{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:30:57Z","timestamp":1760661057736,"version":"build-2065373602"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Acute myeloid leukemia (AML) is a malignant disorder characterized by the accumulation of immature myeloid cells which can be developed and exacerbated through inflammation. Interferon-\u03b2 (IFN-\u03b2) and vitamin D (Vit D) are known for their immunomodulatory and anti-proliferative effects. Key molecules like IL-1\u03b2, Gal-9, \u03b2-catenin, and NF-\u03baB play important roles in AML progression. This study examines the effects of IFN-\u03b2 alone and in combination with Vit D on U937 cell proliferation and the regulation of these key molecules.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Cell counting kit-8 (CCK-8) was applied to assess the effect of IFN-\u03b2 and Vit D on U937 cells proliferation. Real-time PCR was carried out to evaluate the impact of IFN-\u03b2 and Vit D on <jats:italic>IL-1\u03b2, IL-10, Gal-9, \u03b2-<jats:italic>catenin<\/jats:italic><\/jats:italic>, and <jats:italic>NF-\u03ba<jats:italic>B<\/jats:italic><\/jats:italic> genes. ELISA was performed to estimate the protein levels of IL-1\u03b2 and IL-10. Western-blotting was applied to evaluate the NF-\u03baB signaling pathway.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The proliferation of U937 cells reduced significantly in the presence of IFN-\u03b2, while it did not show a remarkable change following treatment with Vit D. <jats:italic>IL-1\u03b2<\/jats:italic> gene expression was reduced following either IFN-\u03b2 or Vit D treatment, while <jats:italic>IL-10<\/jats:italic> gene expression underwent a gentl increase following treatment with IFN-\u03b2, which was in contrast to Vit D treatment. IFN-\u03b2 in contrast to Vit D decreased <jats:italic><jats:italic>Gal-9<\/jats:italic><\/jats:italic> gene expression. <jats:italic>\u03b2-<jats:italic>catenin<\/jats:italic><\/jats:italic> gene expression increased after IFN-\u03b2 or Vit D treatment. <jats:italic>NF-\u03ba<jats:italic>B<\/jats:italic><\/jats:italic> gene expression reduced following either IFN-\u03b2 or Vit D treatment, except for the highest concentration of Vit D. At protein level, IFN-\u03b2 and Vit D treatment leads to a reduction of both IL-1\u03b2 and IL-10 as well as p-NF-\u03baB.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our findings suggest that IFN-\u03b2 effectively inhibits U937 cell proliferation and modulates key inflammatory and immune-related molecules involved in AML pathogenesis. These results highlight IFN-\u03b2 as a promising agent for targeting critical pathways in AML and suggest a modulatory, but less potent role for Vit D.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0330865","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:24:19Z","timestamp":1760635459000},"page":"e0330865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison the impact of IFN-\u03b2 alone or in combination with vitamin D on critical pathways involved in AML 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Hosseini","family":"Rouzbahan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalda","family":"Babaei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-5597","authenticated-orcid":true,"given":"Khodayar","family":"Ghorban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"pone.0330865.ref001","doi-asserted-by":"crossref","first-page":"101346","DOI":"10.1016\/j.genrep.2021.101346","article-title":"Association of HLA alleles with hematologic malignancies","volume":"25","author":"MH Kazemi","year":"2021","journal-title":"Gene Reports"},{"key":"pone.0330865.ref002","doi-asserted-by":"crossref","first-page":"579351","DOI":"10.3389\/fonc.2021.579351","article-title":"TIM-3 as a Prognostic Marker and a Potential 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