Archives of oral biology最新文献_第4页

Accuracy of dental age estimation methods in children with chromosomal syndromes: A systematic review and network meta-analysis 染色体综合征儿童牙龄估计方法的准确性：系统回顾和网络荟萃分析

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-11-05 DOI: 10.1016/j.archoralbio.2025.106445

Ilham Wan Mokhtar , Norsaima Ismail , Mohd Yusmiaidil Putera Mohd Yusof

Objective

The study aims to systematically examine the accuracy of the application of different dental age estimation (DAE) methods on children with chromosomal syndromes and evaluate its performance based on various populations and regions.

Design

A systematic search of the literature applying the PRISMA-NMA-compliant method was conducted using the databases PubMed, Web of Science, Science Direct, Google Scholar, and Scopus between 1981 and 2020; that estimate dental development of children with chromosomal syndrome based on populations, intervention, comparisons, and outcomes (PICO) search strategy identified. The literature quality was assessed using QUADAS-2. A network meta-analysis was performed to compare the effects of different chromosomal syndromes on the accuracy of estimated dental age (DA). Mean differences were calculated for difference of DA to chronological age (CA) by using the random effects model.

Results

From 60 titles retrieved utilising a standardized search strategy, 45 titles met the qualitative analysis criteria, and 28 titles qualified for the quantitative analysis requirements. Twenty-four comparative studies and twenty-one non-comparative studies suggested five DAE methods within this population used in combination or alone, namely Demirjian, Willems, Nolla, Haavikkoo, and London Atlas. Down’s syndrome is the highest contributing literature relating to DAE and chromosomal syndrome.

Conclusions

Underestimations were seen in Amelogenesis Imperfecta and Osteogenesis Imperfecta for Demirjian method. Other methods were lacking primary studies to make a reliable inference. This suggests that no single dental age estimation (DAE) method works consistently across diverse syndromes, emphasizing the importance of personalized approaches in clinical and forensic settings. Publication bias was minor, indicating solid findings.

目的系统考察不同牙龄估计（DAE）方法在染色体综合征患儿中应用的准确性，并基于不同人群和地区评价其效果。采用符合prisma - nma标准的方法，对1981 - 2020年PubMed、Web of Science、Science Direct、谷歌Scholar和Scopus等数据库的文献进行了系统检索；基于人群、干预、比较和结果（PICO）搜索策略来估计染色体综合征儿童的牙齿发育。采用QUADAS-2评价文献质量。进行网络荟萃分析，比较不同染色体综合征对估计牙龄（DA）准确性的影响。采用随机效应模型计算DA与实足年龄（CA）差异的均值差异。结果通过标准化检索策略检索到的60篇文献中，45篇文献符合定性分析标准，28篇文献符合定量分析要求。24项比较研究和21项非比较研究建议在该人群中联合或单独使用5种DAE方法，即Demirjian、Willems、Nolla、Haavikkoo和London Atlas。唐氏综合症是DAE和染色体综合征相关文献中贡献最大的。结论Demirjian法对无骨发育不全和成骨发育不全存在低估。其他方法缺乏初步研究，无法做出可靠的推断。这表明，没有单一的牙龄估计（DAE）方法在不同的综合征中始终有效，强调了个性化方法在临床和法医环境中的重要性。发表偏倚较小，表明研究结果可靠。

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引用次数: 0

Temporal dynamics and predictive modeling of oral epithelial dysplasia features during carcinogenesis 口腔上皮发育不良在癌变过程中的时间动态和预测模型

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-11-04 DOI: 10.1016/j.archoralbio.2025.106444

André Luis Santana de Freitas , Gustavo Guth , Anna Luíza Damaceno Araújo , Marília De Marco Pinto Paiva dos Santos , Giovana Radomille Tofoli , Aguinaldo Silva Garcez , Victor Angelo Martins Montalli , Marcelo Sperandio

Objective

To investigate the temporal evolution and predictive value of individual histopathological features of oral epithelial dysplasia (OED) during carcinogenesis, and to evaluate the diagnostic utility of optical fluorescence imaging in a murine model.

Design

A 4-nitroquinoline 1-oxide (4NQO) mouse model was used to induce oral squamous cell carcinoma (OSCC). Histological evaluation of 20 architectural and cytological OED features was performed at seven time points over 24 weeks. Data were analyzed using descriptive statistics, Spearman's correlation, logistic regression, and principal component analysis (PCA). A random forest model was developed to classify malignant transformation and evaluated using F1-score, cross-validation, ROC, and precision-recall curves. Optical fluorescence imaging was assessed for early lesion detection.

Results

Cumulative feature burden, particularly involving loss of stratification, reverse polarity, nuclear atypia, and mitotic activity, was more predictive of transformation than any single feature. PCA revealed two major axes—structural disorganization and proliferative instability. The random forest model achieved high predictive performance (F1 = 0.88, ROC-AUC = 0.97, PR-AUC = 0.98). Autofluorescence failed to improve early detection.

Conclusion

Feature accumulation is a robust predictor of OSCC risk in dysplastic lesions. Histological quantification combined with machine learning offers potential for improved prognostic modeling in oral precancer.

