The development of caries management materials has concentrated on the dual objectives of inhibiting cariogenic microorganisms and promoting remineralization. In this study, 2 dual-functional ionic liquid (IL) varnishes, exhibiting both antibacterial and remineralization capabilities, were synthesized as novel anticaries agents. The ionic liquids (ILs) were prepared by modifying 1-hexylimidazolium IL with 3-chloropropyltriethoxysilane, followed by anion exchange with F- and a coordination reaction with Sr2+, respectively. The ILs were characterized using energy-dispersive spectroscopy (EDS), ion chromatography (IC), inductively coupled plasma optical emission spectrometry (ICP-OES), and Fourier transform infrared spectroscopy (FTIR). The antibacterial efficacy of the ILs was evaluated through colony counting, live/dead staining, and scanning electron microscopy (SEM). Subsequently, the ILs were blended with rosin to form IL varnishes. The remineralization potential of the IL varnishes was assessed through microhardness test, acid resistance test, SEM, EDS, and X-ray diffraction. In addition, in vivo anticaries treatment with the IL varnishes was conducted using a dental caries animal model. Histopathological and oral microbiome analyses were performed to evaluate the in vivo biocompatibility of the materials. The comprehensive analysis by EDS, IC, ICP-OES, and FTIR collectively confirmed the successful synthesis of the ILs. Antibacterial assays revealed that ILs at concentrations as low as 25 µM eliminated more than 80% of cariogenic bacteria within 60 min and significantly decreased viable bacteria in biofilms within 24 h. Following a 7-d treatment with the IL varnishes, SEM analysis of acid-etched enamel demonstrated reduced interspace depth, along with substantially increased microhardness and significantly improved acid resistance versus the negative control group. As compared with the fluoride varnish, the IL varnishes are more effective in preventing dental caries in rats, without harming oral buccal mucosa, major organs, or microbiota diversity. In conclusion, the IL varnishes developed in this study are not only straightforward to synthesize but also exhibit significant potential against dental caries.
{"title":"Dual-Functional Ionic Liquid Varnishes for Dental Caries Management.","authors":"H-W Chen,Y-F Yuan,C-L Wang,D-Y Wang,Z-C Zhou,L Fan,Q-X Zhang,Y-N He,W-K Jiang,S-C Wang","doi":"10.1177/00220345251397916","DOIUrl":"https://doi.org/10.1177/00220345251397916","url":null,"abstract":"The development of caries management materials has concentrated on the dual objectives of inhibiting cariogenic microorganisms and promoting remineralization. In this study, 2 dual-functional ionic liquid (IL) varnishes, exhibiting both antibacterial and remineralization capabilities, were synthesized as novel anticaries agents. The ionic liquids (ILs) were prepared by modifying 1-hexylimidazolium IL with 3-chloropropyltriethoxysilane, followed by anion exchange with F- and a coordination reaction with Sr2+, respectively. The ILs were characterized using energy-dispersive spectroscopy (EDS), ion chromatography (IC), inductively coupled plasma optical emission spectrometry (ICP-OES), and Fourier transform infrared spectroscopy (FTIR). The antibacterial efficacy of the ILs was evaluated through colony counting, live/dead staining, and scanning electron microscopy (SEM). Subsequently, the ILs were blended with rosin to form IL varnishes. The remineralization potential of the IL varnishes was assessed through microhardness test, acid resistance test, SEM, EDS, and X-ray diffraction. In addition, in vivo anticaries treatment with the IL varnishes was conducted using a dental caries animal model. Histopathological and oral microbiome analyses were performed to evaluate the in vivo biocompatibility of the materials. The