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Comparison of Implant Precision with Robots, Navigation, or Static Guides 机器人、导航或静态导引器的植入精度比较
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-11-26 DOI: 10.1177/00220345241285566
J.-Y. Shi, X.-Y. Wu, X.-L. Lv, M. Liu, X.-J. Fu, B.-L. Liu, H.-C. Lai, M.S. Tonetti
Precise surgical positioning according to a digital plan is important for aesthetic and biologically stable dental implant restorations. This randomized controlled trial compared implant placement assisted by robotic surgery (RS), dynamic navigation (DN), or 3-dimensional printed static guide (SG). An overall 45 patients with a missing tooth in the premolar/molar region were randomly assigned to 1 of the 3 groups. Implant positional accuracy (primary outcome), early wound healing, soft tissue microcirculation, patient-reported outcome measures, and surgeon preference were measured by calibrated blind examiners. One adverse event occurred in DN and RS. In RS ( n = 15), the global platform, apex deviation, and angular deviations (mean ± SD) were 1.1 ± 0.4 mm, 1.5 ± 0.6 mm, and 4.7° ± 2.5°, respectively. Similarly, deviations were 1.3 ± 0.6 mm, 1.9 ± 0.9 mm, and 5.5° ± 3.5° in the DN group ( n = 14) and 1.1 ± 0.6 mm, 2.0 ± 1.2 mm, and 6.2° ± 4.0° in the SG group ( n = 13). Significantly smaller differential deviations (mesial-distal) at the platform and apex levels were found in the RS group than the SG group ( P < 0.05). Surgery was significantly shorter with a SG ( P < 0.001), and this was associated with better postoperative recovery at 3 d. The surgeon assessed DN as providing easier access to reach the surgical site. No significant differences were found upon comparing soft tissue microcirculation and oxygen saturation immediately, 1 h, or 7 d after surgery. Patient-reported outcomes were comparable in the 3 groups, except that patients in the SG group reported better oral health–related quality of life 3 d after surgery. It can be concluded that RS showed near-zero 3-dimensional systematic error in implant position, while DN and SG demonstrated a centrifugal error pattern. All 3 guided approaches had uneventful wound healing and acceptable patient-reported outcomes. The 3 groups had specific cost-benefit profiles. After additional technical developments, future trials with larger sample sizes and longer follow-up periods should be performed to analyze the cost-effectiveness of different guided surgical approaches.
根据数字化计划进行精确的手术定位对于美观且具有生物稳定性的种植牙修复非常重要。这项随机对照试验比较了机器人手术(RS)、动态导航(DN)或三维打印静态导板(SG)辅助下的种植体植入。总共 45 名前磨牙/臼齿缺失患者被随机分配到 3 组中的一组。种植体位置准确性(主要结果)、早期伤口愈合、软组织微循环、患者报告结果和外科医生偏好均由校准过的盲人检查员进行测量。DN 和 RS 均发生了一起不良事件。在 RS 中(n = 15),整体平台、顶点偏差和角度偏差(平均值 ± SD)分别为 1.1 ± 0.4 mm、1.5 ± 0.6 mm 和 4.7° ± 2.5°。同样,DN 组(n = 14)的偏差为 1.3 ± 0.6 mm、1.9 ± 0.9 mm 和 5.5° ± 3.5°,SG 组(n = 13)的偏差为 1.1 ± 0.6 mm、2.0 ± 1.2 mm 和 6.2° ± 4.0°。在平台和顶点水平上,RS 组的差异偏差(内侧-远侧)明显小于 SG 组(P < 0.05)。SG组的手术时间明显更短(P <0.001),术后3 d的恢复情况更好。比较术后即刻、术后 1 小时或术后 7 d 的软组织微循环和血氧饱和度未发现明显差异。三组患者报告的结果相当,只是 SG 组患者在术后 3 d 报告的口腔健康相关生活质量更好。可以得出的结论是,RS组种植体位置的三维系统误差几乎为零,而DN和SG组则表现出离心误差模式。所有三种引导方法的伤口愈合都很顺利,患者报告的结果也都可以接受。三组的成本效益情况各不相同。随着技术的进一步发展,今后应进行样本量更大、随访时间更长的试验,以分析不同引导手术方法的成本效益。
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引用次数: 0
