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Background Psoriasis is an immune-mediated inflammatory skin disease, in which an interplay between infiltrating immune cells and keratinocytes sustains chronic skin inflammation. Interleukin (IL)-17A is a key inflammatory cytokine in psoriasis and its main cellular targets are keratinocytes. Objectives To explore the role of miR-378a in psoriasis. Methods Keratinocytes obtained from psoriatic skin and healthy epidermis were separated by magnetic sorting, and the expression of miR-378a was analysed by quantitative polymerase chain reaction. The regulation and function of miR-378a was studied using primary human keratinocytes. The expression of miR-378a was modulated by synthetic mimics, and nuclear factor kappa B (NF-κB) activity and transcriptomic changes were studied. Synthetic miR-378a was delivered to mouse skin in conjunction with induction of psoriasiform skin inflammation by imiquimod. Results We show that miR-378a is induced by IL-17A in keratinocytes through NF-κB, C/EBP-β and IκBζ and that it is overexpressed in psoriatic epidermis. In cultured keratinocytes, ectopic expression of miR-378a resulted in the nuclear translocation of p65 and enhanced NF-κB-driven promoter activity even in the absence of inflammatory stimuli. Moreover, miR-378a potentiated the effect of IL-17A on NF-κB nuclear translocation and downstream activation of the NF-κB pathway. Finally, injection of miR-378a into mouse skin augmented psoriasis-like skin inflammation with increased epidermal proliferation and induction of inflammatory mediators. Mechanistically, miR-378a acts as a suppressor of NFKBIA/IκBζ, an important negative regulator of the NF-κB pathway in keratinocytes. Conclusions Collectively, our findings identify miR-378a as an amplifier of IL-17A-induced NF-κB signalling in keratinocytes and suggest that increased miR-378a levels contribute to the amplification of IL-17A-driven skin inflammation in psoriasis.

N, N-Dimethylacetamide is an FDA approved solvent widely used in pharmaceutical industry to facilitate the solubility of lipophilic, high molecular weight drugs with poor water solubility. However, the cytotoxic effects of DMA raises the concern about its use in clinical applications. In the present study, we address the effect of DMA on spermatogenesis. Male Sprague Dawley rats were injected intra-peritoneally for 8 weeks, once a week at a dose of 862 mg/kg. Analysis of reproductive parameters revealed that DMA treated animals exhibit spermatid formation defects within the testis describing the characteristics of oligozoospermia. A subsequent decrease in epididymal sperm concentration along with distortion of sperm morphology was observed. The mitochondrial and microtubule organization in the sperm is considerably modified by DMA. This disrupts the sperm kinetics thus decreasing the total and progressive sperm motility. Finally, DMA treatment resulted in loss of fertility. Our results indicate that exposure to DMA has a negative impact on spermatogenesis and leads to infertility in male rats by inhibiting the post meiotic stages of sperm development. Therefore, the use of DMA in humans must be closely monitored.

Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality in patients of bilateral ocular surface disease (OSD) with incapacitating dry eye. Mycophenolate mofetil (MMF) has been found to upregulate the mucin production in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of OMEC.With informed consent, oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were cultured on human amniotic membrane (HAM) scaffold for 2 weeks. Mucin expression was quantified using RT-PCR and qPCR before and after treating cultured OMEC with MMF.Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells. Mucin mRNAs were elucidated by RT-PCR. Compared to untreated controls, MUC1, MUC15 and MUC16 mRNAs and MUC1 protein expression were found to be upregulated in MMF treated primary cultures of OMEC, as assessed by qPCR and immunocytochemistry respectively.Our findings demonstrate that MMF can act as a novel enhancer of mucin production in OMEC in vitro. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD.