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Expert consensus on irrigation and intracanal medication in root canal therapy 根管治疗中的灌洗和根管内用药专家共识
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-03-01 DOI: 10.1038/s41368-024-00280-5
Xiaoying Zou, Xin Zheng, Yuhong Liang, Chengfei Zhang, Bing Fan, Jingping Liang, Junqi Ling, Zhuan Bian, Qing Yu, Benxiang Hou, Zhi Chen, Xi Wei, Lihong Qiu, Wenxia Chen, Wenxi He, Xin Xu, Liuyan Meng, Chen Zhang, Liming Chen, Shuli Deng, Yayan Lei, Xiaoli Xie, Xiaoyan Wang, Jinhua Yu, Jin Zhao, Song Shen, Xuedong Zhou, Lin Yue

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

化学清洗和消毒是根管治疗中消除感染的关键步骤。然而,灌洗剂的选择或灌洗程序却远未明确。根尖区的蒸汽锁效应尚未解决,阻碍了灌洗效果,导致残余感染,影响治疗效果。此外,根管用药的临床适应症不明确以及敷料方案不规范等问题也必须得到澄清。不适当的根管内用药可能会产生副作用,影响治疗效果。事实上,临床医生多年来一直意识到这些问题。根据目前的研究证据,本文回顾了各种冲洗剂和龋内药物的特性,并阐明了它们的有效性和相互作用。文章还讨论了不同动力灌洗方法的演变、其效果、局限性、范式转变、当前适应症以及有关龈内药物的有效操作程序。本专家共识旨在制定根管冲洗的临床操作指南和根管内用药的立场声明,从而促进对感染控制的更好理解,规范临床实践,最终提高根管治疗的成功率。
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引用次数: 0
Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma. 单细胞转录组学揭示了细胞图谱,并确定了导致母细胞瘤复发的循环肿瘤细胞。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-29 DOI: 10.1038/s41368-024-00281-4
Gan Xiong, Nan Xie, Min Nie, Rongsong Ling, Bokai Yun, Jiaxiang Xie, Linlin Ren, Yaqi Huang, Wenjin Wang, Chen Yi, Ming Zhang, Xiuyun Xu, Caihua Zhang, Bin Zou, Leitao Zhang, Xiqiang Liu, Hongzhang Huang, Demeng Chen, Wei Cao, Cheng Wang

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

釉母细胞瘤是一种良性肿瘤,其特点是局部侵袭性表型,导致面部骨骼破坏和高复发率。然而,人们对肿瘤发生和复发的机制知之甚少。在这里,我们以单细胞分辨率揭示了导致母细胞瘤肿瘤复发的细胞景观和机制。我们的研究结果显示,母细胞瘤表现出五个肿瘤亚群,它们在免疫反应(IR)、骨重塑(BR)、牙齿发育(TD)、上皮发育(ED)和细胞周期(CC)特征方面各不相同。值得注意的是,我们发现CC骨髓母细胞瘤细胞具有干性并导致肿瘤复发,而肿瘤复发是由EZH2介导的程序主导的。靶向 EZH2 能有效消除 CC 骨髓母细胞瘤细胞,并抑制骨髓母细胞瘤患者衍生的器官组织中的肿瘤生长。这些数据描述了肿瘤亚群,阐明了CC母细胞瘤细胞的特性、功能和调控机制,为治疗母细胞瘤提供了一个潜在的治疗靶点。
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引用次数: 0
Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss. Tim4 缺乏会减少 CD301b+ 巨噬细胞,加重牙周炎骨质流失。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-28 DOI: 10.1038/s41368-023-00270-z
Ziming Wang, Hao Zeng, Can Wang, Jiaolong Wang, Jing Zhang, Shuyuan Qu, Yue Han, Liu Yang, Yueqi Ni, Wenan Peng, Huan Liu, Hua Tang, Qin Zhao, Yufeng Zhang

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b+ macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b+ macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b+ macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b+ macrophages was significantly upregulated compared to CD301b- macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b+ macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+ macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b+ macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+ macrophages phenotype. In a word, Tim4 might regulate CD301b+ macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