目的探讨口腔上皮异常增生（OED）在癌变过程中的时间演变和个体组织病理学特征的预测价值，并评价光学荧光成像在小鼠模型中的诊断价值。设计采用4-硝基喹啉- 1-氧化物（4NQO）诱导小鼠口腔鳞状细胞癌（OSCC）模型。在24周内的7个时间点对20个建筑和细胞学特征进行组织学评估。数据分析采用描述性统计、Spearman相关、逻辑回归和主成分分析（PCA）。建立随机森林模型对恶性转化进行分类，并使用f1评分、交叉验证、ROC和精确召回率曲线进行评估。评估光学荧光成像早期病变检测。结果累积的特征负担，特别是涉及分层丧失、反极性、核非典型性和有丝分裂活性，比任何单一特征更能预测转化。主成分分析显示两个主要轴-结构紊乱和增殖不稳定。随机森林模型具有较高的预测性能（F1 = 0.88,ROC-AUC = 0.97, PR-AUC = 0.98）。自体荧光未能改善早期检测。结论特征积累是发育不良病变中OSCC风险的可靠预测因子。组织学定量结合机器学习为口腔癌前病变的预后建模提供了改进的潜力。

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引用次数: 0

Extracellular vesicles derived from Filifactor alocis induce interleukin-6 production in osteoblasts via Toll-like receptor 2 signaling 细胞外囊泡来源于细丝因子alocis通过toll样受体2信号传导诱导成骨细胞产生白细胞介素-6。

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-28 DOI: 10.1016/j.archoralbio.2025.106443

Yuma Tsuruta , Tongxin Liu , Haruna Yokoi , Kentaro Maruyama , Eiji Nemoto , Takashi Nishioka , Kenji Matsushita , Hiroyuki Tada

Objective

This study aimed to investigate the effect of the periodontal bacterium Filifactor alocis on proinflammatory cytokine production by osteoblasts. Specifically, we examined the mechanisms underlying interleukin (IL)-6 production by osteoblasts stimulated with live and lyophilized F. alocis, and F. alocis-derived extracellular vesicles (EVs).

Design

MC3T3-E1 mouse osteoblasts were stimulated with live bacteria of F. alocis and, as a comparative control, P. gingivalis. Furthermore, cells were treated with F. alocis lyophilized whole cells or EVs, and IL-6 production was quantified by ELISA; cytokine expression profiled using membrane-based array; and mRNA expression analyzed by RT-qPCR. Signaling pathways were analyzed using specific inhibitors. Statistical analyses were performed using non-parametric tests with significance set at p < 0.05.

Results

F. alocis live bacteria, lyophilized whole cells, and F. alocis-derived EVs induced IL-6, leukemia inhibitory factor, and chemokines in MC3T3-E1 cells. Mechanistically, IL-6 production by F. alocis involved osteoblast activation via Toll-like receptor (TLR) 2 on the bacterial surface or released EVs. Lyophilized F. alocis induced IκB-ζ mRNA expression in osteoblasts. Moreover, F. alocis-derived EVs induced IL-6 production in osteoblasts via protein kinase C (PKC).

Conclusions

Live and lyophilized F. alocis and F. alocis-derived EVs induce the production of proinflammatory cytokines by osteoblasts, including IL-6. Additionally, the induction of IL-6 by F. alocis-derived EVs involves the activation of TLR2 and PKC. Conclusively, these findings suggest that F. alocis-induced cytokine production by osteoblasts may induce osteoclast differentiation, highlighting its role in the pathogenesis of periodontitis.

目的：探讨牙周细菌嗜酸丝状因子对成骨细胞产生促炎细胞因子的影响。具体来说，我们研究了活的和冻干的F. alocis以及F. alocis衍生的细胞外囊泡（EVs）刺激成骨细胞产生白细胞介素(IL)-6的机制。设计：用alocis活菌刺激MC3T3-E1小鼠成骨细胞，并以牙龈假单胞菌作为对照。用冻干的alocis全细胞或ev处理细胞，ELISA法测定IL-6的产量；基于膜的细胞因子表达谱分析RT-qPCR分析mRNA表达情况。使用特定抑制剂分析信号通路。结果：F. alocis活菌、冻干全细胞和F. alocis衍生的ev可诱导MC3T3-E1细胞中的IL-6、白血病抑制因子和趋化因子。从机制上讲，F. alocis产生IL-6涉及通过细菌表面的toll样受体（TLR） 2激活成骨细胞或释放ev。冻干F. alocis诱导成骨细胞i - κ b -ζ mRNA表达。此外，F. alocis衍生的ev通过蛋白激酶C （PKC）诱导成骨细胞产生IL-6。结论：活的和冻干的F. alocis和F. alocis衍生的EVs诱导成骨细胞产生促炎细胞因子，包括IL-6。此外，F. alocis衍生的ev诱导IL-6涉及TLR2和PKC的激活。总之，这些发现表明，F. alocis诱导的成骨细胞产生的细胞因子可能诱导破骨细胞分化，突出了其在牙周炎发病机制中的作用。

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引用次数: 0

Novel missense mutations in the tumor necrosis factor domain of Ectodysplasin-A cause non-syndromic tooth agenesis in two Chinese families

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-27 DOI: 10.1016/j.archoralbio.2025.106441

Chengcan Yang , Nuo Xu , Xiaona Song , Kai Yang , Qian Gao

Objective

Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndromic tooth agenesis, yet their influence on non-syndromic tooth agenesis (NSTA) has not been thoroughly elucidated. This study aimed to investigate the genetic basis of NSTA and to identify pathogenic EDA mutations in two Chinese families using whole-exome sequencing, and explore the underlying mechanisms involved.

