Archives of oral biology最新文献_第4页

Immunohistochemical analysis of immune checkpoint proteins (PD-1, PD-L1 and PD-L2) in giant cell granulomas of the jaws and giant cell tumor of bone 颌骨巨细胞肉芽肿和骨巨细胞瘤中免疫检查点蛋白PD-1、PD-L1和PD-L2的免疫组织化学分析。

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

Archives of oral biology

Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106460

Elton Fernandes Barros , Vanessa Alves de Medeiros , Éricka Janine Dantas da Silveira , João Augusto Vianna Goulart Filho , Pollianna Muniz Alves , Cassiano Francisco Weege Nonaka

Objective

To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], peripheral giant cell granuloma [PGCG]) and giant cell tumor of bone (GCTB).

Design

Thirty CGCG (15 non-aggressive and 15 aggressive), 15 PGCG, and 15 GCTB were selected. The percentages of cytoplasmic (PD-1, PD-L1, and PD-L2) and nuclear (PD-L1) staining in mononuclear cells (MC) and in non-cannibalistic (ncMGC) and cannibalistic MGC (cMGC) were determined.

Results

Cytoplasmic expression of PD-1 and PD-L1 was observed in all groups, with high median percentages of positivity in ncMGC and cMGC. Compared to CGCG and PGCG, GCTB exhibited higher expression of PD-L1 in MC (p < 0.05). In ncMGC, expression of PD-1 was higher in GCTB compared to non-aggressive CGCG (p < 0.05). Similarly, higher PD-L1 immunopositivity was found in ncMGC of GCTB compared to aggressive CGCG and PGCG (p < 0.05). For all cell types, lower median percentages of PD-L2 positivity were observed in GCTB compared to CGCG and PGCG (p > 0.05). In GCTB, there was a strong positive correlation between the cytoplasmic expression of PD-L1 in MC and PD-1 in ncMGC (r = 0.535; p < 0.05). All groups exhibited low nuclear immunoexpression of PD-L1.

Conclusion

The results suggest the potential participation of PD-1, PD-L1, and PD-L2 in the pathogenesis of CGCG, PGCG, and GCTB. The locally aggressive behavior of GCTB could be associated with a higher osteoclastogenic and immunosuppressive microenvironment in these neoplasms.

目的：探讨程序性细胞死亡蛋白1 （PD-1）和程序性细胞死亡配体1 （PD-L1）、2 （PD-L2）在颌骨巨细胞肉芽肿（中央巨细胞肉芽肿[CGCG]、外周巨细胞肉芽肿[PGCG]）和骨巨细胞瘤（GCTB）中的免疫表达。设计：选择30例CGCG（非侵袭性15例，侵袭性15例），PGCG 15例，GCTB 15例。测定单核细胞（MC）、非同类相食（ncMGC）和同类相食MGC （cMGC）细胞质（PD-1、PD-L1和PD-L2）和核（PD-L1）染色百分比。结果：PD-1和PD-L1在所有组的细胞质中均有表达，ncMGC和cMGC的中位阳性百分比较高。与CGCG和PGCG相比，GCTB在MC中的PD-L1表达更高（p  0.05）。在GCTB中，MC细胞质中PD-L1的表达与ncMGC中PD-1的表达呈正相关（r = 0.535;p ）。结论：提示PD-1、PD-L1和PD-L2可能参与了CGCG、PGCG和GCTB的发病过程。GCTB的局部侵袭行为可能与这些肿瘤中较高的破骨细胞生成和免疫抑制微环境有关。

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引用次数: 0

RAW 264.7-derived exosomal miR-494–3p regulates inflammation and osteogenic differentiation of human periodontal ligament stem cells through regulating CAMK2D RAW 264.7衍生的外泌体miR-494-3p通过调节CAMK2D调节人牙周韧带干细胞的炎症和成骨分化

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

Archives of oral biology

Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106457

Yue Zhang, Yufu Liang, Yue Zhou

Objective

This study aimed to investigate the effect of M2-exos on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs) and the underlying mechanism.

Design

Exosomes were isolated from M2-polarized RAW 264.7 macrophages and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. hPDLSCs were treated with M2-exos, and osteogenic differentiation was assessed using alkaline phosphatase and Alizarin Red S staining, along with reverse transcription-quantitative polymerase chain reaction analysis of osteogenic markers. Inflammation-related cytokines were measured by enzyme-linked immunosorbent assay. Bioinformatics analysis identified miR-494–3p as a key miRNA in M2-exos, and its interaction with calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was validated by RNA pull-down and dual luciferase reporter assays. Functional experiments were performed using a miR-494–3p inhibitor and CAMK2D knockdown in hPDLSCs.

