{"title":"Uncovering the Molecular Networks of Extracellular Vesicles in the Pathogenesis of Periodontitis","authors":"Wenjie Yu , Wuda Huoshen , Wenjie Zhong , Xiang Gao , Jinlin Song","doi":"10.1016/j.identj.2025.103936","DOIUrl":"10.1016/j.identj.2025.103936","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of the study is to explore EV-related genes (ERGs) networks underlying periodontitis by integrating bulk RNA-seq, single-cell RNA-seq, and causal genetic analysis.</div></div><div><h3>Methods</h3><div>Using GEO and eQTLGen datasets, we identified periodontitis-associated ERGs through SMR and differential gene analysis. Potential therapeutics were predicted via drug repurposing and molecular docking, while machine learning built validated predictive models. Functional enrichment revealed pathogenic pathways, and scRNA-seq explored ERGs in tissue, peripheral blood, and diabetes-comorbid periodontitis cases</div></div><div><h3>Results</h3><div>SMR prioritised nine causal ERGs (<em>CD34, TLR4, TIMD4, ENPP4, HLA-DRA, HLA-B, ENDOD1, PSMA4</em> and <em>HSPB1</em>) that were mainly expressed in NK cells and CD8⁺ T cells in the subsequent single cell sequence and deconvolution analysis analysis. Dexamethasone emerged as the most promising drug via binding to <em>HSPB1</em>. The predictive models developed using machine learning achieved robust accuracy (XGBoost: AUC = 0.836) in validation. Key biological pathways included blood coagulation, hemostasis cell, and adhesion molecules, and so on.</div></div><div><h3>Conclusion</h3><div>Through multiple analyses integration, we defined an ERG network central to periodontitis pathogenesis. The diagnostic model and repurposed drugs offer translational avenues, requiring further experimental validation.</div></div><div><h3>Clinical Relevance</h3><div>This study identified and prioritised periodontitis-associated ERGs, elucidated their molecular mechanisms, and established a foundation for future functional validation and clinical risk assessment.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103936"},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting MSR1 to Facilitate Efferocytosis: A Novel Strategy for Immune Homeostasis Regulation in Irreversible Pulpitis","authors":"Sitong Liu , Longrui Dang , Xiaolan Guo , Kailun Wu , Xiaofei Qu , Jing Xu , Buling Wu , Zhao Chen","doi":"10.1016/j.identj.2025.103968","DOIUrl":"10.1016/j.identj.2025.103968","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the role of macrophage-mediated efferocytosis in resolution of inflammation during irreversible pulpitis, with a focus on the functional relevance of macrophage scavenger receptor 1 (<em>MSR1</em>).</div></div><div><h3>Methods</h3><div>Whole-transcriptome sequencing was performed on pulp tissue from 3 healthy individuals and 3 with pulpitis, integrated with Gene Expression Omnibus (GEO) datasets (GSE77459, GSE92681; total n = 30). After batch correction, differentially expressed genes (DEGs) were identified (|Fold Change|>1.5, <em>P < .</em>05) and analyzed by Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, CIBERSORT immune cell deconvolution, and machine learning. Efferocytosis activity was validated by immunofluorescence, Quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot (WB). MSR1 was selected for in vivo validation via small interfering RNA (siRNA) knockdown in a rat pulpitis model.</div></div><div><h3>Results</h3><div>A total of 467 differentially expressed genes were identified, which were enriched in immune response and phagosome-related pathways. Macrophage infiltration was significantly increased in pulpitis tissues, accompanied by upregulation of efferocytosis markers. Immunofluorescence showed that MER proto-oncogene tyrosine kinase (MERTK)-positive macrophages in human inflammatory dental pulp could phagocytize apoptotic cells positive for caspase 3 (CASP3) and poly(ADP-ribose) polymerase (PARP). MSR1 is regarded as a key regulatory factor. Knockdown of <em>Msr1</em> in rats can impair the clearance of apoptotic cells, reduce the expression of <em>Mertk</em>, and aggravate inflammation.</div></div><div><h3>Conclusion</h3><div>MSR1 maintains immune homeostasis in the dental pulp by promoting macrophage efferocytosis, providing a theoretical basis for targeted vital pulp therapy.