Cells, Free Full-Text
Por um escritor misterioso
Last updated 10 julho 2024
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The phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is aberrantly activated in psoriatic lesions and contributes to disease pathogenesis. Among PI3Ks enzymes, PI3Kα, β, and δ isoforms are known to bind the p85 regulatory subunit and mediate activation of AKT and other downstream effectors. In this study, we deepened our understanding of the expression and function of PI3Kδ in skin lesions of patients affected by psoriasis. For the first time, we found that PI3Kδ is overexpressed in psoriatic plaques, and its expression is not only confined to infiltrating immune cells but also accumulates in proliferating keratinocytes of the epidermal basal layer. We investigated the function of PI3Kδ in psoriatic skin by evaluating the impact of seletalisib, a newly developed selective PI3Kδ inhibitor, in both in vitro and in vivo experimental models of psoriasis. Of note, we found that PI3Kδ sustains keratinocyte hyperproliferation and impaired terminal differentiation induced by IL-22, as well as induces epithelial inflammation and resistance to apoptosis mediated by TNF-α in human keratinocytes. Mechanistically, PI3Kδ promotes PDK1 phosphorylation and signals through AKT-dependent or -independent pathways. It is worth mentioning that PI3Kδ inhibition by seletalisib attenuates the severity of psoriasiform phenotype induced in the Imiquimod-induced mouse model of psoriasis by restoring the physiological proliferation and differentiation programs in epidermal keratinocytes and contrasting the cutaneous inflammatory responses. Therefore, we suggest PI3Kδ as a potential topically druggable target in psoriasis and skin diseases characterized by epidermal hyperproliferation and skin inflammation.
IAPP/amylin-induced interaction between NLRP3 and ASC in a cell-free
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Cell-free mutant analysis combined with structure prediction of a lasso peptide biosynthetic protein B2
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Viruses, Free Full-Text
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Cancer type classification using plasma cell-free RNAs derived from human and microbes
Cell-free Macromolecular Synthesis
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Cells, Free Full-Text
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The emerging impact of cell-free chemical biosynthesis - ScienceDirect
Nature Reviews Molecular Cell Biology on X: From May cover Challenges and directions in studying cell–cell communication by #ExtracellularVesicles @DaveCarter1234 @guillaume_niel @VaderPieter Clayton Lambert & Raposo #EVsAreCool FREE pdf: https
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Remote immune processes revealed by immune-derived circulating cell-free DNA
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Cells, Free Full-Text
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Cells, Free Full-Text
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Towards reproducible cell-free systems
THE LIVES OF A CELL : LEWIS THOMAS : Free Download, Borrow, and Streaming : Internet Archive
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