Ian Wesley Rocha dos Santos, Deiweson Souza-Monteiro, Deborah Ribeiro Frazão, Zuleni Alexandre Lisboa da Silva, João Daniel Mendonça de Moura, Jorddy Neves Cruz, Fabrício Mezzomo Collares, Renata Duarte de Souza-Rodrigues, Luciano Tavares Ângelo Cintra, Rafael Rodrigues Lima
{"title":"N-Acetylcysteine Reduces Alveolar Bone Loss and Mitigates Systemic Oxidative Damage in Rats With Apical Periodontitis","authors":"Ian Wesley Rocha dos Santos, Deiweson Souza-Monteiro, Deborah Ribeiro Frazão, Zuleni Alexandre Lisboa da Silva, João Daniel Mendonça de Moura, Jorddy Neves Cruz, Fabrício Mezzomo Collares, Renata Duarte de Souza-Rodrigues, Luciano Tavares Ângelo Cintra, Rafael Rodrigues Lima","doi":"10.1111/iej.70108","DOIUrl":"10.1111/iej.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to evaluate the effects of N-acetylcysteine (NAC) supplementation in apical periodontitis (AP) induced in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Eighteen male Wistar rats were randomly assigned to three groups: control, AP, and AP plus NAC. NAC was administered by oral gavage (100 mg/kg/day), beginning 1 day after lesion induction and continued daily until the day preceding euthanasia. AP induction was performed by exposing the dental pulp of the lower first molars bilaterally, maintaining this condition for 28 days. After this period, the animals were euthanized, and the following biological materials were collected: blood (for systemic oxidative stress analysis) and hemimandibles for histopathological and histochemical, and micro-computed tomography analyses, aiming to measure bone quality parameters and periapical volume. Statistical analyses were performed using one-way ANOVA and Tukey's post hoc test. In addition, correlation analyses and multivariate analyses of variance (MANOVA) were performed on the biochemical parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study results showed that animals supplemented with NAC had greater preservation of bone quality parameters and a reduction in periapical volume progression when compared to the only apical periodontitis group. Additionally, in the analysis of systemic oxidative stress, supplemented animals showed higher antioxidant parameter levels and lower oxidant levels compared to non-supplemented animals, which also showed reduced preservation of bone collagen content.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study findings suggest that NAC supplementation promoted greater preservation of bone quality, reduced periapical volume development, and modulation of endogenous antioxidant and oxidant aspects. This indicates that NAC can decrease local and systemic damage caused by AP, highlighting its potential as an adjunctive agent in processes involving systemic oxidative stress and the preservation of biological structures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"890-902"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matheus Ferreira Lima Rodrigues, Deborah Ribeiro Frazão, Deiweson Souza-Monteiro, Vinicius Ruan Neves dos Santos, Felipe Oliveira Nunes, João Daniel Mendonça de Moura, Thamires Campos Gomes, Jorddy Neves Cruz, Cristiane do Socorro Ferraz Maia, Rodrigo A. Cunha, Fabrício Mezzomo Collares, Rogerio de Castilho Jacinto, Rafael Rodrigues Lima
{"title":"Integrative Computational and Experimental Approaches Reveal the Protective Role of Moderate Caffeine Intake Against Apical Periodontitis Induced Bone Loss","authors":"Matheus Ferreira Lima Rodrigues, Deborah Ribeiro Frazão, Deiweson Souza-Monteiro, Vinicius Ruan Neves dos Santos, Felipe Oliveira Nunes, João Daniel Mendonça de Moura, Thamires Campos Gomes, Jorddy Neves Cruz, Cristiane do Socorro Ferraz Maia, Rodrigo A. Cunha, Fabrício Mezzomo Collares, Rogerio de Castilho Jacinto, Rafael Rodrigues Lima","doi":"10.1111/iej.70105","DOIUrl":"10.1111/iej.