{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:08:02Z","timestamp":1788851282644,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methotrexate is a widely used chemotherapeutic agent associated with significant cytotoxic side effects, including xerostomia and salivary gland dysfunction. Exosomes have recently emerged as prospective therapeutic agents owing to their capacity to transfer bioactive compounds, including nucleic acids, proteins, and lipids. Therefore, this study was conducted to evaluate the effect of systemic injection of bone marrow mesenchymal stem cell\u2010derived exosomes on submandibular glands of rats receiving Methotrexate. In this study, 36 adult albino rats were randomly divided into three groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912): Group I received phosphate\u2010buffered saline (PBS); Group II received intraperitoneal Methotrexate (40\u2009mg\/kg); and Group III received Methotrexate followed by intravenous injection of BMMSC\u2010derived exosomes (100\u2010\u03bcg\/kg\/dose suspended in 0.2\u2010mL PBS) via the tail vein after 7\u2009days. After 5\u2009weeks, rats were sacrificed, and submandibular glands were dissected out and prepared for histological and immunohistochemical examination. Statistical analysis was performed on the outcomes. Histological evaluation showed that BMMSC\u2010derived exosomes markedly restored the normal glandular architecture and repaired most of the distortion created by Methotrexate. Immunohistochemically, BCL\u20102 expression was significantly upregulated, whereas TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    expression was significantly downregulated in the treated group. Our results concluded that systemically administrated BMMSC\u2010derived exosomes exhibit therapeutic potential against Methotrexate\u2010induced cytotoxicity in the submandibular salivary glands.\n                  <\/jats:p>","DOI":"10.1002\/jat.70432","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:21:27Z","timestamp":1788848487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Role of Bone Marrow Mesenchymal Stem Cell\u2010Derived Exosomes in Methotrexate\u2010Induced Submandibular Salivary Gland Injury in Rats"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7278-2026","authenticated-orcid":false,"given":"Shrouk Essam El\u2010Dien","family":"Mohamed","sequence":"first","affiliation":[{"name":"Oral and Maxillofacial Pathology, Faculty of Dentistry Assiut University  Asyut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loay Abd Ellatef","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Pathology, Faculty of Dentistry Minia University  Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3568-8767","authenticated-orcid":false,"given":"Rahma Gamal","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Pathology, Faculty of Dentistry Assiut University  Asyut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-6304","authenticated-orcid":false,"given":"Enas Alaa Eldin Abd","family":"El\u2010Aziz","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Pathology, Faculty of Dentistry Minia University  Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.HELIYON.2020.E03789"},{"key":"e_1_2_8_3_1","volume-title":"Submandibular Sialadenitis and Sialadenosis","author":"Adhikari 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