Wnt/β-catenin Promotes Cementum Apposition in Periodontal Regeneration Wnt/β-catenin 促进牙周再生过程中的牙本质附着
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-11-26 DOI: 10.1177/00220345241286490
Y. Ono, M. Kaku, L. Thant, H. Iwama, M. Arai, M. Mizukoshi, A. Dobashi, M. Kitami, M.M. Taketo, A. Ohazama, I. Saito, K. Uoshima
Regeneration of periodontal tissue, particularly the cementum–periodontal ligament (PDL)–bone complex, has long been challenging because the differentiation kinetics of cells and the molecular pathways contributing to the regeneration process are largely unknown. We aimed to evaluate the cell behavior and molecular pathways that contribute to periodontal tissue regeneration in vivo. We analyzed the process of periodontal tissue regeneration through subrenal capsule transplantation of immediately extracted molars in mice. We showed that the regenerated periodontal tissue in the subrenal capsule was morphologically comparable to the intact periodontal tissue, with increased cellular cementum thickness in the apical region. Cell tracing analysis revealed that the cells comprising the regenerated periodontal tissue were derived from transplanted teeth and were indispensable for periodontal tissue regeneration, whereas recipient mouse-derived cells partly contributed to angiogenesis. Bioinformatics analysis based on the gene expression profile in the transplanted teeth indicated that Wnt/β-catenin signaling is involved in periodontal tissue regeneration, which was further confirmed through β-catenin immunohistochemistry. Moreover, the constitutive activation of β-catenin in the cells of transplanted teeth was found to promote accelerated cellular cementum apposition, while the conditional knockout of β-catenin in the cells of transplanted teeth suppressed cellular cementum apposition. Notably, the manipulation of Wnt/β-catenin signaling did not interfere with the bone–PDL–cementum complex, while endogenous osteoclast activity was affected in bone. Our results demonstrated the essential roles of endogenous PDL cells in periodontal tissue regeneration and that Wnt/β-catenin signaling is involved in this process, particularly cellular cementum apposition. Hence, controlling this pathway could promote cementum regeneration, which is a critical process for the regeneration of the cementum–PDL–bone complex. This study provides novel insights into cell behavior and signaling pathways that will advance practical periodontal tissue regeneration.
长期以来,牙周组织,尤其是牙骨质-牙周韧带(PDL)-骨复合体的再生一直是一项挑战,因为细胞的分化动力学和促进再生过程的分子途径在很大程度上都是未知的。我们的目的是评估细胞行为和促进体内牙周组织再生的分子途径。我们分析了通过肾下囊移植即拔臼齿小鼠牙周组织再生的过程。我们发现,肾下囊内再生的牙周组织在形态上与完整的牙周组织相似,根尖区的细胞骨水泥厚度增加。细胞追踪分析表明,组成再生牙周组织的细胞来自移植牙齿,是牙周组织再生不可或缺的细胞,而受体小鼠衍生细胞在一定程度上促进了血管生成。基于移植牙齿基因表达谱的生物信息学分析表明,Wnt/β-catenin 信号参与了牙周组织再生,这一点通过 β-catenin 免疫组化得到了进一步证实。此外,研究还发现,在移植牙的细胞中构成性激活β-catenin可促进细胞骨水泥的加速贴合,而在移植牙的细胞中条件性敲除β-catenin则可抑制细胞骨水泥的贴合。值得注意的是,对Wnt/β-catenin信号传导的操作并没有干扰骨-PDL-骨水泥复合体,而骨中的内源性破骨细胞活性却受到了影响。我们的研究结果表明了内源性 PDL 细胞在牙周组织再生中的重要作用,而 Wnt/β-catenin 信号转导参与了这一过程,尤其是细胞骨水泥膜的附着。因此,控制这一通路可促进牙骨质再生,而牙骨质再生是牙骨质-PDL-骨复合体再生的关键过程。这项研究为细胞行为和信号通路提供了新的见解,将推动实际的牙周组织再生。
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引用次数: 0
Global, Regional, and Country-Level Economic Impacts of Oral Conditions in 2019 2019 年口腔疾病对全球、地区和国家层面的经济影响
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-11-13 DOI: 10.1177/00220345241281698
M. Jevdjevic, S. Listl
The recent World Health Organization (WHO) Oral Health Resolution and the subsequent WHO Global Oral Health Action Plan highlight the key relevance of providing information on the economic impacts of oral conditions. The purpose of this study was to provide updated estimates for the global, regional, and country-level economic impacts of oral conditions in 2019. Extending previously established methods, dental expenditures (costs for treatments) and productivity losses for 5 oral conditions (caries in deciduous and permanent teeth, periodontitis, edentulism, other oral diseases) were estimated for the year 2019. The estimated total worldwide economic impacts of oral conditions in 2019 were US $710B, of which US $387B (US $327B to US $404B) was due to direct costs and US $323B (US $186 to US $460) was due to productivity losses for the 5 main oral conditions. Low-income countries spent an average of US $0.52 (US $0.22 to US $0.96) per capita on dental care, while high-income countries spent an average of US $260 (US $257 to US $268) per capita—a 500-fold difference. These findings suggest that oral conditions continue to substantiate an enormous economic burden to individuals and society. The comprehensiveness of estimates supersedes that of previous work as the primary information on direct costs was identified for a larger number of countries. The need for more and better routine reporting and monitoring of the economic impact of oral conditions is emphasized. The relevance of such information is also highlighted by its inclusion in the first-ever WHO Global Oral Health Status Report and Global Strategy on Oral health 2023 to 2030. Given the persistently high economic burden of oral conditions, there is a key role for better prioritization of cost-efficient oral health programs as well as needs-responsive capacity planning.
最近的世界卫生组织(WHO)口腔健康决议和随后的世界卫生组织全球口腔健康行动计划强调了提供有关口腔疾病经济影响的信息的重要意义。本研究旨在提供 2019 年全球、地区和国家层面口腔疾病经济影响的最新估计值。通过扩展以前确定的方法,估算了 2019 年 5 种口腔疾病(乳牙和恒牙龋齿、牙周炎、牙齿缺失症、其他口腔疾病)的牙科支出(治疗费用)和生产力损失。据估计,2019 年口腔疾病对全世界造成的经济影响总额为 7100 亿美元,其中 3870 亿美元(3270 亿美元至 4040 亿美元)为直接成本,3230 亿美元(186 美元至 460 美元)为 5 种主要口腔疾病造成的生产力损失。低收入国家的人均牙科保健费用为 0.52 美元(0.22 美元至 0.96 美元),而高收入国家的人均费用为 260 美元(257 美元至 268 美元),相差 500 倍。这些研究结果表明,口腔疾病继续给个人和社会带来巨大的经济负担。由于确定了更多国家的直接成本的主要信息,因此估算的全面性超过了以前的工作。报告强调了对口腔疾病的经济影响进行更多更好的例行报告和监测的必要性。世卫组织首次发布的《全球口腔健康状况报告》和《2023 至 2030 年全球口腔健康战略》也强调了这些信息的相关性。鉴于口腔疾病造成的经济负担长期居高不下,更好地确定具有成本效益的口腔健康计划的优先次序以及根据需求进行能力规划具有关键作用。
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引用次数: 0
Small Nucleolar RNAs in Head and Neck Squamous Cell Carcinomas 头颈部鳞状细胞癌中的小核极 RNA
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-25 DOI: 10.1177/00220345241279369
C. Duan, Y. Abola, J. Zhao, Y. Wang
