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PdLFs and macrophages were TGF\u2010\u03b21\u2010cultured in a Transwell system and exposed for 48\u2009h to normoglycemic or hyperglycemic conditions (HG\u2009+\u2009AGEs), with or without supernatants from 7\u2010day mono\u2010 or dual\u2010species biofilms of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Enterococcus faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    ). Biofilm biomass, colony\u2010forming units, mitochondrial metabolic activity, and cytokine production were assessed.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    showed higher bacterial counts, whereas\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    produced greater biomass. Hyperglycemia intensified the inhibitory effect of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    and the stimulatory effect of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    on mitochondrial activity. The dual\u2010species supernatant induced an intermediate metabolic response but the most dysregulated inflammatory profile under hyperglycemia, with increased TNF\u2010\u03b1 and reduced TGF\u2010\u03b21. Hyperglycemia reprograms host responses to biofilm\u2010derived products, while polymicrobial interactions amplify inflammatory dysregulation.\n                  <\/jats:p>","DOI":"10.1111\/aej.70121","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:44:26Z","timestamp":1789706666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperglycemia Dysregulates Host Responses to Dual Species Endodontic Biofilm\u2010Derived Products: An In\u00a0Vitro Study"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4711-3841","authenticated-orcid":false,"given":"Mirela Cesar","family":"de Barros","sequence":"first","affiliation":[{"name":"Department of Dentistry, Endodontics and Biomaterials, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5222-8981","authenticated-orcid":false,"given":"Prabha","family":"Lal","sequence":"additional","affiliation":[{"name":"The Kishen Lab, Dental Research Institute University of Toronto  Toronto Ontario Canada"},{"name":"Faculty of Dentistry University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-2160","authenticated-orcid":false,"given":"Flaviana Bombarda","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Endodontics and Biomaterials, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-2633","authenticated-orcid":false,"given":"Anil","family":"Kishen","sequence":"additional","affiliation":[{"name":"The Kishen Lab, Dental Research Institute University of Toronto  Toronto Ontario Canada"},{"name":"Faculty of Dentistry University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2004.10.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1079\u20102104(99)70145\u20109"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010016\u20101805\u20104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0902\u20100055.2003.00116.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13677"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12753"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.105"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12072"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13927"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2014.12.024"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2016.11.012"},{"issue":"10","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/iej.12507","article-title":"Endodontic Medicine: Connections Between Apical Periodontitis and Systemic Diseases","volume":"48","author":"Segura\u2010Egea J. 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