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      Call for Papers: Digital Platforms and Artificial Intelligence in Dementia

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      Challenges in Psoriasis Research: A Systematic Review of Preclinical Models

      systematic-review

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          Abstract

          Introduction: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. Methods: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. Results: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease’s research were also discussed. On the other hand , in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. Conclusions: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

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          Most cited references79

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Is Open Access

            Psoriasis Pathogenesis and Treatment

            Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
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              Pathogenesis of psoriasis and development of treatment.

              The pathogenesis of psoriasis can be explained by dysregulation of immunological cell function as well as keratinocyte proliferation/differentiation. Recently, the immunological pathomechanism has been clarified substantially. Whereas T-helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has been demonstrated that Th17 cells play a key role. Th17 development is maintained by interleukin (IL)-23 mainly produced by dendritic cells. Th17 cells produce various cytokines, including IL-17A, IL-17F and IL-22. IL-17A and IL-22 induce not only keratinocyte proliferation, but also tumor necrosis factor (TNF)-α, chemokine (C-X-C motif) ligand (CXCL)1 and CXCL8 production. TNF-α accelerates the infiltration of inflammatory cells, including lymphocytes, monocytes and neutrophils, from the peripheral blood into skin with dendritic cell activation. In addition, antimicrobial peptides are overexpressed in psoriatic skin lesions, and the antimicrobial peptide, LL-37, activates dendritic cells, which leads to the development of inflammation. Furthermore, activation of nuclear factor-κB signal induces the expression of keratins 6 and 16 in keratinocytes, which are associated with acanthosis and reduced turnover time in the epidermis. The progression of the pathomechanism contributes to the development of new therapies for psoriasis.

                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2024
                August 2024
                10 June 2024
                : 240
                : 4
                : 620-652
                Affiliations
                [a ]Cell Production and Tissue Engineering Unit, Virgen de Las Nieves University Hospital, Granada, Spain
                [b ]Biosanitary Institute of Granada (ibs.GRANADA), Granada, Spain
                [c ]Andalusian Network of Design and Translation of Advanced Therapies, Seville, Spain
                [d ]Department of Dermatology, Faculty of Medicine, University of Granada, Granada, Spain
                [e ]Department of Dermatology, Virgen de Las Nieves University Hospital, Granada, Spain
                Author notes
                *Ana Fernández-González, ana.fernandez.gonzalez@juntadeandalucia.es
                Author information
                https://orcid.org/0000-0002-3626-1558
                Article
                538993 Dermatology 2024;240:620–652
                10.1159/000538993
                38857576
                f2c100ae-430f-4b6e-86b9-8a00c555cb5f
                © 2024 S. Karger AG, Basel
                History
                : 18 November 2022
                : 15 April 2024
                Page count
                Figures: 4, Tables: 5, Pages: 33
                Funding
                The work of Ana Ubago-Rodríguez is supported by a contract within a Youth Employment program of the European Social Fund.The work of María I. Quiñones Vico is supported by a FPU predoctoral fellowship (FPU19/05455) from the Ministry of Science, Innovation and Universities of Spain.
                Categories
                Review Article

                Medicine
                Animal models,Bioengineered skin,Preclinical models,Psoriasis,Ex vivo models
                Medicine
                Animal models, Bioengineered skin, Preclinical models, Psoriasis, Ex vivo models

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