牙周炎是一种常见的慢性炎症性疾病,会造成牙周骨破坏,最终可能导致牙齿脱落。随着牙周炎的发展,牙周炎的骨免疫微环境遭到破坏,导致病理性牙槽骨吸收的形成。CD301b+ 巨噬细胞是骨免疫微环境的特异性巨噬细胞,正在成为促进骨再生的重要助推器。然而,CD301b+巨噬细胞的上游关键靶点及其在牙周炎中的潜在机制仍未确定。在本研究中,我们重点研究了 CD301b+ 巨噬细胞的潜伏上游调控因子 Tim4 的作用。我们首先通过高通量 RNA 测序证明,与 CD301b- 巨噬细胞相比,CD301b+ 巨噬细胞中 Timd4(Tim4 的基因名)的转录水平显著上调。此外,CD301b+巨噬细胞还对凋亡细胞清除、吞噬和吞噬等几种与Tim4相关的功能进行了正向调节。单细胞 RNA 测序分析随后发现,Cd301b 和 Timd4 在巨噬细胞中特异性共表达。随后的流式细胞分析表明,随着牙周炎的发展,巨噬细胞总数中的 Tim4 阳性表达率与 CD301b+ 巨噬细胞的比例呈高度同步的动态变化。此外,小鼠缺乏 Tim4 会减少 CD301b+ 巨噬细胞的数量,并最终加剧牙周炎的牙槽骨吸收。此外,Tim4 还能控制 p38 MAPK 信号通路,最终介导 CD301b+ 巨噬细胞的表型。总之,Tim4可能通过p38 MAPK信号通路调控牙周炎中的CD301b+巨噬细胞,这为牙周炎的免疫调节提供了新的视角,也有助于开发创新的牙周炎治疗靶点和治疗策略。
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引用次数: 0
The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats. 磨牙中根根尖远端区域的破骨细胞活性会影响大鼠牙齿的正畸移动和牙根吸收。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-28 DOI: 10.1038/s41368-024-00284-1
Wenhao Zheng, Xiaofeng Lu, Guangjin Chen, Yufeng Shen, Xiaofei Huang, Jinfeng Peng, Jiajia Wang, Ying Yin, Wencheng Song, Mengru Xie, Shaoling Yu, Lili Chen

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.

在正畸治疗过程中,使用最佳正畸力对于防止不良副作用和确保牙齿有效移动至关重要。然而,现有检测技术的灵敏度不够,最佳力的评估标准也尚未确立。在此,通过采用三维有限元分析方法,我们发现大鼠中牙根的根尖远端区域(A-D 区域)对正畸力特别敏感。抗酒石酸磷酸酶(TRAP)阳性破骨细胞在 40 克(g)的力作用下开始在 A-D 区聚集,导致牙槽骨吸收和牙齿移动。当作用力达到 80 克时,A-D 区的牙根表面开始出现 TRAP 阳性破骨细胞。此外,显微计算机断层扫描显示 80 g 时牙根有明显的吸收。值得注意的是,A-D 区被确定为整个牙根吸收的主要区域。根据对牙齿移动、倾斜和透明化的分析,40 克是牙齿移动的最小有效力,且副作用最小。这些研究结果表明,在评估大鼠模型的正畸力时,A-D 区及其牙根表面的变化是一个重要的考虑因素和敏感指标。总之,我们对这一区域的研究将有助于在患者的正畸治疗过程中预防和减少牙根吸收。
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引用次数: 0
The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis 中性粒细胞-成骨细胞轴促进牙周炎中的骨质破坏
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-27 DOI: 10.1038/s41368-023-00275-8
Yutaro Ando, Masayuki Tsukasaki, Nam Cong-Nhat Huynh, Shizao Zang, Minglu Yan, Ryunosuke Muro, Kazutaka Nakamura, Masatsugu Komagamine, Noriko Komatsu, Kazuo Okamoto, Kenta Nakano, Tadashi Okamura, Akira Yamaguchi, Kazuyuki Ishihara, Hiroshi Takayanagi

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

免疫细胞与基质细胞之间的相互作用在健康和疾病中发挥着关键作用。牙周炎是人类最常见的传染性疾病,免疫细胞聚集在口腔黏膜中,通过诱导成骨细胞(如成骨细胞和牙周韧带细胞)中核因子κB配体受体激活剂(RANKL)的表达,促进骨质破坏。然而,牙周炎中免疫-骨细胞相互作用的详细机制尚不完全清楚。在此,我们对小鼠牙周病变进行了单细胞 RNA 序列分析,结果表明,中性粒细胞-成骨细胞串联参与了牙周炎诱导的骨质流失。牙周病灶显示出明显的中性粒细胞浸润,硅学分析表明中性粒细胞通过产生细胞因子与成骨细胞相互作用。在牙周中性粒细胞表达的细胞因子中,oncostatin M(OSM)能有效诱导原发性成骨细胞中 RANKL 的表达,而成骨细胞中 OSM 受体的缺失能显著改善牙周炎诱导的骨质流失。表观基因组数据分析确定了成骨细胞中受OSM调控的RANKL增强子区域,缺乏该增强子的小鼠在维持生理骨代谢的同时,牙周骨质流失也有所减少。这些发现揭示了细菌感染期间中性粒细胞在骨调节中的作用,凸显了骨免疫串扰的新机制。
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引用次数: 0
Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts 基于数字病理学的人工智能模型用于散发性牙源性角化囊肿的鉴别诊断和预后判断
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-26 DOI: 10.1038/s41368-024-00287-y
Xinjia Cai, Heyu Zhang, Yanjin Wang, Jianyun Zhang, Tiejun Li

