Journal of Applied Oral Science
type: channel
description: O Journal of Applied Oral Science é uma continuação da Revista da Faculdade de Odontologia de Bauru. O Journal of Applied Oral Science opera na modalidade de publicação contínua eletrônica, formato que permite a publicação de volumes anuais sem especificações de fascículos. A Revista da Faculdade de Odontologia de Bauru foi publicada no período de 1993-2001, sendo continuada, em 2002, pelo Journal of Applied Oral Science, volume 11, número 1, mantendo a numeração de sua antecessora. O Journal of Applied Oral Science tem como objetivo principal publicar resultados de pesquisas originais, e a convite do editor, revisões nos campos da Odontologia, Fonoaudiologia e áreas correlatas. A abreviatura de seu título é J. Appl. Oral Sci., que deve ser usada em bibliografias, notas de rodapé e referências.
publisher: Universidade de São Paulo. Faculdade de Odontologia de Bauru
language: en
publication name: Journal of Applied Oral Science
issn: 1678-7757
copyright: Todo o conteúdo do periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons do tipo atribuição CC-BY.
items: Polyphenol-functionalized silver nanoparticles promote differential remineralization and reinforcement of demineralized dentin
items: Statin-loaded carbonated hydroxyapatite nanoemulsion controls matrix metalloproteinase-1 activity to enhance post-orthodontic stability in rats
items: Comparison of root coverage by injectable-platelet rich fibrin in thick and thin phenotypes
items: Influence of impacted mandibular third molars on pathological changes on themselves and adjacent tissues across different age groups
items: Expression of caspase-8 in non-alcoholic fatty liver disease related to ligature-induced periodontitis in rats
items: Can angiotensin II affect the inflammatory response of human dental pulp cells in vitro?
items: Clinical and aesthetic outcomes of enamel matrix derivative and subepithelial connective tissue graft using the modified coronally advanced tunnel technique
items: Parkinson's disease and Porphyromonas gingivalis levels
items: Cognitive and Orofacial Intersections
items: Apical delta filling with calcium silicate and epoxy resin sealers using different obturation techniques by microcomputed tomography
items: Effects of highly leukotoxic Aggregatibacter actinomycetemcomitans associated with ligature-induced periodontitis on oral and gut tissues in male rats
items: Effects of live and heat-killed Bifidobacterium lactis in rats with induced periodontitis
items: Hydrogel microarchitecture as a regulatory cue for in vitro odontogenic differentiation
items: The effect of Stage I-II periodontitis on the mechanical, structural, and biological properties of leukocyte and platelet-rich fibrin
items: Bond strength in class V cavities: an in vitro study on beveling, universal adhesive strategy, and composite type
items: Comparative analysis of connective tissue graft versus ozone-enriched platelet-rich fibrin in the treatment of Cairo class I gingival recessions
items: Saliva liquid biopsy
items: Assessment of chitosan addition to at-home bleaching gel with and without calcium on the physical properties of tooth enamel
items: Integrated analysis identifies CCNA2 as a candidate diagnostic and prognostic biomarker in oral tongue squamous cell carcinoma
items: Evaluation of bleaching efficacy and cytotoxicity of an experimental hydrogel containing MnO-Doped Biosilicate® activated by violet LED light
items: Notch2 is involved in regulating apical tissue repair following severe intrusive luxation
items: Bioactive luting cements on the adhesive interface of fiber post and root dentin
items: Shades of knowledge
items: Effects of bromelain, melatonin, and thymoquinone on neutrophil extracellular trap formation and macrophage polarization in experimental periodontitis
items: DNA methyltransferases expressions in mice tongue exposed to waterpipe smoke
items: Maqui berry cystatin inhibits cathepsin k activity and stimulates osteogenic differentiation of human dental pulp cells
items: Diversity of Streptococcus mutans serotypes isolated from dental plaque of Brazilian patients with a history of acute myocardial infarction
items: SHED-exosomes functionalized micro-nano bioactive glass/PCL membrane regulates macrophage polarization and promotes osteogenic differentiation
items: Factors associated with orofacial myofunctional condition in patients with temporomandibular disorder and somatosensory tinnitus
items: Genetic variants of EBI3, tumor Epstein-Barr virus, and human cytomegalovirus status in HPV-negative oral cancer

Polyphenol-functionalized silver nanoparticles promote differential remineralization and reinforcement of demineralized dentin
type: item
description: Silver nanoparticles (AgNPs) have gained relevance in restorative dentistry due to their antimicrobial and remineralizing properties. However, the role of AgNPs functionalized with different polyphenols in dentin remineralization remains insufficiently understood. Objectives This study aimed to synthesize and characterize AgNPs functionalized with crosslinking polyphenols extracted from grape seed extract (GSE) and green tea leaves (GT), and to evaluate their biocompatibility and their effects on the mechanical and physicochemical properties of demineralized dentin. Methodology AgNPs were characterized by TEM, XRD, TGA, and zeta potential analysis to determine particle morphology, crystalline structure, chemical composition, and surface charge. Biocompatibility was assessed using fibroblast cytotoxicity assays. In total, 40 human mid-coronal dentin specimens were randomly assigned to four groups (n=10): Control- (sound dentin), Control+ (pH-cycled dentin without treatment), AgGSE (pH-cycled + AgGSE, 1 min), and AgGT (pH-cycled + AgGT, 1 min). Treated dentin was analyzed by ATR-FTIR, XRD, TGA, and three-point bending tests. Results Both AgNPs were successfully synthesized and exhibited high biocompatibility. AgGSE demonstrated greater dentin matrix interaction, resulting in significantly higher flexural strength (p≤0.001). In contrast, AgGT induced pronounced remineralization with increased PO4/Amide I ratio (p=0.003) and CO3/PO4 ratios (p=0.007 by TGA; p=0.03 by ATR-FTIR), consistent with carbonated apatite deposition. Conclusions Green-synthesized AgNPs functionalized with GT or GSE promoted reinforcement and remineralization of demineralized dentin through distinct mechanisms of action. These findings highlight their potential as biocompatible agents for dental therapies.
subject: Original Articles
  topic: section
subject: Dental caries
  topic: keywords
subject: Metal nanoparticles
  topic: keywords
subject: Tooth remineralization
  topic: keywords
subject: Crosslinking reagents
  topic: keywords
subject: Flexural strength
  topic: keywords
creator: Tattiana Enrich
creator: Santiago González-López
creator: Alejandro B. Rodríguez-Navarro
creator: María V. Bolaños-Carmona
creator: Carolina Cifuentes-Jiménez
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-05-01
publication date: 2026-05-01
starting page: e20250848
ending page: e20250848
doi: 10.1590/1678-7765-2025-0848

Statin-loaded carbonated hydroxyapatite nanoemulsion controls matrix metalloproteinase-1 activity to enhance post-orthodontic stability in rats
type: item
description: Background The persistence of periodontal ligament (PDL) and alveolar bone remodeling following appliance removal is a key factor in orthodontic relapse, which is a significant barrier to treatment stability. In this study, a statin-loaded carbonated hydroxyapatite (CHA) nanoemulsion was evaluated as a local therapy to control relapse rate by modulating matrix metalloproteinase-1 (MMP-1) in rats. Methodology A total of 48 rats (n=48) were allocated to control, simvastatin, CHA hydrogel, or CHA–simvastatin nanoemulsion groups. Treatments were delivered intrasulcularly during stabilization, and relapse was measured at days zero, one, seven, and 14 post-debonding. MMP-1 expression in the PDL was assessed using immunofluorescence at the same time points. Collected data were evaluated using analysis of variance. Results Relapse occurred in all groups, with the highest relapse rate during early observation. At day one, the relapse rate was significantly reduced in treatment groups compared with the control, and the CHA–simvastatin group showed the lowest relapse rate (control 1048±20.20 vs. CHA–simvastatin 549.33±27.22 μmd−1; p=0.001). MMP-1 expression peaked at day one and was significantly lower in all treatment groups than control, with the greatest suppression in the CHA–simvastatin group (16.33±2.08 vs. 7.33±0.57 positive cells/field; p=0.001). By day 14, relapse rates and MMP-1 expression decreased across groups, with persisting advantages for the combined treatment. Conclusion Local CHA-simvastatin nanoemulsion decreased early relapse and downregulated MMP-1 expression in rats, suggesting a promising adjunctive strategy to enhance post-orthodontic stability.
subject: Original Articles
  topic: section
subject: Carbonated hydroxyapatite
  topic: keywords
subject: Matrix metalloproteinase
  topic: keywords
subject: Nanoemulsion
  topic: keywords
subject: Relapse
  topic: keywords
subject: Simvastatin
  topic: keywords
creator: Ananto Ali Alhasyimi
creator: Niswati Fathmah Rosyida
creator: Pinandi Sri Pudyani
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-04-17
publication date: 2026-04-17
starting page: e20260023
ending page: e20260023
doi: 10.1590/1678-7765-2026-0023