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103968"},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alignment of Oral Health Care With ISO Standards","authors":"","doi":"10.1016/j.identj.2025.103998","DOIUrl":"10.1016/j.identj.2025.103998","url":null,"abstract":"","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"76 1","pages":"Article 103998"},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145340592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Jian , Fang Ma , Ying Xian , Xingyan Shi , Hairong Ma , Shenglan Ma , Ling Qin , Rui Zhang , Hualin Zhang
{"title":"Dental Pulp Stem Cell–Derived Multicellular Microtissue Spheres: A Synergistic Strategy for Dental Pulp Regeneration","authors":"Wei Jian , Fang Ma , Ying Xian , Xingyan Shi , Hairong Ma , Shenglan Ma , Ling Qin , Rui Zhang , Hualin Zhang","doi":"10.1016/j.identj.2025.103970","DOIUrl":"10.1016/j.identj.2025.103970","url":null,"abstract":"<div><h3>Objective</h3><div>Restoring pulp tissue to its natural state is the ultimate goal of pulp regeneration, during which vascularization and neuralization of regenerated pulp are key factors. Hence, this study aimed to construct multicellular microtissue spheres derived from dental pulp stem cells to promote the vascularization and neuralization of regenerated dental pulp tissue.</div></div><div><h3>Methods</h3><div>First, we induced dental pulp stem cells (DPSCs) to differentiate into endothelial-like cells and neural-like cells. Then, 7 types of multicellular microtissue spheres were constructed from DPSCs, endothelial-like cells and neural-like cells, and their gross morphology, tissue morphology, and endothelial cell marker and neuronal marker expression were evaluated. Additionally, the microtissue spheres were placed in rabbit molars, which were implanted subcutaneously into mice to assess dental pulp tissue regeneration.</div></div><div><h3>Results</h3><div>Internally dense microtissue spheres with a stable morphology were successfully constructed via the low adhesion method. The spheres containing endothelial-like cells displayed enhanced CD31-positive expression, and those with neural-like cells showed elevated expression of the neuronal marker Nestin. Cell activity was maintained in all 7 spheres, and compared with those derived from DPSCs only, the cell survival rates in the spheres constructed from endothelial-like and neural-like cells together or separately combined with DPSCs were greater. Neovascularized pulp-like tissue with neuronal marker-positive cells appeared in the root canals of each group, indicating that these spheres promoted pulp regeneration.</div></div><div><h3>Conclusions</h3><div>The results of this study indicate that DPSC-derived multicellular microtissue spheres facilitated neovascularization and expressed neuronal markers in newly formed pulp-like tissue, providing an experimental and theoretical basis for their application in pulp regeneration.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103970"},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Jia , Seo-Hyun Kim , Yuchuan Xu , Chen Ma , Kwang-Mahn Kim , Heng Bo Jiang , Jae-Sung Kwon
{"title":"Mechanical Properties and Microstructure of 3D-Printed Zirconia Based on Sintering Placement Orientation","authors":"Qi Jia , Seo-Hyun Kim , Yuchuan Xu , Chen Ma , Kwang-Mahn Kim , Heng Bo Jiang , Jae-Sung Kwon","doi":"10.1016/j.identj.2025.103972","DOIUrl":"10.1016/j.identj.2025.103972","url":null,"abstract":"<div><h3>Objective</h3><div>Sintering is a critical step in fabricating 3D-printed zirconia (3Dp/ZrO<sub>2</sub>) restorations and is significantly influenced by gravity. Additionally, the layer-by-layer structure of 3Dp/ZrO<sub>2</sub> introduces anisotropy. Therefore, this study aims to investigate the influence of sintering placement orientation on the mechanical properties and microstructure of 3Dp/ZrO<sub>2</sub>.