{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:44:04Z","timestamp":1792176244377,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"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":["Int Endodontic J"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>A growing body of research supports an association between periapical inflammation and an increased risk of various systemic effects. However, there is currently no scientific evidence demonstrating a causal relationship between this inflammation and changes in epithelial or endothelial permeability in patients with apical periodontitis (AP). This study aimed to evaluate the potential association between AP, circulating inflammatory cytokines known to affect cellular permeability, and serum proteins associated with an impaired cellular barrier permeability. Additionally, we investigated the effect of endodontic treatment on in\u00a0vitro endothelial barrier integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>A total of 27 patients with AP and 27 healthy control subjects were enrolled. AP patients underwent root canal treatment and were followed up at 6 and 12\u2009months post\u2010treatment. Serum levels of human ZO\u20101, Claudin\u20105, and VE\u2010cadherin were measured using enzyme\u2010linked immunosorbent assays (ELISA). An in\u00a0vitro model of the microvascular endothelial blood\u2013brain barrier (hCMEC\/D3 cells) was used to assess the biological activity of patient sera on barrier function and cellular permeability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, patients with AP showed significantly higher serum levels of ZO\u20101 and Claudin\u20105 compared with controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas VE\u2010cadherin levels did not differ significantly between groups. Serum ZO\u20101 and Claudin\u20105 levels progressively decreased at 6 and 12\u2009months following root canal treatment. In adjusted analyses, the baseline between\u2010group differences for ZO\u20101 and Claudin\u20105 remained significant after adjustment for BMI and smoking status. ZO\u20101 and Claudin\u20105 levels showed moderate correlations with IL\u20101\u03b2 and IL\u20106 in the AP group at baseline. In\u00a0vitro, exposure to baseline AP sera increased endothelial permeability, indicating barrier disruption, while sera collected after treatment did not impair barrier integrity. Moreover, cellular ZO\u20101 expression remained stable in cells treated with control sera but was markedly reduced after exposure to sera from untreated AP patients (t0), whereas post\u2010treatment sera (t6 and t12) restored ZO\u20101 expression to control levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic inflammation in patients with apical periodontitis to deranged endothelial barrier function. Successful endodontic treatment was associated with reduced levels of inflammatory cytokines and the restoration of serum and cellular proteins essential for barrier integrity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70216","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:32:54Z","timestamp":1782977574000},"page":"2402-2412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endodontic Treatment of Apical Periodontitis Mitigates Systemic Inflammation and Restores the Blood\u2013Brain Barrier Integrity in an In\u00a0Vitro Model"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-7340","authenticated-orcid":false,"given":"Loredana","family":"Bergandi","sequence":"first","affiliation":[{"name":"Department of Oncology University of Turin  Turin Piedmont 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