Journal of dental research最新文献

The coloring process of monolithic dental zirconia caused considerable debate on the possible effects of different coloring methods. The main objective of this study was to investigate the influence of pigments in 3 multilayer 5-mol% yttria partially stabilized zirconia (5Y-PSZ) disks (Lava Esthetic A2 [Zr-AGG_A2] and Bleach [Zr-AGG_BL], both 3M Oral Care, and Katana STML A2 [Zr-NoAGG], Kuraray Noritake). The influence of pigment addition on the translucency parameter (TP₀₀), fracture toughness, Vickers hardness, biaxial strength, and hydrothermal stability was assessed and correlated with the microstructure and phase composition. The pigment composition and distribution were evaluated by light and fluorescence microscopy, electron probe microanalysis, and nano-scanning electron microscopy. The chemical and phase composition and aging behavior were assessed using X-ray fluorescence and X-ray diffraction, respectively, while the aging sensitivity of the pigments was evaluated using micro-Raman spectroscopy. In contrast to Zr-NoAGG, possessing a typical 5Y-PSZ microstructure, the pigment additions in both Zr-AGG_A2/BL zirconia resulted in large yellow and blue fluorescent Er-, Hf-, and Al-containing agglomerates composed of small grains (0.57 µm and 0.38 µm, respectively, vs. 0.92 µm for the surrounding grains) with lower Y₂O₃ content. Zr-AGG_A2 had the lowest aging resistance, with transformation degradation occurring exclusively within the pigment agglomerates. All zirconia grades had a high Y₂O₃ content (4.2%-5.7 mol%) tetragonal ZrO₂ phase and a high (42%-55 wt%) cubic ZrO₂ phase content. Although no statistical differences were measured for hardness and toughness, Zr-NoAGG had a significantly higher TP₀₀, higher flexural strength, and lower mechanical reliability compared to both Zr-AGG_A2/BL zirconia. The rare-earth oxide-containing zirconia agglomerates that were added as pigments to the multilayered monolithic Zr-AGG_A2/BL zirconia are the cause for their lower optical and mechanical properties and reduced aging resistance.

Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. In the current study, we demonstrated that hypercholesterolemia is a predisposing factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data from in vivo (PD mouse model subjected to a high cholesterol diet) and in vitro (cholesterol treatment of gingival fibroblasts [GFs]) experiments showed that excess cholesterol influx into GFs potentially contributes to periodontal inflammation and, subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed GFs. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.

Artificial intelligence systems (AISs) gain relevance in dentistry, encompassing diagnostics, treatment planning, patient management, and therapy. However, questions about the generalizability, fairness, and transparency of these systems remain. Regulatory and governance bodies worldwide are aiming to address these questions using various frameworks. On March 13, 2024, members of the European Parliament approved the Artificial Intelligence Act (AIA), which emphasizes trustworthiness and human-centeredness as relevant aspects to regulate AISs beyond safety and efficacy. This review presents the AIA and similar regulatory and governance efforts in other jurisdictions and lays out that regulations such as the AIA are part of a complex ecosystem of interdependent and interwoven legal requirements and standards. Current efforts to regulate dental AISs require active input from the dental community, with participation of dental research, education, providers, and patients being relevant to shape the future of dental AISs.

Epidemiology is experiencing a significant shift toward the utilization of big data for health monitoring and decision-making. This article discusses the recent example of the World Health Organization (WHO) global oral health status report and regional summaries, which faced criticisms due to its reliance on big data from the Global Burden of Disease (GBD) study. We address the arguments for and against the use of big data in epidemiology and provide an assessment of the value and limitations of big data epidemiology. Moreover, we provide recommendations as to how the oral health community should reconcile traditional epidemiologic approaches with big data and advanced data analytics. This Perspective article highlights the challenges of the current epidemiologic landscape, the potential of big data, and the need for a balanced approach to data utilization in epidemiology.

Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. Six1, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs Six1 deletion mouse models to elucidate the critical regulatory role of Six1 in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that Dlx1, Dlx2, and Dlx5 (Dlx1/2/5) may function as the key TFs that promote the formation of DP. We further show that the deletion of Six1 perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of Dlx1/2/5 to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil Six1's indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.

