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International Dental Journal[JOURNAL]

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κ-Carrageenan-Based Hydrogels Support Viability and Odontogenic Differentiation of Stem Cells From the Apical Papilla.

Alajlan MA, Lambarte RNA, Sumague TS … +1 more , Niazy AA

Int Dent J · 2026 Jun · PMID 42308664 · Full text

INTRODUCTION AND AIMS: Immature teeth with pulp necrosis remain challenging because conventional root canal treatment does not restore pulp-dentin vitality. Hydrogel scaffolds for regenerative endodontics should support... INTRODUCTION AND AIMS: Immature teeth with pulp necrosis remain challenging because conventional root canal treatment does not restore pulp-dentin vitality. Hydrogel scaffolds for regenerative endodontics should support stem cell viability and provide a microenvironment favourable for dentin-pulp regeneration. This study evaluated κ-Carrageenan (κC)-based hydrogels, with and without gelatin, as scaffolds for stem cells from the apical papilla (SCAP), and examined how formulation-dependent properties influenced SCAP viability and odontogenic differentiation. METHODS: Hydrogels were prepared as 1% gelatin, 1.5% κC, 2.5% κC, 1.5% κC+gelatin (κCG) and 2.5% κCG, with cells cultured without hydrogel as a control. Physicochemical characterisation included scanning electron microscopy, Fourier-transform infrared spectroscopy, rheology, degradation and swelling at days 1, 3, 7 and 14. SCAP were isolated and characterised using flow cytometry. Cell viability, metabolic activity, spreading, migration, alkaline phosphatase activity, Alizarin Red S staining and qPCR of differentiation-related markers were also assessed. RESULTS: The hydrogels showed formulation-dependent microstructure, degradation, swelling and viscoelastic properties. κC-containing formulations behaved as viscoelastic solids, and 2.5% κCG exhibited the highest storage modulus and lowest Tan (δ). SCAP remained predominantly viable in all groups. Gelatin-containing hydrogels improved long-term cytocompatibility and greater cell spreading compared to lower-concentration κC alone. Migration was comparable across groups. During differentiation, κC-containing formulations showed higher alkaline phosphatase activity and mineral deposition, with increased late-stage mineralisation observed in 2.5% κCG. Gene expression analysis indicated early upregulation of RUNX2 and BSP and increased late-stage expression of OPN, OCN, DMP1 and DSPP, with a more evident maturation-associated response in 2.5% κCG. CONCLUSION: κC-based hydrogels supported SCAP viability and promoted odontogenic differentiation in vitro. Gelatin incorporation improved late-stage mineralisation and odontogenic marker expression, with 2.5% κCG demonstrating the most favourable overall response. CLINICAL RELEVANCE: κC-gelatin hydrogels may serve as promising scaffold candidates for dentin-pulp regenerative strategies by supporting SCAP survival and odontogenic maturation within a tunable hydrogel microenvironment.

Global, Regional, and National Burden of Caries Among Women of Childbearing Age From 1990 to 2021 and Prediction.

Chen H, Hu M, Liu L … +3 more , Pan T, Chen X, Guo J

Int Dent J · 2026 Jun · PMID 42308663 · Full text

INTRODUCTION AND AIMS: Caries is a major global oral health issue. However, a critical gap persists in understanding its burden and temporal trends among women of childbearing age (WCBA). This study aims to analyse carie... INTRODUCTION AND AIMS: Caries is a major global oral health issue. However, a critical gap persists in understanding its burden and temporal trends among women of childbearing age (WCBA). This study aims to analyse caries burden among WCBA from 1990 to 2021, project trends to 2040, and provide evidence for targeted oral health interventions. METHODS: Data from the Global Burden of Disease study 2021 were used to assess caries burden among WCBA, including incidence, prevalence, and disability-adjusted life-years (DALYs). Temporal trends were analysed using joinpoint regression, associations with the sociodemographic index(SDI) were examined via Spearman correlation analyses, and future trends were projected using the Nordpred model. RESULTS: In 2021, caries among WCBA resulted in 817.5 million incident cases and 688,430 DALYs globally, with South Asia recording the highest numbers of both indicators. The highest age-standardized incidence rate (ASIR) and age-standardized DALYs rate (ASDR) were observed in Tropical Latin America and Andean Latin America, respectively. From 1990 to 2021, the global ASIR increased (AAPC = 0.27%), whereas the ASDR declined modestly (AAPC = -0.03%). Both incidence and DALYs peaked in the 20-24 age group. Projections from 2022 to 2040 suggest that the ASIR will rise by 2.83%, while the ASDR is expected to decrease by 5.00%. CONCLUSION: Despite modest declines in ASDR, the rising ASIR, particularly in lower-SDI regions, underscores caries among WCBA as a persistent public health challenge requiring targeted interventions. CLINICAL RELEVANCE: Caries among WCBA affects not only oral health but also systemic conditions, particularly metabolic disorders, adverse pregnancy outcomes, and offspring oral health. Assessing WCBA as a whole, as conducted in this study, provides an important basis and proxy for evaluating maternal oral health needs. Therefore, early screening and prevention should be prioritized in oral and primary care settings for young women and integrated into prenatal and maternal health programs to improve maternal and child health outcomes.