Design

Two unrelated individuals with NSTA and their families were enrolled in this study, and genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing was performed, followed by variants detection and filtering to identify pathogenic genes and mutations. The identified genetic mutations were further validated by Sanger sequencing and confirmed to be absent in 300 unrelated healthy individuals. Conservation analysis, three-dimensional (3D) modeling, and electrostatic potential calculations were conducted accordingly.

Results

We identified a novel mutation c.827 G>T (p.Arg276Leu) and a previously reported mutation c.1069 C>T (p.Arg357Trp) in the EDA gene, with the latter showing previously unreported phenotypic characteristics. Both mutations are located in the tumor necrosis factor (TNF) domain of EDA, which is crucial for binding with ectodysplasin A receptor (EDAR). Conservation analysis indicated that these mutations are evolutionarily conserved across various species. In silico predictions and 3D modeling analyses suggested that these mutations may be pathogenic, potentially due to alterations in the hydrogen bonding and electrostatic potential, thereby affecting EDA-EDAR interaction.

Conclusions

Our findings broaden the mutation spectrum of EDA gene associated with NSTA by identifying a novel mutation and provide a basis for future genetic counseling.

目的：体外发育不良蛋白a （Ectodysplasin-A， EDA）基因突变通常与综合征性牙齿发育有关，但其对非综合征性牙齿发育（NSTA）的影响尚未完全阐明。设计：本研究招募了两名无血缘关系的NSTA患者及其家人，并从外周血样本中提取基因组DNA。进行全外显子组测序，然后进行变异检测和过滤以鉴定致病基因和突变。通过Sanger测序进一步验证了所鉴定的基因突变，并证实在300名不相关的健康个体中不存在。据此进行了守恒分析、三维（3D）建模和静电势计算。结果：我们在EDA基因中发现了一个新的突变C .827 G>T （p.a g276leu）和一个先前报道的突变C .1069 C>T (p.a g357trp)，后者显示出以前未报道的表型特征。这两个突变都位于EDA的肿瘤坏死因子（TNF）结构域，该结构域对于与外胞质异常蛋白A受体（EDAR）结合至关重要。保守性分析表明，这些突变在不同物种间具有进化保守性。计算机预测和3D建模分析表明，这些突变可能是致病的，可能是由于氢键和静电势的改变，从而影响EDA-EDAR相互作用。结论：我们的发现拓宽了与NSTA相关的EDA基因的突变谱，为未来的遗传咨询提供了基础。

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引用次数: 0

NFIC activates DEPTOR and blocks mTOR signaling to inhibit glycolysis and immune escape in oral squamous cell carcinoma NFIC激活DEPTOR并阻断mTOR信号，抑制口腔鳞状细胞癌的糖酵解和免疫逃逸

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-26 DOI: 10.1016/j.archoralbio.2025.106442

Jian Xu , Mohang Sun , Xin Wang , Yuxin Zou , Lina Wang

Objective

Oral squamous cell carcinoma (OSCC) has a poor prognosis and high mortality. This study aims to investigate the potential molecular mechanisms of NFIC/DEPTOR/mTOR signaling in glycolysis and tumor immune escape in OSCC.

Design

In vitro, the effects of the NFIC/DEPTOR/mTOR axis on the proliferative capacity and apoptosis of HN30 and SCC-25 cells were investigated using colony formation assays, EdU staining, and TUNEL after lentiviral gene interference. The glycolytic activity of OSCC cells was analyzed through glucose uptake, ECAR, and lactate production. CD8⁺ T cells were co-cultured with OSCC cells to analyze the cytotoxic activity of CD8⁺ T cells. SCC-25 cells with different genetic interventions were injected subcutaneously into NOG mice to investigate the effects of NFIC/DEPTOR/mTOR on subcutaneous tumor growth, tumor microenvironment (TME) acidity, and CD8⁺ T cell infiltration and activity. ChIP-qPCR and dual-luciferase assays were used to investigate the regulatory relationship between NFIC and the DEPTOR promoter in OSCC cells.

Results

NFIC and DEPTOR were significantly downregulated in OSCC cells and tissues, accompanied by enhanced mTOR signaling. NFIC activated DEPTOR by binding to its promoter. Overexpression of either NFIC or DEPTOR significantly inhibited OSCC cell proliferation, glycolytic activity, and enhanced CD8⁺ T cell killing capacity. Similarly, they inhibited tumor growth in vivo, blocked TME acidification, and weakened tumor immune escape. Combined DEPTOR knockdown rescued the malignant progression of OSCC inhibited by NFIC overexpression.

Conclusion

NFIC mediates DEPTOR transcription to repress mTOR signaling, thereby hindering OSCC progression by suppressing cell proliferation, glycolytic activity, and CD8⁺ T cell-related immune escape.