The association between periodontal diseases and the risk of gastrointestinal cancers, especially site-specific gastrointestinal cancers, remains unclear. Here, we comprehensively searched PubMed, EMBASE, Web of Science, and Google Scholar from inception to April 2024 to identify relevant studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to confirm the robustness of the main findings in different populations. This study was reported according to PRISMA 2020 guidelines. In total, we identified 19 studies, including 16.6 million participants. Individuals with periodontal diseases had an increased risk of overall gastrointestinal cancers compared with those without periodontal diseases (HR 1.31, 95% CI 1.16-1.49). Periodontal diseases significantly increased the risk of esophageal cancer by 39% (HR 1.39, 95% CI 1.15-1.68), gastric cancer by 13% (HR 1.13, 95% CI 1.01-1.26), colorectal cancer by 21% (HR 1.21, 95% CI 1.05-1.39), pancreatic cancer by 35% (HR 1.35, 95% CI 1.00-1.82), and liver cancer by 9% (HR 1.09, 95% CI 1.04-1.13). The risk of gastrointestinal cancers was significantly increased by periodontitis (HR 1.45, 95% CI 1.14-1.85), gingivitis (HR 1.03, 95% CI 1.01-1.04), and periodontitis/gingivitis (HR 1.27, 95% CI 1.07-1.51). Furthermore, severe periodontal diseases showed a significantly increased risk of gastrointestinal cancer (HR 1.79, 95% CI 1.07-2.99). Results of sensitivity analyses for site-specific gastrointestinal cancers were robust with the main findings. In summary, periodontal diseases, especially severe periodontitis, increase the risk of overall and site-specific gastrointestinal cancers. Interventions to prevent and manage periodontal diseases may reduce the risk of developing gastrointestinal cancers.

Psychosocial properties of oral health have been reported. The present study aimed to investigate the causal effect of complete loss of natural teeth on loneliness by using fixed-effects analysis to control for confounding factors, including unmeasured time-invariant factors. Data from older adults participating in at least 2 consecutive waves of the English Longitudinal Study of Ageing in waves 3 (2006/2007), 5 (2010/2011), and 7 (2014/2015) were analyzed (N = 18,682 observations from 7,298 individuals). The association between complete loss of natural teeth and loneliness score (ranging from 3 to 9) was examined using fixed-effect linear regression analysis adjusting for time-varying confounders, including sociodemographic and health characteristics. The prevalence of complete tooth loss was 12.7%, 12.8%, and 10.6% in waves 3, 5, and 7, respectively. Individuals who transitioned to complete tooth loss during any 2 consecutive waves had an increase in loneliness score by 0.27 (95% confidence interval [CI] 0.03, 0.52), which was greater than those who maintained natural teeth (-0.03; 95% CI -0.05, -0.01). Fixed-effects analysis adjusting for time-varying confounders revealed a significant association between complete loss of natural teeth and an increase in loneliness score by 0.31 (95% CI 0.17, 0.46). Complete loss of natural teeth among older adults in England was associated with loneliness, even after accounting for measured time-varying and (un)measured time-invariant confounders. Retaining natural teeth may reduce the risk of loneliness.

Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4⁺, CD14⁺, CD68⁺, and FOXP3⁺ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.

Sleep bruxism (SB) affects a considerable part of the population and is associated with neuroticism, stress, and anxiety in various studies. However, the causal mechanisms between neuroticism and SB have not been examined. Understanding the reasons for SB is important as understanding bruxism may allow improved comprehensive management of the disorders and comorbidities related to it. Previous studies on the association of risk factors to SB have provided important symptomatic insight but were mainly questionnaire based or limited in sample size and could not adequately assess causal relationships. The aim of this study was to elaborate the possible causal relationship of neuroticism as a risk factor for SB through a Mendelian randomization (MR) approach by combining questionnaires, registry data, and genetic information in large scale. We performed a two-sample MR study using instrumental genetic variants of neuroticism, including neuroticism subcategories, in the UK Biobank (n = 380,506) and outcome data of probable SB using FinnGen (n [cases/controls] = 12,297/364,980). We discovered a causal effect from neuroticism to SB (odds ratio [OR] = 1.38 [1.10-1.74], P = 0.0057). A phenotype sensitive to stress and adversity had the strongest effect (OR = 1.59 [1.17-2.15], P = 0.0028). Sensitivity analyses across MR methods supported a causal relationship, and we did not observe pleiotropy between neuroticism and SB (MR-Egger intercept, P = 0.87). Our findings are in line with earlier observational studies that connect stress and SB. Furthermore, our results provide evidence that neurotic traits increase the risk of probable SB.

The average age and obesity prevalence are increasing globally. Both aging and metabolic disease burden increase the risk of oral squamous cell carcinoma (OSCC) through profound effects on the immunological and metabolic characteristics within the OSCC tumor microenvironment. While the mechanisms that link aging and obesity to OSCC remain unclear, there is evidence that the antitumor responses are diminished in both conditions. Remarkably, however, immune checkpoint blockade, a form of cancer immunotherapy, remains intact despite the enhanced immunosuppressive tumor microenvironment in the context of either aging or obesity. Herein, we review the current knowledge of how aging and systemic metabolic changes affect antitumor immunity with an emphasis on the role of tumor-associated macrophages that greatly contribute to tumor immunosuppression. Key aspects discussed include the mechanisms of angiogenesis, cytokine release, phagocytosis attenuation, and immune cell recruitment during obesity and aging that create an immune-suppressive tumor microenvironment by recruitment and repolarization of tumor-associated macrophages. Through a deeper appreciation of these mechanisms, the development of novel therapeutic approaches to control OSCC will provide more refined management of the tumor microenvironment in the context of aging and obesity.