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898–0.973) and prognosis (AUC = 0.840, 95%CI: 0.751–0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

牙源性角化囊肿(OKC)是一种常见的颌骨囊肿,复发率很高。OKC合并基底细胞癌以及骨骼和其他发育异常被认为与戈林综合征有关。此外,OKC 需要与正角化牙源性囊肿和其他颌骨囊肿相鉴别。由于预后不同,对几种囊肿进行鉴别诊断有助于临床治疗。我们收集了 519 个病例,共 2 157 张苏木精和伊红染色的图像,开发了基于数字病理学的人工智能(AI)模型,用于 OKC 的诊断和预后。利用 Inception_v3 神经网络来训练和测试根据斑块级图像开发的模型。最后,通过将深度学习生成的病理特征与多种机器学习算法相结合,开发出了整张切片图像级人工智能模型。这些人工智能模型在 OKC 的诊断(AUC = 0.935,95%CI:0.898-0.973)和预后(AUC = 0.840,95%CI:0.751-0.930)方面表现出色。通过与单切片模型的比较,证明了多切片模型在整合组织病理学信息方面的优势。此外,该研究还探讨了深度学习生成的人工智能特征与病理结果之间的相关性,凸显了人工智能模型在病理学领域的解释潜力。在这里,我们为 OKC 开发了稳健的诊断和预后模型。基于数字病理学的人工智能模型有望应用于颌骨牙源性疾病。
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引用次数: 0
Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis 基质凝血酶原 1 抑制口腔黏膜下纤维化的血管生成
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-26 DOI: 10.1038/s41368-024-00286-z
Xiao Yang, Hui Zhao, Rui Li, Yang Chen, Zhi Xu, Zhengjun Shang

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

口腔黏膜下纤维化(OSF)是一种主要由咀嚼槟榔诱发的恶性前疾病,其组织学特征是黏膜血管减少。然而,由于缺乏可用的模型,对 OSF 中血管生成的研究面临挑战。在这里,我们发现在 OSF 组织的基质中,内源性血管促进蛋白血栓形成蛋白 1(THBS1)的表达升高。利用成纤维细胞附着的类器官(FAO)模型,我们在体外稳定地再现了THBS1在OSF中的过表达。在 FAO 模型中,使用山苍子中的一种主要致病成分--山苍子碱处理可增强上皮细胞分泌转化生长因子 (TGF)-β1,从而促进成纤维细胞中 THBS1 的表达。此外,人脐静脉内皮细胞(HUVECs)也被加入到 FAO 中,以模拟血管成分。成纤维细胞中THBS1的过表达大大抑制了血管化FAO(vFAO)中内皮细胞的萌发能力。同样,用异甲唑啉处理会降低血管化 FAO 中 CD31 的表达,而当内皮细胞与 THBS1 受体 CD36 的中和抗体预孵育时,这种效应会减弱。最后,在arecoline诱导的大鼠OSF模型中,抑制THBS1可减轻胶原沉积和体内血管活力的下降。总之,我们利用组装的类器官模型研究了OSF的发病机制,并为靶向THBS1提供了理论依据。
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引用次数: 0
PRX1-positive mesenchymal stem cells drive molar morphogenesis. PRX1阳性间充质干细胞驱动臼齿形态发生。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-19 DOI: 10.1038/s41368-024-00277-0
Xiaoqiao Xu, Xuyan Gong, Lei Zhang, Han Zhang, Yao Sun

Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

哺乳动物牙齿的发育离不开上皮细胞和间充质细胞的相互作用,它们的形状多种多样,而影响牙齿形态的关键因素也值得探究。通过将单细胞 RNA 测序分析与品系追踪模型相结合,我们发现了小鼠臼齿的对比形态与 M1 中 PRX1+ 细胞的特异性存在之间的惊人关联。这些 PRX1+ 细胞通过牙齿间充质细胞增殖的显著分化,在塑造牙齿形态方面承担着重要责任。深入研究其机制,我们发现间质 PRX1+ 细胞赋予的 Wnt5a 可刺激间质细胞增殖,同时通过 WNT 信号通路协调磨牙的形态发生。缺失 Wnt5a 会表现出与 siPrx1 类似的缺陷表型。外源添加 WNT5A 能成功逆转 Prx1 缺失牙胚的细胞增殖受抑制以及由此产生的异常外观。这些发现有力地证明了 PRX1 阳性间充质细胞是调控牙齿形态的潜在目标。
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引用次数: 0
A novel saliva-based miRNA profile to diagnose and predict oral cancer. 基于唾液的新型 miRNA 图谱可用于诊断和预测口腔癌。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-18 DOI: 10.1038/s41368-023-00273-w
Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Gunter Hartel, Roberto A Barrero, Touraj Taheri, Liz Kenny, Sarju Vasani, Martin Batstone, Omar Breik, Chamindie Punyadeera

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n = 50), OPMD (n = 52), and controls (n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

口腔癌(OC)是最常见的头颈部癌症。尽管口腔癌发病率高,对患者的预后不利,但目前还没有用于早期检测口腔癌的生物标志物。本研究旨在发现、开发和验证一种基于唾液的新型 microRNA 标志,用于口腔潜在恶性疾病(OPMD)的早期诊断和 OC 风险预测。研究利用癌症基因组图谱(TCGA)的miRNA测序数据和唾液样本的小RNA测序数据来发现差异表达的miRNA。利用定量实时 PCR 技术在 OC(n = 50)、OPMD(n = 52)和对照组(n = 60)的唾液样本中验证了识别出的 miRNA。在发现阶段发现并验证了八个差异表达的 miRNA(miR-7-5p、miR-10b-5p、miR-182-5p、miR-215-5p、miR-431-5p、miR-486-3p、miR-3614-5p 和 miR-4707-3p)。我们的 8 个 miRNA 标志区分 OC 和对照组的效率为:曲线下面积(AUC)为 0.954,灵敏度为 86%:0.954,灵敏度:86%,特异性:90%,阳性预测值(PPV):87.8%,阴性预测值(PPV):87.8%:87.8%,阴性预测值 (NPV):88.5%:88.5%,而 OC 和 OPMD 之间的差异为AUC:灵敏度:90%,特异性:82.7%,PPV:74.2%,NPV:89.6%。我们制定了一个风险概率评分,以预测 OPMD 患者是否存在 OC 或 OC 的风险。我们建立的唾液 miRNA 特征可帮助诊断和预测 OC,从而彻底改变 OPMD 患者的治疗方法。我们的研究结果为利用唾液miRNA管理OC提供了新的思路,也为利用从唾液样本中提取的miRNA的临床实用性提供了新的思路。
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引用次数: 0
Genomic alterations in oral multiple primary cancers. 口腔多发性原发性癌症的基因组变化。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2024-02-18 DOI: 10.1038/s41368-023-00265-w
Xuan Zhou, Xinjia Cai, Fengyang Jing, Xuefen Li, Jianyun Zhang, Heyu Zhang, Tiejun Li

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

口腔鳞状细胞癌(OSCC)是口腔癌的主要类型,但也有一些患者可能患上病因不明的口腔多原发癌(MPCs)。本研究旨在探讨口腔多原发癌的临床病理特征和基因组改变。研究收集并比较了口腔单发原发性癌(SPC,n = 202)和口腔多发性原发性癌(MPCs,n = 34)患者的临床病理数据。进行了拷贝数改变(CNA)分析,以确定口腔MPC、复发性OSCC病例和淋巴结转移的OSCC患者之间的染色体不稳定性差异。采用全外显子组测序来确定口腔 MPCs 患者中潜在的独特基因突变。此外,我们还采用了CNA和系统发生树分析,以初步了解患者体内不同原发肿瘤的分子特征。我们的研究结果显示,与口腔 SPC 不同,口腔 MPCs 患者以女性为主(70.59%),而吸烟和酗酒在 MPCs 中并不常见。此外,口腔多发性骨髓瘤患者的长期生存结果较差。从CNA角度来看,口腔多发性骨髓瘤患者与复发和淋巴结转移患者之间没有明显差异。除了 CASP8、TP53 和 MUC16 等常见突变基因外,我们还在口腔 MPCs 中发现了 HS3ST6 和 RFPL4A 等相对罕见的突变基因。此外,本研究还表明,大多数口腔多发性硬化症患者的某些基因组区域在个体内部表现出相似性,而同步口腔多发性硬化症和非同步口腔多发性硬化症之间的相似程度存在明显差异。
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引用次数: 0
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International Journal of Oral Science
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