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The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials. 牙间质干细胞在人类临床试验中的治疗用途。
Pub Date : 2024-11-01 Epub Date: 2024-10-06 DOI: 10.1177/00220345241261900
S Ivanovski, P Han, O A Peters, M Sanz, P M Bartold

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.

间充质干细胞(MSCs)具有未分化和多潜能的特点,可从骨髓、脂肪和牙科组织等各种来源获得。其中,牙科间充质干细胞(DSCs)具有间充质干细胞的普遍特征,在再生口腔和颅面组织方面备受关注。本综述概述了近期发表的将 DSCs 用于各种口腔和颌面部再生应用(包括骨、牙周和牙髓再生)的临床研究。报告还探讨了利用 DSCs 治疗全身性疾病的情况,例如 DSCs 在治疗 COVID-19 和骨关节炎等疾病中的应用。现有证据强调了DSCs及其分泌组作为再生医学有效工具在牙科和非牙科临床应用中的潜力,支持了干细胞疗法的持续前景。然而,很明显,有一些重要的挑战限制了干细胞的广泛应用,即自体制备难以标准化、细胞表面标记表征不足、生产成本高以及监管合规要求。此外,牙科应用的独特要求,特别是牙周等复杂结构,需要对愈合过程进行时间空间控制,因此必须根据组织工程学原理,将干细胞与适当的支架相结合。目前还没有足够的证据支持将干细胞转化为临床实践,需要进行第三阶段临床试验,并制定细胞来源、繁殖、剂量和输送的标准化方案,以推动该领域的发展。总之,这篇综述概述了干细胞疗法不断发展的现状,深入分析了最新的发展和趋势,以及广泛应用以DSC为基础的细胞疗法需要应对的挑战。
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引用次数: 0
Genetically Supported Drug Targets and Dental Traits: A Mendelian Randomization Study. 基因支持药物靶点与牙齿特征:孟德尔随机化研究。
Pub Date : 2024-11-01 Epub Date: 2024-10-06 DOI: 10.1177/00220345241272045
L Liu, T Wang, C Duan, S Mao, B Wu, Y Chen, D Huang, Y Cao

Current interventions for oral/dental diseases heavily rely on operative/surgical procedures, while the discovery of novel drug targets may enable access to noninvasive pharmacotherapy. Therefore, this study aims to leverage large-scale data and Mendelian randomization (MR) techniques, utilizing genetic variants as instruments, to identify potential therapeutic targets for oral and dental diseases supported by genetic evidence. By intersecting 4,302 druggable genes with expression quantitative trait loci from 31,684 blood samples, we identified 2,580 druggable targets as exposures. Single nucleotide polymorphisms associated with dental disease/symptom traits were collected from FinnGen R9, the Gene-Lifestyle Interactions in Dental Endpoints consortium, and the UK Biobank to serve as outcomes for both discovery and replication purposes. Through MR analysis, we identified 43 druggable targets for various dental disease/symptom traits. To evaluate the viability of these targets, we replicated the analysis using circulating protein quantitative trait loci as exposures. Additionally, we conducted sensitivity, colocalization, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotation, protein-protein interaction analyses, and validated dental trait-associated druggable gene expression in animal models. Among these targets, IL12RB1 (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01-1.01) and TNF (OR, 0.98; 95% CI, 0.97-0.99) exhibited therapeutic promise for oral ulcers, whereas CXCL10 (OR, 0.84; 95% CI, 0.76-0.91) was for periodontitis. Through a rigorous quality control and validation pipeline, our study yields compelling evidence for these druggable targets, which may enhance the clinical prognosis by developing novel drugs or repurposing existing ones.

目前对口腔/牙科疾病的干预在很大程度上依赖于手术/外科手术,而新型药物靶点的发现则可能使人们获得非侵入性的药物治疗。因此,本研究旨在利用大规模数据和孟德尔随机化(Mendelian randomization,MR)技术,以基因变异为工具,找出有基因证据支持的口腔和牙科疾病潜在治疗靶点。通过将 31,684 份血液样本中的 4,302 个可用药基因与表达定量性状位点相交叉,我们确定了 2,580 个可用药靶点作为暴露因子。与牙科疾病/症状特征相关的单核苷酸多态性是从 FinnGen R9、牙科终点基因与生活方式相互作用联盟和英国生物库中收集的,作为发现和复制的结果。通过磁共振分析,我们确定了 43 个可用于治疗各种牙科疾病/症状特征的靶点。为了评估这些靶点的可行性,我们使用循环蛋白定量性状位点作为暴露因子进行了重复分析。此外,我们还进行了灵敏度、共定位、基因本体/京都基因和基因组百科全书注释、蛋白-蛋白相互作用分析,并在动物模型中验证了与牙齿性状相关的可药用基因的表达。在这些靶点中,IL12RB1(几率比 [OR],1.01;95% 置信区间 [CI],1.01-1.01)和 TNF(OR,0.98;95% CI,0.97-0.99)对口腔溃疡有治疗前景,而 CXCL10(OR,0.84;95% CI,0.76-0.91)则对牙周炎有治疗前景。通过严格的质量控制和验证流程,我们的研究为这些可药用靶点提供了令人信服的证据,这些靶点可通过开发新型药物或重新利用现有药物来改善临床预后。
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引用次数: 0
A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia. 预测口腔白斑病上皮发育不良的深度学习系统
Pub Date : 2024-11-01 Epub Date: 2024-10-09 DOI: 10.1177/00220345241272048
J Adeoye, A Chaurasia, A Akinshipo, I K Suleiman, L-W Zheng, A W I Lo, J J Pu, S Bello, F O Oginni, E T Agho, R O Braimah, Y X Su

Oral leukoplakia (OL) has an inherent disposition to develop oral cancer. OL with epithelial dysplasia (OED) is significantly likely to undergo malignant transformation; however, routine OED assessment is invasive and challenging. This study investigated whether a deep learning (DL) model can predict dysplasia probability among patients with leukoplakia using oral photographs. In addition, we assessed the performance of the DL model in comparison with clinicians' ratings and in providing decision support on dysplasia assessment. Retrospective images of leukoplakia taken before biopsy/histopathology were obtained to construct the DL model (n = 2,073). OED status following histopathology was used as the gold standard for all images. We first developed, fine-tuned, and internally validated a DL architecture with an EfficientNet-B2 backbone that outputs the predicted probability of OED, OED status, and regions-of-interest heat maps. Then, we tested the performance of the DL model on a temporal cohort before geographical validation. We also assessed the model's performance at external validation with opinions provided by human raters on OED status. Performance evaluation included discrimination, calibration, and potential net benefit. The DL model achieved good Brier scores, areas under the curve, and balanced accuracies of 0.124 (0.079-0.169), 0.882 (0.838-0.926), and 81.8% (76.5-87.1) at testing and 0.146 (0.112-0.18), 0.828 (0.792-0.864), and 76.4% (72.3-80.5) at external validation, respectively. In addition, the model had a higher potential net benefit in selecting patients with OL for biopsy/histopathology during OED assessment than when biopsies were performed for all patients. External validation also showed that the DL model had better accuracy than 92.3% (24/26) of human raters in classifying the OED status of leukoplakia from oral images (balanced accuracy: 54.8%-79.7%). Overall, the photograph-based intelligent model can predict OED probability and status in leukoplakia with good calibration and discrimination, which shows potential for decision support to select patients for biopsy/histopathology, obviate unnecessary biopsy, and assist in patient self-monitoring.

口腔白斑病(OL)具有发展成口腔癌的固有倾向。上皮发育不良(OED)的口腔白斑发生恶性转化的可能性很大;然而,常规的 OED 评估具有侵入性和挑战性。本研究探讨了深度学习(DL)模型能否利用口腔照片预测白斑病患者的发育不良概率。此外,我们还评估了深度学习模型与临床医生评分的比较以及在提供发育不良评估决策支持方面的性能。我们获取了活检/组织病理学检查前拍摄的白斑病回顾性图像来构建 DL 模型(n = 2,073)。组织病理学检查后的 OED 状态被用作所有图像的金标准。我们首先开发、微调并在内部验证了带有 EfficientNet-B2 主干网的 DL 架构,该架构可输出 OED 预测概率、OED 状态和感兴趣区热图。然后,我们在地理验证之前,在一个时间群组上测试了 DL 模型的性能。我们还利用人类评分者提供的关于 OED 状态的意见评估了该模型的外部验证性能。性能评估包括判别、校准和潜在净效益。DL 模型的 Brier 分数、曲线下面积和平衡准确度都很高,测试结果分别为 0.124 (0.079-0.169)、0.882 (0.838-0.926) 和 81.8% (76.5-87.1),外部验证结果分别为 0.146 (0.112-0.18)、0.828 (0.792-0.864) 和 76.4% (72.3-80.5)。此外,与对所有患者进行活检相比,该模型在OED评估期间选择OL患者进行活检/组织病理学检查的潜在净收益更高。外部验证还表明,在根据口腔图像对白斑病的 OED 状态进行分类时,DL 模型的准确率高于 92.3%(24/26)的人类评分员(平衡准确率:54.8%-79.7%)。总之,基于照片的智能模型可以预测白斑病的 OED 概率和状态,并具有良好的校准和辨别能力,在选择患者进行活检/组织病理学检查、避免不必要的活检以及协助患者进行自我监测等方面具有决策支持的潜力。
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引用次数: 0
Oral Health Research in the WHO African Region between 2011 and 2022: A Scoping Review. 2011 至 2022 年世界卫生组织非洲地区口腔健康研究:范围界定审查。
Pub Date : 2024-11-01 Epub Date: 2024-10-29 DOI: 10.1177/00220345241272024
T F Labarca, D Ortuño, L Neira, G Andrade, F J Bravo, C R Cantarutti, M Dallaserra, A Gatarayiha, J Karajgikar, R J Kulchar, X Liu, C C Martins-Pfeifer, N Olivares, L Pilcher, S Pahlke, C Pirela, J M Sanchez, A Song, O Urquhart, J P Vargas, C Véliz, F Verdugo-Paiva, P Vergara, V Zaffiri, J Zuñiga, Y Makino, M Glick, A Carrasco-Labra

The status of oral health research in the World Health Organization (WHO) African region is unclear, yet the need for such information is central to moving an oral health agenda forward. Such an agenda is essential for effectively translating research into actionable practices and supporting regional strategies. The aim of this scoping review was to provide data on the scope and output of oral health research in the WHO African region to be used as a starting point for establishing a research agenda that can affect oral health in the region. We conducted a systematic search in PubMed; EMBASE; Epistemonikos; Scopus; the International Association for Dental, Oral, and Craniofacial Research General and Regional Sessions; ProQUEST; PROSPERO; and African regional databases such as Regional African Index Medicus and the African Journal Online. We included primary and secondary studies published in English, French, or Portuguese between January 1, 2011, and December 31, 2022, addressing oral health-related research having individuals, groups, or populations as units of analysis. These reports either addressed a topic relevant to the WHO African region assessed using the title and study objective or were conducted in a country in the region. We excluded in vitro and in vivo studies focusing on cells, biomarkers, or animals. We assessed 24,014 records, and 1,379 proved eligible. Our findings indicate a preference for particular research designs less suitable for evidence-informed practice guidelines and oral policies, a limited scope of oral health research topics, and important regional differences in research capacity. Furthermore, publications by researchers in the WHO African region tend to be published in journals with a limited readership. A discussion of our findings among oral health researchers at academic institutions in the WHO African region on how to create within- and across-country collaborations could potentially improve both health and oral health in the region.

世界卫生组织(WHO)非洲地区的口腔健康研究状况尚不清楚,但需要此类信息对于推进口腔健康议程至关重要。这种议程对于有效地将研究成果转化为可操作的实践和支持区域战略至关重要。本次范围界定综述的目的是提供世界卫生组织非洲地区口腔健康研究的范围和成果数据,并以此为起点制定能够影响该地区口腔健康的研究议程。我们在 PubMed、EMBASE、Epistemonikos、Scopus、国际牙科、口腔和颅面研究协会大会和地区会议、ProQUEST、PROSPERO 以及非洲地区 Index Medicus 和非洲期刊在线等非洲地区数据库中进行了系统检索。我们收录了 2011 年 1 月 1 日至 2022 年 12 月 31 日期间以英语、法语或葡萄牙语发表的主要和次要研究报告,这些报告涉及以个人、群体或人口为分析单位的口腔健康相关研究。这些报告要么涉及与世界卫生组织非洲地区相关的主题,使用标题和研究目标进行评估,要么是在该地区的某个国家进行的。我们排除了以细胞、生物标记物或动物为重点的体外和体内研究。我们评估了 24,014 条记录,其中 1,379 条符合条件。我们的研究结果表明,人们更倾向于特定的研究设计,而不太适合循证实践指南和口腔政策,口腔健康研究课题的范围有限,而且研究能力存在重大地区差异。此外,世卫组织非洲地区研究人员的出版物往往发表在读者群有限的期刊上。世界卫生组织非洲地区学术机构的口腔健康研究人员就我们的研究结果展开讨论,探讨如何建立国家内部和国家之间的合作,这有可能改善该地区的卫生和口腔健康状况。
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引用次数: 0
Advanced Imaging in Dental Research: From Gene Mapping to AI Global Data. 牙科研究中的先进成像技术:从基因图谱到人工智能全球数据。
Pub Date : 2024-10-27 DOI: 10.1177/00220345241293040
D T Graves, S E Uribe

Advances in imaging technologies combined with artificial intelligence (AI) are transforming dental, oral, and craniofacial research. This editorial highlights breakthroughs ranging from gene expression mapping to visualizing the availability of global AI data, providing new insights into biological complexity and clinical applications.

成像技术与人工智能(AI)的结合正在改变牙科、口腔和颅面研究。这篇社论重点介绍了从基因表达图谱到可视化全球人工智能数据等方面的突破,为生物复杂性和临床应用提供了新的见解。
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引用次数: 0
Spatial Transcriptomics Unravel the Tissue Complexity of Oral Pathogenesis. 空间转录组学揭示口腔发病的组织复杂性
Pub Date : 2024-10-09 DOI: 10.1177/00220345241271934
J Haller, N Abedi, A Hafedi, O Shehab, M S Wietecha

Spatial transcriptomics (ST) is a cutting-edge methodology that enables the simultaneous profiling of global gene expression and spatial information within histological tissue sections. Traditional transcriptomic methods lack the spatial resolution required to sufficiently examine the complex interrelationships between cellular regions in diseased and healthy tissue states. We review the general workflows for ST, from specimen processing to ST data analysis and interpretations of the ST dataset using visualizations and cell deconvolution approaches. We show how recent studies used ST to explore the development or pathogenesis of specific craniofacial regions, including the cranium, palate, salivary glands, tongue, floor of mouth, oropharynx, and periodontium. Analyses of cranial suture patency and palatal fusion during development using ST identified spatial patterns of bone morphogenetic protein in sutures and osteogenic differentiation pathways in the palate, in addition to the discovery of several genes expressed at critical locations during craniofacial development. ST of salivary glands from patients with Sjögren's disease revealed co-localization of autoimmune antigens with ductal cells and a subpopulation of acinar cells that was specifically depleted by the dysregulated autoimmune response. ST of head and neck lesions, such as premalignant leukoplakia progressing to established oral squamous cell carcinomas, oral cancers with perineural invasions, and oropharyngeal lesions associated with HPV infection spatially profiled the complex tumor microenvironment, showing functionally important gene signatures of tumor cell differentiation, invasion, and nontumor cell dysregulation within patient biopsies. ST also enabled the localization of periodontal disease-associated gene expression signatures within gingival tissues, including genes involved in inflammation, and the discovery of a fibroblast subtype mediating the transition between innate and adaptive immune responses in periodontitis. The increased use of ST, especially in conjunction with single-cell analyses, promises to improve our understandings of craniofacial development and pathogenesis at unprecedented tissue-level resolution in both space and time.