目的口腔鳞状细胞癌（OSCC）预后差，死亡率高。本研究旨在探讨NFIC/DEPTOR/mTOR信号在OSCC糖酵解和肿瘤免疫逃逸中的潜在分子机制。在体外实验中，采用集落形成法、EdU染色法和TUNEL法研究NFIC/DEPTOR/mTOR轴对HN30和SCC-25细胞增殖能力和凋亡的影响。通过葡萄糖摄取、ECAR和乳酸生成来分析OSCC细胞的糖酵解活性。将CD8+ T细胞与OSCC细胞共培养，分析CD8+ T细胞的细胞毒活性。将不同基因干预的SCC-25细胞皮下注射到NOG小鼠体内，研究NFIC/DEPTOR/mTOR对皮下肿瘤生长、肿瘤微环境（TME）酸度、CD8+ T细胞浸润和活性的影响。采用ChIP-qPCR和双荧光素酶法研究了OSCC细胞中NFIC与DEPTOR启动子之间的调控关系。结果snfic和DEPTOR在OSCC细胞和组织中显著下调，并伴有mTOR信号增强。NFIC通过结合其启动子激活DEPTOR。过表达NFIC或DEPTOR均可显著抑制OSCC细胞增殖、糖酵解活性和增强CD8+ T细胞杀伤能力。同样，它们在体内抑制肿瘤生长，阻断TME酸化，减弱肿瘤免疫逃逸。联合敲除detor可挽救被NFIC过表达抑制的OSCC的恶性进展。结论nfic介导DEPTOR转录抑制mTOR信号，通过抑制细胞增殖、糖酵解活性和CD8+ T细胞相关免疫逃逸，从而阻碍OSCC进展。

{"title":"NFIC activates DEPTOR and blocks mTOR signaling to inhibit glycolysis and immune escape in oral squamous cell carcinoma","authors":"Jian Xu , Mohang Sun , Xin Wang , Yuxin Zou , Lina Wang","doi":"10.1016/j.archoralbio.2025.106442","DOIUrl":"10.1016/j.archoralbio.2025.106442","url":null,"abstract":"<div><h3>Objective</h3><div>Oral squamous cell carcinoma (OSCC) has a poor prognosis and high mortality. This study aims to investigate the potential molecular mechanisms of NFIC/DEPTOR/mTOR signaling in glycolysis and tumor immune escape in OSCC.</div></div><div><h3>Design</h3><div><em>In vitro</em>, the effects of the NFIC/DEPTOR/mTOR axis on the proliferative capacity and apoptosis of HN30 and SCC-25 cells were investigated using colony formation assays, EdU staining, and TUNEL after lentiviral gene interference. The glycolytic activity of OSCC cells was analyzed through glucose uptake, ECAR, and lactate production. CD8<sup>+</sup> T cells were co-cultured with OSCC cells to analyze the cytotoxic activity of CD8<sup>+</sup> T cells. SCC-25 cells with different genetic interventions were injected subcutaneously into NOG mice to investigate the effects of NFIC/DEPTOR/mTOR on subcutaneous tumor growth, tumor microenvironment (TME) acidity, and CD8<sup>+</sup> T cell infiltration and activity. ChIP-qPCR and dual-luciferase assays were used to investigate the regulatory relationship between NFIC and the DEPTOR promoter in OSCC cells.</div></div><div><h3>Results</h3><div>NFIC and DEPTOR were significantly downregulated in OSCC cells and tissues, accompanied by enhanced mTOR signaling. NFIC activated DEPTOR by binding to its promoter. Overexpression of either NFIC or DEPTOR significantly inhibited OSCC cell proliferation, glycolytic activity, and enhanced CD8<sup>+</sup> T cell killing capacity. Similarly, they inhibited tumor growth <em>in vivo</em>, blocked TME acidification, and weakened tumor immune escape. Combined DEPTOR knockdown rescued the malignant progression of OSCC inhibited by NFIC overexpression.</div></div><div><h3>Conclusion</h3><div>NFIC mediates DEPTOR transcription to repress mTOR signaling, thereby hindering OSCC progression by suppressing cell proliferation, glycolytic activity, and CD8<sup>+</sup> T cell-related immune escape.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106442"},"PeriodicalIF":2.1,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Gingival crevicular fluid levels of soluble triggering receptor expressed on myeloid cells 1 in chronic periodontitis: A systematic review and meta-analysis 慢性牙周炎患者龈沟液中髓样细胞1可溶性触发受体表达水平的系统回顾和荟萃分析

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-25 DOI: 10.1016/j.archoralbio.2025.106440

Jingsong Kong, Weiqiu Jin, Min Wang, Fuhua Yan , Yanfen Li

Objectives

To compare gingival crevicular fluid (GCF) levels of soluble Triggering Receptor Expressed on Myeloid cells 1 (sTREM-1) between patients with chronic periodontitis (CP) and those with healthy periodontal (HP) status, and evaluate its predictive value for periodontal disease progression.

Design

Systematic review and meta-analysis.

Data sources

PubMed, MEDLINE, Cochrane, Web of Science, EMBASE, CNKI, and Wanfang were searched through December 2024. Manual searches were performed.

Eligibility criteria

Only studies reporting GCF sTREM-1 CP patients and HP controls were included. Clinical trials, cross-sectional, and observational studies were included.

Data extraction and synthesis

Two independent reviewers extracted data and assessed the quality. Sensitivity analyses ensured result stability. Quality assessment was performed according to the Newcastle-Ottawa Scale. Random-effects model calculated standardized mean differences (SMD)with 95 % CI via Review Manager software. Publication bias was evaluated using funnel plots and Egger's tests. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Results

Among 128 screened studies, 9 articles met eligibility criteria of the systematic review, and 6 articles (147 CP patients, 116 HP controls) were included in the meta-analysis. GCF sTREM-1 levels were higher in the CP group than HP group (SMD = 0.70;

Z

= 3.25;

P

<0.001, 95 % CI).

Conclusions

This study found higher GCF sTREM-1 levels in CP patients compared to HP controls, suggesting potential as a diagnostic marker. However, small sample sizes and methodological variability limit the findings.

PROSPERO registration number

CRD42022326022

目的：比较慢性牙周炎（CP）患者和健康牙周（HP）患者龈沟液（GCF）可溶性髓样细胞触发受体1 （sTREM-1）水平，并评估其对牙周病进展的预测价值。设计：系统回顾和荟萃分析。数据来源：PubMed， MEDLINE, Cochrane, Web of Science， EMBASE， CNKI，万方检索截止到2024年12月。执行手动搜索。入选标准：仅纳入报告GCF sTREM-1 CP患者和HP对照的研究。包括临床试验、横断面研究和观察性研究。数据提取和综合：两名独立的审稿人提取数据并评估质量。敏感性分析确保了结果的稳定性。根据纽卡斯尔-渥太华量表进行质量评估。随机效应模型通过Review Manager软件计算标准化平均差异（SMD）， 95% % CI。采用漏斗图和Egger检验评估发表偏倚。采用推荐、评估、发展和评价分级（GRADE）方法评估证据的确定性。结果：在128项筛选的研究中，9篇文章符合系统评价的资格标准，6篇文章（147例CP患者，116例HP对照）被纳入meta分析。CP组GCF sTREM-1水平高于HP组（SMD = 0.70; Z = 3.25; p）结论：本研究发现CP患者GCF sTREM-1水平高于HP对照组，提示其有作为诊断标志物的潜力。然而，小样本量和方法的可变性限制了研究结果。普洛斯彼罗注册号：CRD42022326022。

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引用次数: 0

Influence of head and neck radiotherapy doses on apical periodontitis progression: An animal-based study 头颈部放疗剂量对根尖牙周炎进展的影响：一项基于动物的研究。

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-24 DOI: 10.1016/j.archoralbio.2025.106422

Gustavo Guimarães Guerrero , Giovanna B. Minhoto , Camilla dos S. Tibúrcio-Machado , Rayana D. Khoury , Carolina O. Lima , Emmanuel J.N.L. Silva , Claudio A. Federico , Marcia C. Valera

Aim

The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats.

Methods

Forty-five animals were divided into five groups based on radiation dose and apical periodontitis induction (n = 9): AP-RT7 (irradiated with a dose of 7.5 Gy + AP); AP-RT10 (10 Gy dose + AP); AP-RT15 (15 Gy dose + AP); AP (AP without radiation), and Control (no intervention). Radiation therapy was administered on the first day of the experiment. After seven days, the apical periodontitis induction was carried out in all groups except Control. All animals were euthanized after 21 days of AP progression (day 28), and the area and volume of AP were analyzed using radiography, micro-CT, and histological analyses. Inflammation intensity and extent were assessed histologically. Statistical analysis was performed using ANOVA and Student's t test for quantitative data, and Kruskal-Wallis for ordinal data (P < 0.05).

Results

The AP-RT15 group exhibited significantly larger apical periodontitis lesions compared to the AP-RT7.5, AP-RT10, and AP groups, as demonstrated by radiographic (p < 0.05), micro-CT (p < 0.0001), and histological analyses (p < 0.0001). Histological examination further revealed a more extensive and intense inflammatory response in the AP-RT15 group (p < 0.01). Overall, radiotherapy contributed to increased apical bone resorption and exacerbated inflammation in a dose-dependent manner.

Conclusions

The progression of apical periodontitis in irradiated animals follows a dose-dependent pattern, with higher radiation doses markedly amplifying the lesion's area, volume, and inflammatory severity.

目的：本研究的目的是评估放射治疗对大鼠根尖牙周炎（AP）进展的剂量依赖性。方法：45只动物根据辐照剂量和对根尖牙周炎的诱导程度分为5组（n = 9）：AP- rt7（辐照剂量为7.5 Gy + AP）；AP- rt10(10 Gy剂量+ AP)；AP- rt15(15 Gy剂量+ AP)；AP（无放疗）和Control（无干预）。在实验的第一天进行放射治疗。7 d后，除对照组外，其余各组均行根尖牙周炎诱导。所有动物在AP进展21天后（第28天）被安乐死，并通过x线摄影、显微ct和组织学分析AP的面积和体积。用组织学方法评估炎症强度和程度。对定量数据采用方差分析和学生t检验，对有序数据采用Kruskal-Wallis检验（P ）结果：AP- rt15组与AP- rt7.5、AP- rt10和AP组相比，显示出明显更大的根尖牙周炎病变，x线摄影证实（P ）。受辐射动物的根尖牙周炎的进展遵循剂量依赖模式，较高的辐射剂量显著放大病变的面积、体积和炎症严重程度。