Small nucleolar RNAs (snoRNAs), a distinct class of noncoding RNAs, encompass highly diverse structures and have a range of 60 to 300 nucleotides in length. About 90% of human snoRNAs are intronic and embedded within introns of their host gene transcripts. Most snoRNAs enriched in specific tissue correlate in abundance with their parental host genes. Advancements in high-throughput sequencing have facilitated the discovery of dysregulated snoRNA expression in numerous human malignancies including head and neck squamous cell carcinoma (HNSCC). Hundreds of differentially expressed snoRNAs have been identified in HNSCC tissues. Among 1,524 snoRNA genes in a 567 HNSCC cohort, 113 snoRNAs were found to be survival related. As for snoRNA’s roles in HNSCC, based on the available evidence, dysregulated snoRNAs are closely associated with the carcinogenesis and development of HNSCC. Upregulated snoRNAs have been shown to augment the expression of other oncogenes or activate the Wnt/β-catenin signaling pathway, thereby promoting tumor cell viability, glycolysis, migration, and the epithelial-mesenchymal transition while inhibiting apoptosis in vitro. In vivo animal studies have further elucidated the functional roles of snoRNAs. Knockdown of host genes of these snoRNAs suppressed the Wnt/β-catenin signaling pathway and restrained tumor proliferation and aggressiveness in mice. The putative mechanisms underlying these observations are associated with the biological functions of snoRNAs, primarily involving microRNA-like functions through the generation of microRNA-like fragments and regulation of alternative splicing to yield diverse transcripts. While most of the snoRNAs are upregulated in HNSCC, 4 downregulated snoRNAs have been identified and annotated. SNORA36B (implicated in the regulation of DNA templates) and U3 (chr17, influencing cell proliferation) may serve as protective factors associated with prolonged overall survival. This review describes the viable structures of snoRNAs, endeavors to refine snoRNA sequencing technology, and summarizes snoRNAs’ expression profile as well as their role in HNSCC progression for potential diagnostic and therapeutic strategies for HNSCC management.
小核仁 RNA(snoRNA)是一类独特的非编码 RNA,具有高度多样化的结构,长度在 60 至 300 个核苷酸之间。大约 90% 的人类 snoRNA 位于其宿主基因转录本的内含子中。特定组织中富集的大多数 snoRNA 与其亲代宿主基因的丰度相关。高通量测序技术的进步促进了在包括头颈部鳞状细胞癌(HNSCC)在内的多种人类恶性肿瘤中发现表达失调的 snoRNA。在 HNSCC 组织中发现了数百种不同表达的 snoRNA。在 567 个 HNSCC 队列中的 1,524 个 snoRNA 基因中,发现 113 个 snoRNA 与生存相关。至于 snoRNA 在 HNSCC 中的作用,根据现有证据,调控失调的 snoRNA 与 HNSCC 的癌变和发展密切相关。有研究表明,上调的 snoRNA 可增强其他癌基因的表达或激活 Wnt/β-catenin 信号通路,从而促进肿瘤细胞的活力、糖酵解、迁移和上皮-间质转化,同时抑制体外细胞凋亡。体内动物研究进一步阐明了 snoRNA 的功能作用。敲除这些 snoRNA 的宿主基因可抑制 Wnt/β-catenin 信号通路,抑制小鼠肿瘤的增殖和侵袭性。这些观察结果的推测机制与 snoRNAs 的生物功能有关,主要涉及通过生成 microRNA 样片段和调节替代剪接产生不同转录本的 microRNA 样功能。虽然大多数 snoRNA 在 HNSCC 中上调,但有 4 个下调的 snoRNA 已被鉴定和注释。SNORA36B(与 DNA 模板调控有关)和 U3(chr17,影响细胞增殖)可能是与延长总存活期有关的保护性因素。这篇综述描述了 snoRNA 的可行结构,致力于完善 snoRNA 测序技术,并总结了 snoRNA 的表达谱及其在 HNSCC 进展中的作用,从而为 HNSCC 的治疗提供潜在的诊断和治疗策略。
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引用次数: 0
Publicly Available Dental Image Datasets for Artificial Intelligence. 用于人工智能的公开牙科图像数据集。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-18 DOI: 10.1177/00220345241272052
S E Uribe,J Issa,F Sohrabniya,A Denny,N N Kim,A F Dayo,A Chaurasia,A Sofi-Mahmudi,M Büttner,F Schwendicke