空间转录组学(ST)是一种前沿方法,可同时分析组织学切片中的全局基因表达和空间信息。传统的转录组学方法缺乏必要的空间分辨率,无法充分研究疾病和健康组织状态下细胞区域之间复杂的相互关系。我们回顾了 ST 的一般工作流程,从标本处理到 ST 数据分析,以及使用可视化和细胞解卷积方法对 ST 数据集进行解读。我们展示了最近的研究如何利用 ST 来探索特定颅面部区域的发育或发病机制,包括颅骨、腭、唾液腺、舌、口底、口咽和牙周。利用 ST 对发育过程中的颅缝通畅性和腭部融合进行分析,确定了缝中骨形态发生蛋白的空间模式和腭部的成骨分化途径,此外还发现了颅面发育过程中在关键位置表达的几个基因。对斯约格伦病患者唾液腺的 ST 发现了自身免疫抗原与导管细胞的共定位,以及因自身免疫反应失调而特异性耗竭的尖突细胞亚群。对头颈部病变(如进展为口腔鳞状细胞癌的前恶性白斑、有神经周围侵犯的口腔癌以及与人乳头瘤病毒感染相关的口咽部病变)进行的 ST 分析对复杂的肿瘤微环境进行了空间剖析,显示了患者活检组织中肿瘤细胞分化、侵袭和非肿瘤细胞失调的重要功能基因特征。ST 还能定位牙龈组织中牙周疾病相关基因的表达特征,包括参与炎症的基因,并发现了一种介导牙周炎先天性免疫反应和适应性免疫反应之间转变的成纤维细胞亚型。越来越多地使用 ST,特别是与单细胞分析相结合,有望在空间和时间上以前所未有的组织级分辨率提高我们对颅面发育和发病机制的认识。
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引用次数: 0
Recent Advances in Intraoral Scanners. 口内扫描仪的最新进展。
Pub Date : 2024-10-09 DOI: 10.1177/00220345241271937
F Eggmann, M B Blatz

Intraoral scanners (IOSs) have emerged as a cornerstone technology in digital dentistry. This article examines the recent advancements and multifaceted applications of IOSs, highlighting their benefits in patient care and addressing their current limitations. The IOS market has seen a competitive surge. Modern IOSs, featuring continuous image capture and advanced software for seamless image stitching, have made the scanning process more efficient. Patient comfort with IOS procedures is favorable, mitigating the discomfort associated with conventional impression taking. There has been a shift toward open data interfaces, notably enhancing interoperability. However, the integration of IOSs into large dental institutions is slow, facing challenges such as compatibility with existing health record systems and extensive data storage management. IOSs now extend beyond their use in computer-aided design and manufacturing, with software solutions transforming them into platforms for diagnostics, patient communication, and treatment planning. Several IOSs are equipped with tools for caries detection, employing fluorescence technologies or near-infrared imaging to identify carious lesions. IOSs facilitate quantitative monitoring of tooth wear and soft-tissue dimensions. For precise tooth segmentation in intraoral scans, essential for orthodontic applications, developers are leveraging innovative deep neural network-based approaches. The clinical performance of restorations fabricated based on intraoral scans has proven to be comparable to those obtained using conventional impressions, substantiating the reliability of IOSs in restorative dentistry. In oral and maxillofacial surgery, IOSs enhance airway safety during impression taking and aid in treating conditions such as cleft lip and palate, among other congenital craniofacial disorders, across diverse age groups. While IOSs have improved various aspects of dental care, ongoing enhancements in usability, diagnostic accuracy, and image segmentation are crucial to exploit the potential of this technology in optimizing patient care.