comprehensive analysis by EDS, IC, ICP-OES, and FTIR collectively confirmed the successful synthesis of the ILs. Antibacterial assays revealed that ILs at concentrations as low as 25 µM eliminated more than 80% of cariogenic bacteria within 60 min and significantly decreased viable bacteria in biofilms within 24 h. Following a 7-d treatment with the IL varnishes, SEM analysis of acid-etched enamel demonstrated reduced interspace depth, along with substantially increased microhardness and significantly improved acid resistance versus the negative control group. As compared with the fluoride varnish, the IL varnishes are more effective in preventing dental caries in rats, without harming oral buccal mucosa, major organs, or microbiota diversity. In conclusion, the IL varnishes developed in this study are not only straightforward to synthesize but also exhibit significant potential against dental caries.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"13 1","pages":"220345251397916"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710897","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}
Pub Date : 2025-12-09DOI: 10.1177/00220345251394281
K M Desai,N A Tadkalkar,M Amin,R Kumar,S U Rahman,S Ponnusamy,P Angadi,W Liu,R V Dayani,A D Kale,J Slone,D Chandra,P R Arany
Cell survival, differentiation, and death are tightly regulated processes that maintain tissue homeostasis. Arecoline and transforming growth factor-beta (TGF-β) have been implicated as key mediators in oral submucous fibrosis (OSMF). The persistent, overactive fibroblasts in fibrotic lesions have altered metabolism and cytoskeletal changes. The present work evaluated the effects of arecoline and TGF-β on the mitochondrial bioenergetics and phenotype of oral fibroblasts. Human oral fibroblasts were treated with arecoline, TGF-β1, and combinations and evaluated for cell survival using AlamarBlue and vital staining. To assess mitochondrial fusion, MF18 inhibitor and OPA-1, MFN-2, and fission, Mdivi inhibitor and DRP-1 were used. Changes in cell responses were assessed with real-time quantitative polymerase chain reaction, immunofluorescence, and Seahorse analysis. Following institutional review board approval, archival human tissue biopsies from OSMF at various grades were evaluated for correlation with modulation of fibroblast metabolism and cytoskeletal changes. Arecoline-treated fibroblasts showed significant (n = 3, P < 0.05) cell death rescued by TGF-β1 treatments (n = 3, P < 0.05). Further examination revealed that arecoline-treated cells exhibited mitochondrial fission with a glycolytic (reduced transcription factor of mitochondria [TFAM], increased hexokinase II, n = 3, P < 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-β1 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-β1 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin-actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.
细胞的存活、分化和死亡是维持组织稳态的严格调控过程。槟榔碱和转化生长因子β (TGF-β)被认为是口腔粘膜下纤维化（OSMF）的关键介质。纤维化病变中持续的、过度活跃的成纤维细胞改变了代谢和细胞骨架的变化。本研究探讨槟榔碱和TGF-β对口腔成纤维细胞线粒体生物能量学和表型的影响。用槟榔碱、TGF-β1和组合处理人口腔成纤维细胞，并使用AlamarBlue和vital染色评估细胞存活率。为了评估线粒体融合，使用MF18抑制剂和OPA-1， MFN-2，以及裂变，Mdivi抑制剂和DRP-1。通过实时定量聚合酶链反应、免疫荧光和海马分析来评估细胞反应的变化。在机构审查委员会批准后，评估了不同级别OSMF的档案人体组织活检与成纤维细胞代谢调节和细胞骨架变化的相关性。槟榔碱处理的成纤维细胞经TGF-β1处理后出现显著的细胞死亡（n = 3, P < 0.05）。进一步的研究表明，槟榔碱处理的细胞表现出线粒体分裂，糖酵解（线粒体转录因子[TFAM]减少，己糖激酶II增加，n = 3, P < 0.05）代谢谱和降低OPA1表达。相比之下，TGF-β1处理表现为线粒体融合，并伴有OPA1表达增加。槟榔碱和TGF-β1联合治疗可提高细胞存活率，减少裂变，改善线粒体生物能量学。这些结果与TFAM和vimentin-actin （VA）表达增加相关，代表了合成的、过度活跃的成纤维细胞表型。最后，来自OSMF患者的临床样本在晚期临床疾病中表现出TFAM和va阳性成纤维细胞的进行性增加，证实了体外观察。TGF-β1似乎在槟榔碱诱导的细胞毒性中调节线粒体反应，导致成纤维细胞存活，导致纤维化表型。这些观察结果表明，选择性靶向线粒体驱动这些存活的肌成纤维细胞可能作为临床翻译的新治疗靶点。
