2O2) may have a biphasic effect on melanin synthesis and melanosome transfer. High H2O2 concentrations are involved in impaired melanosome transfer in vitiligo. However, low H2O2 concentration promotes the beneficial proliferation and migration of melanocytes. The aim of this study was to explore low H2O2 and its mechanism in melanosome transfer, protease-activated receptor-2 (PAR-2) expression and calcium balance. Melanosomes were fluorescein-labeled for clear visualization of their transfer. The expression of protease-activated receptor-2 (PAR-2) in keratinocytes was determined by western blot analysis. Flow cytometry was employed to evaluate the effects of H2O2 on calcium levels in keratinocytes. Fluorescence microscopy showed the upregulation of melanosome transfer into keratinocytes following 0.3 mM H2O2 treatment in the co-cultures rather than in the untreated control groups, which was associated with higher expression of PAR-2 protein and increased calcium concentration. The addition of a PAR-2 antagonist inhibited the positive activity of H2O2 and calcium flow in keratinocytes. When calcium flow was blocked by a calcium chelator, the addition of H2O2 did not increase the PAR-2 expression level in keratinocytes, therefore, inhibiting dendrite formation and melanosome transfer. Low H2O2 concentration promotes melanosome transfer with increased PAR-2 expression level and calcium concentration in keratinocytes. In addition, the interaction between melanocytes and keratinocytes is more beneficial to enhance calcium levels in keratinocytes which mediate melanin transfer. Moreover, low H2O2 concentration promotes dendrite formation, in which extracellular calcium and Par-2 were involved.

Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata.

There is mounting evidence that T helper (Th)17 cells and regulatory T cells (Treg) play parts in the pathogenesis of autoimmune disease. Hence, levels of these T-cell subsets in patients with alopecia areata (AA) merit investigation. Our goal was to assess Th17 and Treg levels in peripheral blood mononuclear cells (PBMC) and scalp lesions of patients with AA, correlating the findings with clinical characteristics. PBMC of 177 patients with AA (test group) and 42 healthy controls and scalp tissues of 33 patients and 15 healthy controls were collected. Levels of Th17 and Treg subsets were then determined via flow cytometry and immunohistochemical staining, correlating results in test subjects with clinical features of AA. Th17 levels were significantly higher in patients, whereas Treg levels were lower by comparison. Furthermore, Th17 levels in patients with disease of short duration or in the active phase were significantly higher, relative to their respective counterparts. Th17 levels also negatively correlated with disease duration. While Treg levels were higher in severe AA than in mild AA. Results of lesions were parallel to findings of PBMC. Our data indicates an imbalance in the immune state of patients with AA.