The development of artificial intelligence (AI) in dentistry requires large and well-annotated datasets. However, the availability of public dental imaging datasets remains unclear. This study aimed to provide a comprehensive overview of all publicly available dental imaging datasets to address this gap and support AI development. This observational study searched all publicly available dataset resources (academic databases, preprints, and AI challenges), focusing on datasets/articles from 2020 to 2023, with PubMed searches extending back to 2011. We comprehensively searched for dental AI datasets containing images (intraoral photos, scans, radiographs, etc.) using relevant keywords. We included datasets of >50 images obtained from publicly available sources. We extracted dataset characteristics, patient demographics, country of origin, dataset size, ethical clearance, image details, FAIRness metrics, and metadata completeness. We screened 131,028 records and extracted 16 unique dental imaging datasets. The datasets were obtained from Kaggle (18.8%), GitHub, Google, Mendeley, PubMed, Zenodo (each 12.5%), Grand-Challenge, OSF, and arXiv (each 6.25%). The primary focus was tooth segmentation (62.5%) and labeling (56.2%). Panoramic radiography was the most common imaging modality (58.8%). Of the 13 countries, China contributed the most images (2,413). Of the datasets, 75% contained annotations, whereas the methods used to establish labels were often unclear and inconsistent. Only 31.2% of the datasets reported ethical approval, and 56.25% did not specify a license. Most data were obtained from dental clinics (50%). Intraoral radiographs had the highest findability score in the FAIR assessment, whereas cone-beam computed tomography datasets scored the lowest in all categories. These findings revealed a scarcity of publicly available imaging dental data and inconsistent metadata reporting. To promote the development of robust, equitable, and generalizable AI tools for dental diagnostics, treatment, and research, efforts are needed to address data scarcity, increase diversity, mandate metadata completeness, and ensure FAIRness in AI dental imaging research.
牙科人工智能(AI)的发展需要大量的、有良好标注的数据集。然而,公共牙科成像数据集的可用性仍不明确。本研究旨在全面概述所有公开可用的牙科成像数据集,以填补这一空白并支持人工智能的发展。这项观察性研究搜索了所有公开可用的数据集资源(学术数据库、预印本和人工智能挑战),重点关注2020年至2023年的数据集/文章,PubMed搜索可追溯到2011年。我们使用相关关键词全面搜索了包含图像(口内照片、扫描、X光片等)的牙科人工智能数据集。我们纳入了从公开来源获得的大于 50 幅图像的数据集。我们提取了数据集的特征、患者人口统计学特征、来源国、数据集大小、伦理许可、图像细节、FAIRness 指标和元数据完整性。我们筛选了 131,028 条记录,提取了 16 个独特的牙科成像数据集。这些数据集来自 Kaggle(18.8%)、GitHub、Google、Mendeley、PubMed、Zenodo(各占 12.5%)、Grand-Challenge、OSF 和 arXiv(各占 6.25%)。主要重点是牙齿分割(62.5%)和标记(56.2%)。全景放射摄影是最常见的成像方式(58.8%)。在 13 个国家中,中国提供的图像最多(2,413 幅)。75%的数据集包含注释,但用于建立标签的方法往往不明确且不一致。只有 31.2% 的数据集报告了伦理批准,56.25% 的数据集没有说明许可证。大多数数据来自牙科诊所(50%)。口内X光片在 FAIR 评估中的可查找性得分最高,而锥形束计算机断层扫描数据集在所有类别中得分最低。这些发现揭示了公开可用的牙科成像数据稀缺以及元数据报告不一致的问题。为了促进开发用于牙科诊断、治疗和研究的强大、公平和可推广的人工智能工具,需要努力解决数据稀缺问题、增加多样性、规定元数据的完整性并确保人工智能牙科成像研究的 FAIR 性。
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引用次数: 0
Oral Health Care Out-of-Pocket Costs and Financial Hardship: A Scoping Review 口腔医疗自付费用和经济困难:范围审查
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-17 DOI: 10.1177/00220345241253191
D. Proaño, H. Huang, S. Allin, B.M. Essue, S. Singhal, C. Quiñonez