Results

M2-exos exhibited typical exosomal characteristics and were internalized by hPDLSCs. Additionally, M2-exos suppressed inflammation and enhanced osteogenic differentiation. Mechanistically, miR-494–3p was highly enriched in M2-exos and directly targeted CAMK2D. Moreover, inhibition of miR-494–3p exacerbated inflammation and impaired osteogenesis, while CAMK2D knockdown reversed these effects, restoring osteogenic potential.

Conclusions

RAW 264.7-derived exosomes inhibited inflammation and promoted osteogenic differentiation in hPDLSCs, a process that involves, at least in part, the delivery of miR-494–3p. These findings highlight a novel mechanism and the therapeutic potential of targeting the miR-494–3p/CAMK2D axis in periodontal bone regeneration.

目的探讨M2-exos对人牙周韧带干细胞成骨分化的影响及其机制。design nexosomes从m2极化的RAW 264.7巨噬细胞中分离出来，并通过透射电子显微镜、纳米颗粒跟踪分析和Western blot对其进行了表征。用M2-exos处理hPDLSCs，用碱性磷酸酶和茜素红S染色评估成骨分化，并对成骨标志物进行逆转录-定量聚合酶链反应分析。采用酶联免疫吸附法检测炎症相关细胞因子。生物信息学分析发现miR-494-3p是M2-exos中的关键miRNA，并且通过RNA下拉和双荧光素酶报告基因试验验证了其与钙/钙调素依赖性蛋白激酶II δ (CAMK2D)的相互作用。在hPDLSCs中使用miR-494-3p抑制剂和CAMK2D敲低进行功能实验。结果sm2 -exos表现出典型的外泌体特征，并被hPDLSCs内化。此外，M2-exos抑制炎症并增强成骨分化。在机制上，miR-494-3p在M2-exos中高度富集，并直接靶向CAMK2D。此外，miR-494-3p的抑制加重了炎症和成骨损伤，而CAMK2D的敲低逆转了这些作用，恢复了成骨潜能。结论：raw264.7衍生的外泌体抑制hPDLSCs的炎症并促进成骨分化，这一过程至少部分涉及miR-494-3p的传递。这些发现强调了靶向miR-494-3p /CAMK2D轴在牙周骨再生中的新机制和治疗潜力。

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引用次数: 0

In vivo immunological evaluation of indomethacin and omega-3 nanocapsules for the treatment of rheumatoid arthritis in the temporomandibular joints of rats 吲哚美辛和omega-3纳米胶囊治疗大鼠颞下颌关节类风湿关节炎的体内免疫学评价

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

Archives of oral biology

Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106456

Victor Augusto Benedicto dos Santos , Francisco Carlos Groppo , Thomas Barbin , Adilson Sartoratto , Luiz Eduardo Nunes Ferreira , Michael Henrique Araujo Monteiro , Sidney Raimundo Figueroba

Objective

This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form administration on cytokines IL-1β, IL-10, IL-6, and TNF-α in temporomandibular joint.

Design

Nanocapsules were synthesized with omega-3 as the oil phase containing indomethacin. They were characterized for mean hydrodynamic diameter, polydispersity index, zeta potential, morphology (TEM), encapsulation efficiency (HPLC), and cytotoxicity in RAW 264.7 macrophages (MTT assay). For in vivo evaluation, forty-eight adult male Wistar rats (n = 6) underwent rheumatoid arthritis induction via intradermal injection of Complete Freund's Adjuvant (CFA) and bovine type II collagen (CII) at the base of the tail. Rats were treated for 7 days by oral gavage with either nanocapsules (NC5, NC2.5), free indomethacin (IND5, IND2.5), or indomethacin combined with omega-3 (IND5 +ω3, IND2.5 +ω3). Cytokine levels in the temporomandibular joint were subsequently assessed.

Results

Nanocapsules displayed a spherical, well-defined morphology with diameters < 250 nm and exhibited lower cytotoxicity in RAW 264.7 cells compared to free-form treatments. In vivo, all treated groups showed significant reductions in IL-1β, IL-6, and TNF-α compared to the CFA group, along with a significant increase in IL-10.

Conclusions

Indomethacin nanocapsules with omega-3 effectively reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10, demonstrating a superior immunomodulatory profile compared to free-form treatments.