{"title":"TGF-β1 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis.","authors":"K M Desai,N A Tadkalkar,M Amin,R Kumar,S U Rahman,S Ponnusamy,P Angadi,W Liu,R V Dayani,A D Kale,J Slone,D Chandra,P R Arany","doi":"10.1177/00220345251394281","DOIUrl":"https://doi.org/10.1177/00220345251394281","url":null,"abstract":"Cell survival, differentiation, and death are tightly regulated processes that maintain tissue homeostasis. Arecoline and transforming growth factor-beta (TGF-β) have been implicated as key mediators in oral submucous fibrosis (OSMF). The persistent, overactive fibroblasts in fibrotic lesions have altered metabolism and cytoskeletal changes. The present work evaluated the effects of arecoline and TGF-β on the mitochondrial bioenergetics and phenotype of oral fibroblasts. Human oral fibroblasts were treated with arecoline, TGF-β1, and combinations and evaluated for cell survival using AlamarBlue and vital staining. To assess mitochondrial fusion, MF18 inhibitor and OPA-1, MFN-2, and fission, Mdivi inhibitor and DRP-1 were used. Changes in cell responses were assessed with real-time quantitative polymerase chain reaction, immunofluorescence, and Seahorse analysis. Following institutional review board approval, archival human tissue biopsies from OSMF at various grades were evaluated for correlation with modulation of fibroblast metabolism and cytoskeletal changes. Arecoline-treated fibroblasts showed significant (n = 3, P < 0.05) cell death rescued by TGF-β1 treatments (n = 3, P < 0.05). Further examination revealed that arecoline-treated cells exhibited mitochondrial fission with a glycolytic (reduced transcription factor of mitochondria [TFAM], increased hexokinase II, n = 3, P < 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-β1 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-β1 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin-actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"140 1","pages":"220345251394281"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710734","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}
Pub Date : 2025-12-09DOI: 10.1177/00220345251398027
A Orlenko,J D Mure,J I Gluch,J Gregg,C W Compher,Z Ren,H Koo,J H Moore
National Health and Nutrition Examination Survey (NHANES), one of the largest curated repositories of population-level health indicators including physical examinations, blood/urine biochemistry, self-reported surveys, and dietary intake, offers rich resources for oral health research but presents challenges for machine learning analysis due to heterogeneity, missing data, and complexity. Dental caries, the most prevalent chronic disease worldwide, is a multifactorial disease and exhibits variability in clinical manifestation, calling for advanced analytical approaches for deeper understanding. Here, we develop an integrated data-cleaning and subtype discovery pipeline using unsupervised machine learning for comprehensive analysis and visualization of data patterns in the NHANES database. Our multidimensional pipeline declutters and optimizes the NHANES dataset by addressing missingness and outliers to streamline data integration and create a machine learning-ready version. Applying this pipeline reveals data patterns that led to the discovery of previously unrecognized subtypes and variables associated with the clinical heterogeneity of dental caries. We observed diverging patterns of similarity across age groups and variable subsets, identifying distinct clusters particularly in children (<5 y) and senior adults (>65 y). We also discovered unexpected associations involving lead exposure and specific laboratory markers and, importantly, identified novel dietary signatures by linking food type and co-occurring consumption patterns to caries. Altogether, we report a comprehensive data-processing and data-analysis approach that reveals significant dental caries heterogeneity in NHANES data and can support the development of more precise and robust machine learning models for dental caries and other health conditions.
{"title":"Uncovering Dental Caries Heterogeneity in NHANES Using Machine Learning.","authors":"A Orlenko,J D Mure,J I Gluch,J Gregg,C W Compher,Z Ren,H Koo,J H Moore","doi":"10.1177/00220345251398027","DOIUrl":"https://doi.org/10.1177/00220345251398027","url":null,"abstract":"National Health and Nutrition Examination Survey (NHANES), one of the largest curated repositories of population-level health indicators including physical examinations, blood/urine biochemistry, self-reported surveys, and dietary intake, offers rich resources for oral health research but presents challenges for machine learning analysis due to heterogeneity, missing data, and complexity. Dental caries, the most prevalent chronic disease worldwide, is a multifactorial disease and exhibits variability in clinical manifestation, calling for advanced analytical approaches for deeper understanding. Here, we develop an integrated data-cleaning and subtype discovery pipeline using unsupervised machine learning for comprehensive analysis and visualization of data patterns in the NHANES database. Our multidimensional pipeline declutters and optimizes the NHANES dataset by addressing missingness and outliers to streamline data integration and create a machine learning-ready version. Applying this pipeline reveals data patterns that led to the discovery of previously unrecognized subtypes and variables associated with the clinical heterogeneity of dental caries. We observed diverging patterns of similarity across age groups and variable subsets, identifying distinct clusters particularly in children (<5 y) and senior adults (>65 y). We also discovered unexpected associations involving lead exposure and specific laboratory markers and, importantly, identified novel dietary signatures by linking food type and co-occurring consumption patterns to caries. Altogether, we report a comprehensive data-processing and data-analysis approach that reveals significant dental caries heterogeneity in NHANES data and can support the development of more precise and robust machine learning models for dental caries and other health conditions.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"29 1","pages":"220345251398027"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704377","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}
Pub Date : 2025-12-09DOI: 10.1177/00220345251388919
M S Rahman,A Martinez,H W Elani
Access to general dental care remains a widespread challenge in the United States. In addition, many oral health conditions require treatment by dental specialists. Little is known about the geographic distribution and accessibility of these providers, particularly in rural areas. A national, block group-level analysis of geographic access to 6 core dental specialties-endodontics, oral and maxillofacial surgery, orthodontics, pediatric dentistry, periodontics, and prosthodontics-was conducted. The provider locations from a 2023 national database of practicing dental specialists (N = 38,698) were geocoded. An enhanced 2-step floating catchment area model was applied to generate spatial accessibility scores and drive-time estimates from population-weighted centers. The analysis of these data showed that on average, more than one-third of the US population had adequate access to specialty clinics, while less than 15% resided more than 30 min away from these specialists. Adequate accessibility was highest for orthodontics (61.6%, n = 204.1 million) and lowest for prosthodontics (6.7%, n = 22.2). Rural residents faced average driving times 3.2 times longer than urban residents do. The disparity was most severe in states such as Alaska, Montana, Nevada, North Dakota, South Dakota, and Wyoming, where driving times to specialists often exceeded an hour. More than 98% of dental specialists practice in urban areas, leaving rural regions consistently underserved. These findings indicate pronounced and widespread geographic disparities in access to dental specialists across the United States, driven by geographic concentration in metropolitan areas. These gaps have serious implications for access to timely diagnoses, treatment quality, and oral health-related quality of life. Workforce policies must expand beyond general dentistry to address dental specialty shortages. Integrating dental specialists into shortage designations, loan repayment programs, and training pipelines is essential for achieving equitable access to comprehensive oral health care nationwide.
{"title":"Geographic Access to Dental Specialists in the United States.","authors":"M S Rahman,A Martinez,H W Elani","doi":"10.1177/00220345251388919","DOIUrl":"https://doi.org/10.1177/00220345251388919","url":null,"abstract":"Access to general dental care remains a widespread challenge in the United States. In addition, many oral health conditions require treatment by dental specialists. Little is known about the geographic distribution and accessibility of these providers, particularly in rural areas. A national, block group-level analysis of geographic access to 6 core dental specialties-endodontics, oral and maxillofacial surgery, orthodontics, pediatric dentistry, periodontics, and prosthodontics-was conducted. The provider locations from a 2023 national database of practicing dental specialists (N = 38,698) were geocoded. An enhanced 2-step floating catchment area model was applied to generate spatial accessibility scores and drive-time estimates from population-weighted centers. The analysis of these data showed that on average, more than one-third of the US population had adequate access to specialty clinics, while less than 15% resided more than 30 min away from these specialists. Adequate accessibility was highest for orthodontics (61.6%, n = 204.1 million) and lowest for prosthodontics (6.7%, n = 22.2). Rural residents faced average driving times 3.2 times longer than urban residents do. The disparity was most severe in states such as Alaska, Montana, Nevada, North Dakota, South Dakota, and Wyoming, where driving times to specialists often exceeded an hour. More than 98% of dental specialists practice in urban areas, leaving rural regions consistently underserved. These findings indicate pronounced and widespread geographic disparities in access to dental specialists across the United States, driven by geographic concentration in metropolitan areas. These gaps have serious implications for access to timely diagnoses, treatment quality, and oral health-related quality of life. Workforce policies must expand beyond general dentistry to address dental specialty shortages. Integrating dental specialists into shortage designations, loan repayment programs, and training pipelines is essential for achieving equitable access to comprehensive oral health care nationwide.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"140 1","pages":"220345251388919"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710896","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}
Pub Date : 2025-12-08DOI: 10.1177/00220345251388641
S Wang,W Kang,D Wang,X Liu,J Feng,T Wang,W Zhao,J Li,S Ge
Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC12). The self-assembled SCDC12 nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC12 inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC12 hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC12 as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.
{"title":"A Polyamine-Capturing Cyclodextrin Hydrogel for Periodontitis Treatment.","authors":"S Wang,W Kang,D Wang,X Liu,J Feng,T Wang,W Zhao,J Li,S Ge","doi":"10.1177/00220345251388641","DOIUrl":"https://doi.org/10.1177/00220345251388641","url":null,"abstract":"Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC12). The self-assembled SCDC12 nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC12 inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC12 hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC12 as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"6 1","pages":"220345251388641"},"PeriodicalIF":7.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704378","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}
Pub Date : 2025-12-06DOI: 10.1177/00220345251379445
K.D. Cox, M. Makara, J.O. Maldonado, J. Frantsve-Hawley, S. E. Carsons, V. Sankar
Sjögren’s disease (SjD) exemplifies the intricate relationship between oral health and overall systemic wellness. Characterized by autoimmune-mediated destruction of exocrine glands, it commonly manifests as xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), yet its reach extends well beyond the salivary and lacrimal glands to involve musculoskeletal, renal, pulmonary, and neurological systems. Insights from national patient surveys underscore considerable unmet needs in SjD management, emphasizing the importance of early recognition of oral health challenges. Concurrently, advances in clinical and translational research deepen our understanding of SjD’s underlying mechanisms, revealing novel diagnostic and therapeutic strategies that target immunological pathways, foster glandular regeneration, and may alter disease progression. By providing a cohesive synthesis of state-of-the-art evidence, this review aims to expand clinicians’ and researchers’ understanding of SjD pathogenesis, address new research areas and key gaps, highlight the critical role of medical partnerships in addressing both systemic and oral manifestations, and advance patient-centered strategies to improve detection, treatment, and long-term disease management of this multifaceted autoimmune disorder. We discuss immune-mediated tissue damage, the potential of emerging biomarkers, and innovative treatments, including biologic agents and regenerative techniques. Patient perspectives further illuminate the daily challenges posed by SjD, underscoring the need for interdisciplinary care models that integrate oral medicine, rheumatology, and other medical specialties. Taken together, these insights underscore the pressing need for heightened awareness and collaborative approaches to pave the way for precision medicine interventions that can transform current management paradigms and ultimately improve the lives of individuals affected by Sjögren’s disease.
{"title":"Exploring the Interplay of Oral and Systemic Pathology in Sjögren’s Disease","authors":"K.D. Cox, M. Makara, J.O. Maldonado, J. Frantsve-Hawley, S. E. Carsons, V. Sankar","doi":"10.1177/00220345251379445","DOIUrl":"https://doi.org/10.1177/00220345251379445","url":null,"abstract":"Sjögren’s disease (SjD) exemplifies the intricate relationship between oral health and overall systemic wellness. Characterized by autoimmune-mediated destruction of exocrine glands, it commonly manifests as xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), yet its reach extends well beyond the salivary and lacrimal glands to involve musculoskeletal, renal, pulmonary, and neurological systems. Insights from national patient surveys underscore considerable unmet needs in SjD management, emphasizing the importance of early recognition of oral health challenges. Concurrently, advances in clinical and translational research deepen our understanding of SjD’s underlying mechanisms, revealing novel diagnostic and therapeutic strategies that target immunological pathways, foster glandular regeneration, and may alter disease progression. By providing a cohesive synthesis of state-of-the-art evidence, this review aims to expand clinicians’ and researchers’ understanding of SjD pathogenesis, address new research areas and key gaps, highlight the critical role of medical partnerships in addressing both systemic and oral manifestations, and advance patient-centered strategies to improve detection, treatment, and long-term disease management of this multifaceted autoimmune disorder. We discuss immune-mediated tissue damage, the potential of emerging biomarkers, and innovative treatments, including biologic agents and regenerative techniques. Patient perspectives further illuminate the daily challenges posed by SjD, underscoring the need for interdisciplinary care models that integrate oral medicine, rheumatology, and other medical specialties. Taken together, these insights underscore the pressing need for heightened awareness and collaborative approaches to pave the way for precision medicine interventions that can transform current management paradigms and ultimately improve the lives of individuals affected by Sjögren’s disease.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"26 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680106","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}
Pub Date : 2025-12-02DOI: 10.1177/00220345251399105
G.G. Nascimento, N.S. Jakubovics, G.P. Garlet
The oral–systemic relationship has long been a focus of vigorous debate. Spanning experimental studies that elucidate underlying mechanisms, critical reviews and advances in data architecture, and clinical and population-based investigations, this editorial highlights the compelling findings presented in this special issue.
{"title":"The Oral-Systemic Relationship: Lessons Learned and the Road Ahead","authors":"G.G. Nascimento, N.S. Jakubovics, G.P. Garlet","doi":"10.1177/00220345251399105","DOIUrl":"https://doi.org/10.1177/00220345251399105","url":null,"abstract":"The oral–systemic relationship has long been a focus of vigorous debate. Spanning experimental studies that elucidate underlying mechanisms, critical reviews and advances in data architecture, and clinical and population-based investigations, this editorial highlights the compelling findings presented in this special issue.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"127 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651144","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}
Serum antibody levels against microbial biomarkers of periodontitis, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, are associated especially with the presence of these species in the oral cavity. We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against A. actinomycetemcomitans and P. gingivalis were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade. A. actinomycetemcomitans IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near HLA-DRB1, P = 3.6 × 10-8) and P. gingivalis IgG in chromosome 14 with lead SNP rs146761521 (near NUBPL, 5.5 × 10-8). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that A. actinomycetemcomitans IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and P. gingivalis IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to A. actinomycetemcomitans and P. gingivalis, highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.