The objective of this study is to characterize how financial hardship related to oral health care (OHC) out-of-pocket (OOP) spending has been conceptualized, defined, and measured in the literature and to identify evidence gaps in this area. This scoping review follows Arksey and O’Malley’s framework and synthesizes financial hardship from OHC concepts, methodologies, and evidence gaps. We searched Ovid-Medline, Ovid-Embase, PubMed, Web of Science, Scopus, EconLit, Business Source Premier, and the Cochrane Library. Gray literature was sourced from institutional websites (World Health Organization, United Nations, World Bank Group, Organisation for Economic Co-operation and Development, and governmental health agencies) as well as ProQuest Dissertations and Thesis Global. We used defined inclusion and exclusion criteria to select studies published between 2000 and 2023. Of the 1,876 records, 65 met our criteria. The studies conceptualized financial hardship as catastrophic spending, impoverishment, negative coping strategies, bankruptcy, financial burden, food insecurity, and personal financial hardship experience. We found heterogeneity in defining OHC OOP payments and services. Also, financial hardship was frequently measured as catastrophic health expenditure using cross-sectional designs and national household spending surveys from high-income and to a lesser extent lower-middle-income countries. We identify and discuss challenges in terms of conceptualizing financial hardship, study designs, and measurement instruments in the OHC context. Some of the common evidence gaps identified include studying the causal relationship in financial hardship from OHC, assessing the financial hardship and unmet dental needs due to cost relationship, and distinguishing the effect between pain/discomfort and esthetic/cosmetic dental treatments on financial hardship. Financial hardship in OHC needs further exploration and the use of consistent definitions as well must distinguish between treatments alleviating pain/discomfort from esthetic/cosmetic treatments. Our study is relevant for policy makers and researchers aiming to monitor financial protection of OOP payments on OHC in the wake of universal health coverage for oral health.
本研究的目的是描述与口腔健康护理(OHC)自付(OOP)支出相关的经济困难在文献中是如何被概念化、定义和衡量的,并找出该领域的证据差距。本范围界定综述遵循 Arksey 和 O'Malley 的框架,从口腔健康护理的概念、方法和证据差距方面综合了经济困难。我们检索了 Ovid-Medline、Ovid-Embase、PubMed、Web of Science、Scopus、EconLit、Business Source Premier 和 Cochrane 图书馆。灰色文献来自机构网站(世界卫生组织、联合国、世界银行集团、经济合作与发展组织和政府卫生机构)以及 ProQuest Dissertations and Thesis Global。我们采用明确的纳入和排除标准来选择 2000 年至 2023 年间发表的研究。在 1,876 条记录中,有 65 条符合我们的标准。这些研究将经济困难概念化为灾难性支出、贫困化、消极应对策略、破产、经济负担、粮食不安全和个人经济困难经历。我们发现,对老年健康保险自付费用和服务的定义存在差异。此外,通过横截面设计和高收入国家的全国家庭支出调查,经济困难经常被衡量为灾难性医疗支出,中低收入国家的情况较少。我们确定并讨论了在老年保健背景下,经济困难的概念化、研究设计和测量工具方面所面临的挑战。一些常见的证据缺口包括:研究OHC经济困难的因果关系,评估经济困难和因费用关系而未满足的牙科需求,以及区分疼痛/不适和美学/美容牙科治疗对经济困难的影响。口腔健康方面的经济困难需要进一步探讨,并使用一致的定义,同时必须区分减轻疼痛/不适的治疗和美容/整容治疗。我们的研究对政策制定者和研究人员很有意义,他们的目标是在口腔健康全民医保之后,监测口腔健康方面的自费项目支付的经济保护情况。
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引用次数: 0
Colin Dawes In Memoriam: JDR Editor Emeritus and Pioneer in Salivary Research. 缅怀科林-道斯(Colin Dawes):唾液研究的先驱、《唾液研究杂志》荣誉编辑。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-14 DOI: 10.1177/00220345241280026
J M Richman,W L Siqueira
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引用次数: 0
β-catenin Orchestrates Gli1+ Cell Fate in Condylar Development and TMJOA. β-catenin在髁突发育和颞下颌关节发育中协调Gli1+细胞的命运
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-14 DOI: 10.1177/00220345241274354
J Wang,X Dong,J Lei,Y Zhang,S Chen,Y He
The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA.