本研究旨在开发和表征含有omega-3油芯的吲哚美辛纳米胶囊，并评估其治疗大鼠类风湿关节炎的潜力，比较其与自由给药对颞下颌关节细胞因子IL-1β、IL-10、IL-6和TNF-α的影响。设计以omega-3为油相，含吲哚美辛合成纳米胶囊。采用平均水动力直径、多分散性指数、zeta电位、形态（TEM）、包封效率（HPLC）和RAW 264.7巨噬细胞的细胞毒性（MTT法）对其进行表征。为了进行体内评估，48只成年雄性Wistar大鼠（n = 6）通过在尾巴底部皮内注射完全弗氏佐剂（CFA）和牛II型胶原（CII）诱导类风湿关节炎。大鼠分别口服纳米胶囊（NC5、NC2.5）、游离吲哚美辛（IND5、IND2.5）或吲哚美辛联合omega-3 （IND5 +ω3, IND2.5 +ω3）治疗7 d。随后评估了颞下颌关节的细胞因子水平。结果纳米胶囊呈球形，直径为<； 250 nm，在RAW 264.7细胞中表现出较低的细胞毒性。在体内，与CFA组相比，所有治疗组的IL-1β、IL-6和TNF-α水平均显著降低，IL-10水平显著升高。结论含omega-3的辛多美辛纳米胶囊可有效降低促炎细胞因子，增加抗炎IL-10，与自由形式的治疗相比，具有优越的免疫调节作用。

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引用次数: 0

Effects of Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri on oral microbial balance and host cell functions: Implications for the prevention and management of oral diseases 长双歧杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌对口腔微生物平衡和宿主细胞功能的影响：对口腔疾病预防和管理的影响

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

Archives of oral biology

Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106458

Zhigang Zhu , Xiang Li , Jianwei Liu , Liang Chen , Yutong Zhan , Li Wang , Luxian Zhou , Dandan Jiang , Xianwu Peng , Xiuyu Jiang

Objectives

This study aimed to evaluate the effects of three probiotic samples—Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri—on oral pathogens, commensal bacteria, and host oral cells, thereby exploring their potential roles in maintaining microbial balance and promoting host defense.

Design

Probiotic culture supernatants (postbiotic fractions) were tested against oral pathogens (S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans) and commensal species (S. sanguinis, V. parvula) using optical density assays. Primary human gingival fibroblasts and oral keratinocytes were co-cultured with probiotic preparations to assess cell viability, inflammatory cytokine secretion, and barrier gene expression (FLG, LOR).

Results

B. longum, L. rhamnosus, and L. reuteri samples showed strain- and concentration-dependent inhibition of oral pathogens, while exhibiting minimal effects on beneficial commensals. Appropriate concentrations of probiotic samples preserved fibroblast viability and enhanced keratinocyte survival. Notably, B. longum, L. rhamnosus, and L. reuteri upregulated barrier-associated genes (FLG, LOR) and suppressed IL-6 secretion in inflamed keratinocytes, suggesting immunomodulatory and protective roles.

Conclusions

Probiotic-derived metabolites exert selective antimicrobial and cytoprotective effects in the oral microenvironment. These findings support the dual functions of probiotics in reshaping oral microbial balance and modulating host cell functions and highlight the potential for personalized probiotic strategies in oral disease prevention and management.Further exploration of combined probiotic formulations is warranted to optimize clinical translation.

目的研究长双歧杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌三种益生菌样品对口腔病原菌、共生菌和宿主口腔细胞的影响，探讨其在维持微生物平衡和促进宿主防御方面的潜在作用。设计采用光密度法检测益生菌培养上清液（生后组分）对口腔病原菌（变形链球菌、牙龈卟啉卟啉链球菌、核核卟啉卟啉卟啉链球菌、放线菌卟啉卟啉链球菌）和共生菌（血源性卟啉链球菌、细小弧菌）的抑制作用。用益生菌制剂对原代人牙龈成纤维细胞和口腔角化细胞进行共培养，观察细胞活力、炎性细胞因子分泌和屏障基因表达（FLG， LOR）。龙舌兰、鼠李糖乳杆菌和罗伊氏乳杆菌样品显示出菌株和浓度依赖性的口腔病原体抑制，而对有益共生菌的影响最小。适当浓度的益生菌样品可以保存成纤维细胞的活力，提高角质细胞的存活率。值得注意的是，长芽孢杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌上调了屏障相关基因（FLG、LOR），抑制了炎症角质形成细胞中IL-6的分泌，提示其具有免疫调节和保护作用。结论益生菌衍生代谢物在口腔微环境中具有选择性抗菌和细胞保护作用。这些发现支持了益生菌在重塑口腔微生物平衡和调节宿主细胞功能方面的双重功能，并强调了个性化益生菌在口腔疾病预防和管理中的潜力。进一步探索联合益生菌制剂是必要的，以优化临床转化。