Public Dental Workforce Capacity and Inequality in Spain.

Enciso-Ripoll MJ, Iranzo-Cortés JE, Bravo M … +1 more , Silvestre FJ

Int Dent J · 2026 Jun · PMID 42302486 · Publisher ↗

INTRODUCTION AND AIMS: Spain combines one of Europe's highest dentist densities with limited public oral health coverage and marked regional variation in publicly funded provision. This study quantified total, salaried p... INTRODUCTION AND AIMS: Spain combines one of Europe's highest dentist densities with limited public oral health coverage and marked regional variation in publicly funded provision. This study quantified total, salaried public and privately accredited dental workforce capacity across Spain and assessed implications for public oral health system planning and equity. METHODS: A cross-sectional national workforce analysis was conducted across the 17 Autonomous Communities and the Autonomous Cities of Ceuta and Melilla. Data were obtained through formal transparency requests to all administrations, supplemented by official professional registration data, population statistics and Ministry of Health records. Indicators included total and salaried public dentists per 100,000 inhabitants, population load per public dentist, the public/total ratio and a Structural Dependence Index (SDI) quantifying reliance on accredited private providers. RESULTS: In 2024-2025, Spain registered 42,860 active dentists (84.68/100,000) but only 1685 salaried public dentists (mean territorial density: 3.36/100,000; mean territorial load: 31,590 inhabitants per public dentist). The public/total ratio ranged from 2.0% in Madrid to 7.6% in Castilla-La Mancha. A further 6810 privately accredited providers participated in publicly funded programmes across 11 mixed-model regions, yielding an effective public-system workforce of 8495 professionals (17.21/100,000). Among territories with reported individual accredited-provider counts, SDI ranged from 0% in direct public-provision regions to 95.4% in País Vasco; ten of eleven mixed-model regions recorded SDI values above 80%. CONCLUSION: Spain does not face a shortage of dentists, but a structural imbalance between abundant private professional supply and limited, unevenly distributed public-system capacity. CLINICAL RELEVANCE: High aggregate dentist density is a poor proxy for public oral health system capacity. Workforce planning standards and stronger monitoring systems are needed to translate expanded publicly funded oral health coverage into effective and equitable access.

Edentulism in China and the Group of Twenty (G20): Epidemiological Trends, Decomposition Analysis, and Forecasts to 2038.

Zhang Y, Zhao L, Xu XS … +5 more , Wang H, He F, Liu Y, Li J, Xu X

Int Dent J · 2026 Jun · PMID 42302485 · Full text

AIMS: Edentulism is a severe global oral health burden, particularly in aging societies. While previous studies have documented epidemiological trends, a direct comparison of the drivers and future trajectories between a... AIMS: Edentulism is a severe global oral health burden, particularly in aging societies. While previous studies have documented epidemiological trends, a direct comparison of the drivers and future trajectories between a rapidly aging economy like China and the broader Group of Twenty (G20) nations are lacking. This study aimed to compare temporal trends, decompose contributing factors, and forecast the future burden of edentulism in China versus the G20 aggregate from 1990 to 2038. METHODS: Using Global Burden of Disease 2023 data, we analysed age-standardised incidence rates (ASIR) and disability-adjusted life years (DALYs) for edentulism. We employed Joinpoint regression to assess temporal trends (1990-2023), and demographic decomposition analysis to quantify contributions from population growth, aging, and epidemiological change, and Autoregressive Integrated Moving Average models to forecast burden through 2038. RESULTS: From 1990 to 2023, China's ASIR declined modestly by 5.9% and DALYs by 11.0%, lagging behind reductions achieved by top-performing G20 nations. Decomposition analysis revealed a fundamental divergence in drivers: population aging accounted for over 80% of the net increase in China's burden, whereas population growth was the predominant contributor (78.7%) for the G20 overall. ARIMA forecasts indicate that China's burden will experience a brief decline followed by a sustained rebound, stabilizing at a level higher than the G20 average. CONCLUSION: China's edentulism burden is predominantly driven by population aging, contrasting with the G20's reliance on population growth as the primary driver. Future trajectories suggest China will face greater long-term oral health pressures than the G20 average. CLINICAL RELEVANCE: Oral health strategies in China must pivot from generic prevention toward age-specific interventions. Integrating comprehensive oral healthcare into geriatric medicine and national chronic disease frameworks is imperative to mitigate the escalating burden driven by an unprecedented aging population.

Identification of Drug Associated Factors for Gingival Disorders: A Real-World Pharmacovigilance Study.