Comparison of root coverage by injectable-platelet rich fibrin in thick and thin phenotypes
type: item
description: Objective This study aimed to compare the effectiveness of injectable platelet-rich fibrin (I-PRF) using a submucosal injection technique for creeping attachment in thin and thick phenotypes with gingival recession. Methodology The study was designed as a prospective clinical trial. Participants were divided into two groups based on gingival thickness (GT): thin phenotype group (≤1.0 mm) and thick phenotype group (>1.0 mm). I-PRF was applied once a month to each gingival site using the submucosal injection technique, for a total of three applications. Periodontal parameters were measured at baseline (T0), nine months after treatment (T1), and 12–48 months after treatment (T2). Root coverage percentage (RC%) was calculated. Results Twelve systemically healthy, non-smoking patients (seven males and five females; mean age: 36.5±9.4), comprising 66 teeth, were analyzed. The primary outcome, RC%, demonstrated a statistically significant intergroup difference at T1 (p=0.032); however, this difference was not statistically significant at T2. In the thick phenotype group, RC% was 20.91±30.80% in T1 and increased to 31.40±30.92% in T2 (p=0.040). Conversely, the thin phenotype group showed higher RC% values at T1 (35.04±29.76%), which were not sustained at T2 (30.70±28.46%; p=0.355). Recession depth decreased in both groups at all time points, but this difference was not statistically significant. Keratinized tissue width showed a significant increase in both groups, from 2.34±1.08 and 2.73±0.95 at T0, respectively, to 2.89±1.17 and 3.28±1.12 at T1 (p<0.05). In the intergroup comparison, GT values were significantly higher in the thick phenotype group than in the thin phenotype group at T0 and T2, while no significant difference was observed at T1. Conclusion I-PRF application was shown to enhance RC% in both phenotypes. A significant increase in GT was observed in the thin phenotype; however, these increases in GT and RC% were not fully sustained during long-term follow-up i…
subject: Original Articles
  topic: section
subject: Injectable platelet-rich fibrin
  topic: keywords
subject: Gingival thickness
  topic: keywords
subject: Gingival phenotype
  topic: keywords
subject: Gingival recession
  topic: keywords
subject: Root coverage
  topic: keywords
creator: Berceste Guler Ayyildiz
creator: Busra Terzioglu
creator: Seyma Eken
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-04-17
publication date: 2026-04-17
starting page: e20250702
ending page: e20250702
doi: 10.1590/1678-7765-2025-0702

Influence of impacted mandibular third molars on pathological changes on themselves and adjacent tissues across different age groups
type: item
description: Objective To investigate the effects of different types of impacted mandibular third molar (IMTM) on lesions in situ and on adjacent tissues at different ages. Methodology Cone Beam Computed Tomography (CBCT) images of 1007 IMTM cases were retrospectively analyzed. Associations between age, gender, impaction type, distal alveolar bone condition of mandibular second molar (MSM), IMTM-MSM contact status and occurrence of lesions on IMTM and its adjacent tissues were evaluated using Pearson’s chi-squared test and Fisher’s exact test. Results MSM distal alveolar bone defects showed the highest incidence among all IMTM-related lesions (79.2%), followed by MSM distal external root resorption (ERR) (25.5%) and MSM distal caries (10.4%). Mesioangular (96.2%, p<0.001) and horizontal (95.9%, p<0.001) IMTM were associated with more severe bone defects and the incidence increased with age. IMTM-MSM surface-to-surface contact was significantly associated with MSM distal caries severity (12.5%, p<0.001) and distal ERR (29.5%, p<0.001). Inflammatory resorption of MSM distal alveolar bone was significantly correlated with MSM distal caries (47.1%, p<0.001), ERR (36.5%, p<0.05), distal alveolar bone defects (100%, p<0.001), and IMTM caries (14.1%, p<0.05). Study design followed the STROBE guidelines. Conclusion Mesioangular impaction, horizontal impaction, MSM-IMTM surface-to-surface contact, and MSM distal alveolar bone in a state of inflammatory resorption greatly affect lesions on IMTM and its surrounding tissues. These findings suggest the prophylactic extraction in young adults (18–25 years) with high-risk impactions, while recommending observation or cautious management for asymptomatic older patients without signs of inflammatory bone resorption.
subject: Original Articles
  topic: section
subject: Third molar
  topic: keywords
subject: Alveolar bone loss
  topic: keywords
subject: Cone-beam computed tomography
  topic: keywords
creator: Xiaoyue Ge
creator: Yixiao Cui
creator: Ning Li
creator: Tianyang Lv
creator: Yuntong Liang
creator: Haochen Wu
creator: Yuxuan Gu
creator: Meiting Li
creator: Changkui Liu
creator: Yayuan Guo
creator: Kaijin Hu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-30
publication date: 2026-03-30
starting page: e20250677
ending page: e20250677
doi: 10.1590/1678-7765-2025-0677

Expression of caspase-8 in non-alcoholic fatty liver disease related to ligature-induced periodontitis in rats
type: item
description: Aim This study aimed to evaluate the oral and hepatic changes, as well as the expression of caspase-8 in liver tissue damage, both associated with ligature-induced periodontitis in rats. Methodology A total of 16 female Wistar rats were divided into two groups (n=8): one received ligature around the first lower molar to promote periodontitis, and the other was the control group with no ligature. After the period of induction of the disease the animals were evaluated by clinical measures for periodontitis, euthanized, and the samples of gingival tissue, hepatic tissue, and serum were collected to the measurement of biomarkers for inflammation (myeloperoxidase), oxidative stress (glutathione, malonaldehyde, and nitrate [NO3]), liver damage and histopathological evaluation with immunohistochemistry for caspase-8. The data were expressed as mean and standard deviation for data with normal distribution or median and interquartile range for data with non-normal distribution. We used ANOVA followed by the Student-Newman-Keuls test for multiple comparisons of normally distributed data, and the Kruskal-Wallis test followed by Dunn's test for non-normally distributed data. The statistical tests were performed with GraphPad Prism Software (version 5.0), in which a p-value <0.05 was considered significant. Results Our study demonstrates that the group with ligature-induced periodontitis showed increased measurement of periodontal destruction, local and systemic biomarkers of inflammation as well as liver damage which we observed several hepatocytes with loss of conformation and steatosis in the periodontitis group. The histopathological evaluation evidenced the periodontitis-related steatosis and higher expression of Caspase-8 in comparison with the control group (p<0.0006). Conclusion Our study demonstrates the high expression of Caspase-8 in liver damage related to ligature-induced periodontitis in rats.
subject: Original Articles
  topic: section
subject: Apoptosis
  topic: keywords
subject: Periodontal Disease
  topic: keywords
subject: Liver dysfunction
  topic: keywords
subject: Oxidative stress
  topic: keywords
creator: Felipe Rodolfo Pereira da Silva
creator: Victor Brito Dantas Martins
creator: Hélio Mateus Silva Nascimento
creator: Paulo Roberto Carneiro Gomes
creator: Nikaely Brandão Barbosa
creator: Vinícius da Silva Caetano
creator: Ivana Márcia Alves Diniz
creator: Karine Duarte da Silva
creator: Any Carolina Cardoso Guimarães Vasconcelos
creator: Daniel Fernando Pereira Vasconcelos
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-04-06
publication date: 2026-04-06
starting page: e20250717
ending page: e20250717
doi: 10.1590/1678-7765-2025-0717

Can angiotensin II affect the inflammatory response of human dental pulp cells in vitro?
type: item
description: Dental pulp fibroblasts respond to various stimuli, including microbial agents, endodontic materials, restorative procedures, pulp protection treatments, and inflammatory molecules. Its inflammatory response to injury involves a complex set of mechanisms that have been increasingly studied for their roles in this intricate biological process. Among these mechanisms is angiotensin II (ANG-II), the involvement of which in inflammation has been shown in several pathological conditions via its local generation and action. Objective This study aimed to evaluate the capacity of fibroblasts from permanent and deciduous dental pulp to express inflammatory mediators when exposed to bacterial and inflammatory antigens. It also sought to assess the presence of components of the renin-angiotensin system (RAS) and the potential modulatory role of ANG-II in this response. Methodology Fibroblasts were cultured from the pulp of permanent and deciduous teeth obtained from three adult and four pediatric donors with informed consent. Cells were stimulated with Porphyromonas gingivalis and Escherichia coli lipopolysaccharides (LPS) either alone or in combination with ANG-II and, in some cases, with IL-1β. Gene expression of RAS components and various inflammatory mediators was analyzed by qRT-PCR. ANG-II receptor expression was quantified by flow cytometry. Results The results showed that both bacterial antigens and IL-1β significantly upregulated the expression of genes encoding key inflammatory mediators. However, ANG-II, either alone or in combination with other antigens, failed to alter the expression levels of these mediators. Conclusion These findings clearly show that ANG-II has no influence on the expression of inflammatory mediators by human dental pulp fibroblasts under the tested conditions.
subject: Original Articles
  topic: section
subject: Pulp fibroblasts
  topic: keywords
subject: Angiotensin II
  topic: keywords
subject: Inflammatory mediators
  topic: keywords
creator: Bella Luna Colombini-Ishikiriama
creator: Thiago José Dionisio
creator: Thais Francini Garbieri
creator: Rafaela Alves da Silva
creator: Sandra Helena Penha Oliveira
creator: Vanessa Soares Lara
creator: Andrew Seth Greene
creator: Carlos Ferreira dos Santos
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-04-06
publication date: 2026-04-06
starting page: e2025
ending page: 0822
doi: 10.1590/1678-7765-2025-0822