{"title":"Effects of Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri on oral microbial balance and host cell functions: Implications for the prevention and management of oral diseases","authors":"Zhigang Zhu , Xiang Li , Jianwei Liu , Liang Chen , Yutong Zhan , Li Wang , Luxian Zhou , Dandan Jiang , Xianwu Peng , Xiuyu Jiang","doi":"10.1016/j.archoralbio.2025.106458","DOIUrl":"10.1016/j.archoralbio.2025.106458","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the effects of three probiotic samples—<em>Bifidobacterium longum</em>, <em>Lactobacillus rhamnosus</em>, and <em>Lactobacillus reuteri</em>—on oral pathogens, commensal bacteria, and host oral cells, thereby exploring their potential roles in maintaining microbial balance and promoting host defense.</div></div><div><h3>Design</h3><div>Probiotic culture supernatants (postbiotic fractions) were tested against oral pathogens (<em>S. mutans</em>, <em>P. gingivalis</em>, <em>F. nucleatum</em>, <em>A. actinomycetemcomitans</em>) and commensal species (<em>S. sanguinis</em>, <em>V. parvula</em>) using optical density assays. Primary human gingival fibroblasts and oral keratinocytes were co-cultured with probiotic preparations to assess cell viability, inflammatory cytokine secretion, and barrier gene expression (<em>FLG</em>, <em>LOR</em>).</div></div><div><h3>Results</h3><div><em>B. longum, L. rhamnosus, and L. reuteri</em> samples showed strain- and concentration-dependent inhibition of oral pathogens, while exhibiting minimal effects on beneficial commensals. Appropriate concentrations of probiotic samples preserved fibroblast viability and enhanced keratinocyte survival. Notably, <em>B. longum</em>, <em>L. rhamnosus</em>, and <em>L. reuteri</em> upregulated barrier-associated genes (<em>FLG</em>, <em>LOR</em>) and suppressed IL-6 secretion in inflamed keratinocytes, suggesting immunomodulatory and protective roles.</div></div><div><h3>Conclusions</h3><div>Probiotic-derived metabolites exert selective antimicrobial and cytoprotective effects in the oral microenvironment. These findings support the dual functions of probiotics in reshaping oral microbial balance and modulating host cell functions and highlight the potential for personalized probiotic strategies in oral disease prevention and management.Further exploration of combined probiotic formulations is warranted to optimize clinical translation.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106458"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577799","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

Biomechanical impact of tooth root morphology to inform dental implant design 牙根形态对种植体设计的生物力学影响。

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

Archives of oral biology

Pub Date : 2025-11-09 DOI: 10.1016/j.archoralbio.2025.106455

Amber P. Wood-Bailey , Chris Smith , Laura C. Fitton , Alana C. Sharp

Objective

Using finite element analysis (FEA), this study aims to investigate the impact of different tooth root morphologies and implant designs, including a standard implant and a custom root-analogue implant on stress and strain distribution across the mandible.

Design

Six models were created by varying the root morphology of one tooth (the mandibular first molar) under identical loading scenarios: an original molar root, an incisor root, a canine root, a taurodont root, a standard implant, and a custom root-analogue implant replicating the original root morphology.

Results

Models with the original molar and custom implant exhibited similar stress and strain distributions over the mandible and had higher principal strains (tensile and compressive) compared to the single-rooted and standard implant models. Specifically, the maximum tensile and compressive strain values in the mandible of the custom implant model reach 94.89 % and 99.15 % of those in the original tooth root model. In contrast, the other models show less than 55.68 % similarity.

Conclusions

Custom root-analogue implants, which mimic natural root morphology, demonstrated more favourable stress distribution patterns, similar to those of the natural molar, compared to single-root implants. Our findings suggest that multi-rooted teeth are biomechanically optimized for dissipating masticatory loads, and standard single-root implants may not adequately replicate these properties, leading to poor load distribution and increased failure risk in posterior locations. Further research is needed to refine custom root-analogue implant designs and optimize their clinical application to better match the natural biomechanical environment of the maxilla and mandible.