Xiao Q, Wang C, Yang C

Int Dent J · 2026 Jun · PMID 42302484 · Full text

OBJECTIVE: This study aimed to evaluate the reports of drug adverse events associated with gingival disorders and explore potential drug associated factors. METHODS: Data were extracted from the Food and Drug Administrat... OBJECTIVE: This study aimed to evaluate the reports of drug adverse events associated with gingival disorders and explore potential drug associated factors. METHODS: Data were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024. Reporting odds ratio (ROR) were calculated using disproportionality analysis to identify signals of potential associations. For drugs that met the criteria, the least absolute shrinkage and selection operator (LASSO) regression, and multifactor logistic regression were performed to further explore the potential associated factors. RESULTS: A total of 34,354 relevant reports were collected, with 62.1% of the cases being female. Forty-three drugs were identified as associated factors for gingival disorders, including antineoplastic agents, immunosuppressants, and antithrombotic drugs. The median time from drug use to the onset of gingival disorders was 35 days, with variations observed among different drugs. CONCLUSIONS: This study is the first comprehensive correlative associations of drugs related to gingival disorders using the Food and Drug Administration Adverse Event Reporting System database, providing preliminary safety signals for the rational monitoring of gingival disorders in clinical practice. Further research is required to validate these potential associations.

Meta-Analysis and Systematic Review of Immune Checkpoint Expression in Predicting the Risk of Malignant Transformation in Oral Potentially Malignant Disorders.

Cui Y, Sima Z, Ding C … +1 more , Cai X

Int Dent J · 2026 Jun · PMID 42302483 · Full text

INTRODUCTION AND AIMS: Immune checkpoints (ICPs) play a critical role in tumour immune evasion, yet their significance in oral potentially malignant disorders (OPMDs) remains poorly defined. This study evaluates the evid... INTRODUCTION AND AIMS: Immune checkpoints (ICPs) play a critical role in tumour immune evasion, yet their significance in oral potentially malignant disorders (OPMDs) remains poorly defined. This study evaluates the evidence regarding ICPs in predicting malignant transformation (MT) of OPMDs and identifies research gaps. METHODS: A systematic synthesis was conducted of studies investigating ICP expression in predicting the MT risk of OPMDs. A search strategy was developed and applied across the PubMed, Scopus, and Web of Science Core Collection databases to identify articles relevant to this topic. RESULTS: Of the 231 publications retrieved, 5 met the inclusion criteria, encompassing a total of 613 patients, among whom 129 experienced MT, corresponding to an MT rate of 21.04%. A total of 2 ICPs were evaluated. Among these, PD-L1 was identified in several studies as having potential utility in predicting the MT risk of OPMDs. However, its clinical application requires further investigation, and clinical evidence regarding the role of other ICPs in predicting MT risk remains lacking. CONCLUSION: The role of ICPs in predicting the MT risk of OPMD remains underexplored with fragmented evidence. While the PD-1/PD-L1 axis shows promise, its clinical utility remains unestablished. Prospective studies and randomized trials are further needed. CLINICAL RELEVANCE: Elucidating ICP roles in OPMDs could enable precise risk stratification and immunopreventive strategies, facilitating early intervention and reducing oral cancer incidence.

Robot-Assisted Oral Examination: Challenges and Innovations.

Ge Y, Wang W, Zhao T … +6 more , Liu D, Fan S, Liu P, Li W, Sun H, Liu X

Int Dent J · 2026 Jun · PMID 42296618 · Full text

OBJECTIVES: To summarize and evaluate the core components, functional modules, and developmental challenges of intelligent oral examination robots, and to clarify their potential clinical relevance as well as the mechani... OBJECTIVES: To summarize and evaluate the core components, functional modules, and developmental challenges of intelligent oral examination robots, and to clarify their potential clinical relevance as well as the mechanisms by which robotics and artificial intelligence can enhance diagnostic efficiency and standardization in dentistry. MATERIALS AND METHODS: This study employed a systematic literature review methodology, retrieving relevant publications from the PubMed and ScienceDirect databases up to September 2025. The search strategy utilized Boolean operators to combine keywords such as 'robot,' 'AI,' 'oral diagnosis,' and 'intraoral scanner,' aiming to comprehensively cover the fields of robotic technology, oral diagnostics, artificial intelligence, and related sensing technologies. The initial search yielded approximately 1,027 articles, of which 134 were ultimately included after screening. Inclusion criteria comprised studies related to oral robotic technologies, applications of artificial intelligence in diagnosis, and robotic navigation, while exclusion criteria included non-peer-reviewed publications and studies with insufficient methodological descriptions. A combined approach of narrative review and critical analysis was adopted, with a focus on key technical domains, including hardware architecture, software integration, multimodal perception systems, and force feedback mechanisms. RESULTS: The analysis identified several key technological components of intelligent oral examination robots, including high-resolution intraoral imaging systems, multimodal data fusion frameworks, force-sensing and adaptive control technologies, automated navigation systems, and AI-driven data-processing algorithms. These systems contribute to improved image acquisition accuracy, standardized diagnostic procedures, enhanced data management, and optimized clinical workflow. However, challenges remain in system integration, safety assurance, real-time responsiveness, and clinical validation. CONCLUSIONS: Current technological advances suggest that intelligent oral examination robots have significant potential to reduce clinician workload, improve diagnostic accuracy, and enhance consistency in oral examinations. Continued refinement in hardware-software integration, safety mechanisms, and clinical adaptability will be essential for broader implementation. CLINICAL RELEVANCE: Intelligent oral examination robots may significantly improve diagnostic quality through automation, standardized data acquisition, and enhanced imaging capabilities. Their application could facilitate early disease detection, improve patient management, and streamline clinical workflows in modern dental practice.

Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.

Yan W, Guo X, Zhao B … +4 more , Li Y, Shen Z, Shi R, Zhang C

Int Dent J · 2026 Jun · PMID 42288015 · Full text

OBJECTIVES: Odontogenic differentiation of stem cells from apical papilla (SCAPs) is critical for pulp regeneration therapy. Protein arginine methyltransferase 6 (PRMT6) plays an important role in stem cell differentiati... OBJECTIVES: Odontogenic differentiation of stem cells from apical papilla (SCAPs) is critical for pulp regeneration therapy. Protein arginine methyltransferase 6 (PRMT6) plays an important role in stem cell differentiation, but the specific functions and mechanisms remain unclear. This study aimed to explore the role of PRMT6 nuclear localization sequence (NLS) in regulating SCAPs osteogenic and odontogenic differentiation and its underlying mechanism. MATERIALS AND METHODS: SCAPs were isolated and identified by flow cytometry. Wild-type PRMT6 and NLS-deleted PRMT6 (PRMT6ΔNLS) overexpression models were constructed via lentiviral infection. Osteogenic and odontogenic differentiation was evaluated via alkaline phosphatase staining, Alizarin Red staining, western blot, and in vivo nude mouse transplantation. Mitochondrial function was analysed by transmission electron microscopy, mitochondrial stress testing, and JC-10 membrane potential assays. Downstream gene expression and β-catenin pathway activity were examined via real-time RT-PCR, western blot, and rescue experiments were performed by exogenous Dickkopf‑1 (DKK1) supplementation. RESULTS: PRMT6 exhibited nucleocytoplasmic redistribution during early odontogenic differentiation of SCAPs, with increased nuclear export. NLS mutation reduced PRMT6 nuclear accumulation, reversed PRMT6-mediated inhibition of in vitro mineralization and osteogenic and odontogenic marker expression, and promoted in vivo bone-/dentin-like tissue formation. Additionally, PRMT6ΔNLS rescued mitochondrial ultrastructural damage, increased OCR and mitochondrial membrane potential, and improved mitochondrial function. Mechanistically, PRMT6ΔNLS downregulated Wnt antagonist DKK1, activated the β-catenin pathway, and exogenous DKK1 abolished this pro-differentiation effect. CONCLUSIONS: PRMT6 nuclear localization is essential for its inhibitory effect on SCAPs osteogenic and odontogenic differentiation. NLS-deleted PRMT6 promotes SCAPs differentiation by rescuing mitochondrial function and activating the β-catenin pathway via downregulating DKK1. CLINICAL SIGNIFICANCE: This study provides a theoretical basis and potential targets for promoting dentin-pulp regeneration by modulating PRMT6 nuclear transport.

Association of Apical Maturity With Clinical and Biological Outcomes After Regenerative Endodontic Procedures: A Systematic Review and Meta-Analysis.

Zhan S, Yan Q, Zhang Y

Int Dent J · 2026 Jun · PMID 42288014 · Full text

OBJECTIVES: To systematically evaluate the outcomes of regenerative endodontic procedures (REPs) in teeth with varying degrees of root maturity and investigate how initial apical diameter influences clinical success, too... OBJECTIVES: To systematically evaluate the outcomes of regenerative endodontic procedures (REPs) in teeth with varying degrees of root maturity and investigate how initial apical diameter influences clinical success, tooth survival, complete apical closure and pulp vitality recovery rates. METHODS: Electronic databases, including PubMed, Embase, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials, were systematically searched without date restrictions up to July 2025. Studies reporting REP outcomes (clinical success, tooth survival, complete apical closure and pulp vitality recovery) in immature and mature permanent teeth were deemed eligible. Eligibility criteria were structured using the population, intervention, comparison and outcome framework. Data extraction and quality assessment were independently performed by 2 reviewers using the Cochrane Risk of Bias tool 2 and the Newcastle-Ottawa scale. Meta-analysis, dose-response meta-analysis and trial sequential analysis were conducted to assess outcome stability and evidence robustness. RESULTS: Ten studies involving 508 teeth were included in this review. The pooled clinical success rate was 90% (95% confidence interval [CI]: 83%-95%; n = 496 teeth), and the tooth survival rate was 98% (95% CI: 95%-99%; n = 453 teeth). Complete apical closure (53%, 95% CI: 36%-70%; n = 196) and pulp vitality recovery (21%, 95% CI: 7%-49%; n = 224) rates exhibited significant variability. Dose-response meta-analysis suggested that clinical success and tooth survival rates were relatively stable across apical diameters, whereas complete apical closure rates showed a possible negative association with increasing apical diameter. Trial sequential analysis suggested that the cumulative evidence for clinical success and tooth survival outcomes was relatively stable, though these findings should be interpreted in light of the heterogeneity and limited event counts across the included studies. Sensitivity analyses generally supported the robustness of the main findings. CONCLUSIONS: Regenerative endodontic procedures appear to achieve high rates of clinical success and tooth survival across varying degrees of root maturity. However, complete apical closure and pulp vitality recovery remain more variable and may be associated with initial apical maturity. Importantly, high clinical success and tooth survival rates do not necessarily indicate true pulp-dentin regeneration. These findings should be interpreted cautiously, given the heterogeneous protocols, mixed study designs and inconsistent outcome definitions of the included studies. Larger, well-designed, randomised controlled trials with standardised outcome definitions, uniform apical diameter measurement methods and longer follow-up periods are needed to refine these conclusions.

