{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:36:31Z","timestamp":1773005791641,"version":"3.50.1"},"reference-count":112,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":92,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Dentistry"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Fluorouracil (5\u2010FU) is one of the most popular chemotherapeutic agents used in various cancer therapy protocols. Cell\u2010free therapy utilizing exosomes is gaining increased popularity as a safer option due to concerns over potential tumor progression following stem cell therapy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Parotid glands of albino were treated with a single bone marrow mesenchymal stem cell (BMMSC)\u2010derived exosomes injection (100\u2009\u03bcg\/kg\/dose suspended in 0.2\u2009mL phosphate\u2010buffered saline [PBS]), a single 5\u2010Fu injection (20\u2009mg\/kg), and BMMSC\u2010derived exosomes plus 5\u2010FU and compared to control group (daily saline injections). After 30 days, the parotid glands were examined using qualitative histological evaluation, immunohistochemical evaluation using rabbit polyclonal mouse antibody to Ki\u201067, caspase 3, and\n                    <jats:italic>iNOS<\/jats:italic>\n                    , as well as quantitative real\u2010time polymerase chain reaction (RT\u2010PCR) to evaluate gene expression of\n                    <jats:italic>TGF\u03b21<\/jats:italic>\n                    ,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>BCL-2<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Histological examination of the parotid gland revealed that BMMSC\u2010derived exosomes restored the glands\u2019 architecture and repaired most of the distortion created by 5\u2010FU. Immunohistochemical expression of tumor proliferation and cell death markers were restored to normal levels in the exosome\u2010treated groups that were similar to the control group. Furthermore, BMMSC\u2010derived exosomes reversed the effects of 5\u2010FU on quantitative gene expression levels and showed a significant decrease in\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) and a significant increase in\n                    <jats:italic>TGF\u03b2<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001) and\n                    <jats:italic>BCL-2<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05) when compared to 5\u2010FU treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Within the limitations of the current study, BMMSC\u2010derived exosomes have the potential to counteract the cytotoxic effects of 5\u2010FU on the parotid glands of rats in vivo. Further studies are deemed necessary to simulate clinical scenarios.\n                  <\/jats:p>","DOI":"10.1155\/ijod\/5517092","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T21:25:51Z","timestamp":1743801951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Protective Effects of MSC\u2010Derived Exosomes Against Chemotherapy\u2010Induced Parotid Gland Cytotoxicity"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-5870","authenticated-orcid":false,"given":"Mahmoud M.","family":"Bakr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-4619","authenticated-orcid":false,"given":"Mahmoud","family":"Al Ankily","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-5163","authenticated-orcid":false,"given":"Mohamed","family":"Shamel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01047-x"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcab032"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c06394"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2022.017"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.08.024"},{"key":"e_1_2_10_6_2","first-page":"E108","article-title":"Oral Signs of Intravenous Chemotherapy With 5-Fluorouracil and Leucovorin Calcium in Colon Cancer Treatment","volume":"14","author":"Mazzeo M. 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