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The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma ( Gastrodia elata Blume ), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N -methyl- d -aspartate (NMDA) receptors, and Ca 2 + /calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC). The GluN2A and GluN2B subunits of NMDA receptors, the GluR1 type of AMPA receptor, and CaMKII-α are key molecules responsible for neuroplasticity involved in chronic pain and the accompanying anxiety. Moreover, GAS administration reduced the activation of astrocyte and microglia and the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Therefore, GAS administration relieved chronic pain, exerted anxiolytic effects by regulating neuroplasticity molecules, and attenuated the inflammatory response by reducing the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. [ABSTRACT FROM AUTHOR]

• WTAP was highly expressed in the epidermis rather than the dermis in psoriasis. • WTAP promoted keratinocytes proliferation. • WTAP accelerated cell cycle progression of keratinocytes by regulating CDK2 and cyclinA2. Wilms' tumor 1-associating protein (WTAP) is a ubiquitously expressed nuclear protein, and involved in multiple pathophysiological processes, including cell cycle, RNA splicing and stabilization, N6-methyladenosine RNA modification, cell proliferation, and apoptosis as well as embryonic development. Here, we investigated the specific role of WTAP in the pathogenesis of psoriasis and its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analyses and multi-spectrum immunohistochemistry were applied to evaluate the level of WTAP expression in psoriatic skin and normal skin. HaCaT cells was stably transfected with WTAP small interfering (si)RNA and plasmid using Lipofectamine®2000 and proliferation was determined by CCK8. Apoptosis and cell cycle analysis were conducted by flow cytometry. Western blot assay was used to explore the expression levels of cell cycle-related proteins in HaCaT cells after WTAP overexpression or inhibition. Furthermore, HaCaT cells were stimulated with proinflammatory cytokines (ie, IL-17A, IL-22, IL-1a, oncostatin M, and TNF-a) to assess WTAP expression. We demonstrated that the mRNA and protein levels of WTAP were significantly increased in lesional skins of psoriasis patients and psoriatic cell model compared with normal controls. WTAP was highly expressed in epidermis rather than dermis. Overexpression of WTAP promoted keratinocytes proliferation, which might be related to the up-regulation of cyclinA2 and CDK2. These results indicate that overexpression of WTAP may contribute to the pathogenesis of psoriasis by regulating cell cycle progression and highlight WTAP as a potential therapeutic target for psoriasis treatment. [ABSTRACT FROM AUTHOR]