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate whether moderate systemic caffeine intake modulates the progression of apical periodontitis (AP) and associated alveolar bone loss, combining in vivo rat experiments with <i>in silico</i> molecular docking to explore potential mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Male Wistar rats were randomly assigned to four groups (<i>n</i> = 8 per group): control, caffeine, AP, AP + caffeine. AP was induced by pulp exposure of mandibular first molars and allowed to develop for 28 days. Animals in caffeine groups received 10 mg/kg/day by orogastric gavage during the experimental period. The antioxidant capacity of caffeine was assessed by DPPH• and ABTS• + assays. Systemic oxidative status was evaluated by blood reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Histology, Picro-Sirius red staining for collagen, and micro-computed tomography (micro-CT) analysis of alveolar bone (BV/TV, Tb.N, Tb.Sp, porosity, lesion volume) were performed. Molecular docking against adenosine A<sub>1</sub> and A<sub>2</sub><sub>A</sub> receptors was used to probe caffeine–receptor interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Caffeine showed relevant radical-scavenging activity in vitro (DPPH• assay). AP induced systemic redox imbalance, marked inflammatory infiltration, collagen loss and increased lesion volume. Moderate caffeine intake restored redox markers (↑GSH, ↓TBARS), attenuated inflammatory infiltrate, preserved collagen content and reduced lesion volume (AP + caffeine vs. AP; <i>p</i> < 0.05). Micro-CT demonstrated improved alveolar bone microarchitecture in AP + caffeine group (increased BV/TV and Tb.N; reduced Tb.Sp and porosity). Molecular docking indicated stable hydrophobic and hydrogen-bond interactions of caffeine within A<sub>1</sub> and A<sub>2</sub><sub>A</sub> receptor binding pockets, supporting an antagonistic effect on adenosine signalling consistent with reduced pro-inflammatory activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Moderate systemic caffeine (10 mg/kg/day) attenuates apical periodontitis progression and preserves alveolar bone quality in rats, associated with antioxidant activity and a probable modulation of adenosine receptor-mediated inflammatory pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"873-889"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco A. Versiani, Michael Solomonov, Felipe G. Belladonna, Emmanuel J. N. L. Silva, Erick Souza, Rebecca R. G. Frota, Joe Ben-Itzhak, Gustavo De-Deus
{"title":"Time-Dependent Debridement Quality of the SAF Infinitum System in Flat-Shaped Root Canals","authors":"Marco A. Versiani, Michael Solomonov, Felipe G. Belladonna, Emmanuel J. N. L. Silva, Erick Souza, Rebecca R. G. Frota, Joe Ben-Itzhak, Gustavo De-Deus","doi":"10.1111/iej.70099","DOIUrl":"10.1111/iej.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the shaping ability, debris removal efficiency and morphological alterations induced by the SAF Infinitum system during progressive instrumentation of flat-shaped root canals of mandibular incisors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Twelve extracted mandibular incisors with flat-shaped canals were selected using micro-CT and instrumented with 1.5-mm Self-Adjusting File (SAF) Infinitum instruments under continuous NaOCl-HEDP irrigation for 2, 4 and 6 min. Micro-CT scans were performed before and after each step to evaluate changes in canal volume, surface area, debris removal, unprepared canal walls and dentine thickness. Following the preparation procedures, all instruments were examined under a microscope for defects. Data were analysed using GLM for repeated measures and the Related-Samples Friedman test (<i>α</i> = 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Root canal preparation with the SAF Infinitum significantly increased canal volume and surface area (<i>p</i> = 0.000), while progressively reducing unprepared canal wall areas and hard tissue debris (<i>p</i> = 0.000). Unprepared surfaces decreased by 77.8% and debris volume by 77.2% from 2 to 6 min, with improved cleaning efficiency over time. Dentine thickness also declined significantly (<i>p</i> < 0.001), particularly on the lingual surface at the pericervical area and the mesial surface at midroot. Buccolingual walls consistently remained above 1.0 mm, whereas only two mesiodistal cross-sections at the midroot level exhibited dentine thickness below 0.5 mm. After 6 min, all instruments showed structural deformations, and one specimen exhibited a minor intracanal fragment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first study to evaluate the progressive, time-dependent effects of the SAF Infinitum system in challenging flat-shaped root canals. The system