{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:59:30Z","timestamp":1791388770577,"version":"4.3.3"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/4\/2\u20103\/OH\/2022\u2010NCD\u2010II"],"award-info":[{"award-number":["5\/4\/2\u20103\/OH\/2022\u2010NCD\u2010II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral submucous fibrosis is a progressive, oral potentially malignant condition that can affect the oral cavity and is often linked to areca nut consumption. This study aimed to investigate the potential of dental pulp mesenchymal stem cells secretome (DPMSCs\u2010S) in the reversal of areca nut\u2010induced fibrosis in human fibroblast cells and patient\u2010derived buccal mucosa tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The cytokine and growth factor levels in DPMSCs\u2010S were analyzed by flow cytometry. Cytotoxicity and apoptotic features were analyzed using a cell viability assay and microscopy, respectively. Cellular senescence and reactive oxygen species generation were assessed in human fibroblast cells using a \u03b2\u2010galactosidase assay and 2\u2032,7\u2032\u2010dichlorodihydrofluorescein diacetate probe, respectively. Fibrosis\u2010related gene expression (COL15A1, COL1, COL3, \u03b1\u2010SMA, TGF\u03b21, and TGF\u03b22) and protein expression (COL1 and Ki67) were assessed by RT\u2010PCR and fluorescence microscopy, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Areca nut extract and arecoline resulted in a dose\u2010dependent reduction in cell viability. Secretome treatment reduced cell death, apoptotic and senescent features in fibroblast cells exposed to areca nut extract and arecoline, decreased ROS levels, and significantly downregulated areca nut\u2010induced fibrotic gene expressions (COL15A1, COL3, \u03b1\u2010SMA, TGF\u03b22), and protein expression of COL1. Heat\u2010inactivated secretome retained the activity, implying the involvement of heat\u2010stable biomolecules in the reversal of fibrosis. Ex\u00a0vivo results corroborated these findings, with reduced expression of COL15A1, COL3, and \u03b1\u2010SMA in buccal tissues from oral submucous fibrosis patients treated with DPMSCs\u2010S.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Secretome exhibited promising cytoprotective and anti\u2010fibrotic properties, reduction in cell death, senescence, collagen expression, and oxidative stress. These findings support the potential of secretome as a novel therapeutic candidate for oral submucous fibrosis, meriting further investigation in preclinical and clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70090","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T08:22:46Z","timestamp":1764145366000},"page":"317-330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Stem Cell Secretome Reverse Areca Nut Extract Induced Fibrosis in Human Fibroblast and Patient\u2010Derived Biopsies"],"prefix":"10.1111","volume":"55","author":[{"given":"Pranjali","family":"Potdar","sequence":"first","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Kheur","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"},{"name":"Department of Oral Maxillofacial Pathology &amp; Oral Microbiology, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Sanap","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-2056","authenticated-orcid":false,"given":"Ramesh","family":"Bhonde","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant","family":"Mante","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Kharat","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Pande","sequence":"additional","affiliation":[{"name":"Launceston General Hospital  Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyashri","family":"Takbhate","sequence":"additional","affiliation":[{"name":"Central Research Facility, Dr. D. Y. Patil Medical College, Hospital and Research Centre Dr. D. Y. Patil Vidyapeeth  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitika","family":"Monga","sequence":"additional","affiliation":[{"name":"Division of Development Research, Indian Council of Medical Research Headquarters  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/JCM11071793"},{"issue":"6","key":"e_1_2_12_3_1","first-page":"985","article-title":"Oral Submucous Fibrosis: Etiology, Pathogenesis, and Future Research","volume":"72","author":"Rajendran R.","year":"1994","journal-title":"Bulletin of the World Health Organization"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100714.2012.01168.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.9.1527"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26805"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ODI.15065"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.07.017"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MEHY.2020.110204"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222112018"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/340257"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626\u2010020\u201000481\u20102"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010022\u201001760\u20106"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.18053\/jctres.08.202204.007"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/STEM.3165"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCYT.2024.12.013"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ACS.JAFC.6B05140"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S377502"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12032\u2010022\u201001673\u20104"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.7759\/CUREUS.43739"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24044004"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12370"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129252"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970\u20109290.57356"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDS.2015.04.002"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12186"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378\u20104274(02)00504\u20100"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00784\u2010010\u20100464\u20100"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11050868"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.4103\/jomfp.JOMFP"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910808701111"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS20122940"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061328"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/WOUND.2013.0466"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0429"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/PATH.4104"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/WOUND.2014.0581"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.5005\/jp\u2010journals\u201010001\u20101141"},{"issue":"4","key":"e_1_2_12_39_1","first-page":"279","article-title":"Areca Nut (Areca Catechu Linn.) Extract Induces Cell Cycle Arrest and Reduces Ki\u201067 Activity in Oral Squamous Cell Carcinoma Cells","volume":"2021","author":"Meutia Sari L.","year":"2021","journal-title":"Journal of Research in Medical and Dental Science"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008078"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2023.105644"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12951\u2010023\u201001921\u20103"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI.INSIGHT.128060"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/SCD.2012.0304"}],"container-title":["Journal of Oral Pathology &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jop.70090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jop.70090","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jop.70090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:44:27Z","timestamp":1773002667000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jop.70090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/jop.70090"],"URL":"https:\/\/doi.org\/10.1111\/jop.70090","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JOP.70090\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v3\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.70090\/v3\/decision1","asserted-by":"object"}]},"ISSN":["0904-2512","1600-0714"],"issn-type":[{"value":"0904-2512","type":"print"},{"value":"1600-0714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"assertion":[{"value":"2024-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}