Mitochondrial Metabolic Biomarkers in Periodontitis: Discovery and Clinical Validation.

Wu J, Wu J, Hong Y … +2 more , Rao L, Chen M

Int Dent J · 2026 Jun · PMID 42288013 · Full text

INTRODUCTION AND AIMS: Mitochondrial metabolic dysregulation is associated with periodontitis (PD); however, related biomarkers remain unclear. In this study, we identified key mitochondrial metabolism-related biomarkers... INTRODUCTION AND AIMS: Mitochondrial metabolic dysregulation is associated with periodontitis (PD); however, related biomarkers remain unclear. In this study, we identified key mitochondrial metabolism-related biomarkers in PD through integrated bioinformatics technology. METHODS: Transcriptomic and single-cell RNA sequencing data from the Gene Expression Omnibus database were analysed using machine learning to identify biomarkers. A diagnostic nomogram was constructed. Immune infiltration, drug prediction, and T-cell dynamic expression were assessed. Putative biomarkers were validated in clinical samples and a rat PD model by reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and Western blot analysis. RESULTS: Six biomarkers were identified, which included ENTPD1, CYP24A1, ADA, TDO2 (upregulated), OSBPL6, and NUDT15 (downregulated). The nomogram exhibited excellent diagnostic efficacy (area under the curve [AUC] = 0.954). The biomarkers correlated with plasma cells and resting dendritic cells. Single-cell analysis revealed dynamic expression during T-cell differentiation. CTA018 exhibited strong binding to CYP24A1. Five biomarkers were validated in clinical samples, and the upregulation of ENTPD1, CYP24A1, and TDO2 protein and messenger RNA was confirmed in a rat model and correlated with PD progression. CONCLUSION: ENTPD1, CYP24A1, and TDO2 are mitochondrial metabolism-related biomarkers with high diagnostic potential in PD and targets for therapy. CLINICAL RELEVANCE: The identified biomarkers, particularly ENTPD1, CYP24A1, and TDO2, have strong diagnostic value. The nomogram contributed to PD risk stratification. Associations with immune infiltration and drug sensitivity may guide immunotherapy and targeted therapy.

Corrigendum to 'AI-Driven Segmentation of Three Oral Diseases: Enabling Precision Diagnosis and Decision Support' [International Dental Journal, Volume 76, Issue 3, June 2026, 109486].

Cheng B, Xiang M, Zhao Z … +6 more , Zhang X, Wang YF, Ge S, Zhao F, Li M, Wang H

Int Dent J · 2026 Jun · PMID 42288012 · Full text

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Potential of Trichloroacetic Acid in Smear Layer and Calcium Hydroxide Removal in Root Canals-Exploratory Pilot Studies In Vitro.

Munoz E, Benbow AB, Russell JC … +4 more , Morrow BR, Pannkuk TF, Xin B, Huang GT

Int Dent J · 2026 Jun · PMID 42275748 · Full text

INTRODUCTION AND AIMS: This study investigated whether trichloroacetic acid (TCA) can function as an adjuvant solution to facilitate pulp dissolution and removal of smear layer and calcium hydroxide (Ca(OH)) during endod... INTRODUCTION AND AIMS: This study investigated whether trichloroacetic acid (TCA) can function as an adjuvant solution to facilitate pulp dissolution and removal of smear layer and calcium hydroxide (Ca(OH)) during endodontic procedures. METHODS: For pulp dissolution studies, fresh pulp was weighed before and after immersion in 90% TCA and/or 6% NaOCl. For smear layer or Ca(OH) removal, each study utilized 25 extracted human teeth with prepared root canal systems. For Ca(OH) removal, canals were filled with Ca(OH) and stored at 37 °C for 14 days. Teeth were divided into five groups (n=5/group) and the canal irrigated with various solutions. Group I: saline; Group II: 17% EDTA; Group III-V: 90% TCA for 15, 30 or 60 seconds, respectively. Samples were subjected to scanning electron microscopy (SEM) or spectrum analysis. RESULTS: Under our experimental conditions, NaOCl alone consistently dissolved more pulp than TCA at all time points (1, 3, and 5 minutes) under static conditions at RT (P < .01 or < .001). Some TCA groups had significantly less smear layer than the saline or EDTA group in the coronal and middle thirds (P < .05 to < .001). In the apical third, there was significantly less smear layer in the TCA 15-second group than the control or EDTA group (P < .01 or P < .001). In Ca(OH) removal studies, the coronal third showed that TCA 30-second group and middle third TCA 60-second group had significantly less Ca(OH) than the EDTA group (P < .05). CONCLUSION: These findings warrant further studies with a larger sample size to validate the potential use of TCA as an adjunctive agent to facilitate smear layer and Ca(OH)₂ removal from root canal walls, CLINICAL RELEVANCE: This is the first study to evaluate whether TCA can be used as an adjunctive endodontic irrigant. Our findings suggest that a brief treatment with TCA is more effective than EDTA for canal smear layer removal and may facilitate Ca(OH) removal.

