Y. Li, M. Hu, H. Yin, Y. Cao, J. Wu, M. Yang, X. Zhang, J. Zhou, X. Fang, J. Luo, M. Hu, D. Li, D. Liu
{"title":"DAPK1 Ablation Promotes Wound Healing by Keratinocyte Modulation","authors":"Y. Li, M. Hu, H. Yin, Y. Cao, J. Wu, M. Yang, X. Zhang, J. Zhou, X. Fang, J. Luo, M. Hu, D. Li, D. Liu","doi":"10.1177/00220345261460758","DOIUrl":"https://doi.org/10.1177/00220345261460758","url":null,"abstract":"Death-associated protein kinase 1 (DAPK1), a Ca²+/calmodulin-regulated serine/threonine kinase, plays a pivotal role in epidermal homeostasis, tissue repair, and cutaneous wound healing. However, its role in oral mucosal repair remains unclear. In this study, we established a global <jats:italic toggle=\"yes\">Dapk1</jats:italic> knockout mouse model to create 1.5-mm circular palatal wounds in mice aged 8 to 12 wk. Our results demonstrated that DAPK1 deficiency significantly accelerated oral wound closure. In vitro experiments further confirmed that DAPK1 modulates the proliferation and migration of human oral keratinocytes. Mechanistic investigations through transcriptome sequencing revealed activation of the Wnt signaling pathway in <jats:italic toggle=\"yes\">Dapk1</jats:italic> knockout mice following injury, characterized by pronounced upregulation of <jats:italic toggle=\"yes\">Wnt3</jats:italic> , <jats:italic toggle=\"yes\">Fosl1</jats:italic> , and <jats:italic toggle=\"yes\">Ctnnd2</jats:italic> , alongside downregulation of innate immune mediators, including <jats:italic toggle=\"yes\">Il7</jats:italic> , <jats:italic toggle=\"yes\">Ccl28</jats:italic> , <jats:italic toggle=\"yes\">Ccr2</jats:italic> , <jats:italic toggle=\"yes\">Ccl5</jats:italic> , and <jats:italic toggle=\"yes\">Cxcr4</jats:italic> . These findings suggest that loss of DAPK1 enhances epithelial proliferation and migration while attenuating local inflammation. Furthermore, we developed a novel microneedle patch for drug delivery, consisting of GelMA tips encapsulating the DAPK1 inhibitor (HS-38) and a hyaluronic acid substrate. This system facilitated efficient mucosal penetration and localized delivery. Application of the microneedle patch significantly improved wound healing in both normal and diabetic mouse models. Collectively, these findings uncover a previously unrecognized role of DAPK1 in oral mucosal repair and highlight its potential as a molecular target to accelerate wound healing.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"153 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459729","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}
A. Alia, B. Fuks, Z. Sharmin, S. Suchy, A. Venigalla, F. Gao, J.Z. Gasiorowski, C.S. Pfeifer, M.R. Carrilho
{"title":"Dentin beyond Its Ontology: A Platform to Produce Dental Adhesives","authors":"A. Alia, B. Fuks, Z. Sharmin, S. Suchy, A. Venigalla, F. Gao, J.Z. Gasiorowski, C.S. Pfeifer, M.R. Carrilho","doi":"10.1177/00220345261461515","DOIUrl":"https://doi.org/10.1177/00220345261461515","url":null,"abstract":"Given its unique composition and physicochemical stability, dentin obtained from teeth extracted for clinical reasons represents a promising source for the development of functional biomaterials. Photopolymerizable compounds based on demineralized dentin modified with acrylamide groups were developed, with the aim of formulating ester-free adhesive primers. Dentin powder obtained from the crown and root was demineralized and reacted with methacrylic anhydride (MA). Following reaction, dialysis, and lyophilization, the resulting granular and sticky materials were evaluated for their degree of functionalization (methacrylation) using the 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay and infrared (attenuated total reflectance Fourier transform infrared [ATR-FTIR]) spectrometry. The compounds were subsequently suspended in phosphate-buffered saline and collagen-methacrylamide, supplemented with lithium acylphosphinate, injected into custom molds, and photopolymerized using a dental-curing unit, producing 3-dimensional constructs. Morphology, water sorption, solubility, degree of swelling, flexural modulus, biodegradability, and biocompatibility were assessed. TNBS analysis indicated a lower degree of functionalization in methacrylated crown dentin (CD-MA, 41%) than in methacrylated root dentin (RD-MA, 55%), consistent with ATR-FTIR results. CD-MA exhibited greater solubility and swelling, as well as a lower flexural modulus (1.8 ± 0.2 MPa), compared with RD-MA (2.2 ± 0.3 MPa). However, CD-MA and RD-MA demonstrated comparable water sorption, biodegradability, and >95% metabolic activity and cell viability in OD-21 and MDPC-23 cell lines. As a proof of concept, CD-MA, which exhibited the higher yield, was selected for evaluation as an adhesive primer and compared with a commercial methacrylate-based etch-and-rinse adhesive. Specimens bonded with the experimental CD-MA primer showed significantly lower bond strength at the initial evaluation (24 h) than the control group. Nonetheless, after 6 mo of storage in simulated body fluid, the experimental group maintained stable bond strength, whereas the control group exhibited an approximately 30% reduction. Taken together, these findings demonstrate that dentin is a viable raw material for the development of methacrylamide-based dental primers, which exhibit greater bond strength stability than a conventional methacrylate-based adhesive system.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"167 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440915","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}
{"title":"Low DYNLL1 Resists Porphyromonas gingivalis-Induced Epithelial Jamming-Like State.","authors":"Q Li,J Li,D Tao,Y Che,Q Yan,H Liu,Y Zhang","doi":"10.1177/00220345261455825","DOIUrl":"https://doi.org/10.1177/00220345261455825","url":null,"abstract":"Incomplete regeneration of the junctional epithelium (JE) following periodontal therapy is associated with persistent alveolar bone resorption and disease recurrence. While pathogen clearance is essential, the host-intrinsic mechanisms dictating epithelial recovery remain obscure. Here, we reveal that Porphyromonas gingivalis challenge induces an aberrant jamming-like phase transition in the epithelium during the early recovery window, mechanically restricting the epithelial remodeling required for proper JE reconstruction. Through a genome-wide CRISPR-Cas9 screen, we identified Dynein Light Chain LC8-Type 1 (DYNLL1) as a central mediator of this pathological transition. Mechanistically, DYNLL1 regulates the abundance and membrane localization of the junction-associated protein JUP, whose overaccumulation strengthens intercellular adhesion and restricts epithelial motility. Partial DYNLL1 deficiency not only reduces junctional rigidity but also enhances Wnt/β-catenin signaling, thereby preserving a more dynamically responsive epithelial state conducive to repair. In a murine periodontitis model, Dynll1 haploinsufficiency facilitated the restoration of JE morphology, improved barrier function, and mitigated bone loss. These findings suggest that modulating epithelial biophysical properties may complement antimicrobial therapies to enhance periodontal healing. Overall, this work provides novel insights into host-intrinsic mechanisms that contribute to impaired periodontal repair and identifies potential therapeutic targets for early-stage intervention.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"21 1","pages":"220345261455825"},"PeriodicalIF":7.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428756","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}
Z L Tian,Y L Zhu,S H Yang,H M Wang,Q H Bai,X Z Han,S W Qiao,Z S Shi,S Zhu
{"title":"A Novel Multi-Cross-linking Diluent System to Stabilize Self-Etch Bonding.","authors":"Z L Tian,Y L Zhu,S H Yang,H M Wang,Q H Bai,X Z Han,S W Qiao,Z S Shi,S Zhu","doi":"10.1177/00220345261457339","DOIUrl":"https://doi.org/10.1177/00220345261457339","url":null,"abstract":"Despite the indispensability of 2-hydroxyethyl methacrylate (HEMA) for improving the wettability of self-etch (SE) adhesives, elevated concentration may compromise the durability of the hybrid layer. This study proposes a modification strategy to preserve the wettability of SE adhesives while reducing excessive HEMA content and enhancing hybrid layer integrity through introducing collagen-protective and hydrophobic features. Thus, a novel diluent system was developed by partially replacing HEMA with 2 hydrophobic cross-linking reagents, 3-(4-formylphenoxy)-2-hydroxypropyl methacrylate (FPA) and glycidyl methacrylate (GMA). Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), confocal laser scanning microscopy (CLSM), wettability, and water contact angle analyses confirmed that FPA induced rapid but transient cross-linking with collagen. Thus, the compatibility of collagen with hydrophobic adhesives was improved. The time-dependent cross-linking efficacy of GMA was evaluated by ATR-FTIR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Guided by these findings, FPA-GMA adhesives were formulated and subjected to physicochemical (flexural strength, Vickers microhardness, and water sorption/solubility) and biological (Cell Counting Kit-8, calcein acetoxymethyl ester/propidium iodide) evaluations. Enzymatic degradation assays, including in situ zymography, gelatin zymography, and the hydroxyproline releasing test, verified that FPA-GMA adhesives built the degradation-resistant hybrid layer during dentin bonding. CLSM, micro-tensile bond strength, and nanoleakage analysis corroborated the establishment of a stable and durable FPA-GMA dentin-bonding interface before and after 10,000 thermocycles. Collectively, this study evaluated whether FPA-GMA formulations improve the physicochemical properties of experimental adhesives and their biological/functional interactions with dentin, as assessed by enzymatic activity and bonding performance at the dentin-bonding interface. The results demonstrated that FPA-GMA provided sustained collagen protection while preserving SE infiltration and enhancing its mechanical properties, which thereby improved the durability of the dentin-bonding interface.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"9 1","pages":"220345261457339"},"PeriodicalIF":7.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428723","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}