{"title":"Influence of head and neck radiotherapy doses on apical periodontitis progression: An animal-based study","authors":"Gustavo Guimarães Guerrero , Giovanna B. Minhoto , Camilla dos S. Tibúrcio-Machado , Rayana D. Khoury , Carolina O. Lima , Emmanuel J.N.L. Silva , Claudio A. Federico , Marcia C. Valera","doi":"10.1016/j.archoralbio.2025.106422","DOIUrl":"10.1016/j.archoralbio.2025.106422","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats.</div></div><div><h3>Methods</h3><div>Forty-five animals were divided into five groups based on radiation dose and apical periodontitis induction (n = 9): AP-RT7 (irradiated with a dose of 7.5 Gy + AP); AP-RT10 (10 Gy dose + AP); AP-RT15 (15 Gy dose + AP); AP (AP without radiation), and Control (no intervention). Radiation therapy was administered on the first day of the experiment. After seven days, the apical periodontitis induction was carried out in all groups except Control. All animals were euthanized after 21 days of AP progression (day 28), and the area and volume of AP were analyzed using radiography, micro-CT, and histological analyses. Inflammation intensity and extent were assessed histologically. Statistical analysis was performed using ANOVA and Student's t test for quantitative data, and Kruskal-Wallis for ordinal data (P < 0.05).</div></div><div><h3>Results</h3><div>The AP-RT15 group exhibited significantly larger apical periodontitis lesions compared to the AP-RT7.5, AP-RT10, and AP groups, as demonstrated by radiographic (p < 0.05), micro-CT (p < 0.0001), and histological analyses (p < 0.0001). Histological examination further revealed a more extensive and intense inflammatory response in the AP-RT15 group (p < 0.01). Overall, radiotherapy contributed to increased apical bone resorption and exacerbated inflammation in a dose-dependent manner.</div></div><div><h3>Conclusions</h3><div>The progression of apical periodontitis in irradiated animals follows a dose-dependent pattern, with higher radiation doses markedly amplifying the lesion's area, volume, and inflammatory severity.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106422"},"PeriodicalIF":2.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The microRNA-34b-3p/SOX5 axis regulates cellular activities and tumor angiogenesis in oral squamous cell carcinoma microRNA-34b-3p/SOX5轴调控口腔鳞状细胞癌的细胞活性和肿瘤血管生成

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-22 DOI: 10.1016/j.archoralbio.2025.106438

Mingke Huang , Yu Ren , Jiwen Zheng , Yang Cao , Yu Zhu , Jun Zhou , Zhuo Ling , Guoyu Xiong , Hangyu Zhou

Objective

This study aimed to ascertain the significance of microRNA-34b-3p (miR-34b-3p) in the prognosis and tumor angiogenesis associated with the development of oral squamous cell carcinoma (OSCC).

Design

The relative abundances of miR-34b-3p and tumor angiogenesis-associated genes were quantified using quantitative real-time polymerase chain reaction. Cellular events were monitored using the Cell Counting Kit-8 and Transwell assays. Additionally, a luciferase reporter assay was carried out to verify the interaction between miR-34b-3p and Sex Determining Region Y-box Protein 5 (SOX5).

Results

MiR-34b-3p was significantly decreased in tissue samples from OSCC patients in comparison to healthy individuals (P < 0.001) and displayed a robust diagnostic accuracy in distinguishing OSCC patients from healthy controls. Moreover, OSCC patients expressing low miR-34b-3p levels displayed a short overall survival time (P = 0.002). Additionally, low miR-34b-3p expression was an independent predictor for the clinical outcome of OSCC patients (P = 0.011, HR=0.447, 95 %CI=0.239–0.834). Through biological experiments, downregulation of miR-34b-3p could promote cell proliferation, migration and invasion of OSCC cells. Notably, following transfection miR-34b-3p inhibitor, VEGFA and MMP9 mRNA expressions were dramatically enhanced (P < 0.001). SOX5 was identified as a potential target of miR-34b-3p. Recovery experiments verified that the knockdown of SOX5 counteracted the impacts of miR-34b-3p on cellular activities and angiogenesis.

Conclusions

Downregulated miR-34b-3p expression promoted OSCC progression by enhancing cellular activities and upregulating the expression of pro-angiogenic factors via targeting SOX5.

目的探讨microRNA-34b-3p （miR-34b-3p）在口腔鳞状细胞癌（OSCC）预后及肿瘤血管生成中的意义。设计采用实时定量聚合酶链反应定量检测miR-34b-3p和肿瘤血管生成相关基因的相对丰度。使用细胞计数试剂盒-8和Transwell法监测细胞事件。此外，我们还进行了荧光素酶报告试验，以验证miR-34b-3p与性别决定区Y-box蛋白5 （SOX5）之间的相互作用。结果与健康人群相比，OSCC患者组织样本中的smir -34b-3p显著降低（P <； 0.001），并且在区分OSCC患者和健康对照组方面显示出强大的诊断准确性。此外，表达低miR-34b-3p水平的OSCC患者总体生存时间较短（P = 0.002）。此外，miR-34b-3p低表达是OSCC患者临床结局的独立预测因子（P = 0.011，HR=0.447, 95 %CI= 0.239-0.834）。生物学实验表明，下调miR-34b-3p可促进OSCC细胞的增殖、迁移和侵袭。值得注意的是，转染miR-34b-3p抑制剂后，VEGFA和MMP9 mRNA的表达显著增强（P <； 0.001）。SOX5被确定为miR-34b-3p的潜在靶标。恢复实验证实，SOX5的敲低抵消了miR-34b-3p对细胞活性和血管生成的影响。结论miR-34b-3p表达下调可通过靶向SOX5增强细胞活性，上调促血管生成因子的表达，从而促进OSCC的进展。