IL-6/STAT3-Mediated miR-181a-5p in Bone Marrow-Derived Mesenchymal Stem Cells Regulates Th17/Treg Balance in Experimental Periodontitis.

Wu S, Wang J, Yang D

Int Dent J · 2026 Jun · PMID 42275747 · Full text

OBJECTIVE: Periodontitis adversely affects oral and overall health. Bone marrow-derived mesenchymal stem cells (BMMSCs) play regulatory roles in the immune system, and the exploration of therapeutic strategies involving... OBJECTIVE: Periodontitis adversely affects oral and overall health. Bone marrow-derived mesenchymal stem cells (BMMSCs) play regulatory roles in the immune system, and the exploration of therapeutic strategies involving BMMSCs has garnered significant attention in the context of inflammatory pathological processes. Interleukin-6 can regulate microRNA expression by activating the signal transducer and activator of transcription 3 (STAT3) and functions in some systemic diseases. Notably, the regulatory mechanisms between IL-6 and miR-181a-5p in BMMSCs underlying periodontitis are still unknown. This study aims to uncover the regulatory mechanisms between IL-6 and miR-181a-5p and create a new treatment strategy for periodontal tissue regeneration. METHODS: In this study, Western blot was used to assess IL-6 and STAT3 levels. Quantitative real-time polymerase chain reaction assessed the expression of miR-181a-5p and the relative genes. Enzyme-linked immunosorbent assay detected the content of IL-6. The Cell Counting Kit-8 was used to evaluate cell viability. Alkaline phosphatase staining was used to analyse the osteogenesis of cells. Chromatin immunoprecipitation and dual luciferase activity assays were used to verify the binding relationship between miR-181a-5p, STAT3, and IL-6. Flow cytometry was used for identifying cell types. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology analysed potential signal pathways of genes targeted by miR-181a-5p. In addition, the present research was further investigated using a ligature-induced periodontitis model in mice. The micro-computed tomography, haematoxylin and eosin, and tartrate-resistant acid phosphatase (TRAP) assays were used for histologic analysis of the degree of inflammation and bone recovery in the experimental periodontitis and treatment group. RESULTS: IL-6 and miR-181a-5p were upregulated in experimental periodontitis in mice. The IL-6 recombinant protein promoted mBMMSC proliferation and upregulated miR-181a-5p levels via STAT3. Functional inhibition of miR-181a-5p alleviated the T helper 17 (Th17) cell/regulatory T cell (Treg) immune imbalance triggered by IL-6 stimulation. Injection of miR-181a-5p inhibitor preconditioned mBMMSCs significantly promoted periodontal tissue regeneration, and osteoclasts and bone resorption were reduced significantly. CONCLUSION: IL-6 may contribute to the progression of experimental periodontitis in mice via modulating STAT3‑mediated miR‑181a‑5p expression in mBMMSCs and may potentially influence periodontal tissue regeneration through regulating the Th17/Treg balance.

Effects of Smoothened Agonist Exposure on Murine Craniofacial Development.

Mao C, Jiang Y, Li Z … +5 more , Zhou W, Lai Y, Wang C, Lu M, Chen W

Int Dent J · 2026 Jun · PMID 42275746 · Full text

OBJECTIVE: While inhibition of Hedgehog (Hh) signalling is known to cause cleft lip, the effects of its hyperactivation on craniofacial development remain systematically unexplored. MATERIALS AND METHODS: Pregnant mice r... OBJECTIVE: While inhibition of Hedgehog (Hh) signalling is known to cause cleft lip, the effects of its hyperactivation on craniofacial development remain systematically unexplored. MATERIALS AND METHODS: Pregnant mice received a single intraperitoneal injection of Smoothened Agonist (SAG) (25 mg/kg) at various time points between E7.5 and E12.5. A median cleft lip model was established at E10.5. Mechanisms were assessed by analysing cell proliferation (PHH3, Ki67), apoptosis (TUNEL), and expression of cell cycle regulators (Cyclin A, B1, D1, E1). RESULTS: SAG administration induced craniofacial defects - including cranial bone abnormalities, hematomas, and cleft lip/palate - in a time-dependent manner. The critical window for cleft lip induction was E9.5-E10.5. Mechanistically, SAG-induced cleft lip was associated with reduced proliferation and altered expression of selected cell-cycle markers, consistent with delayed G0/G1 progression. No significant change in apoptosis was observed. CONCLUSION: SAG is a potent teratogen that can induce cleft lip during a critical developmental window, potentially through suppression of cell proliferation and perturbation of cell-cycle progression. While its prenatal use poses significant risks, SAG also provides a useful experimental tool for generating congenital craniofacial defect models.