针对牙周炎的微生物生物标志物，放线菌聚集菌和牙龈卟啉单胞菌的血清抗体水平，尤其与口腔中这些细菌的存在相关。我们通过全基因组关联研究（GWAS）研究了宿主对这些物种抗体反应的遗传基础，以确定这种免疫反应性的遗传决定因素。采用多血清型酶联免疫吸附法对来自芬兰4项队列研究（FinnTwin、Parogene、FINRISK97和Health-2000）的3719名受试者进行血清免疫球蛋白A （IgA）和免疫球蛋白G （IgG）抗体水平的测定。研究了遗传多态性和人白细胞抗原（HLA）等位基因与抗体水平的关系。所有抗体水平均随牙周炎分期和分级呈显著升高趋势。A.放线菌comitans IgG与6号染色体单核苷酸多态性（SNP）相关，其引物SNP为rs74581129（接近HLA-DRB1， P = 3.6 × 10-8）， P. gingivalis IgG与14号染色体引物SNP rs146761521（接近NUBPL， 5.5 × 10-8）。此外，所有抗体水平都与几个基因座有暗示的关联。详细的HLA分析显示放线菌链球菌IgG与DQA1*01:01、DQB1*05:01和DRB1*01:01等位基因相关，牙龈链球菌IgG与HLA- a *02:01等位基因相关。针对牙周炎微生物标志物物种的IgA和IgG抗体水平随牙周炎的分期和分级而增加，但遗传变异也是一个重要的预测因素。HLA区域内的特定等位基因可能影响对放线菌和牙龈假单胞菌的抗体反应，强调了牙周炎潜在的免疫机制的遗传贡献。
{"title":"GWAS of Serum Antibodies to Microbial Biomarker Species of Periodontitis.","authors":"H Abdelkader,A Salminen,J Leskelä,T Palviainen,E Salasuo,S Paju,P Mäntylä,L Suominen,J Kaprio,V Salomaa,J Sinisalo,P J Pussinen","doi":"10.1177/00220345251387642","DOIUrl":"https://doi.org/10.1177/00220345251387642","url":null,"abstract":"Serum antibody levels against microbial biomarkers of periodontitis, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, are associated especially with the presence of these species in the oral cavity. We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against A. actinomycetemcomitans and P. gingivalis were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade. A. actinomycetemcomitans IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near HLA-DRB1, P = 3.6 × 10-8) and P. gingivalis IgG in chromosome 14 with lead SNP rs146761521 (near NUBPL, 5.5 × 10-8). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that A. actinomycetemcomitans IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and P. gingivalis IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to A. actinomycetemcomitans and P. gingivalis, highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"2 1","pages":"220345251387642"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645017","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}
Pub Date : 2025-11-30DOI: 10.1177/00220345251397369
K T Nguyen,J Xia,C Chang,A Ghosh,M D Hade,X Y Rima,J Y An,S E Oh,B H Min,C K Nagaraj,S M Magaña,L Wang,T J Huang,F Li,Y Kim,D T W Wong,E Reátegui
Liquid biopsies that analyze the molecular content of extracellular vesicles and particles (EVPs) are a formidable opportunity for early and late-stage cancer diagnosis. This study explores the potential of two advanced technologies: Bessel beam excitation separation technology (BEST) and multiparametric biochip assay (MBA), to track single EVP cargo from organs of pathology into biofluids such as plasma and saliva. Using gastric cancer (GC) as a disease model, we conducted high-throughput, multiparametric analyses of EVPs derived from plasma, saliva, and tissue samples from GC patients. Our findings demonstrate the feasibility of these techniques in isolating and characterizing EVPs, revealing consistent EVP morphology and size across biofluids. Furthermore, differential expression patterns of the developed and validated salivary GC biomarkers, miR-140-5p and miR-301a-3p, were observed in the biofluids of GC patients, supporting the diagnostic relevance of these cargo molecules. Notably, saliva emerged as the most promising biofluid for GC diagnosis, achieving superior receiver-operating characteristic curve values compared with plasma and tissue. This study highlights the role of BEST and MBA in advancing single-EVP analysis and elucidating EVP trafficking, paving the way for future diagnostic applications of EVP cargo.
