{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:44:36Z","timestamp":1792071876574,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000576","name":"British Society for Oral and Dental Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000576","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012295","name":"NIHR Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp; Exp Dental Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate how soluble byproducts derived from a four\u2010species endodontic biofilm model impact the viability, transcriptomic profile, and inflammatory response of human dental pulp stem cells (DPSCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A sterile\u2010filtered supernatant was extracted from an established interkingdom endodontic biofilm model comprising\n                      <jats:italic>Streptococcus gordonii<\/jats:italic>\n                      ,\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      ,\n                      <jats:italic>Porphyromonas gingivalis,<\/jats:italic>\n                      and\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      . DPSCs were exposed to the microbial biofilm supernatant (BSN) for 4 and 24\u2009h. Cellular responses were evaluated via MTT, CCK\u20108, LDH assays, and Annexin V\/PI staining. Transcriptomic sequencing was performed to assess gene expression dynamics, with GO and KEGG pathway enrichment analyses. IL6 and IL8 expression was validated by qPCR and ELISA. Data were analyzed using t\u2010tests\/ANOVA and RNA\u2010seq differential expression using DESeq. 2 with FDR adjustment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BSN significantly suppressed DPSC metabolic activity without inducing apoptosis or necrosis. RNA\u2010seq revealed 723 significantly differentially expressed genes at 4\u2009h and 1667 at 24\u2009h. Early responses were dominated by upregulation of inflammatory mediators, with enrichment of TNF, NF\u2010\u03baB, and JAK\u2010STAT signaling pathways. At 24\u2009h, the expression profile shifted toward redox regulation and metabolic suppression, including downregulation of glycolytic and purine metabolism pathways. IL6 and IL8 expression was markedly increased at both transcript and protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Soluble factors produced by a biofilm model representative of deep caries and carious pulp exposures induce a time\u2010dependent transcriptional response in DPSCs. This response is characterized by a biphasic pattern of early immune activation followed by later transcriptional metabolic adaptation. These findings highlight the capacity of soluble biofilm\u2010derived products associated with deep caries to modulate DPSC immune\u2013metabolic signaling. They further emphasize the importance of vital pulp therapy strategies that not only target microorganisms but also account for their secreted byproducts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cre2.70417","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T07:25:39Z","timestamp":1784445939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interkingdom Endodontic Biofilm Supernatant Induces a Biphasic Inflammatory and Metabolic Transcriptional Response in Dental Pulp Stem Cells In Vitro"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8034-0624","authenticated-orcid":false,"given":"Saeed S.","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Restorative Dental Sciences, College of Dentistry Jouf University Al\u2010Jouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4469-4767","authenticated-orcid":false,"given":"Sumaya","family":"Abusrewil","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry and Endodontics, School of Dentistry University of Tripoli Tripoli Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-5596","authenticated-orcid":false,"given":"Othman","family":"Baradwan","sequence":"additional","affiliation":[{"name":"Department of Restorative Dental Sciences, College of Dentistry Jouf University Al\u2010Jouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-463X","authenticated-orcid":false,"given":"Om Alkhir","family":"Alshanta","sequence":"additional","affiliation":[{"name":"Oral Sciences Research Group, Glasgow Dental School University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-4278","authenticated-orcid":false,"given":"Ryan","family":"Kean","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, School for Health and Life Sciences Glasgow Caledonian University Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-7075","authenticated-orcid":false,"given":"William","family":"McLean","sequence":"additional","affiliation":[{"name":"Oral Sciences Research Group, Glasgow Dental School University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-5333","authenticated-orcid":false,"given":"Jason L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Oral Sciences Research Group, Glasgow Dental School University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-2167","authenticated-orcid":false,"given":"Christopher J.","family":"Nile","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, School of Dental Sciences Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8121988"},{"key":"e_1_2_12_3_1","unstructured":"American Association of Endodontists. 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