Validating OHIP-5 for Equitable Oral Healthcare in Nigeria.

Oladayo AM, Akinloye SJ, Olujitan M … +9 more , Alade A, Williams AT, Olanrewaju A, Rysavy O, Dabdoub SM, Caplan DJ, Lawal TA, Butali A, Lawal FB

Int Dent J · 2026 Jun · PMID 42275745 · Full text

INTRODUCTION AND AIMS: Healthcare access in low- and middle-income countries (LMICs) is constrained by structural and socio-cultural barriers, including language. Oral health, despite its importance to general health, is... INTRODUCTION AND AIMS: Healthcare access in low- and middle-income countries (LMICs) is constrained by structural and socio-cultural barriers, including language. Oral health, despite its importance to general health, is often overlooked in universal health coverage efforts. The Oral Health Impact Profile (OHIP-5) is a brief patient-reported outcome measure (PROM) for oral health-related quality of life (OHRQoL) but has not been adapted into indigenous Nigerian languages. This study aimed to translate and evaluate the Yoruba version (OHIP-5Yor), assess its psychometric performance using both English and Yoruba administrations, and explore its relevance for improving patient-centred oral healthcare access in LMICs. METHODS: A cross-sectional survey of 143 adults was conducted at two dental centres in Ibadan, Nigeria. The OHIP-5 was translated using a forward-backward approach with pilot testing. Psychometric evaluation included internal consistency, inter-item correlation, convergent validity, and confirmatory factor analysis. RESULTS: Of the 143 participants, 52 completed the Yoruba version and 91 the English version. The mean OHIP-5 score was 6.6 ± 4.3. The instrument showed acceptable internal consistency (Cronbach's α = 0.67) and supportive construct validity. Structural validity indices, however, indicated that the factorial structure requires further evaluation in larger and more diverse samples. CONCLUSIONS: The findings provide preliminary support for the reliability and validity of the OHIP-5Yor as a culturally adapted tool for assessing OHRQoL among Nigerian adult dental patients. Beyond psychometric evaluation, the instrument may help address an important equity gap by enabling non-English speakers to participate more fully in oral health assessment, thereby supporting patient-clinician communication and highlighting unmet needs. Incorporation of such tools into routine care and public health surveillance represents a potential, scalable approach to strengthening oral healthcare access in low- and middle-income countries (LMICs). CLINICAL RELEVANCE: The OHIP-5Yor enables brief, culturally appropriate assessment of patient-perceived oral health impacts and may support more equitable oral healthcare delivery in multilingual settings.

Oral Health on Sal, Cape Verde: A Population-Based, Cross-Sectional Study.

Volgenant CMC, de Soet HJJ, Hoekstra T … +1 more , Duijster D

Int Dent J · 2026 Jun · PMID 42275744 · Full text

OBJECTIVES: Sal is one of the ten islands of Cape Verde, a lower-middle-income country in Africa. Local reports suggest poor oral health among residents, but no scientific data exists. This study aimed to assess oral hea... OBJECTIVES: Sal is one of the ten islands of Cape Verde, a lower-middle-income country in Africa. Local reports suggest poor oral health among residents, but no scientific data exists. This study aimed to assess oral health status and oral health-related quality of life (OHRQoL) of Sal's dentulous inhabitants, identify risk factors associated with oral health, and explore correlations between oral health and OHRQoL in adults. MATERIALS AND METHODS: A population-based cross-sectional study was conducted among dentulous Sal residents. Final-year dental students from the Academic Centre for Dentistry Amsterdam (ACTA), Faculty of Dentistry in Amsterdam, performed duplicate oral health examinations. Outcomes included caries experience (dmft/DMFT), consequences of untreated caries (pufa/PUFA), and periodontal health (DPSI; in adults only). Data on brushing frequency, toothbrush ownership, toothpaste availability, dental visits, dental insurance, and tobacco use (adults only) were collected. Adults completed the OHIP-14 questionnaire (OHRQoL). Descriptive statistics summarized characteristics; multivariable regressions assessed associations. RESULTS: A total of 1,371 dentulous residents participated (609 children aged 1-17 years; 762 adults aged 18-89 years). Caries prevalence was 87.5% and pufa/PUFA 52.2%. Mean dmft/DMFT was 3.7 ± 3.2 (children) and 7.5 ± 6.2 (adults). 63.1% had DPSI maximum-scores ≥3+ (periodontal disease). Toothbrush ownership was high (>96%), access to toothpaste (<90%) and dental insurance was limited (children 63%; adults 46%). Dental insurance was associated with lower dmft/DMFT (p = .019) and lower pufa/PUFA (p = .005). Higher DMFT, PUFA, and severe periodontal disease was associated with poorer OHRQoL. CONCLUSIONS AND CLINICAL RELEVANCE: Oral health among Sal's residents is poor, with a high disease burden and limited access to care. Improving preventive strategies and access to dental services is important to reduce disease prevalence and enhance quality of life.

A Letter to the Editor: The Role of Artificial Intelligence in Dental Education-A Tool or a Crutch?