{"title":"Extracellular Particles to Track Cancer Biomarkers from Tissue to Biofluids.","authors":"K T Nguyen,J Xia,C Chang,A Ghosh,M D Hade,X Y Rima,J Y An,S E Oh,B H Min,C K Nagaraj,S M Magaña,L Wang,T J Huang,F Li,Y Kim,D T W Wong,E Reátegui","doi":"10.1177/00220345251397369","DOIUrl":"https://doi.org/10.1177/00220345251397369","url":null,"abstract":"Liquid biopsies that analyze the molecular content of extracellular vesicles and particles (EVPs) are a formidable opportunity for early and late-stage cancer diagnosis. This study explores the potential of two advanced technologies: Bessel beam excitation separation technology (BEST) and multiparametric biochip assay (MBA), to track single EVP cargo from organs of pathology into biofluids such as plasma and saliva. Using gastric cancer (GC) as a disease model, we conducted high-throughput, multiparametric analyses of EVPs derived from plasma, saliva, and tissue samples from GC patients. Our findings demonstrate the feasibility of these techniques in isolating and characterizing EVPs, revealing consistent EVP morphology and size across biofluids. Furthermore, differential expression patterns of the developed and validated salivary GC biomarkers, miR-140-5p and miR-301a-3p, were observed in the biofluids of GC patients, supporting the diagnostic relevance of these cargo molecules. Notably, saliva emerged as the most promising biofluid for GC diagnosis, achieving superior receiver-operating characteristic curve values compared with plasma and tissue. This study highlights the role of BEST and MBA in advancing single-EVP analysis and elucidating EVP trafficking, paving the way for future diagnostic applications of EVP cargo.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"198200 1","pages":"220345251397369"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644881","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}
Pub Date : 2025-11-30DOI: 10.1177/00220345251394295
L G Do,D H Ha,A J Spencer,A Rugg-Gunn
Community water fluoridation (CWF) is one of the most significant public health programs targeting oral health. It has contributed to improving population oral health over the past 8 decades. As a public health program, CWF faces numerous evidentiary challenges. This review discusses 3 major controversies related to CWF's evidence of effectiveness, safety, and approaches to its implementation. Scientific evidence of CWF's effectiveness has been summarized. We discuss the need to expand the use of observational data to address the causal effects of fluoridation on dental caries by applying modern causal inference approaches. We present scientific evidence that CWF reduces socioeconomic inequalities in oral health, which has been inadequately acknowledged. The scientific evidence of the safety of established CWF programs worldwide, measured by indicators of child intellectual and behavioral development and executive functioning, is presented and discussed. The review provides consistent evidence to confirm CWF as an effective and safe public health program in preventing dental caries. The third controversy is related to the implementation approaches of CWF as a public health program. The connection between scientific evidence, health policy development, and the engagement of political and other actors in implementing policies to improve health is discussed. Different types of policy implementation are discussed. Maintenance and expansion of CWF as a public health program are needed to improve the population's oral health. A strong collaboration among scientists, public health practitioners, and policymakers will be necessary to address the controversies associated with CWF and continue the implementation of this public health measure.
{"title":"Controversies and Public Health Implications of Community Water Fluoridation.","authors":"L G Do,D H Ha,A J Spencer,A Rugg-Gunn","doi":"10.1177/00220345251394295","DOIUrl":"https://doi.org/10.1177/00220345251394295","url":null,"abstract":"Community water fluoridation (CWF) is one of the most significant public health programs targeting oral health. It has contributed to improving population oral health over the past 8 decades. As a public health program, CWF faces numerous evidentiary challenges. This review discusses 3 major controversies related to CWF's evidence of effectiveness, safety, and approaches to its implementation. Scientific evidence of CWF's effectiveness has been summarized. We discuss the need to expand the use of observational data to address the causal effects of fluoridation on dental caries by applying modern causal inference approaches. We present scientific evidence that CWF reduces socioeconomic inequalities in oral health, which has been inadequately acknowledged. The scientific evidence of the safety of established CWF programs worldwide, measured by indicators of child intellectual and behavioral development and executive functioning, is presented and discussed. The review provides consistent evidence to confirm CWF as an effective and safe public health program in preventing dental caries. The third controversy is related to the implementation approaches of CWF as a public health program. The connection between scientific evidence, health policy development, and the engagement of political and other actors in implementing policies to improve health is discussed. Different types of policy implementation are discussed. Maintenance and expansion of CWF as a public health program are needed to improve the population's oral health. A strong collaboration among scientists, public health practitioners, and policymakers will be necessary to address the controversies associated with CWF and continue the implementation of this public health measure.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":"220345251394295"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645018","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}
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