Journal of dental research最新文献

{"title":"Estimating the Individualized Effect of Tooth Extraction before Radiotherapy on Osteoradionecrosis Using Causal Machine Learning.","authors":"M Moharrami, E Watson, S Singhal, S H Huang, C Yao, A Hosni, C Quinonez, M Glogauer","doi":"10.1177/00220345261424748","DOIUrl":"10.1177/00220345261424748","url":null,"abstract":"<p><p>The purpose of this study was to determine the average treatment effect (ATE) of tooth extraction before radiotherapy on the risk of osteoradionecrosis (ORN) in patients with head and neck cancer (HNC) and to estimate the conditional average treatment effect (CATE) to characterize heterogeneous treatment effects (HTE). In this retrospective cohort study of adults with HNC treated with curative radiotherapy from 2011 to 2018 with ongoing follow-up, the intervention was the extraction of at least 1 tooth before radiotherapy, and the outcome was ORN (ClinRad grade ≥1). Twenty sociodemographic and clinical covariates were recorded. A causal survival forest targeting restricted mean survival time (RMST) was trained with 100 repetitions of 5-fold cross-validation. Calibration used out-of-fold augmented inverse probability weighting (AIPW) scores as pseudo-outcomes, and treatment prioritization was assessed using the rank-weighted average treatment effect (RATE). A best linear projection regression identified covariates with direct associations to the predicted benefit. Among 2,466 patients, 810 underwent preradiotherapy extraction, and 183 developed ORN during the follow-up. The ATE was not significant at -0.26 mo (95% confidence interval [CI]: -0.68 to 0.17). However, the CATE distributions revealed substantial HTE, with patients in the lowest quartile (Q1) experiencing harm and those in the highest quartile (Q4) deriving benefit. Calibration against AIPW scores confirmed median RMST differences of -1.47 mo in Q1 and +0.94 mo in Q4. The RATE was positive at 1.10 (95% CI: 0.04 to 2.15). Best linear projection identified Eastern Cooperative Oncology Group performance status 1 to 4 versus 0 (β = 2.68; 95% CI: 0.19 to 5.17) and periodontal grade III-IV versus 0 (β = 4.33; 95% CI: 1.05 to 7.60) as independent modifiers of benefit. Radiation dose had a nonlinear association with treatment effect. If preradiotherapy tooth extraction was applied across all eligible patients, it would not alter the overall risk of ORN. However, individualized treatment effects varied, with some patients benefiting and others harmed, underscoring the importance of targeted interventions.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1564-1573"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking Myofibroblast Plasticity to Reverse Salivary Gland Fibrosis.","authors":"S Pan, N-N Zhong, B Peng, L Wang, J Kang, W Cao, B Li, Y Cheng","doi":"10.1177/00220345261465355","DOIUrl":"10.1177/00220345261465355","url":null,"abstract":"<p><p>Salivary gland (SG) fibrosis represents a critical pathological feature of exocrine hypofunction driven by the persistent activation of myofibroblasts (MFs). However, the translational gap between the convoluted in vivo regulatory networks governing these cells and the deployment of precise, disease-modifying interventions remains a formidable challenge. This review systematically examines current mechanistic evidence undergirding MF activation, survival, and its phenotypic reversal, focusing on restoring glandular function. We synthesize recent literature mapping in vivo canonical profibrotic signaling cascades, noncanonical crosstalks, and cellular heterogeneity within the injured exocrine stroma. Evidence underscores that the pathological tilt between profibrotic Smad3 and inhibitory Smad7 acts as a critical rheostat for MF differentiation across diverse etiologies. Beyond classical pathways, emerging mechanisms-such as mitochondrial metabolic reprogramming, store-operated calcium entry (SOCE) collapse, and persistent cGAS-STING innate immune sensing-are mechanically reinforced by extracellular matrix rigidity via a YAP/TAZ mechanotransduction loop. These events, coupled with aberrant epigenetic imprinting, structurally lock the persistent MF phenotype and restrict cellular plasticity. Consequently, we evaluate targetable interventions-ranging from small-molecule inhibitors (SB431542, decitabine) and biologics (rituximab) to traditional botanical formulations (Shengmai San) and stem cell-derived extracellular vesicles-that effectively attenuate scar formation and improve salivary flow rates in preclinical or clinical models. Ultimately, this review establishes a novel, etiology-driven \"etiology-origin-pathway-target\" matrix that shifts the paradigm from empirical anti-inflammatory management toward origin-specific precision therapeutics capable of reversing established salivary gland