Abidi S, Azzouz Y, Hanine Y … +4 more , Chraibi R, Finnaoui O, Bouzakhnin H, Chbicheb S

Int Dent J · 2026 Jun · PMID 42275743 · Full text

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Beyond 2D and CNNs: Future Directions for Deep Learning in Periodontal Diagnostics.

Meng K, Lv S, Liu J

Int Dent J · 2026 Jun · PMID 42275742 · Full text

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Potential Years of Life Lost Due to Lip, Oral and Oropharyngeal Cancer in Brazil: Estimates and Forecasting.

Salvi LC, Costa FDS, Collares KF … +5 more , D'avilla OP, Pinto LF, Demarco FF, Vasconcelos ACU, Chisini LA

Int Dent J · 2026 Jun · PMID 42275741 · Full text

INTRODUCTION: This study aims to evaluate the effects of age-period-cohort on potential years of life lost (PYLL) due to lip, oral, and oropharyngeal cancer (LOOPC) in Brazil from 1980 to 2024 and forecast PYLL for 2044.... INTRODUCTION: This study aims to evaluate the effects of age-period-cohort on potential years of life lost (PYLL) due to lip, oral, and oropharyngeal cancer (LOOPC) in Brazil from 1980 to 2024 and forecast PYLL for 2044. METHODS: A retrospective ecological study was performed with all 5570 Brazilian municipalities. PYLL per 100,000 inhabitants and age-standardized-PYLL were calculated. Trends and the annual percent change (APC%) were assessed using the Prais-Winsten regression. Poisson regression was applied to assess age-period-cohort effects. Forecasts were conducted using the Lee-Carter model. RESULTS: A total of 165,467 deaths resulting in 1,574,693 PYLL were observed. Lip cancer accounted for 0.9%, oral cancer for 60.4%, and oropharyngeal 38.7% of the total PYLL. Men accounted for 85.6% of the total PYLL due to LOOPC. The analysis of trends revealed that lip cancer in men shows a significant decreasing trend (β = -0.13, 95% CI [-0.22 to -0.05]), with an APC% = -2.71% (95% CI: -4.09% to -1.33%). The age-period-cohort model demonstrated superior fit compared to alternative models (p<0.001). Projections showed a decrease in lip cancer in men between 5-45 years and 50-60 years, while oral and oropharyngeal cancers are projected to increase before 25 years and decrease between 25 and 70 years for men. In contrast, oral cancer in women is projected to increase before 40 years and from 45 to 65 years. CONCLUSION: Significant regional inequalities were observed in the PYLL projections. Although women have significantly less PYLL due to LOOPC, most projections show a reduction in PYLL for LOOPC in men and an increase in oral cancer in women.

Multi-Omics Integration Reveals the Genetic Mechanisms of Periodontitis and Predicts Therapeutic Drugs.

Cao R, Xu S, Xiang J … +3 more , Qu B, Zhuang Z, Chu T

Int Dent J · 2026 Jun · PMID 42269280 · Full text

BACKGROUND: Periodontitis is a chronic inflammatory disease driven by host immune dysregulation. However, the specific genetic regulatory mechanisms underlying this disease remain unclear. Identifying key molecular targe... BACKGROUND: Periodontitis is a chronic inflammatory disease driven by host immune dysregulation. However, the specific genetic regulatory mechanisms underlying this disease remain unclear. Identifying key molecular targets is crucial for precise therapeutic intervention. METHODS: This study integrated genome-wide association study (GWAS) summary statistics from the Gene-Lifestyle Interactions in Dental Endpoints and FinnGen R11 cohorts, with single-cell spatial transcriptomics and single-cell RNA sequencing profiles. The tissue-specific enrichment of these genetic signals was validated using genetically informed spatial mapping and QTL Enrichment analyses. Furthermore, this study employed methods such as single-cell pathway-based GWAS and single-cell Mendelian randomization to systematically dissect the genetic basis of periodontitis. An artificial intelligence-driven drug screening framework (DrugRefLector) and molecular docking were used to predict potential therapeutic compounds. RESULTS: Tissue-specific enrichment analysis revealed that periodontitis genetic signals were enriched not only in jawbone and teeth, but also significantly in tissues such as the brain and renal cortex. Multi-dimensional single-cell analysis identified monocytes and NK cells as key immune subsets and 23 genes causally associated with periodontitis. Among these, GNLY was prioritized as a computational lead, with evidence from multiple analytical approaches suggesting a potential role in linking innate immune recognition, cytotoxic effects, and tissue damage. The DrugReflector framework predicted 5 candidate compounds with therapeutic potential, all of which exhibited favorable binding affinities to GNLY in molecular docking simulations, providing a structural basis for subsequent drug optimization. CONCLUSION: This study develops a multi-layered analytical framework to systematically investigate the genetic architecture and key regulators of periodontitis. It provides candidate drugs and a theoretical foundation for targeted immunomodulatory therapies. CLINICAL RELEVANCE: The genetic enrichment in the brain and kidney provides a mechanistic basis for the systemic comorbidities of periodontitis, supporting the rationale for integrated oral-systemic health management.
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