{"title":"The microRNA-34b-3p/SOX5 axis regulates cellular activities and tumor angiogenesis in oral squamous cell carcinoma","authors":"Mingke Huang , Yu Ren , Jiwen Zheng , Yang Cao , Yu Zhu , Jun Zhou , Zhuo Ling , Guoyu Xiong , Hangyu Zhou","doi":"10.1016/j.archoralbio.2025.106438","DOIUrl":"10.1016/j.archoralbio.2025.106438","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to ascertain the significance of microRNA-34b-3p (miR-34b-3p) in the prognosis and tumor angiogenesis associated with the development of oral squamous cell carcinoma (OSCC).</div></div><div><h3>Design</h3><div>The relative abundances of miR-34b-3p and tumor angiogenesis-associated genes were quantified using quantitative real-time polymerase chain reaction. Cellular events were monitored using the Cell Counting Kit-8 and Transwell assays. Additionally, a luciferase reporter assay was carried out to verify the interaction between miR-34b-3p and Sex Determining Region Y-box Protein 5 (SOX5).</div></div><div><h3>Results</h3><div>MiR-34b-3p was significantly decreased in tissue samples from OSCC patients in comparison to healthy individuals (<em>P</em> < 0.001) and displayed a robust diagnostic accuracy in distinguishing OSCC patients from healthy controls. Moreover, OSCC patients expressing low miR-34b-3p levels displayed a short overall survival time (<em>P</em> = 0.002). Additionally, low miR-34b-3p expression was an independent predictor for the clinical outcome of OSCC patients (<em>P</em> = 0.011, HR=0.447, 95 %CI=0.239–0.834). Through biological experiments, downregulation of miR-34b-3p could promote cell proliferation, migration and invasion of OSCC cells. Notably, following transfection miR-34b-3p inhibitor, VEGFA and MMP9 mRNA expressions were dramatically enhanced (<em>P</em> < 0.001). SOX5 was identified as a potential target of miR-34b-3p. Recovery experiments verified that the knockdown of SOX5 counteracted the impacts of miR-34b-3p on cellular activities and angiogenesis.</div></div><div><h3>Conclusions</h3><div>Downregulated miR-34b-3p expression promoted OSCC progression by enhancing cellular activities and upregulating the expression of pro-angiogenic factors via targeting SOX5.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106438"},"PeriodicalIF":2.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

MIR375 hypermethylation as a prognostic predictor for head and neck squamous cell carcinoma: Insights from The Cancer Genome Atlas (TCGA) MIR375高甲基化作为头颈部鳞状细胞癌的预后预测因子：来自癌症基因组图谱（TCGA）的见解

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-22 DOI: 10.1016/j.archoralbio.2025.106437

Ana Carolina da Silva Lima , Ileana Gabriela Sanghez de Rubió , Shuting Lin , Carla M. Prado , Peng Qiu , Maria Aderuza Horst

Objective

To conduct exploratory bioinformatics analyses of the potential prognostic value of DNA methylation patterns in MIR375 regulatory regions and of expression levels of its encoded microRNA, hsa‑miR‑375 (miR-375), in head and neck squamous cell carcinoma (HNSCC).

Design

Data from 490 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA), 50 of which were paired non-tumor surgical margins. Clinicopathological data, DNA methylation data from regions associated with MIR375, and miR-375 expression data were analyzed. Kaplan-Meier curves and Cox regression analyses were used to determine overall survival (OS) and disease-free survival (DFS) at 5 years in each group.

Results

Differentially methylated regions were associated with miR-375 expression in HNSCC. Specially, hypermethylation in N shore region was independently associated with poor OS and DFS. After adjusting for methylation patterns in other regions and miR-375 expression, these associations remained significant. DFS was also associated with methylation patterns in the enhancer region. After adjusting for confounding factors (the most robust model), hypermethylation in the N shore region was found to be an unfavorable predictor of OS and DFS. Clinicopathological and lifestyle factors also influenced the OS and DFS rates.

Conclusions

Methylation in DNA regions that may influence MIR375 transcription can be considered as predictors of OS and DFS in HNSCC, particularly those in the N shore region. This region should be a target for future investigations into MIR375 methylation pattern and its role in modulating miR-375 expression in HNSCC.

目的：对头颈部鳞状细胞癌（HNSCC）中MIR375调控区DNA甲基化模式及其编码的microRNA hsa‑miR‑375 （miR-375）表达水平的潜在预后价值进行探索性生物信息学分析。设计：490例HNSCC样本的数据来自癌症基因组图谱（TCGA），其中50例是配对的非肿瘤手术切缘。分析临床病理数据、MIR375相关区域的DNA甲基化数据和miR-375表达数据。采用Kaplan-Meier曲线和Cox回归分析确定各组5年总生存期（OS）和无病生存期（DFS）。结果：HNSCC中差异甲基化区域与miR-375表达相关。特别是，N岸区高甲基化与较差的OS和DFS独立相关。在调整了其他区域的甲基化模式和miR-375表达后，这些关联仍然显著。DFS还与增强子区域的甲基化模式有关。在调整了混杂因素（最稳健的模型）后，发现N岸区域的高甲基化是OS和DFS的不利预测因子。临床病理和生活方式因素也影响OS和DFS率。结论：可能影响MIR375转录的DNA区域甲基化可以被认为是HNSCC中OS和DFS的预测因素，特别是在N岸地区。该区域应该成为未来研究MIR375甲基化模式及其在HNSCC中调节miR-375表达中的作用的目标。