目的：采用有限元分析（FEA），研究不同牙根形态和种植体设计对下颌骨应力应变分布的影响，包括标准种植体和定制模拟牙根种植体。设计：通过改变一颗牙齿（下颌第一磨牙）在相同加载情景下的牙根形态，创建了6个模型：原始磨牙根、门牙根、犬牙根、牛头齿根、标准种植体和复制原始牙根形态的定制牙根模拟种植体。结果：与单根和标准种植体模型相比，原始磨牙和定制种植体模型在下颌骨上表现出相似的应力和应变分布，并且具有更高的主应变（拉伸和压缩）。其中，定制种植体模型下颌骨的最大拉伸应变和最大压缩应变分别达到原牙根模型的94.89 %和99.15 %。相比之下，其他模型的相似度小于55.68 %。结论：与单根种植体相比，模拟天然根形态的定制根模拟种植体表现出与天然磨牙相似的更有利的应力分布模式。我们的研究结果表明，多根牙在生物力学上优化了咀嚼负荷的消散，而标准的单根种植体可能无法充分复制这些特性，导致负荷分布不佳，增加了后牙位置失败的风险。需要进一步的研究来完善定制的根模拟种植体设计并优化其临床应用，以更好地匹配上下颌骨的自然生物力学环境。

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引用次数: 0

Effect of high-lipid environment on human gingival fibroblast on titanium surface: An in-vitro study 高脂环境对钛表面人牙龈成纤维细胞影响的体外研究

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

Archives of oral biology

Pub Date : 2025-11-07 DOI: 10.1016/j.archoralbio.2025.106454

Shuyi Tan, Maoquan Li, Zhiqiang Liu, Aijie Chen, Jialing Wu, Ruiqi Li, Xiachen Li, Shuangquan Wan

Objectives

Hyperlipidemia is associated with dental peri-implantitis. Long-term success of dental implant relies on good peri-implant soft tissue barrier. This study aims to investigate the effect of high-lipid environment on biological activities of gingival fibroblast on titanium surface so as to explore the effect of hyperlipidemia on peri-implant soft tissue.

Design

Human gingival fibroblast-1(HGF-1) was seeded on the titanium surfaces and cultured in normal and high-lipid culture medium for 4 days. Cell adhesion and proliferation were assessed by cell counting and morphological observation following fluorescent staining. RNA sequencing were performed afterwards, followed by differentially expressed genes analysis, several enrichment analyses and Protein-Protein Interaction (PPI) analysis.

Results

The number of HGF-1 cells significantly decreased and the morphology of HGF-1 changed in high-lipid culture environment. Moreover, the expression levels of several hub genes, including Interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), and Activating Transcription Factor 3 (ATF3), as well as the activity of pathways such as the IL-17 signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway, were elevated. Meanwhile, the down-regulation of cell proliferation activities, like DNA replication and cell division was also observed.

Conclusions

High-lipid environment impaired the adhesion and proliferation of HGF-1 on titanium surface, which may be associated with the upregulation of specific genes and pathways, alongside the downregulation of cell proliferation-related activities.

目的：高脂血症与牙体种植周炎相关。种植体的长期成功依赖于良好的种植体周围软组织屏障。本研究旨在通过研究高脂环境对钛表面牙龈成纤维细胞生物活性的影响，探讨高脂血症对种植体周围软组织的影响。设计将人牙龈成纤维细胞-1（HGF-1）接种于钛表面，在正常和高脂培养基中培养4天。荧光染色后通过细胞计数和形态学观察观察细胞粘附和增殖情况。随后进行RNA测序，然后进行差异表达基因分析，一些富集分析和蛋白质-蛋白质相互作用（PPI）分析。结果在高脂培养环境下，HGF-1细胞数量明显减少，HGF-1形态发生改变。此外，白细胞介素-6 （IL-6）、C-X-C基序趋化因子配体8 （CXCL8）、活化转录因子3 （ATF3）等中心基因的表达水平以及IL-17信号通路、核因子κ b （NF-κB）信号通路的活性均升高。同时，DNA复制和细胞分裂等细胞增殖活性也出现下调。结论高脂环境抑制HGF-1在钛表面的粘附和增殖，其机制可能与特定基因和通路的上调有关，同时下调细胞增殖相关活性。

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引用次数: 0

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。

{"title":"Novel missense mutations in the tumor necrosis factor domain of Ectodysplasin-A cause non-syndromic tooth agenesis in two Chinese families","authors":"Chengcan Yang , Nuo Xu , Xiaona Song , Kai Yang , Qian Gao","doi":"10.1016/j.archoralbio.2025.106441","DOIUrl":"10.1016/j.archoralbio.2025.106441","url":null,"abstract":"<div><h3>Objective</h3><div>Mutations of the Ectodysplasin-A (<em>EDA</em>) 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.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>We identified a novel mutation c.827 G>T (p.Arg276Leu) and a previously reported mutation c.1069 C>T (p.Arg357Trp) in the <em>EDA</em> 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.</div></div><div><h3>Conclusions</h3><div>Our findings broaden the mutation spectrum of <em>EDA</em> gene associated with NSTA by identifying a novel mutation and provide a basis for future genetic counseling.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106441"},"PeriodicalIF":2.1,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446809","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