髁突表面的纤维软骨干细胞(FCSCs)在软骨的稳态和再生中发挥着重要作用。然而,用于分析纤维软骨干细胞的细胞命运和调控机制的定义明确的干细胞标记很少。在这项研究中,我们首先绘制了髁状突软骨的转录图谱,并确定了一个Gli1+亚群。标签保留细胞和我们的系谱追踪研究表明,Gli1标记了一组FCSCs。条件性敲除β-catenin抑制了Gli1+细胞向肥大软骨细胞分化。在椎间盘切除术诱发的颞下颌关节骨关节炎(TMJOA)中,Gli1+细胞被进一步激活,并加速分化为肥大软骨细胞,从而诱发干细胞池耗竭。在Gli1+细胞中删除β-catenin可保留FCSC池,缓解TMJOA软骨退化。总之,我们发现Gli1+ FCSC亚群和Wnt/β-catenin信号协调了Gli1+细胞在髁后发育和颞下颌关节损伤中的命运。
{"title":"β-catenin Orchestrates Gli1+ Cell Fate in Condylar Development and TMJOA.","authors":"J Wang,X Dong,J Lei,Y Zhang,S Chen,Y He","doi":"10.1177/00220345241274354","DOIUrl":"https://doi.org/10.1177/00220345241274354","url":null,"abstract":"The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"229 1","pages":"220345241274354"},"PeriodicalIF":7.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436156","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}
引用次数: 0
Ferroptosis Induction Enhances Photodynamic Therapy Efficacy for OLK 诱导铁突变可提高光动力疗法治疗 OLK 的疗效
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-12 DOI: 10.1177/00220345241280257
D. Yang, D. Yang, Y. Song, J. Liu, Y. Wang, X. Feng, X. Zeng, Q. Chen, J. Li, H. Dan
Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)–induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.
口腔白斑病(OLK)是最具代表性的口腔潜在恶性疾病,恶变风险高,发生机制不清。最近,光动力疗法(PDT)在治疗口腔白斑病方面展现出巨大潜力。然而,光动力疗法的疗效很难预测,而且因人而异。许多癌症中与铁突变相关的通路都会上调,铁突变诱导被认为是各种抗肿瘤疗法的潜在协同策略,但它在 OLK 治疗中的作用仍不清楚。本研究旨在确定诱导铁蛋白沉积是否能提高光动力疗法在OLK治疗中的疗效。我们的研究发现,溶质运载家族 7 成员 11(SLC7A11)在对 PDT 无反应的 OLK 患者中高表达,而 SLC7A11 是一个重要的氨基酸转运体的组成成分,也是铁氧化的关键负调控因子。众所周知,5-氨基乙酰丙酸(ALA)-PDT可导致细胞凋亡和坏死,但在我们的研究中,OLK细胞在ALA-PDT作用下也出现了铁凋亡。使用麦拉宁诱导铁凋亡可通过破坏抗氧化系统和进一步提高细胞内活性氧水平来增强ALA-PDT对OLK细胞的疗效,从而导致细胞凋亡增加。此外,这种联合方式还增强了 ALA-PDT 对 4-硝基喹啉-1-氧化物(4NQO)诱导的小鼠 OLK 病变的疗效。总之,诱导铁变态反应可能是提高 ALA-PDT 治疗 OLK 疗效的一种潜在策略。
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引用次数: 0
Immune Dysregulation in the Oral Cavity during Early SARS-CoV-2 Infection 早期 SARS-CoV-2 感染期间口腔内的免疫失调
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-10-12 DOI: 10.1177/00220345241271943
C. Graves, E. Babikow, N. Ghaltakhchyan, T.Q. Ngo, C. Li, S. Wang, A. Shoji, C. Bocklage, S.T. Phillips, M. Markovetz, S.A. Frazier-Bowers, K. Divaris, M. Freire, S. Wallet, D. Wu, L.A. Jacox