</div></div><div><h3>Materials and Methods</h3><div>A digital light processing-type 3D printer and ZrO<sub>2</sub> slurry were used to fabricate green bodies, after which one-step sintering was used to create sintered 3Dp/ZrO<sub>2</sub> products. Group-A: Sintered with the printing layer orientation parallel to the horizontal plane. Group-B: Sintered with the printing layer orientation perpendicular to horizontal plane, with the short axis aligned vertically. Group-C: Sintered with the printing layer orientation perpendicular to horizontal plane, with the long axis aligned vertically. Shrinkage ratio, bulk density, three-point and biaxial flexure tests, scanning electron microscopy with energy dispersive spectrometry, X-ray diffraction, and micro-computed tomography were used to determine the physical, mechanical, and microstructural properties of the sintered 3Dp/ZrO<sub>2</sub> specimens.</div></div><div><h3>Results</h3><div>Group-B (558.28 ± 102.01 MPa) and Group-C (423.47 ± 38.46 MPa) showed a significantly lower flexure strength than Group-A (789.25 ± 57.10 MPa). More grain boundary defects and microdefects were observed in Group-B and Group-C. Different sintering placement orientations did not cause significant differences in shrinkage ratio, density, phase, or grain size.</div></div><div><h3>Conclusions</h3><div>The sintering placement orientation of 3Dp/ZrO<sub>2</sub> influenced its mechanical properties and microstructure. Sintering with the printing layer orientation parallel to horizontal plane showed superior mechanical properties. In contrast, the perpendicular orientation showed compromised performance, likely due to loose grain boundaries and internal microdefects observed within 3Dp/ZrO<sub>2</sub>.</div></div><div><h3>Clinical Significance</h3><div>This study provides practical guidance for dental professionals by demonstrating how sintering placement orientation affects the microstructure of 3Dp/ZrO<sub>2</sub>. Considering placement orientation during sintering process can help reduce defects and improve the mechanical properties of zirconia-based restorations for better clinical outcomes.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103972"},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiu-Yi Lin , Wendy Thompson , Lucy O’Malley , Stefan Listl , Valeska Fehrer , Matthew Byrne
{"title":"Patient Reported Outcome Measures and Patient Reported Experience Measures for Dental Practice Quality Improvement Via Deliberative Stakeholder Consultation in the United Kingdom","authors":"Chiu-Yi Lin , Wendy Thompson , Lucy O’Malley , Stefan Listl , Valeska Fehrer , Matthew Byrne","doi":"10.1016/j.identj.2025.103961","DOIUrl":"10.1016/j.identj.2025.103961","url":null,"abstract":"<div><h3>Introduction and aims</h3><div>Patient feedback have potential to drive quality improvement in dental care. However, there is a lack of clarity regarding which elements of patient feedback should be used. This study aimed to select appropriate patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) for use in audit and feedback-based quality improvement in dental practices in the UK.</div></div><div><h3>Methods</h3><div>A 2-phase, evidence-informed deliberative process—comprising evidence synthesis and Deliberative Stakeholder Consultations (DSCs)—was conducted. Phase 1: PROMs and PREMs candidate items were identified through systematic literature search and thematically analyzed. Phase 2: Dental patients and professionals were recruited for DSCs through purposive and snowball sampling. Inductive thematic analysis of DSC transcripts was conducted, and the final measures were agreed (5 for each dental encounter: check-up, planned treatment, and urgent care).</div></div><div><h3>Results</h3><div>In phase 1, 672 measures (across 8 themes such as psychological/social impacts) were identified. In phase 2, 8 dentists and 5 patients participated (March-May 2024). Stakeholder priorities were as follows. Check-up appointments: dentist’s communication skills regarding treatment options and cost, and the cleanliness of facilities. Planned treatment: effective pain management during procedures and overall satisfaction with treatment. Urgent care: management of patient fear/anxiety and pain relief following a procedure. Communication of treatment progress and provision of post-operative advice were considered important in both planned and routine treatment. Waiting times for appointments were a priority across all encounters.