fibrosis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1515-1526"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETURN Randomized Controlled Trial to Increase Adult Routine Dental Visits.","authors":"R V Harris, V Lowers, J Green, R Kirby, J Hennessy, J E Clarkson, G Burnside","doi":"10.1177/00220345261425929","DOIUrl":"10.1177/00220345261425929","url":null,"abstract":"<p><p>Groups with low socioeconomic status are less likely to make planned dental visits even though routine attenders have fewer caries and less tooth loss. Because behavioral interventions positioned in urgent dental care may improve health and inequalities, RETURN, which involved a nurse conversation supported by videos, booklets, and goal/action-plan setting, was developed. The objective of this study was to investigate the effectiveness of the RETURN intervention at increasing planned dental visits and lessening the oral health impact. Adults attending 14 National Health Service urgent dental services were recruited to a randomized controlled trial and followed up after 6, 12, and 18 mo. Co-primary outcomes were (1) planned visits at 12 mo as measured by Business Services Authority (BSA) data and (2) Oral Health Impact Profile (OHIP) summary score at 12 mo adjusted for baseline. Of the 1,176 consenting adults who were randomized, 591 were allocated to the RETURN group. More than half (55.2%, 315 intervention; 54.7%, 310 control) lived in the lowest Index Multiple Deprivation decile. RETURN participants had a 20% greater odds of planned care as recorded by the BSA at 12 mo (odds ratio [OR] = 1.21; 97.5% confidence interval [CI] = 0.86, 1.70; <i>P</i> = 0.217). There was a reduction (improvement) in OHIP scores at 12 mo in both groups (RETURN group, mean = -7.4, standard deviation [SD] = 12.9; control group, mean = -6.2, SD = 12.9). The least squares mean of the RETURN Modified Dental Anxiety Score decreased with time (anxiety improved) whereas it increased (worsened) in the control group (Modified Dental Anxiety Scale time and treatment group interaction = -0.01; CI = -0.03, 0.00; <i>P</i> = 0.027). RETURN participants had a more than 3 times greater odds of attempting to make an appointment, with the treatment effect increasing with time (at 18 mo: OR = 3.39; 95% CI = 1.83, 6.27; <i>P</i> = 0.0001). We are moderately certain RETURN produced small, consistently favorable effects on routine visits, oral health impact, and dental anxiety despite limited-service availability. RETURN also significantly increased attempts to make routine appointments even in a disadvantaged cohort. This supports integrating behavioral support alongside service reforms to support the transition into continuing care and the optimum use of resources.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1536-1545"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to <i>Porphyromonas gingivalis</i>-Induced NETs Mediate Neuroinflammation via TLR4 Activation.","authors":"","doi":"10.1177/00220345261472458","DOIUrl":"10.1177/00220345261472458","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1655"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchrotron X-rays Uncover Crystalline Phase and Fine Structure of Zirconia.","authors":"K Nakamura, S Shishido, S Barkarmo, P Svanborg, U Örtengren, K Itoh, H Sone","doi":"10.1177/00220345261446264","DOIUrl":"10.1177/00220345261446264","url":null,"abstract":"<p><p>Yttria-stabilized zirconia (YSZ) has become indispensable in restorative dentistry; however, the influence of yttria content on its crystalline phases and fine structure remains incompletely understood. This study investigated how variations in yttria content (3-8 mol%) and low-temperature degradation (LTD) influence the crystalline phase composition and local atomic structures of dental zirconia using synchrotron-based X-ray diffraction (XRD) and X-ray absorption fine structure (XAFS) spectroscopy. Forty-two sintered disc-shaped specimens were prepared from zirconia powders stabilized with 3-8 mol% yttria (3-8YSZ). Half of the specimens were polished, while the other half underwent autoclaving to induce LTD. Synchrotron XRD showed that 3-5YSZ contained 2 tetragonal (<i>t</i> and <i>t'</i>) phases, while 8YSZ contained a cubic (<i>c</i>) phase. The <i>t</i>-phase fraction decreased markedly with increasing yttria content, from 83.1 mass% in 3YSZ to 25.3 mass% in 5YSZ. LTD induced monoclinic (<i>m</i>) and rhombohedral (<i>r</i>) phases in 3YSZ and 4YSZ but not in 5YSZ, indicating improved LTD resistance at higher yttria contents. XAFS showed that the dual-peak white-line profile of zirconia specimens varied with yttria content, reflecting the <i>t</i>-to-<i>t'</i> phase transition, and transformed into a single broadened peak after LTD, consistent with structural disorder induced by phase transformation. Fine structural analysis revealed 2 main coordination shells, Zr-O and Zr-Zr. In the Zr-Zr shell, the Debye-Waller factors changed systematically with yttria content, reflecting structural disorder associated with oxygen vacancies. In conclusion, a combined synchrotron XRD and XAFS approach elucidated the phase composition and atomic-scale structural disorder in dental zirconia across different yttria contents. These insights provide a foundation for the rational design of next-generation translucent dental zirconia, in which crystalline phase composition and local atomic disorder are deliberately tailored to achieve durable clinical performance.