{"title":"Construction of PDA@Ag-Coated Gutta-Percha for Root Canal Therapy.","authors":"W Wang,M Cheng,P Zhang,X Qiu,W Tang,C Shen,Y Zhao,L Song,C Liu,L Miao","doi":"10.1177/00220345261457102","DOIUrl":"https://doi.org/10.1177/00220345261457102","url":null,"abstract":"Root canal therapy is currently the leading treatment method for endodontic and periapical diseases. Gutta-percha (GP), the most widely used root canal filling material, is inert and biocompatible; however, it suffers from the lack of antibacterial properties, and the root canal system is likely to become reinfected. Enterococcus faecalis is one of the primary pathogens of bacterial reinfection in root canals. Herein, silver ions were reduced to silver nanoparticles using polydopamine to modify the surface of the gutta-percha, thereby forming antibacterial gutta-percha and thus filling the root canal. Results obtained through in vitro experimental procedures indicated that the combined application of GP@PDA@Ag and 808 nm near-infrared (NIR) irradiation could eliminate planktonic E. faecalis and prevent the formation of E. faecalis biofilms through inhibiting the expression of the cylA, esp, and gelE genes. In addition, the infected root canal model showed that the combined use of GP@PDA@Ag and 808 nm NIR irradiation inhibited the proliferation of E. faecalis inside the root canal and improved the prognosis of endodontic periapical disease. Meanwhile, GP@PDA@Ag also has good biocompatibility. In brief, the application of the 808 nm NIR-irradiated PDA@Ag-coated gutta-percha introduces a potent new option for root canal filling. This approach is designed to counteract the bacterial infection microenvironment within root canals, thereby enhancing the success rate of root canal therapy.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"33 1","pages":"220345261457102"},"PeriodicalIF":7.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428722","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}
{"title":"MFN2-Mediated MERCs Promote Odontoblast Differentiation and Dentinogenesis.","authors":"J Sheng,L Yan,Z Chen,G Yang,G Yuan","doi":"10.1177/00220345261458702","DOIUrl":"https://doi.org/10.1177/00220345261458702","url":null,"abstract":"Odontoblasts are a tooth-specific cell type responsible for dentin formation. During odontoblast differentiation, dramatic organelle alterations occur with the increase of both mitochondria and endoplasmic reticulum (ER). In multiple cell types, mitochondria-ER contact sites (MERCs) are formed to regulate cellular biological processes via mediating essential interorganelle communications. However, whether MERCs play a role in odontoblast differentiation remains enigmatic. Here, we found a progressive increase of MERCs during the in vitro odontoblastic differentiation using live-cell imaging, transmission electron microscopy (TEM), and in situ proximity ligation assay (PLA). Meanwhile, in situ PLA verified the in vivo elevation of MERCs in the odontoblasts of mouse teeth. Remarkably, the disruption of MERCs via overexpression of FATE1, a protein that increases the distance between mitochondria and ER, suppressed the expression of key odontoblast markers, alkaline phosphatase (ALP) activity, and mineralized nodule formation in the mouse dental papilla cells (mDPCs) after differentiation induction, suggesting a positive role of MERCs for odontoblastic differentiation. Among all MERC-associated genes, Mfn2 expression is significantly increased in the RNA sequencing data of odontoblast-like cells versus undifferentiated mDPCs. Further experiments showed that knockdown of Mfn2 resulted in diminished MERC formation as well as impaired odontoblastic differentiation, as evidenced by the downregulated expression of odontoblast markers, compromised ALP activity, and mineralized nodule formation. The impaired odontoblastic differentiation upon Mfn2 knockdown was rescued by the overexpression of Linker, an enhancer of MERC formation, suggesting that MFN2 enhances MERC formation to promote odontoblastic differentiation. Consistently, in vivo knockdown of Mfn2 also impaired MERC formation as well as odontoblast differentiation and dentinogenesis, which were restored by in vivo Linker overexpression. Taken together, these findings indicate that MERCs are dynamically increased and essential for odontoblast differentiation and dentinogenesis with MFN2 as an essential mediator, which provides an important mechanism of organelle interaction orchestrating odontoblast differentiation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"370 1","pages":"220345261458702"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408369","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}