{"title":"MIR375 hypermethylation as a prognostic predictor for head and neck squamous cell carcinoma: Insights from The Cancer Genome Atlas (TCGA)","authors":"Ana Carolina da Silva Lima , Ileana Gabriela Sanghez de Rubió , Shuting Lin , Carla M. Prado , Peng Qiu , Maria Aderuza Horst","doi":"10.1016/j.archoralbio.2025.106437","DOIUrl":"10.1016/j.archoralbio.2025.106437","url":null,"abstract":"<div><h3>Objective</h3><div>To conduct exploratory bioinformatics analyses of the potential prognostic value of DNA methylation patterns in <em>MIR375</em> regulatory regions and of expression levels of its encoded microRNA, hsa‑miR‑375 (miR-375), in head and neck squamous cell carcinoma (HNSCC).</div></div><div><h3>Design</h3><div>Data from 490 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA), 50 of which were paired non-tumor surgical margins. Clinicopathological data, DNA methylation data from regions associated with <em>MIR375</em>, and miR-375 expression data were analyzed. Kaplan-Meier curves and Cox regression analyses were used to determine overall survival (OS) and disease-free survival (DFS) at 5 years in each group.</div></div><div><h3>Results</h3><div>Differentially methylated regions were associated with miR-375 expression in HNSCC. Specially, hypermethylation in N shore region was independently associated with poor OS and DFS. After adjusting for methylation patterns in other regions and miR-375 expression, these associations remained significant. DFS was also associated with methylation patterns in the enhancer region. After adjusting for confounding factors (the most robust model), hypermethylation in the N shore region was found to be an unfavorable predictor of OS and DFS. Clinicopathological and lifestyle factors also influenced the OS and DFS rates.</div></div><div><h3>Conclusions</h3><div>Methylation in DNA regions that may influence <em>MIR375</em> transcription can be considered as predictors of OS and DFS in HNSCC, particularly those in the N shore region. This region should be a target for future investigations into <em>MIR375</em> methylation pattern and its role in modulating miR-375 expression in HNSCC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106437"},"PeriodicalIF":2.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Traditional Chinese medicine Pudilan synergizes with smc gene to impair cell growth and exopolysaccharides synthesis of Streptococcus mutans 中药蒲地兰与smc基因协同作用抑制变形链球菌细胞生长和胞外多糖合成。

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology

Pub Date : 2025-10-22 DOI: 10.1016/j.archoralbio.2025.106439

Hongyu Zhang, Yiting Cheng, Yalan Deng, Yingming Yang, Lei Lei, Tao Hu

Objective

This study examines the impact of Pudilan mouthwash in conjunction with the smc gene of Streptococcus mutans (S. mutans) on biofilm formation.

Design

We constructed the smc gene null mutant strains of S. mutans (Δsmc) via homologous recombination, and overexpression strains (smc^OE) and complementary strains (smc^Comp) through chemical transformation of smc recombinant plasmid. We then tested Pudilan's MIC and MBC on UA159 parent strains and smc mutants. Growth curves were used to analyze growth rates. Bacterial viability was assessed with Live/Dead Staining. Biofilm formation and structure were examined using crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy. Genes involved in exopolysaccharides (EPS) metabolism were quantified by qRT-PCR. Network pharmacology built a compound-target network, and molecular docking studied interactions between Pudilan's components and S. mutans proteins.

Results

The combination of Pudilan and knockout of smc gene exhibited a synergistic antibacterial effect on S. mutans. Results indicated that this pairing effectively inhibited the growth and viability of S. mutans, reduced biofilm biomass, and rearranged the structure of 8-hour and 24-hour biofilms. Additionally, Pudilan treatment downregulated gene expression related to water-soluble glucan in Δsmc. Compounds like (S)-cheilanthifoline in Pudilan may significantly influence dental plaque development by modulating GtfD activity.

Conclusions

This finding demonstrates that Pudilan enhances the inhibitory effect caused by smc deletion on S. mutans growth and viability, reduces biofilm EPS, and downregulates the expression of genes involved in water-soluble glucan synthesis.

目的：研究蒲地兰漱口水联合突变链球菌smc基因对生物膜形成的影响。设计：通过同源重组构建S. mutans的smc基因零突变株（Δsmc），通过smc重组质粒化学转化构建过表达株（smc^OE）和互补株（smc^Comp）。然后对UA159亲本株和smc突变株进行了Pudilan的MIC和MBC检测。生长曲线用于分析生长速率。采用活/死染色法评估细菌活力。采用结晶紫染色、激光共聚焦扫描显微镜和扫描电镜观察生物膜的形成和结构。采用qRT-PCR技术对外多糖（EPS）代谢相关基因进行定量分析。网络药理学构建化合物-靶点网络，分子对接研究蒲地兰成分与变形链球菌蛋白的相互作用。结果：蒲地兰联合敲除smc基因对变形链球菌具有协同抑菌作用。结果表明，这种配对有效抑制了变形链球菌的生长和生存能力，减少了生物膜的生物量，并重新排列了8小时和24小时生物膜的结构。此外，蒲地兰处理下调了Δsmc中水溶性葡聚糖相关基因的表达。蒲地兰中的(S)-cheilanthifoline等化合物可能通过调节GtfD活性显著影响牙菌斑的形成。结论：蒲地兰增强了smc缺失对变形链球菌生长和活力的抑制作用，降低了生物膜EPS，下调了水溶性葡聚糖合成相关基因的表达。

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引用次数: 0