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1574-1582"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partnership with Purpose: Presidential Speech.","authors":"J E Gallagher","doi":"10.1177/00220345261463177","DOIUrl":"10.1177/00220345261463177","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1509-1511"},"PeriodicalIF":5.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peri-implant Soft Tissue Cell Behavior on Experimental β-Ti Alloys.","authors":"C Montet, C Labadi, H Abouelleil, D-M Gordin, G Vinault, T Gloriant, A Lafon, N Attik","doi":"10.1177/00220345261486419","DOIUrl":"https://doi.org/10.1177/00220345261486419","url":null,"abstract":"<p><p>Titanium alloys based on Ti6Al4V (TA6V) are widely employed as metallic materials for dental implants owing to their overall mechanical and biological performance. However, challenges remain, particularly the mismatch in elastic modulus between the alloy and bone tissue, as well as concerns regarding the potential release of cytotoxic ions such as aluminum (Al) and vanadium (V). Therefore, optimizing alloy composition is crucial to improve peri-implant tissue integration and enhance long-term implant stability. In this in vitro study, the cytocompatibility of a newly developed β-titanium alloy, Ti20Zr3Mo (at%) free of Al and V and exhibiting a reduced elastic modulus compared to that of TA6V, was evaluated using primary human gingival fibroblasts, representative of peri-implant soft tissues. The experimental alloy was compared to conventional TA6V and commercially pure titanium (Cp-Ti40). Several endpoints were investigated to characterize cell-material interactions. Cell viability and cytotoxicity were analyzed by Live/Dead fluorescence staining, while metabolic activity was assessed using the Alamar Blue assay. Cell adhesion and surface colonization were observed through scanning electron microscopy and confocal laser imaging. In addition, extracellular matrix production, including collagen deposition, was examined to evaluate the potential for soft tissue integration. Results demonstrated that Ti20Zr3Mo alloy supported comparable cell viability to Cp-Ti40 while exhibiting enhanced surface colonization by fibroblasts. These findings suggest that the substitution of Al and V with Zr and Mo in specific proportions may promote suitable fibroblast-Ti-alloy interactions, which could improve peri-implant soft tissue sealing and contribute to the long-term success of dental implants. This work highlights a promising strategy for developing next-generation titanium alloys that combine improved biological responses with suitable mechanical properties, with the ultimate goal of enhancing the long-term clinical performance of dental implants.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261486419"},"PeriodicalIF":5.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fanconi Anemia: Matrix Remodeling and Oral Carcinogenesis.","authors":"T A Silva, N C M Santana, J A A de Arruda, P A Rocha, S Macari, V Z Drumond, W C S Silva, L M Malard, J M Amenábar, C C Torres-Pereira, S Del Marro, A Pascual, A Page, R Errazquin, C Lorz, R Garcia-Escudero, F C Ferré, N Dupré, A Berdal, B P J Fournier","doi":"10.1177/00220345261478636","DOIUrl":"https://doi.org/10.1177/00220345261478636","url":null,"abstract":"<p><p>Fanconi anemia (FA) increases the risk of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma; however, the stromal alterations associated with FA-related oral lesions remain poorly defined. We investigated whether extracellular matrix (ECM) remodeling represents a quantifiable feature of FA-associated OPMDs. A total of 119 participants were included: controls with normal mucosa or oral leukoplakia (OL) and individuals with FA. Histopathological and immunohistochemical analyses (p53, Ki-67, α-SMA, and elastin), picrosirius red staining, and multiphoton microscopy combining second-harmonic generation and 2-photon fluorescence were performed, complemented by salivary and transcriptomic profiling. Additionally, <i>Fanca</i>-deficient mice were used to assess stromal remodeling. Compared with sporadic OL, FA-OL exhibited reduced collagen density and elastin autofluorescence, a higher collagen-to-elastin ratio, and diminished p53 immunoreactivity. Salivary procollagen type I N-terminal propeptide showed exploratory associations with matrix-derived optical parameters. RNA sequencing of bulk biopsy tissue revealed an altered matrisome transcriptional signature, including enrichment of ECM structural gene sets and downregulation of selected ECM regulatory programs. In FA-related mouse models, collagen and elastin signals were similarly reduced. Collectively, these multimodal data identify ECM disruption as a reproducible feature associated with FA-OL. Matrix disorganization, together with altered epithelial p53 immunoreactivity, supports the hypothesis that epithelial and stromal alterations coexist across the FA-associated oral lesion spectrum.