exhibited a time-dependent shaping effect, with most morphological changes occurring within the first 2 min, followed by continued, although more gradual, improvements up to 6 min. Cleaning efficacy increased steadily over time, while remaining dentine thickness generally stayed above critical safety thresholds. All instruments showed structural deformations after 6-min preparation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"903-913"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimising Outcomes in Endodontic Microsurgery: Evidence, Uncertainties and Future Directions","authors":"Ukseong Kim, Euiseong Kim","doi":"10.1111/iej.70100","DOIUrl":"10.1111/iej.70100","url":null,"abstract":"<p>Endodontic microsurgery (EMS) is a reliable treatment modality for managing persistent or recurrent periapical pathologies, particularly when conventional nonsurgical retreatment is infeasible or has failed. Various factors influence EMS outcomes, among which the lesion type is a key determinant. Isolated endodontic lesions generally exhibit favourable outcomes, whereas combined endodontic–periodontal lesions and through-and-through defects are clinically challenging and associated with less predictable outcomes. The adjunctive use of regenerative procedures, such as bone grafts, barrier membranes and biologically active agents, aims to enhance periapical healing; however, current evidence remains inconclusive, and further studies with clear lesion-type classification are required to determine their true benefits. Guided surgical approaches, including static, dynamic and robot-assisted systems, have been introduced in EMS to enhance surgical precision and predictability. These technologies appear particularly beneficial in small isolated lesions or when critical anatomical structures must be protected, but further studies are required to validate their clinical effectiveness. This review encourages clinicians to approach EMS with a clear understanding of the effect of lesion type on the prognosis, and to critically assess the usefulness of adjunctive regenerative procedures and advanced technologies based on lesion-specific considerations. Although predictable outcomes are mostly dependent on sound diagnosis, thoughtful case selection, and meticulous surgical techniques, accumulating evidence and technical progress suggest that the indications for EMS may be reasonably expanded in well-selected cases.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"746-761"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KDM4D-RPS5 Complex Promoted Osteo/Dentinogenic Differentiation of DPSCs via CNR1-Maintained Mitochondrial Functional Homeostasis","authors":"Xiaoli Guo, Wanhao Yan, Wenting Wang, Benxiang Hou, Chen Zhang","doi":"10.1111/iej.70102","DOIUrl":"10.1111/iej.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Despite significant advances in dental pulp stem cell (DPSC)-based regeneration of the pulp-dentine complex, regulating the directed differentiation of these cells remains a key challenge. The present study investigated the role and underlying mechanism of the KDM4D-RPS5 complex in modulating the odontogenic differentiation of DPSCs, with the goal of providing insights to inform strategies for tooth tissue regeneration and repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>To assess the osteo/dentinogenic differentiation capacity of DPSCs, multiple techniques were employed, including alkaline phosphatase (ALP) activity assays, Alizarin Red S staining, quantitative calcium analysis, and detection of osteo/dentinogenic marker expression. Gene expression levels were quantified using quantitative real-time polymerase chain reaction and Western blot. Chromatin immunoprecipitation and co-immunoprecipitation (Co-IP) assays were performed to investigate the underlying molecular mechanisms. Mitochondrial morphology in DPSCs was observed via transmission electron microscopy (TEM), while the oxygen consumption rate was measured using a Seahorse XF Analyser, and mitochondrial membrane potential was assessed with a JC-10 assay. Finally, the in vivo efficacy of odontogenic differentiation was validated through a subcutaneous transplantation assay in nude mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first demonstrated that KDM4D significantly promoted