{"title":"Neutrophils Orchestrate Osteoclastogenesis in Orthodontic Tooth Movement.","authors":"F Ohori,H Kitaura,K Narita,A Marahleh,J Ma,K Kanou,Z Fan,A Lin,K Murakami,H Kanetaka","doi":"10.1177/00220345261459909","DOIUrl":"https://doi.org/10.1177/00220345261459909","url":null,"abstract":"Precise control of orthodontic tooth movement (OTM) requires a deep understanding of the biological mechanisms underlying alveolar bone remodeling. Although the immune system is known to influence osteoclastogenesis, the functional significance of neutrophils in the noninfectious, sterile inflammatory environment of OTM remains largely unexplored. Here, we aimed to elucidate the mechanisms by which neutrophils contribute to bone resorption during OTM. OTM was induced in mice using a 10-g mesial force. Single-cell RNA sequencing (scRNA-seq) was performed on periodontal ligament tissues to characterize cellular heterogeneity and intercellular communication. In addition, neutrophil subpopulations and developmental trajectories were analyzed using pseudotime analysis. Finally, the functional role of neutrophils was validated in vivo by systemic depletion using an anti-Ly6G antibody. scRNA-seq identified 11 cell clusters, revealing that neutrophils are a primary source of proinflammatory cytokines, including tumor necrosis factor (TNF), interleukin (IL)-1β, and Oncostatin M (OSM). Immunofluorescence analysis confirmed that neutrophils preferentially accumulated on the compression side. CellChat analysis and transcriptomic profiling identified a TNF-TNF receptor 2 (TNFR2) signaling axis directed from neutrophils to macrophages. Subclustering revealed an \"Inflammatory-Neu\" subset that expands during OTM and expresses CC ligand chemokine family members to recruit macrophages. In vivo, neutrophil depletion significantly attenuated macrophage accumulation on the compression side, resulting in diminished tooth movement distance and reduced osteoclastogenesis. Our findings demonstrate that neutrophils are indispensable upstream regulators of OTM. By maturing into a proinflammatory phenotype, neutrophils coordinate macrophage recruitment and activation via the TNF-TNFR2 axis, thereby driving osteoclastogenesis. This study provides a novel biological framework for understanding the osteoimmunological microenvironment during orthodontic loading, and it also identifies potential targets for controlling tooth movement.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"22 1","pages":"220345261459909"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408368","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}
Z Cui,H Wu,L C Woerner,S R Long,C N Peterson,N K VanLandingham,A Nazarenko,M-O Kim,J R Grandis,D E Johnson
{"title":"Caspase-8 Mutation Promotes HNSCC Development and Resistance to Anti-PD-1.","authors":"Z Cui,H Wu,L C Woerner,S R Long,C N Peterson,N K VanLandingham,A Nazarenko,M-O Kim,J R Grandis,D E Johnson","doi":"10.1177/00220345261457066","DOIUrl":"https://doi.org/10.1177/00220345261457066","url":null,"abstract":"Heterozygous mutations of the gene encoding caspase-8 protease occur in 10% of human head and neck squamous cell carcinomas (HNSCCs). Cell line studies indicate that these mutations block apoptosis induced by death ligands. However, the in vivo role of caspase-8 mutations in the development of HNSCC and their impact on response to immune checkpoint blockade have not been determined. We generated mice with heterozygous, epithelium-specific knock-in of a representative, HNSCC-associated caspase-8 mutation (D305G). The impact of the caspase-8 mutation was assessed following treatment with the carcinogen 4-nitroquinoline-1-oxide (4NQO) in drinking water. Treatment of the D305G caspase-8 mutant mice with 4NQO resulted in a greater number of tongue tumors per mouse and a higher percentage of advanced-stage invasive carcinomas than was observed in 4NQO-treated mice with wild-type caspase-8, and tumors from the mutant mice were more resistant to anti-PD-1. We also engineered the murine oral cancer cell line MOC1 for heterozygous expression of caspase-8 mutations. Tumors generated from these engineered cells in syngeneic, immunocompetent mice demonstrated reduced responsiveness to anti-PD-1, relative to tumors with wild-type caspase-8. Further, the caspase-8 mutant tumors displayed reduced intratumoral and splenic CD8+ T cells and impaired recruitment of monocytes and dendritic cells during PD-1 blockade. Collectively, these findings demonstrate that caspase-8 mutation promotes carcinogen-induced HNSCC development and resistance to anti-PD-1. Investigation of caspase-8 mutations as potential biomarkers of poor response to immunotherapy in patients with HNSCC is warranted.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"36 1","pages":"220345261457066"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408367","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}