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261478636"},"PeriodicalIF":5.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 Receptor Agonists in Dentistry: Promise, Pitfalls, and Evidence Gaps.","authors":"N Werner, V Pitchika, C V Bumm, K Heck, M Folwaczny, F Schwendicke","doi":"10.1177/00220345261488338","DOIUrl":"https://doi.org/10.1177/00220345261488338","url":null,"abstract":"<p><p>GLP-1RAs (glucagon-like peptide-1 receptor agonists) have become one of the fastest-growing drug classes worldwide, with prescriptions for obesity treatment increasing by 587% from 2019 to 2024. While their metabolic and cardiovascular benefits are well established, the implications for oral health remain largely unexamined. Preclinical evidence consistently demonstrates anti-inflammatory and osteoprotective effects on periodontal and peri-implant tissues: GLP-1RAs promote osteogenic differentiation of periodontal ligament stem cells, reduce alveolar bone resorption in animal models of periodontitis, and enhance implant osseointegration in diabetic rats. However, these findings are based exclusively on in vitro and animal studies, with only a single retrospective cohort study providing limited clinical data. Conversely, several oral adverse effects have been reported based on pharmacovigilance analyses, including xerostomia, dysgeusia, and anosmia, particularly for semaglutide. Gastrointestinal side effects, particularly nausea (15% to 50%), vomiting (5% to 24%), and gastroesophageal reflux, pose a plausible but unquantified risk for tooth erosion and secondary caries. A bidirectional link between GLP-1 signaling and the oral microbiota, mediated by bacterial dipeptidyl peptidase (DPP)-4-like enzymes that degrade endogenous GLP-1, adds further complexity. Despite this breadth of potential interactions, no prospective study has used any dental outcome as an endpoint in patients receiving GLP-1RAs. This critical appraisal synthesizes the evidence across multiple dental disciplines, grades it in each domain, and identifies the gaps that demand urgent investigation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261488338"},"PeriodicalIF":5.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Porphyromonas gingivalis</i> Promotes Lipid Droplet-Mediated Microglial Dysfunction.","authors":"M S Riaz Rajoka, K N Valladares, C L Prairie, W Li, P King, J Katz, S M Michalek, P Zhang","doi":"10.1177/00220345261478558","DOIUrl":"10.1177/00220345261478558","url":null,"abstract":"<p><p>Growing evidence supports a strong association between periodontitis and Alzheimer's disease (AD), yet the mechanisms linking these conditions remain poorly defined. In neurodegenerative disorders, including AD, microglia are often characterized by increased accumulation of lipid droplets (LD), heightened activation, and impaired function. In this study, we examined whether <i>Porphyromonas gingivalis</i> (<i>Pg</i>), a keystone periodontal pathogen, promotes LD accumulation in microglia and disrupts their function. We found that infection with <i>Pg</i> (ATCC 33277) induces robust LD accumulation in BV2 microglial cells and in microglia from <i>Pg</i>-infected <i>App</i> knock-in mice. This <i>Pg</i>-driven LD buildup was closely associated with elevated reactive oxygen species (ROS) production, impaired phagocytic ability, and altered activation. Notably, pharmacologic inhibition of LD with a long-chain fatty acyl-CoA synthetase inhibitor effectively reversed <i>Pg</i>-induced LD accumulation, mitigated ROS production, and restored phagocytic function, thus underscoring the critical role of lipid metabolism in regulating microglial function. These findings support a model in which, in the context of periodontitis, systemic dissemination of periodontal pathogens and inflammatory mediators promotes LD accumulation in microglia, and this metabolic alteration exacerbates microglia dysfunction via a self-reinforcing cycle of excessive oxidative stress and impaired phagocytosis, potentially accelerating AD progression.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261478558"},"PeriodicalIF":5.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}