Clinical and aesthetic outcomes of enamel matrix derivative and subepithelial connective tissue graft using the modified coronally advanced tunnel technique
type: item
description: Objectives This randomized controlled clinical trial evaluated the short-term clinical outcomes of the modified coronally advanced tunnel technique combined with three different regenerative approaches—subepithelial connective tissue graft (as the gold standard), enamel matrix derivative (as a donor-site-sparing alternative), and their combination (to explore potential synergistic effects)—in treating recession type 1 gingival defects. Methodology A total of 52 systemically healthy patients (aged 18–60) with 90 recession type 1 gingival defects were enrolled and randomly assigned to one of the three treatment groups: Group 1 (n=18; subepithelial connective tissue graft), Group 2 (n=19; enamel matrix derivative), and Group 3 (n=15; both materials). Primary outcome consisted of the percentage of root coverage at 6 months. Secondary outcomes included plaque index, gingival index, gingival recession depth, gingival recession width, clinical attachment level, keratinized tissue width, gingival thickness, wound healing index, probing depth, and root coverage aesthetic score. Clinical parameters were measured at baseline, 3, and 6 months, and aesthetic outcomes were assessed at 6 months. Results All groups showed significant improvements in clinical parameters. Mean root coverage was 80.4% for Group 1, 76.2% for Group 2, and 73.6% for Group 3, with no significant differences among them. Keratinized tissue width significantly increased in Group 1 and Group 3, but not in Group 2. Mean root coverage aesthetic score values were 7.74 ± 2.35, 7.54 ± 2.39, and 7.62 ± 1.97, respectively (p > 0.05). Conclusion Within the limitations of this study, including its short-term follow-up period and baseline differences in recession width, all three groups exhibited comparable clinical and aesthetic outcomes at 6 months. Clinical Trial Registration Number: NCT06504329
subject: Original Articles
  topic: section
subject: Gingival recession
  topic: keywords
subject: Graft
  topic: keywords
subject: Enamel matrix proteins
  topic: keywords
subject: Minimally invasive surgical procedures
  topic: keywords
subject: Subepithelial connective tissue
  topic: keywords
creator: Fatma Altiparmak
creator: Fatma Ucan Yarkac
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-23
publication date: 2026-03-23
starting page: e2025
ending page: 0775
doi: 10.1590/1678-7765-2025-0775

Parkinson's disease and Porphyromonas gingivalis levels
type: item
description: Neurodegenerative diseases have been associated with periodontal diseases. Objectives This study aimed to evaluate the clinical and epidemiological aspects of the association between Parkinson's disease (PKD) and periodontitis (PE), including the quantification of Porphyromonas gingivalis and the influence of different risk variables on this association. Methodology This case-control study included 172 individuals: 86 cases (PKD) and 86 controls (without any neurodegenerative disease). Participants underwent a complete periodontal examination (plaque index and probing depth), and clinical subgingival sampling was conducted to quantify Porphyromonas gingivalis counts. The association between PKD and PE was evaluated through univariate and binary logistic regression analyses. Results A high prevalence of PE (73.2%) was observed among individuals with PKD [OR=3.99 (2.00-7.59); p<0.001]. Variables that were significantly retained in the final binary logistic regression model for the occurrence of PKD were: PE (OR=3.23; p=0.003), mean P. gingivalis counts (OR= 3.39; p=0.036), lower number of teeth (OR= 2.21, p<0.001), low frequency of toothbrushing/day (OR=1.95; p=0.006), and bleeding on probing (OR=2.45; p<0.001). The significant positive correlations observed between P. gingivalis counts and clinical periodontal parameters were considered moderate to strong in individuals with PKD. Conclusions A strong association between PKD and PE was demonstrated, with risk increasing in parallel with the severity of periodontal involvement. Furthermore, individuals with PKD exhibited significantly higher levels of P. gingivalis compared to controls.
subject: Original Articles
  topic: section
subject: Case-control study
  topic: keywords
subject: Neurodegeneration
  topic: keywords
subject: Parkinson’s disease
  topic: keywords
subject: Periodontitis
  topic: keywords
subject: Systemic inflammation
  topic: keywords
subject: Porphyromonas gingivalis
  topic: keywords
creator: Nathália Alves Gusmão
creator: Augusto Paixão Moraes Mateus
creator: Victor Bento Oliveira
creator: Rafael Paschoal Esteves Lima
creator: José Roberto Cortelli
creator: Sheila Cavalca Cortelli
creator: Fernando Oliveira Costa
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-23
publication date: 2026-03-23
starting page: e2025
ending page: 0780
doi: 10.1590/1678-7765-2025-0780

Cognitive and Orofacial Intersections
type: item
description: Objective. Despite emerging evidence pointing to a comorbidity between temporomandibular disorders (TMD), bruxism, and neuropsychiatric conditions such as Attention-Deficit/Hyperactivity Disorder (ADHD), limited studies have explored this relationship in adult populations. This study aimed to investigate the prevalence of painful TMD and self-reported bruxism in adults with highly consistent ADHD symptoms. Methodology. In total, 90 adult participants were divided into two groups based on the Adult ADHD Self-Report Scale Screener, G1: individuals with highly consistent ADHD symptomatology (n=60), and G2: controls (n=30). All participants completed validated instruments assessing TMD (TMD Pain Screener), self-reported bruxism (OBC), anxiety (GAD-7), somatization (PHQ-15), perceived stress (PSS), sleep quality (PSQI), pain hypervigilance (PVAQ), and jaw function (JFLS-8). The chi-square test, adjusted using Bonferroni criteria for multiple comparisons, and the Mann-Whitney U-test were used. Results. A higher prevalence of women (p=0.006), South Americans (p=0.008), and individuals with low/lower middle income (p=0.0001) was found in G1. G1 showed a significantly higher prevalence of painful TMD (p=0.001) and awake bruxism (p=0.013) compared to G2. Participants in G1 also exhibited significantly higher levels of anxiety, somatization, stress, poor sleep quality, pain hypervigilance, and jaw limitation (p<0.05). No significant differences in sleep bruxism were found between groups (p>0.05). Conclusion. These findings suggest a potential behavioral and emotional vulnerability to orofacial disorders in adults with highly consistent ADHD symptoms.
subject: Original Articles
  topic: section
subject: Attention deficit disorder with hyperactivity
  topic: keywords
subject: Temporomandibular disorders
  topic: keywords
subject: Bruxism
  topic: keywords
creator: Arthur Alexis Valentin Caron
creator: Rodrigo Lorenz Poluha
creator: Marlon Ferreira Dias
creator: Dyanne Medina Flores
creator: Alfonso Sanchéz-Ayala
creator: Justin Durham
creator: Giancarlo De la Torre Canales
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-23
publication date: 2026-03-23
starting page: e2025
ending page: 0771
doi: 10.1590/1678-7765-2025-0771

Apical delta filling with calcium silicate and epoxy resin sealers using different obturation techniques by microcomputed tomography
type: item
description: Objectives This study aimed to evaluate the filling quality of simulated apical deltas in 3D-printed tooth replicas using microcomputed tomography and comparisons of two obturation techniques and calcium silicate cement-based sealer groups. Methodology A single-rooted, straight maxillary premolar was instrumented and scanned by microcomputed tomography to generate a 3D model. Apical delta configurations were digitally created and integrated into the canal anatomy. In total, 40 translucent resin replicas were 3D printed and randomly assigned for obturation with one of four sealer groups (AH Plus Resin, AH Plus Bioceramic, Bio-C Sealer, and NeoSealer Flo). Following obturation, all specimens were rescanned, and a volumetric analysis was performed to determine the percentage of the filled volume in the apical delta region. Statistical analyses included one-way ANOVA and the Kruskal-Wallis test (α=0.05). Results The continuous wave technique resulted in significantly greater apical delta filling than the single-cone one regardless of sealer. For the single-cone technique, NeoSealer Flo showed the highest filling percentage (42.7±2.0), followed by Bio-C Sealer (28.7±1.1), AH Plus Resin (24.9±1.9), and AH Plus Bioceramic (17.9±1.0). For the continuous wave technique, Bio-C Sealer showed the most filling (66.2±2.0), followed by NeoSealer Flo (54.2±1.4), AH Plus Resin (45.9±1.5) and AH Plus Bioceramic (36.8±1.0). Conclusions The continuous wave technique achieved the most apical filling, with Bio-C sealer showing the highest performance. Bio-C and NeoSealer Flo achieved significantly higher filling percentages than AH Plus Resin and AH Plus Bioceramic under the single-cone technique.
subject: Original Articles
  topic: section
subject: 3D printing
  topic: keywords
subject: Calcium silicate cement-based sealers
  topic: keywords
subject: Micro–computed tomography
  topic: keywords
subject: Obturation
  topic: keywords
subject: Apical delta
  topic: keywords
creator: Washington Soares dos Santos
creator: Jefferson Augusto
creator: Angelo José Sócrates Torres-Carrillo
creator: Igor Bassi Ferreira Petean
creator: Antonio Miranda da Cruz-Filho
creator: Manoel Damião de Sousa-Neto
creator: Fabiane Carneiro Lopes-Olhê
creator: Jardel Francisco Mazzi-Chaves
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-23
publication date: 2026-03-23
starting page: e2025
ending page: 0744
doi: 10.1590/1678-7765-2025-0774