口内扫描仪 (IOS) 已成为数字牙科的一项基础技术。本文探讨了口内扫描仪的最新进展和多方面应用,强调了其在患者护理方面的优势,并探讨了其目前存在的局限性。IOS 市场竞争激烈。现代的 IOS 具有连续图像捕捉功能和先进的无缝图像拼接软件,使扫描过程更加高效。患者对 IOS 程序的舒适度很高,减轻了传统取模带来的不适感。目前已转向开放式数据接口,显著提高了互操作性。然而,IOS 与大型牙科机构的整合进展缓慢,面临着与现有健康记录系统的兼容性和大量数据存储管理等挑战。目前,综合观测系统已不仅仅局限于用于计算机辅助设计和制造,软件解决方案已将其转化为诊断、患者交流和治疗规划的平台。一些 IOS 配备了龋病检测工具,利用荧光技术或近红外成像技术来识别龋损。口内观察系统有助于对牙齿磨损和软组织尺寸进行定量监测。对于口内扫描中的精确牙齿分割(这对正畸应用至关重要),开发人员正在利用基于深度神经网络的创新方法。事实证明,根据口内扫描制作的修复体的临床性能可与使用传统印模获得的修复体相媲美,这证明了 IOS 在牙科修复中的可靠性。在口腔颌面外科,IOS 提高了取模过程中气道的安全性,并有助于治疗唇腭裂等不同年龄段的先天性颅面疾病。虽然 IOS 改善了牙科护理的各个方面,但要发挥这项技术在优化患者护理方面的潜力,还必须不断提高其可用性、诊断准确性和图像分割能力。
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引用次数: 0
ALKBH5 Regulates Osteogenic Differentiation via the lncRNA/mRNA Complex. ALKBH5通过lncRNA/mRNA复合物调控成骨细胞分化
Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1177/00220345241266775
Y Song, H Gao, Y Pan, Y Gu, W Sun, Y Wang, J Liu

Human adipose-derived stem cells (hASCs) are commonly used in bone tissue regeneration. The N6-methyladenosine (m6A) modification has emerged as a novel regulatory mechanism for gene expression, playing a critical role in osteogenic differentiation of stem cells. However, the precise role and mechanism of alkylation repair homolog 5 (ALKBH5) in hASC osteogenesis remain incompletely elucidated and warrant further investigation. Herein, we employed methylated RNA immunoprecipitation sequencing, RNA sequencing, and weighted gene coexpression network analysis to identify a key long noncoding RNA (lncRNA) in hASCs: lncRNA AK311120. Functional experiments demonstrated that lnc-AK311120 promoted the osteogenic differentiation of hASCs, while a mutation at the m6A central site A of lnc-AK311120 was found to decrease the level of m6A modification. The osteogenic effect of ALKBH5 was confirmed both in vitro and in vivo using a mandibular defect model in nude mice. Subsequent investigations revealed that knockdown of ALKBH5 resulted in a significant increase in the m6A modification level of lnc-AK311120, accompanied by a downregulation in the expression level of lnc-AK311120. Additional rescue experiments demonstrated that overexpression of lnc-AK311120 could restore the phenotype after ALKBH5 knockdown. We observed that AK311120 interacted with the RNA-binding proteins DExH-Box helicase 9 (DHX9) and YTH domain containing 2 (YTHDC2) to form a ternary complex, while mitogen-activated protein kinase kinase 7 (MAP2K7) served as the shared downstream target gene of DHX9 and YTHDC2. Knockdown of AK311120 led to a reduction in the binding affinity between DHX9/YTHDC2 and the target gene MAP2K7. Furthermore, ALKBH5 facilitated the translation of MAP2K7 and activated the downstream JNK signaling pathway through the AK311120-DHX9-YTHDC2 complex, without affecting its messenger RNA level. Collectively, we have investigated the regulatory effect and mechanism of ALKBH5-mediated demethylation of lncRNA in hASC osteogenesis for the first time, offering a promising approach for bone tissue engineering.