the osteo/dentinogenic differentiation of DPSCs. Furthermore, KDM4D bound directly to RPS5 via a specific structural domain to form a functional complex; disruption of this binding site abolished its capacity to drive differentiation. Mechanistically, ChIP assays revealed that the KDM4D–RPS5 complex epigenetically activated the downstream gene CNR1 by demethylating H3K9me2 at its promoter, thereby facilitating DPSC differentiation. Additionally, mitochondrial functional analysis showed that overexpression of KDM4D, RPS5, or CNR1 enhanced mitochondrial membrane potential and augmented energy metabolism, further supporting the differentiation process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KDM4D bound to RPS5 to form a protein complex, which regulated the demethylation of CNR1 H3K9me2 and further influenced the osteo/dentinogenic differentiation of DPSCs by promoting mitochondrial energy metabolism. These findings identify the KDM4D-RPS5-CNR1 axis as a promising therapeutic target for enhancing DPSC-based dental tissue regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"836-851"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katrine Johannsen, Jennifer Christensen, Lise-Lotte Kirkevang, Louise Hauge Matzen, Rubens Spin-Neto
{"title":"Dental-Dedicated MRI in the Assessment of Pulp Vitality and Apical Periodontitis: A Feasibility Study","authors":"Katrine Johannsen, Jennifer Christensen, Lise-Lotte Kirkevang, Louise Hauge Matzen, Rubens Spin-Neto","doi":"10.1111/iej.70101","DOIUrl":"10.1111/iej.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This feasibility study presents the diagnostic accuracy of a novel dental-dedicated magnetic resonance imaging (ddMRI) system for assessing pulp vitality and diagnosing apical periodontitis (AP), as an adjunct to clinical assessment and cone beam CT (CBCT) imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten consecutive patients with possible endodontic problems were screened, and ultimately 18 teeth in nine patients (10 healthy teeth, five necrotic teeth with suspected AP and three necrotic or root canal treated teeth with no suspicion of AP) with a recent CBCT were included. The teeth were tested for vitality and clinical signs of AP. The CBCT volumes were assessed by three trained observers for signs of AP. The teeth were scanned using the Magnetom Free.Max Dental Edition ddMRI system (Siemens Healthineers, Forchheim, Germany), operating at 0.55 T with a seven-channel dental-dedicated surface coil. Six pulse sequences optimised for periapical diagnostics were applied, with a total scanning time of approximately 18 min per tooth. Images were assessed by three trained observers for anatomical structure conspicuity (root tip, periapical bone and lamina dura), pulp vitality determined by presence of signal and presence of AP determined by accumulation of fluid in the periapical area. The assessed pulp vitality status and presence of AP on ddMRI were compared to the clinical and radiological findings. Inter-modality agreement was calculated using kappa statistics, and diagnostic accuracy was evaluated with consensus between clinical findings and CBCT imaging as the reference standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All anatomical structures were visible in all cases. ddMRI showed high diagnostic accuracy. For pulp vitality, the inter-modality agreement kappa was 0.77 and accuracy was 0.88. For AP, the inter-modality agreement kappa was 0.87 and accuracy was 0.94.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ddMRI show promising results as a non-ionising imaging modality for assessment of pulp vitality and diagnosis of AP. This feasibility study demonstrates the potential of ddMRI to provide accurate diagnostic support, laying a foundation for larger-scale validation studies and clinical applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"776-787"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chloé Le Fournis, Thomas Giraud, Sandra Roumani, Charlotte Jeanneau, Imad About