Effects of highly leukotoxic Aggregatibacter actinomycetemcomitans associated with ligature-induced periodontitis on oral and gut tissues in male rats
type: item
description: Objective To evaluate the effects of gastric administration of the highly leukotoxic Aggregatibacter actinomycetemcomitans JP2 strain (Aa JP2), with or without ligature-induced periodontitis, on periodontal and small intestinal tissues in a rat model. Methodology Forty-eight-week-old male Wistar rats were divided into four groups (n=10/group): Control (CG), Periodontitis (PG), Periodontitis and Aa JP2 (PAaG), and Aa JP2 only (AaG). Ligatures were placed in PG and PAaG on day one and maintained for 42 days. After six weeks of twice-weekly gastric Aa JP2 inoculation, mandibles and small intestines were analyzed using stereomicroscopy, micro-computed tomography (CT), and histopathology to assess alveolar bone loss, trabecular architecture, inflammatory infiltrate, vascular congestion, goblet cell density, and villus morphology. Statistical analyses included the Kruskal–Wallis, Mann–Whitney, and Chi-square tests for group comparisons (p<0.05), as well as Spearman’s correlation test. Results PG and PAaG exhibited significantly greater bone loss compared to CG and AaG (p<0.05). Micro-CT analysis revealed reduced trabecular thickness in AaG (342.4±23.1µm) compared to PG (378.2±28.1µm) and PAaG (385.5±45.1µm) (p<0.05). PAaG and AaG presented higher inflammatory infiltrate scores (>751 inflammatory cells) compared to CG and/or PG (p<0.05). Elevated vascular congestion and/or goblet cell hyperplasia in the jejunum and ileum were observed in PAaG and AaG compared to CG and PG (p<0.05). Villus height (duodenum/ileum) and villus width (jejunum/ileum) differed significantly among groups (p<0.0001). Significant correlations were identified: the alveolar bone volume/total volume ratio was positively associated with duodenal vascular congestion (rho=0.738; p=0.037); the periodontal inflammatory infiltrate was positively associated with jejunal goblet cell counts (rho=0.704; p=0.007); alveolar bone loss was positively associated with both duodenal and jejunal villus height (rho≥0.762…
subject: Original Articles
  topic: section
creator: Gabriela Furian Trama Ferraz
creator: Camila Philipe de Araujo Camilo
creator: Ana Luisa Palhares de Miranda
creator: Mariana Alves Soares
creator: Carmelo Sansone
creator: Ricardo Tadeu Lopes
creator: Aline Correa Abrahão
creator: Ana Paula Vieira Colombo
creator: Carina Maciel Silva-Boghossian
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-09
publication date: 2026-03-09
starting page: e2025
ending page: 0731
doi: 10.1590/1678-7765-2025-0731

Effects of live and heat-killed Bifidobacterium lactis in rats with induced periodontitis
type: item
description: Background Probiotics and postbiotics have emerged as promising adjunctive therapies in managing periodontal disease. Bifidobacterium animalis subsp. lactis HN019 has shown antimicrobial and immunomodulatory effects in both experimental and clinical settings when administered orally. However, the systemic impact of this strain, independent of local oral effects, remains unclear. Objective To evaluate the systemic effects of live and heat-killed B. animalis subsp. lactis HN019 in a rat model of ligature-induced periodontitis, excluding direct contact with the oral cavity. Methodology A total of 32 Wistar rats were randomly assigned to four groups (n=8): control (C), periodontitis only (EP), periodontitis + probiotic (PRO), and periodontitis + postbiotic (POS). Periodontitis was induced by placing a cotton ligature around the cervical region of the lower right first molar, inserted into the gingival sulcus. Treatments were administered via oral gavage for 30 days before and 15 days after periodontitis induction. Alveolar bone loss and periodontal parameters were assessed using micro-computed tomography (microCT) and histomorphometric analysis. Results MicroCT revealed that ligature effectively induced periodontitis, reducing BV/TV and Tb.N and increasing Tb.Sp and Po.Tot. Probiotic and postbiotic treatments did not improve outcomes. Bone loss was lowest in the control group, with no differences between EP, PRO, and POS. Conclusion Systemic administration of Bifidobacterium animalis subsp. lactis HN019 or its derived postbiotic resulted in no significant improvements in periodontal outcomes in this experimental model. Further investigations using integrative approaches are needed to better characterize the systemic effects of probiotics and postbiotics.
subject: Original Articles
  topic: section
subject: Periodontitis
  topic: keywords
subject: Probiotics
  topic: keywords
subject: Bifidobacterium animalis subsp lactis
  topic: keywords
subject: Postbiotics
  topic: keywords
creator: Tainá da Silva Tricoly
creator: Thais Aguiar Santos
creator: Camila Lopes Ferreira
creator: Itza Amarilis Ribeiro Pinto
creator: Victoria Clara da Silva Lima
creator: Camilla Magnoni Moretto Nunes
creator: Ana Lia Anbinder
creator: Maria Aparecida Neves Jardini
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-09
publication date: 2026-03-09
starting page: e2025
ending page: 0634
doi: 10.1590/1678-7765-2025-0634

Hydrogel microarchitecture as a regulatory cue for in vitro odontogenic differentiation
type: item
description: Objective This study introduces an innovative, cost-effective, and easily reproducible strategy for engineering three-dimensional bioprinted GelMA-based scaffolds, designed with ordered macroporous and tubular architectures, and integrated microfluidic channels to advance structural and functional performance. Their geometric features were specifically designed to investigate how microarchitectural cues influence the mineralizing cell differentiation of human dental pulp cells (HDPCs). Methodology The scaffolds were fabricated via an indirect bioprinting process using resin molds, resulting in cylindrical structures with distinct grid or honeycomb surface architectures. Biomaterials were characterized for morphology, surface topography, porosity, pore diameter, and degradability. Biological performance was evaluated by culturing HDPCs for 21 days to assess viability, proliferation, and mineralizing differentiation (ANOVA/Tukey; α=0.05). Results Both scaffold designs exhibited interconnected porous networks, with the honeycomb configuration presenting significantly larger pores. HDPCs cultured on the scaffolds showed high viability and proliferation, with the honeycomb architecture promoting elevated ALP activity. However, the grid architecture more effectively influenced odontoblastic differentiation and mineralized matrix deposition. Conclusion Our findings highlight the impact of biomaterial architecture on cellular behavior and reveal the potential of this novel bioprinting approach for bioactive dentin regeneration in dental tissue engineering.
subject: Original Articles
  topic: section
subject: GelMA
  topic: keywords
subject: Hydrogel
  topic: keywords
subject: Dentin
  topic: keywords
subject: Human dental pulp cells
  topic: keywords
subject: Regenerative dentistry
  topic: keywords
subject: Tissue engineering
  topic: keywords
creator: Letícia Alves Martins de Carvalho
creator: Vitor de Toledo Stuani
creator: Isabela Sanches Pompeo da Berteli
creator: Thayná Souza Berteli
creator: Nicoly Gabriely Gonçalves
creator: Diana Gabriela Soares
creator: Ester Alves Ferreira Bordini
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-09
publication date: 2026-03-09
starting page: e2025
ending page: 0607
doi: 10.1590/1678-7765-2025-0607

The effect of Stage I-II periodontitis on the mechanical, structural, and biological properties of leukocyte and platelet-rich fibrin
type: item
description: Objective This study aimed to compare the mechanical, biological, and structural properties of a leukocyte- and platelet-rich fibrin (L-PRF) membrane in periodontally healthy patients and those with periodontitis. A total of 30 individuals (17 men and 13 women) with a median age of 41 years were divided into two groups as periodontally healthy (control group) and as having periodontitis (test group). Methodology Blood samples were collected and centrifuged at 2700 rpm for 12 minutes. A tensile test was performed to determine the mechanical properties of L-PRF membranes. Elasticity-modulus, tensile strength, and stretch at rupture were calculated. Platelet and leucocyte counts and ratios were calculated. Fibril thickness and density were evaluated by scanning electron microscopy imaging. The comparisons between groups were analyzed by the Mann–Whitney U test, and a p<0.05 value was considered statistically significant. Results In the comparison of the control group versus the test group, pocket depth (3.55 (1.59-3.97) vs. 1.52 (1.47-3.53)), clinical attachment level (3.11 (1.77-4.23) vs. 0.06 (0.05-3.68)), plaque index (1.63 (0.05-1.75) vs. 0.04 (0.04-1.58)), gingival index (1.55 (0.04-1.63) vs. 0.05 (0.04-1.49)), and bleeding on probing (56.25 (3.7-70.11) vs. 3.57 (2.67-47.12)) were statistically significantly higher in the test group than in the control group (p= 0.009, p=0.008, p=0.008, p=0.009, p=0.009, respectively). Elasticity-modulus, tensile strength, and stretch at rupture values showed no statistically significantly differences between groups (p=0.745, p=0.754, p=0.602, respectively). Fibril thickness and density values showed no statistically significant differences between groups (p=1.000, p=0.753, respectively). Platelet count and platelet and leukocyte ratio values showed no statistically significant differences between groups (p=0.754, p=0.600, p=0.142, respectively). Leukocyte count was found to be statistically significantly higher in the control gro…
subject: Original Articles
  topic: section
subject: Leukocyte
  topic: keywords
subject: Periodontitis
  topic: keywords
subject: Platelet-rich fibrin
  topic: keywords
subject: Tensile strength
  topic: keywords
creator: Sarvar Ibrahimli
creator: Meltem Karsiyaka Hendek
creator: Kubilay Baris
creator: Ebru Olgun
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-09
publication date: 2026-03-09
starting page: E2025
ending page: 0483
doi: 10.1590/1678-7765-2025-0483

