{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:49:13Z","timestamp":1791449353872,"version":"4.3.3"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation, altered differentiation, barrier dysfunction, and oxidative stress. Currently available therapies, including monoclonal antibodies and JAK inhibitors, have improved AD management but do not address all aspects of the disease, supporting the investigation of natural\u2010product strategies as complementary approaches to long\u2010term care. An acute in\u00a0vitro model of canine atopic\u2010like inflammation was established by exposing canine progenitor epidermal keratinocytes (CPEK) for 24\u2009h to a defined cytokine cocktail (IFN\u2010\u03b3, IL\u20104, IL\u201013), followed by 24\u2009h of treatment with hemp oil, blackcurrant seed oil, vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , or their combination. Proliferation (Ki\u201067, cell\u2010cycle), differentiation (KRT5, KRT10, TGM1, involucrin), tight\u2010junction organization (CLDN1, TJP1, ZO\u20101, TEER), wound closure, nitrosative stress (3\u2010nitrotyrosine), the NRF2\/BACH1\/HMOX1 axis, and the secretion of STAT1\u2010 and NF\u2010\u03baB\u2010dependent inflammatory mediators (CXCL9, CXCL10, IL\u20108, IL\u20106) and the STAT6\u2010targeted chemokine CCL17 were assessed. The cytokine cocktail induced a coherent AD\u2010like phenotype: increased Ki\u201067, downregulated CLDN1, sustained nitrosative stress, NRF2 elevation paralleled by BACH1 induction, and robust secretion of STAT1\u2010 and NF\u2010\u03baB\u2010dependent mediators. The four treatments modulated this phenotype according to clearly differential, pathway\u2010specific profiles. Vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , alone or combined, emerged as the most effective modulator of proliferation and acted preferentially on the downstream redox arm, inducing HMOX1 and reducing BACH1; both vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    \u2010containing formulations exerted broad anti\u2010inflammatory activity across the STAT1 and NF\u2010\u03baB axes. Hemp oil acted preferentially on tight\u2010junction integrity (CLDN1 recovery), on the upstream NRF2 arm (NFE2L2 induction), on the STAT1 chemokine arm (CXCL9, CXCL10 reduction), and on wound closure. Blackcurrant seed oil acted preferentially on NF\u2010\u03baB\u2010dependent IL\u20108 and on early wound\u2010closure dynamics. This differential pharmacological footprint provides a rational basis for further investigation of these formulations as nutraceutical adjuncts in canine AD.\n                  <\/jats:p>","DOI":"10.1002\/biof.70137","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:21:32Z","timestamp":1786422092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Modulation of Keratinocyte Proliferation, Differentiation, and Barrier Function by Hemp Oil, Blackcurrant Seed Oil, and Vitamin D\n                    <sub>3<\/sub>\n                    Under Atopic\u2010Associated Cytokine Stimulation"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-9023","authenticated-orcid":false,"given":"Daniel","family":"Tortolani","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"},{"name":"European Center of Brain Research\/Fondazione Santa Lucia IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Scipioni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"},{"name":"European Center of Brain Research\/Fondazione Santa Lucia IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0448-3570","authenticated-orcid":false,"given":"Alessandro","family":"Anselmucci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-8628","authenticated-orcid":false,"given":"Francesca","family":"Ciaramellano","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"},{"name":"European Center of Brain Research\/Fondazione Santa Lucia IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meri","family":"Di Leonardo","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale di Teramo  Teramo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isa","family":"Fusaro","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-698X","authenticated-orcid":false,"given":"Sergio","family":"Oddi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"},{"name":"European Center of Brain Research\/Fondazione Santa Lucia IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-0239","authenticated-orcid":false,"given":"Alessandro","family":"Gramenzi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Teramo  Teramo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/vde.12965"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/vde.13210"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/vde.13215"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/vde.13192"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/vde.13300"},{"issue":"1","key":"e_1_2_8_7_1","first-page":"46","article-title":"Tight Junction Proteins in the Canine Epidermis: A Pilot Study on Their Distribution in Normal and in High IgE\u2010Producing Canines","volume":"79","author":"Roussel A. 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