{"title":"Multilevel Modeling for Causal Inference in Oral Health Research.","authors":"H Li,M C M Wong,R K Celeste,M A Peres","doi":"10.1177/00220345261452997","DOIUrl":"https://doi.org/10.1177/00220345261452997","url":null,"abstract":"Multilevel modeling (MLM) is increasingly applied in oral health research to reflect the hierarchical structure of dental data, in which teeth are nested within individuals and individuals are embedded within social and environmental contexts. By partitioning both within- and between-individual variability, MLM improves estimate precision, reduces bias, and strengthens causal interpretation, thereby enhancing the evidence base for preventive strategies, clinical practice, and public health policy. This review synthesizes recent methodological developments and ongoing challenges in the application of MLM to oral health research, with particular emphasis on causal inference. Key issues include reciprocal relationships between individual- and contextual-level factors, establishing temporality, collinearity among contextual variables, population mobility, and the selection of appropriate geographic or institutional levels. We also highlight methodological advances, such as integrating propensity score weighting within multilevel frameworks, which offer promising approaches to improving causal assessment in observational studies. Accumulating evidence demonstrates the importance of contextual determinants, such as school and neighborhood environments, in shaping oral health outcomes across the life course. However, causal inference regarding these distal exposures remains underdeveloped. Persistent threats to validity include measurement error in contextual indicators, unmeasured multilevel confounding, and limited consideration of cross-level interactions. Using a school-based example, we illustrate how food insecurity mediates the association between household income and active dental caries, highlighting the value of analytical approaches that jointly address individual- and contextual-level determinants. Overall, MLM provides a robust framework for clarifying causal pathways, improving analytical rigor, and guiding interventions that target both behavioral and structural drivers of oral health inequalities.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"24 1","pages":"220345261452997"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408364","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}
{"title":"Global Landscape of Publicly Available Human Oral Microbiome Data.","authors":"X Chen,L Jamieson,L S Weyrich,S Nath","doi":"10.1177/00220345261456612","DOIUrl":"https://doi.org/10.1177/00220345261456612","url":null,"abstract":"Despite rapid growth in oral microbiome research, it remains unclear how well publicly available data reflect the diversity of the global human population. This study systematically evaluated the geographic and sampling-type representativeness of publicly available human oral microbiome data. A global meta-research analysis of publicly available human oral microbiome records in the NCBI BioSample database released up to December 31, 2025, was conducted. Records were retrieved, harmonized, and analyzed across 4 dimensions: geographic origin, oral sampling type, temporal trends, and population-adjusted representation using a derived representation index (RI). A total of 222,454 BioSamples from 1,600 studies were identified, spanning 92 countries and 4 major oral sampling-type groups: oral fluids, oral mucosa and surfaces, dental plaque and calculus, and special or lesion-associated sites. Geographic distribution was highly concentrated; nearly half of all geographically annotated samples originated from the United States and China, while 61% of countries worldwide contributed no samples. Low- and middle-income regions, including Central and Southern Asia (RI = -12.76) and Sub-Saharan Africa (RI = -11.21), were underrepresented relative to their population sizes. Sampling-type distribution was similarly uneven, with saliva samples comprising more than half of all samples. In contrast, disease-relevant sites, including carious lesions, periapical lesions, and the dental pulp, each represented less than 0.2% of the dataset. Together, these findings underscore that publicly available human oral microbiome data remain unevenly distributed across geographic origin and sampling types, reflecting structural and practical factors that have persisted over time. Deliberate efforts to improve global representation, sampling diversity, and metadata standardization are needed to build a more scientifically robust oral microbiome evidence base.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"15 1","pages":"220345261456612"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408366","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}