Bond strength in class V cavities: an in vitro study on beveling, universal adhesive strategy, and composite type
type: item
description: Cervical Class V lesions present restorative challenges due to their multifactorial etiology and complex bonding substrates. Objectives: This study evaluated the influence of marginal bevel, bonding using a universal adhesive (etch-and-rinse or self-etch), and the resin composite type (conventional or bulk-fill) on the bond strength of simulated Class V cavities. Methodology: A total of 80 dental fragments (7mm×7 mm×2 mm) were obtained from bovine incisors. Cylindrical cavities with enamel margins and internal dentin walls were prepared centrally in each specimen. Samples were randomly assigned to groups based on three factors: presence or absence of bevel, bonding strategy (etch-and-rinse or self-etch), and resin composite type (conventional or bulk-fill). Groups with bevel received a 1 mm enamel bevel along the preparation margins using a conical diamond bur. Adhesive and restorative procedures were performed following the manufacturer’s recommendations. Bond strength was assessed using a push-out test on a universal testing machine. Data were analyzed using three-way ANOVA and Tukey’s post-hoc test (α=5%). Results: Presence of a marginal bevel did not significantly influence bond strength. The etch-and-rinse bonding strategy resulted in significantly higher bond strength than the self-etch approach, and bulk-fill composites presented superior performance compared with conventional composites. Conclusions: Combining a universal adhesive applied with the etch-and-rinse strategy and a bulk-fill composite proved to be an effective approach for enhancing bond strength with enamel and dentin substrates. Beveling of enamel margins did not improve the bond strength of Class V restorations, suggesting that this procedure may be unnecessary when margins are in enamel. Avoiding beveling in such situations contributes to preserve sound tooth structure and supports a more conservative restorative approach.
subject: Original Articles
  topic: section
subject: Dentin-bonding agents
  topic: keywords
subject: Cavity preparation
  topic: keywords
subject: Composite resins
  topic: keywords
creator: Felipe José Ribeiro de Melo
creator: Viviane Rocha
creator: Vivian Leite Martins
creator: Marcos Vinícius Salvador
creator: Adriano Fonseca Lima
creator: Andrea Nóbrega Cavalcanti
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20250608
ending page: e20250608
doi: 10.1590/1678-7765-2025-0608

Comparative analysis of connective tissue graft versus ozone-enriched platelet-rich fibrin in the treatment of Cairo class I gingival recessions
type: item
description: Gingival recession is characterized by the apical displacement of the marginal gingiva, exposing the root surface and causing aesthetic and functional issues such as dentin hypersensitivity and cervical lesions. Subepithelial connective tissue grafts (SCTG) are considered the gold standard for root coverage. Recently, ozone-enriched advanced platelet-rich fibrin (A-PRF) has emerged as a promising alternative due to its regenerative potential and biocompatibility. Objectives: To compare the clinical efficacy of ozone-enriched A-PRF and SCTG combined with the coronally advanced flap (CAF) technique to treat Cairo Class I gingival recessions. Methodology: This randomized, double-blind, controlled clinical trial included 22 healthy patients (mean age 32.23±11.86 years, range 20–60 years), each with bilateral Cairo Class I recessions. Sites were treated with either CAF + SCTG (control) or CAF + ozone-enriched A-PRF (test). Clinical parameters were assessed at baseline, 90, and 180 days. Data were analyzed using the Shapiro-Wilk, repeated measures ANOVA, Tukey, and Friedman tests (α=0.05) on GraphPad Prism 8.0®. This study adhered to the CONSORT guidelines for randomized clinical trials. Results: Complete root coverage (100%) was achieved in 13 of 22 sites (60%) in the SCTG group and in nine of 22 cases (43%) in the ozone-enriched A-PRF group. Both groups statistically and significantly improve over time in selected clinical parameters (p<0.05). The SCTG group showed significant gains in all evaluated outcomes, whereas the ozone-enriched A-PRF group showed significant improvements in clinical attachment level, recession height, recession width, and dentin hypersensitivity. SCTG more greatly increased gingival thickness (0.77±0.52 mm) and keratinized tissue width (0.81±0.95 mm) than ozone-enriched A-PRF (0.27±0.55 mm and 0.22±0.42 mm, respectively). Conclusions: Both treatment approaches effectively managed Cairo Class I gingival recessions. SCTG promoted superior soft tis…
subject: Original Articles
  topic: section
subject: Connective tissue
  topic: keywords
subject: Gingival recession
  topic: keywords
subject: Platelet-rich fibrin
  topic: keywords
subject: Oxygen
  topic: keywords
subject: Ozone therapy
  topic: keywords
creator: Marina Pereira Silva
creator: Maria Ritha Veiga Colognese
creator: Carlos Augusto Nassar
creator: Veridiana Camilotti
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-03
publication date: 2026-03-03
starting page: e20250565
ending page: e20250565
doi: 10.1590/1678-7765-2025-0565

Saliva liquid biopsy
type: item
description: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm in the oral cavity, characterized by high morbidity and mortality. Various proteins, including matrix metalloproteinases (MMPs), have been investigated as potential biomarkers for diagnosing and prognosing this disease. Objective: To evaluate the utility of MMP-2, MMP-9, and the tissue inhibitor of metalloproteinase-2 (TIMP-2) as biomarkers in diagnosing and prognosing OSCC. Methodology: This retrospective case-control study involved 60 cases and 30 controls from the University Hospital Fundación Santa Fe de Bogotá, part of the Colombian cohort of the InterChange/Headspace study. Saliva samples were collected using a 60-second mouth rinse with 10 mL of sterile saline solution, along with serum and oral tissue samples and clinical and sociodemographic data. MMP-9, MMP-2, and TIMP-2 concentrations in saliva were determined using ELISA, whereas tissue samples were analyzed by immunohistochemistry. MMP activity in saliva was quantified using a generic activity assay. Results: Salivary MMP-9 and MMP-2 concentrations were significantly higher in cases than in controls, whereas no significant differences were observed for TIMP-2. ROC curve analysis showed excellent discriminatory capacity for salivary MMP-9 (AUC=0.946; sensitivity=0.817; specificity=0.867), good performance for MMP-2 (AUC=0.708; sensitivity=0.717; specificity=0.633), and lower discriminatory ability for TIMP-2 (AUC=0.630; sensitivity = 0.617; specificity=0.500). Elevated MMP-9 concentrations were observed in 33% of the serological samples. The immunohistochemistry of MMP-2, MMP-9, and TIMP-2 showed differences between cases and controls. Conclusions: This study highlights salivary MMP-9 and MMP-2, together with MMP activity, as biomarkers of interest for OSCC that may contribute to the understanding of disease-related molecular changes detectable by liquid biopsy. While elevated salivary levels were observed in OSCC cases when compar…
subject: Original Articles
  topic: section
subject: Squamous cell carcinoma of head and neck
  topic: keywords
subject: Matrix metalloproteinases
  topic: keywords
subject: Tissue inhibitor of metalloproteinase-2
  topic: keywords
subject: Saliva
  topic: keywords
creator: Sergio D. Cruz-Romero
creator: Ana Margarita Baldión
creator: José Antonio Hakim Tawil
creator: Alberto Escallon
creator: Paula A. Rodriguez-Urrego
creator: Paula Alejandra Baldión
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-03
publication date: 2026-03-03
starting page: e20250555
ending page: e20250555
doi: 10.1590/

Assessment of chitosan addition to at-home bleaching gel with and without calcium on the physical properties of tooth enamel
type: item
description: Dental bleaching is a widely used esthetic treatment, but concerns persist regarding its potential effects on enamel integrity. The incorporation of remineralizing and protective agents into bleaching gels, such as calcium and chitosan, has been proposed to mitigate these effects. Objective: This in vitro study evaluated the effects of adding 2% chitosan to at-home bleaching gels with and without calcium on enamel physical properties. Methodology: Bovine enamel specimens stained with black tea were assigned to five groups (n = 12): control (no bleaching), 7.5% hydrogen peroxide (7.5% HP), 7.5% HP + 2% chitosan (7.5% HP+ Chi), 7.5% HP + calcium (7.5% HP + Ca), and 7.5% HP + calcium + chitosan (7.5% HP + Ca + Chi). Bleaching was performed for 14 days (1 hour/day). Color (∆L*, ∆a*, ∆b*, ∆Eab, ∆E00, and ∆WID), surface roughness, and surface microhardness (SMH) were evaluated at baseline (T1) and after treatment (T2). Mineral content (Ca, P, and the Ca/P ratio) was assessed by energy-dispersive X-ray spectroscopy and enamel morphology by scanning electron microscopy. Statistical analyses included the Kruskal-Wallis and Dunn's tests, mixed models, and ANOVA. Results: Groups containing chitosan (7.5% HP + Chi and 7.5% HP + Ca + Chi) showed the lowest surface roughness and the highest microhardness values. For these groups, SMH showed no decrease after treatment (T2), remaining similar to the initial values (T1). Color changes were similar among all bleached groups. Calcium, phosphorus, and Ca/P levels were the same for all groups. Conclusion: Adding 2% chitosan to 7.5% hydrogen peroxide-based at-home bleaching gels appears to be a promising approach to protect enamel against changes in roughness, microhardness, and mineral content without compromising bleaching efficacy.
subject: Original Articles
  topic: section
subject: Chitosan
  topic: keywords
subject: Calcium
  topic: keywords
subject: Bleaching
  topic: keywords
subject: Enamel microhardness
  topic: keywords
subject: Surface roughness
  topic: keywords
creator: Laura Nobre Ferraz
creator: Letícia de Souza Franco
creator: Carolina Meneghin Barbosa
creator: Marcos Roberto de Lima Benati
creator: Tatiane Cristina Dotta
creator: Waldemir Francisco Vieira-Junior
creator: Débora Alves Nunes Leite Lima
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20250513
ending page: e20250513
doi: 10.1590/

