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Association between Periodontal Diseases and the Risk of Site-Specific Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. 牙周疾病与特定部位胃肠道癌症风险之间的关系:系统回顾与元分析》。
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241263768
Q Wang, W-J Gu, F-L Ning, M Sun, Z-M G Zhao, M U Abe, Z-N Li, C-D Zhang

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.

牙周疾病与胃肠道癌症(尤其是特定部位的胃肠道癌症)风险之间的关系仍不清楚。在此,我们全面检索了从开始到2024年4月的PubMed、EMBASE、Web of Science和Google Scholar,以确定相关研究。采用随机效应模型计算了汇总的危险比(HRs)和95%置信区间(CIs)。进行了亚组分析和敏感性分析,以确认主要研究结果在不同人群中的稳健性。本研究根据 PRISMA 2020 指南进行报告。我们总共确定了 19 项研究,包括 1660 万名参与者。与没有牙周疾病的人相比,患有牙周疾病的人罹患总体胃肠道癌症的风险更高(HR 1.31,95% CI 1.16-1.49)。牙周病会使食道癌风险大幅增加39%(HR 1.39,95% CI 1.15-1.68),胃癌风险增加13%(HR 1.13,95% CI 1.01-1.26),结肠直肠癌风险增加21%(HR 1.21,95% CI 1.05-1.39),胰腺癌风险增加35%(HR 1.35,95% CI 1.00-1.82),肝癌风险增加9%(HR 1.09,95% CI 1.04-1.13)。牙周炎(HR 1.45,95% CI 1.14-1.85)、牙龈炎(HR 1.03,95% CI 1.01-1.04)和牙周炎/牙龈炎(HR 1.27,95% CI 1.07-1.51)会显著增加患胃肠道癌症的风险。此外,严重牙周病也会显著增加罹患胃肠道癌症的风险(HR 1.79,95% CI 1.07-2.99)。针对特定部位胃肠道癌症的敏感性分析结果与主要研究结果一致。总之,牙周疾病,尤其是严重牙周炎会增加罹患总体和特定部位胃肠道癌症的风险。预防和控制牙周疾病的干预措施可降低患胃肠道癌症的风险。
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引用次数: 0
Complete Loss of Natural Teeth and Loneliness: A Fixed-Effect Analysis. 完全丧失天然牙齿与孤独感:固定效应分析
Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241263265
Y Matsuyama

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.

口腔健康的社会心理特性已有报道。本研究旨在通过使用固定效应分析来控制混杂因素,包括未测量的时间不变因素,从而研究天然牙齿完全缺失对孤独感的因果效应。研究分析了至少连续两次参加英国老龄化纵向研究第 3 波(2006/2007 年)、第 5 波(2010/2011 年)和第 7 波(2014/2015 年)的老年人的数据(N = 18,682 个观测值,来自 7,298 人)。采用固定效应线性回归分析法研究了天然牙齿完全缺失与孤独感得分(3 至 9 分)之间的关系,并调整了随时间变化的混杂因素,包括社会人口学特征和健康特征。在第 3、5 和 7 波中,全口牙齿缺失率分别为 12.7%、12.8% 和 10.6%。在任何两个连续波次中转变为全口缺牙的人的孤独感得分增加了 0.27(95% 置信区间 [CI] 0.03,0.52),高于保持天然牙齿的人的孤独感得分(-0.03;95% CI -0.05,-0.01)。调整了时变混杂因素的固定效应分析表明,完全丧失天然牙齿与孤独感得分增加 0.31(95% CI 0.17,0.46)之间存在显著关联。即使考虑了测量的时变混杂因素和(未)测量的时间不变混杂因素,英格兰老年人完全丧失天然牙齿仍与孤独感有关。保留天然牙齿可降低孤独的风险。
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引用次数: 0
Salivary Microbiome Relates to Neoadjuvant Immunotherapy Response in OSCC. 唾液微生物组与 OSCC 的新辅助免疫疗法反应有关
Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241262759
X X Wang, Y T Liu, J G Ren, H M Liu, Q Fu, Y Yang, Q Y Fu, G Chen

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.

大多数确诊为口腔鳞状细胞癌(OSCC)的患者都是局部晚期,通常预后较差。虽然免疫疗法有可能提高患者的生存率,但其疗效却因反应率低而受到影响。微生物组广泛参与肿瘤免疫,并可能在免疫疗法中发挥作用。本研究旨在探讨口腔(唾液)微生物组与 OSCC 患者免疫治疗反应之间的潜在关联。在一项临床试验(NCT04649476)中,对47名接受新辅助免疫疗法(NAIT)的OSCC患者进行了唾液元基因组测序。根据病理反应将患者分为有反应者和无反应者。结果显示,在接受新辅助免疫疗法(NAIT)前,无应答者唾液微生物组的物种丰富度低于有应答者。差异分析显示,无反应者的 34 种细菌相对丰度较低,而 4 种细菌相对丰度较高。值得注意的是,唾液中Eubacterium infirmum、Actinobaculum和Selenomas(EAS)的低水平可能与OSCC患者对NAIT无反应有关。为了确定 NAIT 的疗效,我们开发并验证了基于 EAS 的提名图。训练队列的曲线下面积为 0.81(95% 置信区间为 0.66 至 0.81)。定量聚合酶链反应证实,唾液 EAS 含量低可有效识别对 NAIT 无应答者。此外,唾液EAS含量低与瘤内CD4+、CD14+、CD68+和FOXP3+细胞密度低密切相关。代谢功能注释揭示了许多与 EAS 相关的生物合成过程,这些过程在应答者中更为活跃。总之,本研究为唾液微生物组提供了宝贵的数据资源,并揭示了非应答者与应答者在 NAIT 前的唾液微生物组特征不同。低唾液 EAS 水平可作为潜在的生物标志物,用于区分非应答者和应答者。
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引用次数: 0
A Two-Sample Mendelian Randomization Study of Neuroticism and Sleep Bruxism. 神经质与睡眠磨牙症的双样本孟德尔随机研究
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264749
T Strausz, S Strausz, S E Jones, T Palotie, F Lobbezoo, J Ahlberg, H M Ollila

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.

睡眠磨牙症(SB)影响着相当一部分人群,在多项研究中,睡眠磨牙症与神经质、压力和焦虑有关。然而,神经质与睡眠磨牙症之间的因果机制尚未得到研究。了解磨牙症的原因非常重要,因为了解了磨牙症的原因,就可以更好地对与之相关的疾病和合并症进行综合管理。以往关于磨牙症风险因素关联的研究提供了重要的症状洞察,但这些研究主要基于问卷调查或样本量有限,无法充分评估因果关系。本研究旨在通过孟德尔随机化(MR)方法,结合大规模问卷调查、登记数据和遗传信息,阐述神经质作为 SB 风险因素的可能因果关系。我们利用英国生物库(UK Biobank)中神经质的工具性遗传变异(包括神经质子类别)(n = 380,506 个)和芬兰基因(FinnGen)中可能的 SB 结果数据(n [cases/controls] = 12,297/364,980 个)进行了一项双样本 MR 研究。我们发现神经质与 SB 之间存在因果关系(几率比 [OR] = 1.38 [1.10-1.74],P = 0.0057)。对压力和逆境敏感的表型具有最强的效应(OR = 1.59 [1.17-2.15],P = 0.0028)。不同 MR 方法的敏感性分析表明了两者之间的因果关系,我们没有观察到神经质与 SB 之间的多向性(MR-Egger 截距,P = 0.87)。我们的研究结果与之前将压力与 SB 联系起来的观察性研究结果一致。此外,我们的结果还提供了神经质特质会增加可能患 SB 风险的证据。
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引用次数: 0
Metabolic and Aging Influence on Anticancer Immunity in Oral Cancer. 代谢和衰老对口腔癌抗癌免疫的影响
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264728
T P M D Santos, W L Hicks, W J Magner, A Al Afif, K L Kirkwood

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.

在全球范围内,平均年龄和肥胖率都在不断增加。老龄化和代谢性疾病负担都会对口腔鳞状细胞癌(OSCC)肿瘤微环境中的免疫和代谢特征产生深远影响,从而增加患口腔鳞状细胞癌(OSCC)的风险。虽然将衰老和肥胖与 OSCC 联系起来的机制仍不清楚,但有证据表明,在这两种情况下,抗肿瘤反应都会减弱。但值得注意的是,尽管在衰老或肥胖的情况下肿瘤微环境的免疫抑制作用增强,但免疫检查点阻断这种癌症免疫疗法仍能保持完好。在此,我们回顾了有关衰老和全身代谢变化如何影响抗肿瘤免疫的现有知识,重点是对肿瘤免疫抑制起重要作用的肿瘤相关巨噬细胞的作用。讨论的主要方面包括肥胖和衰老过程中的血管生成、细胞因子释放、吞噬作用减弱和免疫细胞招募机制,这些机制通过招募和重新极化肿瘤相关巨噬细胞来创造免疫抑制性肿瘤微环境。通过更深入地了解这些机制,开发控制 OSCC 的新型治疗方法将能在衰老和肥胖的背景下对肿瘤微环境进行更精细的管理。
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引用次数: 0
Autophagy Regulates Age-Related Jawbone Loss via LepR+ Stromal Cells. 自噬通过LepR+基质细胞调控与年龄相关的颌骨丧失
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264810
B Sun, Y Xu, H Wang, F Wang, Q Li, Y Chen, Z Wang

Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre+/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre+/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre+/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.

骨质老化与颌骨自噬活性降低有关,但在颌骨中的研究却很少。本研究旨在描述衰老的颌骨和颌骨衍生基质细胞(JBSCs)的特征,并确定自噬在颌骨质量下降中的作用。我们观察到,老年人和小鼠的颌骨表现出类似的与年龄相关的骨质流失。此外,瘦素受体(LepR)系细胞是体外培养和扩增 JBSCs(称为 LepR-Cre+/JBSCs)的主要来源。来自颌骨和LepR-Cre+/JBSCs的RNA测序数据显示,在衰老过程中,磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶标(mTOR)通路的表达上调。通过单细胞转录组学,我们发现在衰老的骨组织中,成骨系细胞比例下降,LepR系细胞的PI3K/AKT通路被激活。老年小鼠(O-mice;O-JBSCs)的颌骨和 LepR-Cre+/JBSCs 中出现了基础自噬活性降低、自噬通量减少和成骨减少的现象。药物和组成型自噬激活缓解了 O-JBSCs 中受损的成骨过程。此外,抑制 mTOR 诱导的自噬也改善了 O-JBSCs 的衰老表型。使用化学自噬激活剂激活 LepR-Cre+/JBSCs 的自噬可减少 O 型小鼠的牙槽骨吸收。因此,我们的研究证明 ATG 分子和通路在颌骨老化中至关重要,为了解与年龄相关的颌骨损失提供了新的方法。
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引用次数: 0
Engineered 3D Periodontal Ligament Model with Magnetic Tensile Loading. 采用磁拉力加载的工程三维牙周韧带模型
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264792
P Mulimani, N A Mazzawi, A J Goldstein, A M Obenaus, S M Baggett, D Truong, T E Popowics, N J Sniadecki

In vitro models are invaluable tools for deconstructing the biological complexity of the periodontal ligament (PDL). Model systems that closely reproduce the 3-dimensional (3D) configuration of cell-cell and cell-matrix interactions in native tissue can deliver physiologically relevant insights. However, 3D models of the PDL that incorporate mechanical loading are currently lacking. Hence, we developed a model where periodontal tissue constructs (PTCs) are made by casting PDL cells in a collagen gel suspended between a pair of slender, silicone posts for magnetic tensile loading. Specifically, one of the posts was rigid and the other was flexible with a magnet embedded in its tip so that PTCs could be subjected to tensile loading with an external magnet. Additionally, the deflection of the flexible post could be used to measure the contractile force of PDL cells in the PTCs. Prior to tensile loading, second harmonics generation analysis of collagen fibers in PTCs revealed that incorporation of PDL cells resulted in collagen remodeling. Biomechanical testing of PTCs by tensile loading revealed an elastic response at 4 h, permanent deformation by 1 d, and creep elongation by 1 wk. Subsequently, contractile forces of PDL cells were substantially lower for PTCs under tensile loading. Immunofluorescence analysis revealed that tensile loading caused PDL cells to increase in number, express higher levels of F-actin and α-smooth muscle actin, and become aligned to the tensile axis. Second harmonics generation analysis indicated that collagen fibers in PTCs progressively remodeled over time with tensile loading. Gene expression analysis also confirmed tension-mediated upregulation of the F-actin/Rho pathway and osteogenic genes. Our model is novel in demonstrating the mechanobiological behavior that results in cell-mediated remodeling of the PDL tissue in a 3D context. Hence, it can be a valuable tool to develop therapeutics for periodontitis, periodontal regeneration, and orthodontics.

体外模型是解构牙周韧带(PDL)生物复杂性的宝贵工具。模型系统可近似再现原生组织中细胞-细胞和细胞-基质相互作用的三维(3D)结构,从而提供与生理相关的见解。然而,目前还缺乏包含机械负荷的 PDL 三维模型。因此,我们开发了一种模型,通过在一对细长的硅胶柱之间悬浮的胶原凝胶中铸造 PDL 细胞来制作牙周组织构建体 (PTC),从而实现磁性拉伸加载。具体来说,其中一个硅胶柱是刚性的,另一个硅胶柱是柔性的,其顶端嵌入了磁铁,这样 PTC 就能承受外部磁铁的拉伸负荷。此外,柔性支柱的偏转可用于测量 PTC 中 PDL 细胞的收缩力。在拉伸加载之前,对 PTC 中的胶原纤维进行二次谐波生成分析,结果显示 PDL 细胞的加入导致了胶原重塑。通过拉伸加载对 PTC 进行的生物力学测试显示,4 小时后出现弹性反应,1 天后出现永久变形,1 周后出现蠕变伸长。随后,PDL 细胞在拉伸负荷下的收缩力大大低于 PTC。免疫荧光分析表明,拉伸负荷导致 PDL 细胞数量增加,表达更高水平的 F-肌动蛋白和 α 平滑肌肌动蛋白,并与拉伸轴对齐。二次谐波生成分析表明,随着时间的推移,PTCs 中的胶原纤维会随着拉伸负荷而逐渐重塑。基因表达分析也证实了张力介导的 F-actin/Rho 通路和成骨基因的上调。我们的模型在三维环境中展示了导致细胞介导的 PDL 组织重塑的机械生物学行为,具有新颖性。因此,它可以成为开发牙周炎、牙周再生和正畸疗法的重要工具。
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引用次数: 0
The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis. PerioGene North 研究发现了与牙周炎有关的血清蛋白。
Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241263320
M Wänman, S Betnér, A Esberg, C K Holm, C Isehed, A Holmlund, P Palmqvist, A Lövgren, S Lindquist, L Hänström, U H Lerner, E Kindstedt, P Lundberg

The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.

牙周炎的后遗症包括牙齿支持结构的不可逆退化和炎症介质的循环传播。然而,对牙周炎血清蛋白谱的描述并不完善,部分原因是基于大型、特征明确的牙周炎队列的研究数量有限。这项研究的目的是在 PerioGene North 病例对照研究(包括 478 例严重牙周炎病例和 509 例牙周健康对照组)中发现与牙周炎相关的新型循环炎症相关蛋白。研究采用靶向蛋白质组学分析了血清中高敏性 C 反应蛋白(hs-CRP)和 45 种炎症相关蛋白的浓度。牙周炎病例的血清蛋白特征明显不同。这种蛋白质模式可将病例与对照组区分开来,灵敏度为 0.81,特异性为 0.81(曲线下面积 = 0.87)。调整后的 hs-CRP 水平和 45 种蛋白质中的 24 种在病例和对照组之间存在差异。在病例中检测到高水平的 hs-CRP 和基质金属蛋白酶-12,以及低水平的表皮生长因子(EGF)和氧化低密度脂蛋白受体 1(OLR-1)。此外,在牙龈炎症程度较高的病例中,C-C 趋化因子-19、粒细胞集落刺激因子-3(CSF-3)、白细胞介素-7(IL-7)和 hs-CRP 的水平明显较高。在牙周袋较深的病例中,CSF-3 和肿瘤坏死因子配体超家族成员-10 TNFSF-10 的水平较高。PerioGene North 研究包括详细的临床牙周数据,并揭示了牙周炎中独特的血清蛋白特征。研究还特别强调了病例中 EGF 和 OLR-1 含量较低的发现,因为这种情况以前从未出现过。应进一步探讨 EGF 和 OLR-1 在牙周炎发病机制中的作用,并将其作为未来可能的生物标志物。
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引用次数: 0
Visualization of Pulpal Structures by SWIR in Endodontic Access Preparation. 在牙髓通路制备过程中利用 SWIR 对牙髓结构进行可视化。
Pub Date : 2024-08-05 DOI: 10.1177/00220345241262949
L Benz, K Heck, D Hevisov, D Kugelmann, P-C Tseng, Z Sreij, F Litzenburger, J Waschke, F Schwendicke, A Kienle, R Hickel, K-H Kunzelmann, E Walter

Endodontic access preparation is one of the initial steps in root canal treatments and can be hindered by the obliteration of pulp canals and formation of tertiary dentin. Until now, methods for direct intraoperative visualization of the 3-dimensional anatomy of teeth have been missing. Here, we evaluate the use of shortwave infrared radiation (SWIR) for navigation during stepwise access preparation. Nine teeth (3 anteriors, 3 premolars, and 3 molars) were explanted en bloc with intact periodontium including alveolar bone and mucosa from the upper or lower jaw of human body donors. Analysis was performed at baseline as well as at preparation depths of 5 mm, 7 mm, and 9 mm, respectively. For reflection, SWIR was used at a wavelength of 1,550 nm from the occlusal direction, whereas for transillumination, SWIR was passed through each sample at the marginal gingiva from the buccal as well as oral side at a wavelength of 1,300 nm. Pulpal structures could be identified as darker areas approximately 2 mm before reaching the pulp chamber using SWIR transillumination, although they were indistinguishable under normal circumstances. Furcation areas in molars appeared with higher intensity than areas with canals. The location of pulpal structures was confirmed by superimposition of segmented micro-computed tomography (µCT) images. By radiomic analysis, significant differences between pulpal and parapulpal areas could be detected in image features. With hierarchical cluster analysis, both segments could be confirmed and associated with specific clusters. The local thickness of µCTs was calculated and correlated with SWIR transillumination images, by which a linear dependency of thickness and intensity could be demonstrated. Lastly, by in silico simulations of light propagation, dentin tubules were shown to be a crucial factor for understanding the visibility of the pulp. In conclusion, SWIR transillumination may allow direct clinical live navigation during endodontic access preparation.

根管通路准备是根管治疗的初始步骤之一,可能会受到牙髓管阻塞和第三牙本质形成的阻碍。到目前为止,还没有术中直接观察牙齿三维解剖结构的方法。在此,我们评估了短波红外线(SWIR)在分步通路准备过程中的应用。我们从人体捐献者的上颌或下颌取出九颗牙齿(3 颗前牙、3 颗前臼齿和 3 颗臼齿),连同完整的牙周膜(包括牙槽骨和粘膜)进行了整体移植。分别在基线以及制备深度为 5 毫米、7 毫米和 9 毫米时进行分析。反射时,使用波长为 1,550 nm 的西南红外光从咬合方向照射;透射时,使用波长为 1,300 nm 的西南红外光从颊侧和口侧穿过每个样本的边缘牙龈。使用西南红外透射光可以在到达牙髓腔前约 2 毫米处发现暗色区域的牙髓结构,尽管在正常情况下它们是无法区分的。磨牙的毛面区域比有牙槽骨的区域强度更高。牙髓结构的位置是通过叠加分割的微型计算机断层扫描(µCT)图像确认的。通过放射学分析,可以发现牙髓区和副牙髓区在图像特征上存在明显差异。通过分层聚类分析,可以确认这两个区段并与特定的聚类相关联。计算了 µCT 的局部厚度,并将其与西南红外透射图像相关联,从而证明了厚度与强度之间的线性关系。最后,通过对光传播进行硅模拟,证明牙本质小管是了解牙髓可见度的关键因素。总之,在牙髓通路准备过程中,SWIR 透射成像技术可以实现直接的临床现场导航。
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引用次数: 0
Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics. 牙周韧带细胞凋亡激活正畸中的 Lepr+ 骨生成器
Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241262706
H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han

Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.

牙槽骨(AB)重塑,包括形成和吸收,是正畸牙齿移动(OTM)的基础。然而,新骨形成的来源和机制仍不清楚。因此,我们以瘦素受体+(Lepr+)成骨细胞和牙周韧带细胞(PDLCs)为重点,旨在了解 OTM 期间骨形成的潜在机制。我们证明,在正畸骨再生过程中,由力诱导的 PDLC 细胞凋亡激活的 Lepr+ 细胞是一种独特的骨生成细胞。我们研究了体内和体外的骨形成。单细胞RNA测序分析和系谱追踪表明,Lepr代表了在OTM过程中被激活并分化成成骨细胞的干细胞亚群。在小鼠模型中靶向消融 Lepr+ 细胞会破坏正畸力引导的骨再生。此外,细胞凋亡和连续荧光标记实验显示,PDLCs 的凋亡先于新骨沉积。我们发现,PDL干细胞衍生的凋亡囊泡在体外激活了Lepr+细胞。抑制细胞凋亡后,正畸力激活的造骨细胞和成骨作用明显降低。值得注意的是,我们发现在 OTM 过程中,骨形成发生在受压侧;这在本文中是首次报道。总之,我们发现了 OTM 期间骨形成的潜在机制,这可能会为 AB 再生提供新的见解。
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引用次数: 0
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Journal of dental research
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