{"title":"Macrophage-Pulp Fibroblast Interactions Modulate Initial Dental Pulp Regeneration In Vitro","authors":"Chloé Le Fournis, Thomas Giraud, Sandra Roumani, Charlotte Jeanneau, Imad About","doi":"10.1111/iej.70103","DOIUrl":"10.1111/iej.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Injured fibroblasts have been shown to play a significant role in controlling pulp inflammation and regeneration. Recent works have demonstrated that, depending on the stimulation type, fibroblasts induce macrophage differentiation into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. This work was set to study macrophage effects on the initial steps of pulp regeneration, namely on pulp stem cell (DPSC) proliferation/migration as well as on neo-angiogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Human pulp cells were isolated from third molars. DPSCs and pulp fibroblasts were obtained using cell sorting and characterisation. To mimic a deep carious lesion, fibroblasts were physically injured and incubated with Lipoteichoic Acid (LTA). Physically injured fibroblasts without adding LTA were used to simulate an inflammatory state without pathogen exposure. Undifferentiated macrophages (M0) were incubated with stimulated fibroblast supernatants to induce M1/M2 differentiation. After 24 h, the macrophage secretome was used to investigate the effects on DPSC viability with the MTT assay. Its effect on DPSC migration towards macrophages was performed using Boyden chambers. VEGF secretion by macrophages was quantified by ELISA. The macrophage secretome effect on endothelial cell viability was investigated using MTT assay, and that on neo-angiogenesis using endothelial cell organisation on Matrigel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The role played by macrophages in the initial steps of pulp inflammation and regeneration appears to be under the control of fibroblasts which determines macrophage differentiation into M1 or M2. Indeed, incubation of M0 with injured fibroblast supernatants induced a significant increase of DPSCs and endothelial cell viability, VEGF secretion, and endothelial cell organisation into <i>tube-like</i> structures. These effects are comparable to those of M2. However, incubating them with injured and LTA-stimulated fibroblasts induced similar effects to those of M1 macrophages including stem cell migration, VEGF secretion level and endothelial cell viability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This in vitro study shows that, depending on the type of stimulation, pulp fibroblasts induce macrophage differentiation into M1 or M2 which, in turn, modulate DPSC proliferation/migration and neo-angiogenesis. This highlights that interactions between different cell types play a significant role in the initial steps of pulp tissue regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"852-862"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karem Paula Pinto, Isabelle da Cunha Degani, Jenif Braga de Souza, Renata Heisler Neves, Luciana Brandão-Bezerra, Luciana Moura Sassone, Emmanuel João Nogueira Leal da Silva
{"title":"Multiple Periapical Lesions Influence the Expression of TLR4/NF-κB Pathway Components and the Development of Hepatic Injuries in Healthy and Chronic Alcohol-Consuming Rats","authors":"Karem Paula Pinto, Isabelle da Cunha Degani, Jenif Braga de Souza, Renata Heisler Neves, Luciana Brandão-Bezerra, Luciana Moura Sassone, Emmanuel João Nogueira Leal da Silva","doi":"10.1111/iej.70104","DOIUrl":"10.1111/iej.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the impact of multiple apical periodontitis (AP) on the expression of TLR4/NF-κB pathway components, proinflammatory cytokine levels, and development of hepatic injuries in rats with and without chronic alcohol consumption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Thirty-two rats were assigned to four groups (<i>n</i> = 8): Control, AP, Alcohol, and Alcohol+AP. The Alcohol and Alcohol+AP groups received 25% ethanol solution. Multiple AP were induced through pulp exposure of four molars for 28 days. Following euthanasia, the jaws and livers were collected. Micro-computed tomography was used to confirm periapical lesions. Liver samples underwent histopathological analysis and ELISA assay to measure TLR4, NF-κB, IL-6, and TNF-α levels. Histopathological evaluation was performed using hepatic stereology to assess hepatocytes, sinusoids, Kupffer cells, steatosis, leukocyte infiltrate, and necrosis. Statistical analysis was carried out using one-way ANOVA followed by the Student–Newman–Keuls (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hepatic levels of TLR4 and NF-κB were significantly higher in AP and Alcohol+AP groups compared to Control and Alcohol groups (<i>p</i> < 0.05). IL-6 and TNF-α were significantly elevated in all experimental groups compared to the Control group (<i>p</i> < 0.05), with higher levels observed in the Alcohol+AP group compared to the other groups (<i>p</i> < 0.05). Experimental groups showed a significant reduction in hepatocyte density compared to the Control group (<i>p</i> < 0.05), while sinusoidal volume was significantly reduced in the AP group compared to the Control group (<i>p</i> < 0.05). Hepatic steatosis was absent in the Control and AP groups and there was no significant difference in the percentage of steatosis between Alcohol and Alcohol+AP groups (<i>p</i> > 0.05). No significant differences were observed in the number of Kupffer cells among groups (<i>p</i> > 0.05) and leukocyte infiltrate was absent in all groups. Necrosis was significantly higher in the AP and Alcohol+AP groups compared to the Control and Alcohol groups (<i>p</i> < 0.05), with the Alcohol+AP group showing a higher percentage of necrosis compared to the AP group (<i>p</i> < 0.05). Hydropic degeneration, focal inflammatory infiltrates, and hepatocyte necrosis were observed in the AP and Alcohol+AP groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Multiple AP led to elevated TLR4, NF-κB, IL-6, and TNF-α levels and significant hepatic a","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 5","pages":"863-872"},"PeriodicalIF":7.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Foxq1-Wnt5a Axis Activation in Dental Papilla Stem Cells Promotes Odontogenesis on Acellular Matrix: A Laboratory Investigation.","authors":"Jingjing Ke, Mengdan Zhang, Lixian Kong, Hauman Chung, Xiayi Wu, Tingting Ai, Jinxuan Zheng, Yi Li, Yang Cao, Junqi Ling, Lusai Xiang","doi":"10.1111/iej.70160","DOIUrl":"https://doi.org/10.1111/iej.70160","url":null,"abstract":"<p><strong>Aim: </strong>Regeneration of tubular dentine structure is key to its biological function, and the polarity of odontoblasts is crucial for this, but the mechanism is unclear. On the basis of differential gene expression data comparing odontoblasts and donor-matched osteoblasts, we hypothesized that forkhead box Q1 (Foxq1), a key regulator in embryonic development, plays a significant role in the differentiation of polarized odontoblasts. This study aimed to investigate the role of Foxq1 in odontoblast polarization and tubular-dentine formation, and to explore its relationship with Wingless-type family member 5A (Wnt5a) signalling.</p><p><strong>Methodology: </strong>We examined Foxq1's spatiotemporal expression in tooth germs from embryonic to postnatal stages and studied its effect on tooth development by local Foxq1 level manipulation in mesenchymes. Dental papilla stem cells (DPSCs) were isolated from Embryonic 14.5 (E14.5) mouse embryos to evaluate osteogenic, odontogenic, and polarization marker expression and further in vitro studies. The interaction between Foxq1 and Wnt5a was assessed by co-immunoprecipitation and surface plasmon resonance for protein-protein interaction, and dual-luciferase reporter assays and chromatin immunoprecipitation assay for protein-gene regulation. These findings were subsequently validated using an in vivo cell-inoculated scaffolds subcutaneous implantation animal model.</p><p><strong>Results: </strong>Foxq1 was expressed in dental mesenchyme, and its overexpression promoted dentine thickness and odontoblastic polarization, whereas suppression reduced tooth germ size and disrupted polarity and dentine formation. WNT5A protein reversed these changes caused by Foxq1 suppression. We proved Foxq1 could bind to the promoter region of Wnt5a and dentine sialophosphoprotein (Dspp). In vivo, both Foxq1 + DPSCs and Wnt5a + DPSCs promoted regeneration of de novo tubular-dentine-like structures on the basis of original tubular dentine. However, where there is no access to tubular dentine opening, only irregular \"osteodentin\" was formed.</p><p><strong>Conclusions: </strong>The activation of the Foxq1-Wnt5a signalling axis synergizes with acellular dentine scaffolds to promote tubular dentine regeneration.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}