Integrated analysis identifies CCNA2 as a candidate diagnostic and prognostic biomarker in oral tongue squamous cell carcinoma
type: item
description: Background Oral tongue squamous cell carcinoma (OTSCC) is an aggressive malignancy with poor prognosis, necessitating reliable biomarkers. Methodology Genes with significantly higher expression in OTSCC tumor tissues compared to normal tongue tissues were identified via integrated transcriptomic analysis of seven GEO datasets. To assess their diagnostic and prognostic potential, these genes were further characterized using multi-omic and clinical data from the TCGA-OTSCC and CPTAC-OTSCC cohorts. Results A total of 1,117 genes were found to be upregulated in OTSCC tissues, among which only CCNA2 (Cyclin A2) was significantly associated with both reduced overall survival (OS) and disease-free survival (DFS) in the TCGA-OTSCC cohort (n=128), based on Cox proportional hazards regression and Kaplan–Meier analyses. CCNA2 showed moderate prognostic performance (AUC=0.63 for OS; AUC=0.65 for DFS) and was significantly upregulated in higher-grade tumors (p=0.01) and in deceased patients (p=0.03). No somatic mutations or promoter methylation alterations were observed in CCNA2 based on TCGA data. In CPTAC-OTSCC samples (n=18), CCNA2 protein expression was significantly higher in tumor tissues than in non-tumoral tissues (p <0.0001), with a positive correlation between mRNA and protein levels (r=0.56, p=0.01). Both mRNA and protein forms showed strong diagnostic performance (AUC=0.92 and AUC=0.82, respectively), consistent with observations across multiple tumor types. While CCNA2 protein levels showed prognostic relevance for OS (AUC=0.69, p=0.01), the mRNA-based prediction did not reach statistical significance (AUC=0.63, p=0.36). Functional enrichment analysis of CCNA2 co-expressed genes predicted involvement in cell cycle, mismatch repair, and DNA replication pathways. Additionally, protein–protein interaction analysis positioned CCNA2 as a central hub, suggesting its potential role in OTSCC pathogenesis. Conclusions These findings indicate that CCNA2 is a promising diagnos…
subject: Original Articles
  topic: section
subject: Squamous cell carcinoma of head and neck
  topic: keywords
subject: Biomarkers
  topic: keywords
subject: Prognosis
  topic: keywords
subject: Gene expression
  topic: keywords
subject: CCNA2 protein, human
  topic: keywords
creator: Ceren Gumedag
creator: Sevcan Atay
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20260618
ending page: e20260618
doi: 10.1590/1678-7765-2025-0618

Evaluation of bleaching efficacy and cytotoxicity of an experimental hydrogel containing MnO-Doped Biosilicate® activated by violet LED light
type: item
description: Although hydrogen peroxide (HP) at 35% is effective in dental bleaching, the cytotoxicity associated with its use remains a significant concern. In this context, this study aimed to develop a bleaching hydrogel containing 6% HP, Biosilicate® (BioS) doped with manganese oxide (MnO_BioS), and irradiated with violet LED light (LED). Enamel/dentin discs were submitted to the following bleaching treatments (n=08): 35%HP (positive control), 6%HP gel containing BioS or MnO_BioS (0 and 10 wt%), with or without LED irradiation. The discs were adapted to artificial pulp chambers (APCs), with the enamel exposed for bleaching and the dentin facing the culture medium (DMEM). Bleaching was performed in three 30-minute sessions with 7-day intervals. After bleaching, the extracts (DMEM + bleaching gel components diffused through the discs) were collected and applied to the odontoblast-like MDPC-23 cells. Color change (ΔE00) and changes in the whiteness index (ΔWID) were determined before (T0) and after the last bleaching session (T2). Cell viability (MTT, %), HP diffusion (µg/mL), oxidative cell stress (OxS), and cell fluorescence (live/dead assay, by confocal microscopy) were assessed after the first session (T1). The data were analyzed using ANOVA and Tukey’s test (p=0.05). The addition of 6%HP_MnO_BioS_LED exceeded ΔWID compared to 35%HP, showing statistical differences from the other groups, while ΔE00 was statistically similar to 35%HP. 6%HP_MnO_BioS_LED demonstrated higher cell viability, lower HP diffusion, and reduced oxidative stress (OxS) compared to the other groups (p<0.05). 6%HP_MnO_BioS_LED increased bleaching potential and presented lower cytotoxicity compared to 35%HP.
subject: Original Articles
  topic: section
subject: Hydrogen peroxide
  topic: keywords
subject: Biosilicate
  topic: keywords
subject: Cytotoxicity
  topic: keywords
creator: Rafael Dascanio
creator: Rafael Antonio de Oliveira Ribeiro
creator: Marina Trevelin Souza
creator: Matheus Kury
creator: Edgar Dutra Zanotto
creator: Carlos Alberto de Souza Costa
creator: Vanessa Cavalli
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20250503
ending page: e20250503
doi: 10.1590/1678-7765-2025-0503

Notch2 is involved in regulating apical tissue repair following severe intrusive luxation
type: item
description: This study aims to characterize apical repair dynamics in immature permanent teeth after severe intrusive luxation, and to explore Notch signaling pathway regulation in this process using a Sprague-Dawley rat model. Methodology In this study, a modified tool was utilized to establish an intrusive luxation model in SD rats. Tissue repair was assessed via micro-computed tomography (Micro-CT) and hematoxylin-eosin (H&E) staining. Differential gene expression analysis of stem cells from the apical papilla (SCAPs) was performed using the publicly available GEO dataset. Immunohistochemical detection of Notch2 receptor expression in the apical region of injured teeth was subsequently conducted, guided by bioinformatics screening. Finally, the Notch signaling pathway was pharmacologically inhibited using DAPT (γ-secretase inhibitor), and its impact on post-injury prognosis was evaluated. Results Histological analysis revealed prevalent pulp hypoplasia and apical tissue fibrosis after injury. Differential gene analysis suggested that the Notch signaling pathway, particularly Notch2, is involved in the regulation of angiogenesis-related pathways in SCAPs. Immunohistochemistry showed positive Notch2 expression in fibrotic apical regions. Notably, inhibition of Notch signaling significantly reduced aberrant fibrosis while enhancing vascular proliferation in the injury site. Conclusions Severe intrusive luxation is primarily characterized by aberrant fibrous differentiation in the apical region. The Notch signaling pathway may negatively regulate angiogenesis in the damaged apical area, suggesting that targeted inhibition of this pathway could promote tissue repair following embedded dental injuries.
subject: Original Articles
  topic: section
subject: Intrusive luxation
  topic: keywords
subject: Notch signaling pathway
  topic: keywords
subject: Apical repair
  topic: keywords
subject: Angiogenesis
  topic: keywords
subject: Fibrillization
  topic: keywords
creator: Yuanpei He
creator: Xuyan Gong
creator: Cancan Ding
creator: Yang Qiu
creator: Guangwen Li
creator: Shiting Li
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20250490
ending page: e20250490
doi: 10.1590/1678-7765-2025-0490

Bioactive luting cements on the adhesive interface of fiber post and root dentin
type: item
description: Innovative self-etching dental cements have been considered a versatile material with recent formulations incorporating bioactive additives. Objective This study analyzed the role of these ingredients in systems used for luting intracanal posts. Methodology Bond strength (BS), water sorption (WS), water solubility (WSB), and in situ zymography (IZ) were assessed. Three cements were tested: RelyX U200 (RU, bioactive-free control), RelyX Luting Plus (RL, fluoride-containing glass-ionomer), and BeautiCem SA (BC, S-PRG-based). Bond strength was evaluated in bovine root dentin (n=10) at the cervical, middle, and apical thirds at 7 days and 6 months. WS/WSB were assessed using 10 cement disks (10×1 mm) cycled through deionized water immersion (m1), desiccation (m2), and a second immersion (m3). For IZ, the specimens (n=3) were sectioned and incubated with fluorescein-conjugated gelatin for 48h at 37°C at both storage times (7 days and 6 months) for analysis by Confocal Laser Scanning Microscopy. Fluorescence intensity was quantified using Image J. Data were analyzed using ANOVA and Tukey’s test (p<0.05). Results RU presented the highest BS and the lowest WS/WSB, while RL showed the opposite trend. BC demonstrated intermediate performance with no statistical differences from the other materials. For all cements, the cervical third and the 6-month period yielded the highest BS values. WS/WSB were greater for the bioactive cements (BC, RL). IZ results aligned with BS findings, revealing suppressed enzymatic activity over time. Based on these results, it can be concluded that RU exhibited superior mechanical stability despite lacking bioactivity. Conclusion Among bioactive cements, BC emerged as an interesting alternative, offering improved bond strength, water stability, and bioactive potential compared to RL.
subject: Original Articles
  topic: section
subject: Bioactivity
  topic: keywords
subject: Dental cements
  topic: keywords
subject: Sorption and solubility
  topic: keywords
subject: Tensile strength
  topic: keywords
subject: Zymography
  topic: keywords
creator: Tiago Carvalho dos Santos
creator: Giovanna Speranza Zabeu
creator: Ana Carolina Almeida Lima
creator: Mylena Proença Costa
creator: Marcela Rocha Carrilho
creator: Linda Wang
rights: Copyright (c) 2026 Tiago Carvalho dos Santos, Giovanna Speranza Zabeu, Ana Carolina Almeida Lima, Mylena Proença Costa, Marcela Rocha Carrilho, Linda Wang https://creativecommons.org/licenses/by/4.0
date: 2026-03-02
publication date: 2026-03-02
starting page: e20250576
ending page: e20250576
doi: 10.1590/1678-7765-2025-0576