人脂肪源性干细胞(hASCs)常用于骨组织再生。N6-甲基腺苷(m6A)修饰已成为一种新的基因表达调控机制,在干细胞成骨分化过程中发挥着关键作用。然而,烷基化修复同源物5(ALKBH5)在hASC成骨过程中的确切作用和机制仍未完全阐明,值得进一步研究。在此,我们采用甲基化RNA免疫沉淀测序、RNA测序和加权基因共表达网络分析等方法,鉴定了hASCs中的一个关键长非编码RNA(lncRNA):lncRNA AK311120。功能实验证明,lnc-AK311120能促进hASCs的成骨分化,而lnc-AK311120的m6A中心位点A发生突变会降低m6A修饰水平。ALKBH5的成骨作用在体外和裸鼠下颌骨缺损模型中都得到了证实。随后的研究发现,敲除ALKBH5会导致lnc-AK311120的m6A修饰水平显著增加,同时lnc-AK311120的表达水平下调。额外的拯救实验表明,过表达lnc-AK311120可以恢复ALKBH5敲除后的表型。我们观察到,AK311120与RNA结合蛋白DExH-Box螺旋酶9(DHX9)和含YTH结构域的2(YTHDC2)相互作用形成三元复合物,而丝裂原活化蛋白激酶激酶7(MAP2K7)是DHX9和YTHDC2的共同下游靶基因。敲除 AK311120 会降低 DHX9/YTHDC2 与靶基因 MAP2K7 的结合亲和力。此外,ALKBH5 促进了 MAP2K7 的翻译,并通过 AK311120-DHX9-YTHDC2 复合物激活了下游的 JNK 信号通路,而不影响其信使 RNA 水平。综上所述,我们首次研究了ALKBH5介导的lncRNA去甲基化在hASC成骨过程中的调控作用和机制,为骨组织工程提供了一种前景广阔的方法。
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引用次数: 0
Letter to the Editor, "Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis". 致编辑的信,《斯约格伦病不是牙周炎的临床风险因素》。
Pub Date : 2024-10-01 Epub Date: 2024-09-29 DOI: 10.1177/00220345241256583
A Vissink, D J Jager, F Maarse, H Brand
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引用次数: 0
The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Manuscript Checklist. 口腔健康研究观察性研究和临床试验报告 OHStat 指南:手稿核对表。
Pub Date : 2024-10-01 Epub Date: 2024-07-12 DOI: 10.1177/00220345241247028
A M Best, T A Lang, B L Greenberg, J C Gunsolley, E Ioannidou

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.

充分而透明的报告对于批判性地评估已发表的研究是必要的。然而,大量证据表明,口腔健康研究的设计、实施、分析、解释和报告都可以大大改进。因此,口腔健康研究设计与分析工作组--来自学术界和工业界的统计学家和试验专家--确定了报告和评估口腔健康观察研究和临床试验所需的最低限度信息:OHStat 指南。草案已分发给 85 份口腔健康期刊的编辑以及特别小组成员和赞助商,并在 2020 年 12 月的研讨会上进行了讨论,49 名研究人员参加了此次研讨会。随后,工作组的写作小组对指南进行了修订。该指南在很大程度上借鉴了《试验报告统一标准》(CONSORT)、《加强流行病学观察性研究报告》(STROBE)和《CONSORT 危害指南》,并纳入了报告统计数据的 SAMPL 指南、记录图像的 CLIP 原则以及表示证据质量的 GRADE。该指南还建议使用置信区间以有临床意义的单位报告估计值,而不是依赖 P 值。此外,OHStat 还引入了 7 项与文本本身有关的新指南,如检查摘要与文本之间的一致性、安排讨论的结构、列出结论使其更具体等。OHStat并不取代其他报告指南,而是将与口腔医学研究最相关的指南整合到一份文件中。使用OHStat指南的手稿将提供更多与口腔健康研究相关的信息。
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引用次数: 0
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Journal of dental research
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