</div></div><div><h3>Conclusion</h3><div>Eleven measures (after removing duplicates) were selected for the encounters to offer meaningful potential for operationalizing quality improvement in dental practices. DSCs were also perceived as a useful method for prioritizing measures for quality improvement.</div></div><div><h3>Clinical Relevance</h3><div>This study is the first to identify actionable PROMs and PREMs which can be used for audit and feedback loops in dental practices. These measures will be tested in DELIVER case studies.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103961"},"PeriodicalIF":3.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edgar O. Beltrán , James R. Allison , Nicholas S. Jakubovics , Jaime E. Castellanos , Richard Holliday , Myriam L. Velandia-Romero , Eliana P. Calvo , Manuel Forero , Stefania Martignon
{"title":"Control of Viral Aerosol Dispersion During Simulated Dental Procedures","authors":"Edgar O. Beltrán , James R. Allison , Nicholas S. Jakubovics , Jaime E. Castellanos , Richard Holliday , Myriam L. Velandia-Romero , Eliana P. Calvo , Manuel Forero , Stefania Martignon","doi":"10.1016/j.identj.2025.103963","DOIUrl":"10.1016/j.identj.2025.103963","url":null,"abstract":"<div><h3>Aim</h3><div>Although air-cleaning systems (ACS) and high-volume evacuation (HVE) have been shown to reduce dental bioaerosols, few works have looked at viruses. This study aimed to assess the effects of HVE and ACS on dispersion of aerosolised particles and airborne viruses in a simulation model of dental bioaerosols using a detailed and comprehensive sampling approach and different tracer molecules.</div></div><div><h3>Methods</h3><div>MS2 bacteriophage and fluorescein solution were used as viral or dispersion tracers, respectively. These were added independently to the instrument irrigation system and aerosolised during dental procedures. Aerosol mitigation condition groups were ACS, HVE, ACS plus HVE, and No mitigation (control). Aerosols were collected via settlement onto sterile filter papers and agar plates. In addition, a 6-stage Andersen cascade impactor was used for viral air sampling. Fluorescent particles were analysed using ImageJ software, and bacteriophage was quantified using plaque assays and reverse transcription quantitative polymerase chain reaction (RT-qPCR).</div></div><div><h3>Results</h3><div>HVE combined with ACS produced the highest reduction in viral spread among the three aerosol-generating procedures (AGPs). This reduction was evident both in the number of fluorescent particles and that of viruses. The effect was more pronounced at the farthest sites. By plaque assay, viral loads in the largest-sized aerosols (>7.0 μm) from air samples were 93% lower in the ACS plus HVE group compared with control, and the load in the smallest aerosols (0.65-1.1 μm) was reduced by 84% (<em>P</em> < .05). By RT-qPCR, the ACS plus HVE group also reduced viral detection in air samples (>80%) more than ACS or HVE alone compared with the control group (<em>P</em> < .05). In ACS or HVE condition, viral RNA was detected even in the absence of infectious virus detected by plaque assay for anterior versus posterior procedures and in the farthest positions.</div></div><div><h3>Conclusions</h3><div>A synergistic effect was obtained in the reduction of aerosolised particles and viruses from surfaces and air samples when HVE was combined with ACS.</div></div><div><h3>Clinical Relevance</h3><div>Using a comprehensive and depth assessment, this study found that the combination of high-volume evacuation and air-cleaning systems was the most effective measure in mitigating virus dispersion during aerosol-generating dental procedures, translated into lower required waiting (fallow) times between patients’ appointments for dental care depending on the type of AGP conducted. The more aerosols are produced during an AGP, the longer it takes to prevent cross-contamination among dental staff and patients. In addition, our findings support the use of HVE, face shields, and well-fitting masks in dental procedures, not only during pandemics but also in everyday practice.</div></div>","PeriodicalId":13785,"journal":{"name":"International dental journal","volume":"75 6","pages":"Article 103963"},"PeriodicalIF":3.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}