Shades of knowledge
type: item
description: Tooth discoloration is a frequent concern among dental patients. While many professionals and patients choose veneers or other invasive solutions, Minimal Intervention Dentistry (MID) recommends non- and microinvasive approaches to preserve tooth structure. Objective To assess Brazilian dentists’ knowledge and practices on tooth discoloration and how education and professional profile may influence them. Methodology A cross-sectional observational study was conducted with 384 volunteer dentists via an online series of questions on causes, diagnosis, treatment (per tissue removal), and professional-patient relationship. Answers were scored (1=correct/affirmative, 0=incorrect/negative). Descriptive and multivariate regression analyses were performed (α=0.05). Results Most respondents were female, aged 20-49, from the Southeast region. Correct answer rates: 69.9% for causes, 69.4% for diagnosis, 48.8% for treatment, 83.6% for professional-patient relationship, 56.4% overall. Graduation from public universities and holding graduate training in Operative or Pediatric Dentistry or Orofacial Harmonization were associated with better outcomes. Conclusion Knowledge of non- and microinvasive approaches to tooth discoloration remains limited. Broader educational efforts are needed, especially among specific groups of professionals who showed lower performance.
subject: Original Articles
  topic: section
subject: Tooth discoloration
  topic: keywords
subject: Tooth bleaching
  topic: keywords
subject: Resin infiltration
  topic: keywords
subject: Enamel microabrasion
  topic: keywords
subject: Dental education
  topic: keywords
creator: Giovanni Aguirra Giovanni Aguirra
creator: Karin Landmayer
creator: Bruna de Oliveira Iatarola
creator: Maria Paula Novaes Camargo Manna
creator: Raquel Shimizu Mori
creator: Flávia Pardo Salata Nahsan
creator: Heitor Marques Honório
creator: Luciana Fávaro Francisconi-dos-Rios
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-02-16
publication date: 2026-02-16
starting page: e20250589
ending page: e20250589
doi: 10.1590/1678-7765-2025-0589

Effects of bromelain, melatonin, and thymoquinone on neutrophil extracellular trap formation and macrophage polarization in experimental periodontitis
type: item
description: Periodontitis is a chronic inflammatory disease characterized by dysregulated immune responses leading to alveolar bone loss. Formation of neutrophil extracellular traps and macrophage polarization play critical roles in its pathogenesis, and natural agents with immunomodulatory properties are being investigated as potential adjunctive therapies. Objective This study aimed to compare the effects of systemically administered melatonin, bromelain, and thymoquinone on serum neutrophil extracellular trap formation and macrophage polarization in experimental periodontitis. Methodology Forty rats were assigned to five groups: control, experimental periodontitis, and experimental periodontitis treated with melatonin, bromelain, or thymoquinone. Periodontitis was induced by ligature placement for 14 days. After ligature removal, the treatment groups received daily oral doses of melatonin, bromelain, or thymoquinone for 14 consecutive days. Biochemical, histologic, histomorphometric, and immunohistochemical analyses were performed. Comparisons between groups were performed using one-way ANOVA. Neutrophil extracellular trap levels measured before and after treatment within the same group were analyzed using a paired t-test. Results Thymoquinone treatment significantly reduced alveolar bone loss compared to the bromelain and melatonin groups (p=0.00). The highest value was observed in the Periodontitis group and the lowest in the Thymoquinone group for neutrophil extracellular trap levels, with intergroup comparisons showing no statistically significant differences (p=0.597). All immunohistochemical analyses showed significant differences in all treatment groups compared to both the control and periodontitis groups (p=0.000). CD68(+) macrophages were most abundant in the periodontitis group and least in the Melatonin group (p=0.00). CD80 expression was highest in the Melatonin group and lowest in the Thymoquinone group (p=0.000), while CD206 expression was highest in the Brome…
subject: Original Articles
  topic: section
subject: Adjuvants
  topic: keywords
subject: Alveolar bone loss
  topic: keywords
subject: Macrophages
  topic: keywords
subject: Immunologic factors
  topic: keywords
subject: Rats
  topic: keywords
creator: Şükran Acipinar
creator: Mustafa Ozkaraca
creator: Ufuk Okkay
creator: Ali Sefa Mendil
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-02-16
publication date: 2026-02-16
starting page: e20260699
ending page: e20260699
doi: 10.1590/1678-7765-2025-0699

DNA methyltransferases expressions in mice tongue exposed to waterpipe smoke
type: item
description: Objective Waterpipe smoking has gained widespread use nowadays, especially among young adults. As this type of smoke has been described to contain toxins and carcinogens, this study evaluated DNA methyltransferase (DNMT) 1 and 3b expression, and inflammation, on the dorsal surface, ventral surface and lateral border of Swiss mice’s tongues exposed to waterpipe smoke. Methodology Animals were divided into 6 groups (n=60): control, 7, 15, 30, 60, and 90 days of consecutive exposure to waterpipe smoke in a whole-body exposure system. After each period, tongues were analyzed using hematoxylin/eosin staining for inflammation status and immunohistochemistry for DNMT1 and DNMT3b. Results DNMT3b showed lower immunoexpression from 7 to 60 days; at 90 days, expression was similar to that of control or there was upregulation on the ventral surface compared with control. DNMT1 exhibited lower expression at all exposure times, with the ventral surface showing similar expression to that of control at 90 days. Waterpipe smoke was not able to induce acute or chronic inflammation in mice tongue. Conclusion Waterpipe smoke may result in a DNA hypomethylation pattern in initial exposure periods, contributing to activate proto-oncogenes and/or genomic instability. Over long periods, it may lead to a methylation pattern similar to that of control or even to hypermethylation, silencing tumor suppressor genes. These alterations in the genome due to hypo/hypermethylation contribute largely for the development of diseases such as oral cancer.
subject: Original Articles
  topic: section
subject: Waterpipe Smoking
  topic: keywords
subject: Squamous Cell Carcinoma of Head and Neck
  topic: keywords
subject: Epigenomics
  topic: keywords
subject: DNA Methylation
  topic: keywords
subject: DNA (Cytosine-5-)-Methyltransferase 1
  topic: keywords
subject: DNA methyltransferase 3B
  topic: keywords
creator: Carolina Simão Flausino
creator: Sarah Freygang Mendes Pilati
creator: Filipe Ivan Daniel
creator: Filipe Modolo
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-02-20
publication date: 2026-02-20
starting page: e20250665
ending page: e20250665
doi: 10.1590/

Maqui berry cystatin inhibits cathepsin k activity and stimulates osteogenic differentiation of human dental pulp cells
type: item
description: Objectives Cystatins, endogenous inhibitors of cysteine proteases, regulate extracellular matrix degradation. Their plant-derived homologs (phytocystatins) include MaquiCPI-3, a recombinant protein obtained from Aristotelia chilensis (maqui berry). This study aimed to investigate the inhibitory effect of MaquiCPI-3 on human cathepsin K (CTSK) activity and its cytotoxicity and impact on the proliferation, migration, and osteogenic differentiation of human dental pulp cells (hDPCs). Methodology The inhibitory activity of MaquiCPI-3 against CTSK was measured using a spectrofluorometer with the fluorogenic substrate Z-Phe-Arg-AMC. The hDPCs from third molars were characterized by flow cytometry for mesenchymal (CD90, CD73, CD105) and hematopoietic (CD34, CD45) markers. The hDPCs, either exposed to MaquiCPI-3 or left untreated (control), were assessed for viability (MTT assay), proliferation (bromodeoxyuridine incorporation), chemotaxis (Transwell assay), mineralized nodule formation (Alizarin Red S staining), alkaline phosphatase activity (thymolphthalein release), and expression of mineralization-related genes (qPCR). Data were analyzed using one- or two-way ANOVA with appropriate post hoc tests or nonparametric alternatives (α=0.05). Results MaquiCPI-3 potently inhibited CTSK (Ki=1.72 nM, Ki,app=2.08 nM), showed no cytotoxicity, and significantly enhanced ALP activity, mineralized nodule formation, and expression of BMP-2 and osteocalcin, stimulating no hDPC proliferation or migration when compared with the control. Conclusions MaquiCPI-3 increased no cell proliferation or migration, its ability to inhibit CTSK activity and induce an osteogenic phenotype shows promising potential therapeutic strategies aimed at repairing and regenerating pulp and periapical tissues and controlling bone resorption.
subject: Original Articles
  topic: section
subject: Cathepsin K
  topic: keywords
subject: Cystatins
  topic: keywords
subject: Dental pulp
  topic: keywords
creator: Luana Raphael da Silva
creator: Eduardo Pereira de
creator: Bárbara Roma Mendes
creator: Breno Henrique Amancio
creator: Flávio Henrique-Silva
creator: Gisele Faria
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-02-16
publication date: 2026-02-16
starting page: e20250661
ending page: e20250661
doi: 10.1590/1678-7765-2025-0661

