{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:07:08Z","timestamp":1781831228789,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":337,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005117","name":"Birjand University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Dermatology Research and Practice"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Psoriasis, as a common inflammatory skin disease, is characterized by hyperproliferation of epidermal keratinocytes and induction of an inflammatory response. Apoptosis induction and prevention of the proliferation of keratinocytes can help to treat and manage this disease. Thymoquinone (TQ), a bioactive compound with antioxidant and anti\u2010inflammatory properties, has also been reported as a natural antitumor agent. This study aimed to evaluate the effects of TQ on proliferation and apoptosis in human keratinocyte cells (HaCaT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HaCaT cells were treated with increasing concentrations of TQ (1, 2, 4, 6, 8, 16, 32, and 64\u2009\u03bcg\/mL), and cell viability was assessed using the MTT assay. Apoptosis was analyzed via flow cytometry using Annexin V\u2010FITC\/PI staining. Expression levels of p53, Bax, and BCL\u2010xl genes were measured by real\u2010time PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TQ significantly reduced cell viability in a dose\u2010dependent manner, with an IC50 of 11.64\u2009\u03bcg\/mL after 72\u2009h. Flow cytometry revealed a marked increase in early apoptotic cells following treatment with 8\u2009\u03bcg\/mL TQ (41.00%\u2009\u00b1\u20095.04%) compared to control (17.8%\u2009\u00b1\u20092.26%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009\u2264\u20090.001). Gene expression analysis showed significant upregulation of p53, while Bax and BCL\u2010xl levels showed no significant changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      TQ induces apoptosis in human HaCaT cells primarily through p53\u2010dependent pathways, suggesting its potential as a therapeutic agent for skin\u2010related disorders\n                      <jats:bold>.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/drp\/9764336","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T05:25:38Z","timestamp":1764912338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thymoquinone Inhibits Proliferation and Induces Apoptosis in Immortalized Keratinocytes via Upregulation of p53 Expression"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5586-572X","authenticated-orcid":false,"given":"Somaye","family":"Karimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8228-0953","authenticated-orcid":false,"given":"Narges","family":"Fallahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7333-2789","authenticated-orcid":false,"given":"Seyedeh Sindokht","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-9452","authenticated-orcid":false,"given":"Mohammad","family":"Fereidouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-3396","authenticated-orcid":false,"given":"Fahime","family":"Ghasemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-675X","authenticated-orcid":false,"given":"Atena","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4348-272X","authenticated-orcid":false,"given":"Nafiseh","family":"Erfanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-4242","authenticated-orcid":false,"given":"Mehdi","family":"Shakibaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7047-6221","authenticated-orcid":false,"given":"Mitra","family":"Rafiee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063132"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124214"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253734"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061475"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.5mr0120-439r"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-132448"},{"key":"e_1_2_11_7_2","doi-asserted-by":"crossref","unstructured":"JeG. 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