Tissue-specific immune responses are critical determinants of health-maintaining homeostasis and disease-related dysbiosis. In the context of COVID-19, oral immune responses reflect local host-pathogen dynamics near the site of infection and serve as important “windows to the body,” reflecting systemic responses to the invading SARS-CoV-2 virus. This study leveraged multiplex technology to characterize the salivary SARS-CoV-2–specific immunological landscape (37 cytokines/chemokines and 11 antibodies) during early infection. Cytokine/immune profiling was performed on unstimulated cleared whole saliva collected from 227 adult SARS-CoV-2+ participants and 37 controls. Statistical analysis and modeling revealed significant differential abundance of 25 cytokines (16 downregulated, 9 upregulated). Pathway analysis demonstrated early SARS-CoV-2 infection is associated with local suppression of oral type I/III interferon and blunted natural killer–/T-cell responses, reflecting a potential novel immune-evasion strategy enabling infection. This virus-associated immune suppression occurred concomitantly with significant upregulation of proinflammatory pathways including marked increases in the acute phase proteins pentraxin-3 and chitinase-3-like-1. Irrespective of SARS-CoV-2 infection, prior vaccination was associated with increased total α-SARS-CoV-2-spike (trimer), -S1 protein, -RBD, and -nucleocapsid salivary antibodies, highlighting the importance of COVID-19 vaccination in eliciting mucosal responses. Altogether, our findings highlight saliva as a stable and accessible biofluid for monitoring host responses to SARS-CoV-2 over time and suggest that oral-mucosal immune dysregulation is a hallmark of early SARS-CoV-2 infection, with possible implications for viral evasion mechanisms.
组织特异性免疫反应是维持健康的平衡和与疾病相关的菌群失调的关键决定因素。在 COVID-19 的背景下,口腔免疫反应反映了感染部位附近宿主-病原体的动态变化,同时也是重要的 "身体窗口",反映了对入侵的 SARS-CoV-2 病毒的全身反应。本研究利用多重技术描述了早期感染期间唾液中 SARS-CoV-2 特异性免疫景观(37 种细胞因子/凝血因子和 11 种抗体)的特征。细胞因子/免疫图谱分析是在从 227 名 SARS-CoV-2+ 成人参与者和 37 名对照者采集的未经刺激的清澈全唾液中进行的。统计分析和建模显示,25 种细胞因子的丰度存在显著差异(16 种下调,9 种上调)。通路分析表明,SARS-CoV-2 早期感染与口腔 I/III 型干扰素的局部抑制和自然杀伤-/T 细胞反应减弱有关,这反映出一种潜在的新型免疫逃避策略使感染成为可能。这种与病毒相关的免疫抑制与促炎途径的显著上调同时发生,包括急性期蛋白五肽-3 和几丁质酶-3-样-1 的显著增加。无论是否感染了 SARS-CoV-2,事先接种疫苗都会增加唾液中的α-SARS-CoV-2-穗状病毒(三聚体)、-S1 蛋白、-RBD 和-核头状病毒抗体总量,这突出了接种 COVID-19 疫苗在激发粘膜反应方面的重要性。总之,我们的研究结果表明唾液是一种稳定、易获得的生物流体,可用于监测宿主对 SARS-CoV-2 的反应,并表明口腔黏膜免疫失调是早期 SARS-CoV-2 感染的标志,可能对病毒逃避机制产生影响。
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引用次数: 0
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Journal of Dental Research
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