Diversity of Streptococcus mutans serotypes isolated from dental plaque of Brazilian patients with a history of acute myocardial infarction
type: item
description: Background: Streptococcus mutans serotypes (c, e, f, k) are linked to dental caries, with less common serotypes (e, f, k) and collagen-binding genes (CBG: cnm and cbm) suggested to be associated with cardiovascular diseases. Objective: This study investigated the presence of S. mutans serotypes and collagen-binding genes (CBGs) in dental plaque and their possible association with acute myocardial infarction (AMI) in adults. Methodology: A total of 31 infarcted and 17 non-infarcted patients underwent oral and blood examinations. DNA from plaque samples was analyzed using PCR to identify S. mutans serotypes and cnm/cbm genes. S. mutans was detected in 22.6% (7/31) of infarcted patients and 11.8% (2/17) of non-infarcted patients. Results: Serotype c was the most prevalent in infarcted patients (57.1%, 4/7), followed by e (42.9%, 3/7) and k (14.3%, 1/7); serotype f was not detected. Only serotype c was found in non-infarcted patients. Less common serotypes (e, k) and co-occurring serotypes (c, k) were exclusive to infarcted patients. No CBGs were detected in any serotypes. No association was found between S. mutans and dental caries in either group. Patients with cholesterol levels <190 mg/dL and no S. mutans had a 47.4% lower risk of infarction. Conclusion: Although S. mutans, including less common serotypes, was more prevalent in infarcted patients, no significant association with AMI was observed. Further research is needed to elucidate the role of S. mutans in cardiovascular diseases.
subject: Original Articles
  topic: section
subject: Streptococcus mutans
  topic: keywords
subject: Dental caries
  topic: keywords
subject: Cardiovascular diseases
  topic: keywords
subject: Serotyping
  topic: keywords
subject: Collagen-binding genes
  topic: keywords
creator: Francisco Ruliglésio Rocha
creator: Wanessa Fernandes Matias Regis
creator: Rochelle Pinheiro Ribeiro
creator: João Eudes Teixeira Pinho Filho
creator: Tiago Lima Sampaio
creator: Raquel Carvalho Montenegro
creator: Ana Paula Negreiros Nunes Alves
creator: Lidiany Karla Azevedo Rodrigues
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-02-02
publication date: 2026-02-02
starting page: e20250077
ending page: e20250077
doi: 10.1590/1678-7765-2025-0077

SHED-exosomes functionalized micro-nano bioactive glass/PCL membrane regulates macrophage polarization and promotes osteogenic differentiation
type: item
description: Micro-nano bioactive glass (MNBG) has bone regenerative potential. However, the difficulty of MNBG molding restricts its clinical applications in bone regeneration. Exosomes carry proteins, lipids, and nucleic acids for communication between cells. In this study, we adhered human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exos) to electrospun micro-nano bioactive glass/polycaprolactone (MNBG/PCL) membrane to control inflammation and promote bone regeneration. MNBG/PCL membrane showed biocompatibility and osteogenic ability. Next, we demonstrated that SHED-Exos internalized into macrophages attenuated LPS-induced expression of M1-macrophage markers iNOS, IL-6, and IL-1β and upregulated M2-macrophage marker IL-10 expression, indicating a switch from M1 to M2 macrophage phenotype. MNBG/PCL-loaded SHED-Exos membrane supported the survival and growth of mouse bone marrow stromal cells (mBMSCs). When M1 macrophages were co-cultured with mBMSCs on the membrane, the SHED-Exos-loaded membrane showed higher Runx2, Alp, and Ocn gene expression. Our findings indicate that SHED-Exos-functionalized MNBG/PCL membrane has anti-inflammatory and osteoinductive potential, suggesting its potential as a candidate material for bone regeneration.
subject: Original Articles
  topic: section
subject: Micro-nano bioactive glass
  topic: keywords
subject: Exosomes
  topic: keywords
subject: Stem cell
  topic: keywords
subject: Osteogenic differentiation
  topic: keywords
subject: Macrophage polarization
  topic: keywords
creator: Yongyong Yan
creator: Haifeng Lan
creator: Guohou Miao
creator: Haiyan Wang
creator: Zhengmao Li
creator: Qing Zhang
creator: Shuai Wang
creator: Gang Wu
creator: Richard T. Jaspers
creator: Janak L. Pathak
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by/4.0
date: 2026-01-30
publication date: 2026-01-30
starting page: e20250541
ending page: e20250541
doi: 10.1590/1678-7765-2025-0541

Factors associated with orofacial myofunctional condition in patients with temporomandibular disorder and somatosensory tinnitus
type: item
description: Tinnitus is frequently reported in individuals with temporomandibular disorders (TMD), especially in the somatosensory subtype, which can be modulated by afferent input from orofacial and cervical structures. While the impact of orofacial dysfunctions on tinnitus has been explored, the potential reverse relationship remains understudied. Objective To investigate the association between somatosensory tinnitus and orofacial myofunctional condition in individuals with TMD. Methodology An observational, cross-sectional study was conducted with 47 adults aged 18 to 45 years diagnosed with TMD and self-reported tinnitus. Participants were assessed in a university-based outpatient setting. The primary outcome was the orofacial myofunctional condition, measured using the Orofacial Myofunctional Evaluation with Scores (OMES) protocol. Additional variables included tinnitus intensity and frequency (via acuphenometry), tinnitus-related distress (Tinnitus Handicap Inventory – THI), cervical disability (Neck Disability Index – NDI), craniofacial pain and disability (Craniofacial Pain and Disability Inventory – CF-PDI), and psychological symptoms (Hospital Anxiety and Depression Scale – HADS). Data were analyzed using Spearman correlation and multiple linear regression, and adopted statistical significance was set at p<0.05. Results OMES scores showed negative correlations with tinnitus intensity (r=−0.353), THI, NDI, CF-PDI, and age. In the final regression model, only tinnitus intensity remained a predictor of OMES score (β =−0.356; R2=0.127, Confidence Interval −0.20 to −0.02), indicating that greater tinnitus intensity was associated with poorer orofacial myofunctional condition. Conclusion These findings suggest that somatosensory tinnitus may negatively impact orofacial motor function in patients with TMD, underscoring the need for integrated and multidisciplinary assessment approaches.
subject: Original Articles
  topic: section
subject: Tinnitus
  topic: keywords
subject: Temporomandibular joint disorder
  topic: keywords
subject: Stomatognathic system
  topic: keywords
subject: Orofacial pain
  topic: keywords
subject: Craniofacial pain
  topic: keywords
creator: Gislaine Aparecida Folha
creator: Nelma Ellen Zamberlan-Amorim
creator: Carina Ferreira Pinheiro-Araujo
creator: Luana Maria Ramos Mendes
creator: Gesseany Joice Rodrigues dos Santos
creator: Debora Bevilaqua-Grossi
rights: Copyright (c) 2026 Gislaine Aparecida Folha, Nelma Ellen Zamberlan-Amorim, Carina Ferreira Pinheiro-Araujo, Luana Maria Ramos Mendes, Gesseany Joice Rodrigues dos Santos, Debora Bevilaqua-Grossi https://creativecommons.org/licenses/by/4.0
date: 2026-01-16
publication date: 2026-01-16
starting page: e20250515
ending page: e20250515
doi: 10.1590/1678-7765-2025-0515

Genetic variants of EBI3, tumor Epstein-Barr virus, and human cytomegalovirus status in HPV-negative oral cancer
type: item
description: Oral squamous cell carcinoma (OSCC), a malignancy with high recurrence rate and poor survival, may be influenced by immune-related genetic variations and oncogenic viruses. Objective This study evaluated the clinical relevance of EBI3 polymorphisms, along with tumor Epstein–Barr virus (EBV) and Human Cytomegalovirus (HCMV) status, in prognostically adverse HPV-negative OSCCs. Methodology EBI3 (rs4740, rs4905, rs428253) genotyping was performed by qPCR in 95 HPV-negative OSCC patients and 108 age- and sex-matched controls. Tumor HPV, EBV, and HCMV status were assessed by qPCR. EBV viral load was calculated by exponential approach and a relative estimate of EBV copies per 105 cells. Associations with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier and Cox regression analyses. Results EBV-positive tumors showed a significant association with increasing nodal stage (P=0.020). EBV viral load stratification (negative, low, high) presented a non-significant trend toward association with advanced tumor stage (P=0.060). Notably, EBI3 rs428253 predicted worse OS in EBV-positive patients, whereas rs4740 and rs4905 variants were associated with advanced tumor stage (P=0.024 and P=0.018). rs4740 and rs4905 variants were inversely associated with OSCC risk in dominant and overdominant models. Analysis detected HCMV in 7.4% of tumors but was not clinically relevant. Conclusions EBI3 genetic variants and EBV status may have prognostic relevance in HPV-negative OSCC. EBV may interact with the host genetics to influence nodal metastases and outcomes, suggesting a potential EBV-EBI3 axis, which warrants further investigation. Future precision oncology approaches may incorporate host and viral genetic markers to identify and stratify high-risk HPV-negative OSCC patients.
subject: Original Articles
  topic: section
subject: Mouth Neoplasms
  topic: keywords
subject: Oral Squamous Cell Carcinoma
  topic: keywords
subject: Epstein-Barr virus
  topic: keywords
subject: Human Cytomegalovirus
  topic: keywords
subject: Epstein-Barr Virus induced gene 3
  topic: keywords
subject: Single nucleotide polymorphisms
  topic: keywords
creator: Marko Simonovic
creator: Ruzica Kozomara
creator: Sasa Jovic
creator: Gordana Velikic
creator: Elizabeta Ristanovic
creator: Nikoleta Djordjevski
creator: Danijela Djuric-Petkovic
creator: Srboljub Stosic
creator: Gordana Supic
rights: Copyright (c) 2026 Marko Simonovic, Ruzica Kozomara, Sasa Jovic, Gordana Velikic, Elizabeta Ristanovic, Nikoleta Djordjevski, Danijela Djuric-Petkovic, Srboljub Stosic, Gordana Supic https://creativecommons.org/licenses/by/4.0
date: 2026-01-26
publication date: 2026-01-26
starting page: e20250492
ending page: e20250492
doi: 10.1590/1678-7765-2025-0492