{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:09:14Z","timestamp":1760058554159,"version":"build-2065373602"},"reference-count":167,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Foundation for Cancer Research","award":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"],"award-info":[{"award-number":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"]}]},{"name":"Italian Ministry of University and Research","award":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"],"award-info":[{"award-number":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"]}]},{"name":"Next Generation EU","award":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"],"award-info":[{"award-number":["IG20736","2022KME7RY","P20224ZY5P","PNC 0000001 D34Health"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, and colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression of pro-inflammatory cytokines\/chemokines and the recruitment of immune cells into the inflamed mucosa. However, emerging evidence indicates that BUD, unlike classical glucocorticoids, is also a potent modulator of stem and cancer cell behavior\/plasticity. Certainly, BUD stabilizes cell\u2013cell adhesions, preventing embryonic stem cell differentiation and inhibiting the development of 3D gastruloids. In addition, BUD inhibits the motile\/invasive propensity of different cancer cells, including breast, lung, and pancreatic cancer. Finally, it prevents the infection of positive single-stranded human-infecting RNA viruses such as SARS-CoV-2. At a molecular level, BUD induces epigenetic changes and modifies the transcriptome of epithelial, stem, and cancer cells, providing molecular support to the immune cell-independent activity of BUD. Here, we performed an in-depth review of these unexpected activities of BUD, identified by unbiased drug screening programs, and we emphasize the molecular mechanisms modulated by this efficacious drug that deserve further research.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040504","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T03:45:23Z","timestamp":1744343123000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Modulation of Cell Plasticity by Budesonide: Beyond the Metabolic and Anti-Inflammatory Actions of Glucocorticoids"],"prefix":"10.3390","volume":"17","author":[{"given":"Eduardo Jorge","family":"Patriarca","sequence":"first","affiliation":[{"name":"Stem Cell Fate Laboratory, Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"D\u2019Aniello","sequence":"additional","affiliation":[{"name":"Stem Cell Fate Laboratory, Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"De Cesare","sequence":"additional","affiliation":[{"name":"Stem Cell Fate Laboratory, Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-2272","authenticated-orcid":false,"given":"Gilda","family":"Cobellis","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-9043","authenticated-orcid":false,"given":"Gabriella","family":"Minchiotti","sequence":"additional","affiliation":[{"name":"Stem Cell Fate Laboratory, Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199505183322008","article-title":"The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation","volume":"332","author":"Chrousos","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_2","first-page":"5","article-title":"History of the development of corticosteroid therapy","volume":"29","author":"Benedek","year":"2011","journal-title":"Clin. Exp. Rheumatol"},{"key":"ref_3","first-page":"167","article-title":"Budesonide: A new corticosteroid in bronchial asthma","volume":"61","author":"Hansson","year":"1980","journal-title":"Eur. J. Respir. 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