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Smoking and systemic Th17/Treg immune alterations in periodontitis: A cross-sectional study 吸烟和牙周炎患者全身Th17/Treg免疫改变:一项横断面研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-27 DOI: 10.1016/j.archoralbio.2026.106525
Sangamithra Sidharthan , Dharmarajan Gopalakrishnan , Supriya Kheur , Poonam Suryavanshi , Avinash Sanap

Objective

To investigate the impact of smoking on systemic and local immune responses in periodontitis, focusing on Th17 and regulatory T (Treg) cell frequencies and their associated cytokine expression.

Design

Forty-five participants were categorized into healthy controls (n = 15), non-smokers with periodontitis (n = 15), and smokers with periodontitis (n = 15). Clinical periodontal parameters were recorded. Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify CD4⁺ T cells, Th17 (CD4⁺IL-17A⁺), and Treg (CD4⁺CD25⁺FOXP3⁺) populations. Gingival biopsies from a subset of participants (n = 24) were assessed by qRT-PCR for IL-17A, FOXP3, IL-12(p35), and hEBI3 expression. Group comparisons and correlation analyses were performed using appropriate parametric or non-parametric tests.

Results

Smokers with periodontitis exhibited greater probing depth and clinical attachment loss than non-smokers and healthy controls (p < 0.001). Both periodontitis groups showed elevated circulating CD4⁺ T cells and Tregs, with Th17 frequencies highest in smokers. These systemic differences remained significant after false discovery rate (FDR) correction, with moderate effect sizes (η² = 0.25–0.44). Gingival expression of IL-17A, FOXP3, IL-12(p35), and hEBI3 did not differ significantly between groups after FDR adjustment, with small effect sizes (η² ≤ 0.09). No significant correlations were observed between smoking exposure and systemic or local immune markers.

Conclusion

Periodontitis is associated with marked systemic immune alterations, whereas local transcriptional changes are subtle. Smoking modestly enhances systemic Th17 responses without robust changes in gingival cytokine expression, highlighting the need for adequately powered and longitudinal studies to clarify immune mechanisms in periodontitis.
目的探讨吸烟对牙周炎患者全身和局部免疫反应的影响,重点关注Th17和调节性T (Treg)细胞频率及其相关细胞因子的表达。45名参与者被分为健康对照组(n = 15)、患有牙周炎的非吸烟者(n = 15)和患有牙周炎的吸烟者(n = 15)。记录临床牙周参数。采用流式细胞术分析外周血单核细胞,定量CD4 + T细胞、Th17 + (CD4 + IL-17A +)和Treg + (CD4 + CD25 + FOXP3 +)群体。一部分参与者(n = 24)的牙龈活检通过qRT-PCR评估IL-17A、FOXP3、IL-12(p35)和hEBI3的表达。采用适当的参数或非参数检验进行组间比较和相关性分析。结果牙周炎吸烟者比非吸烟者和健康对照组表现出更大的探诊深度和临床依恋丧失(p <; 0.001)。两组牙周炎患者循环CD4 + T细胞和Tregs升高,其中Th17在吸烟者中频率最高。在错误发现率(FDR)校正后,这些系统性差异仍然显著,效应大小适中(η²= 0.25-0.44)。经FDR调整后,各组牙龈IL-17A、FOXP3、IL-12(p35)、hEBI3的表达差异无统计学意义,且效应量较小(η²≤0.09)。吸烟暴露与全身或局部免疫标志物之间没有显著相关性。结论牙周炎与明显的全身免疫改变有关,而局部转录变化则很微妙。吸烟适度地增强全身Th17反应,而不显著改变牙龈细胞因子的表达,强调需要充分有力的纵向研究来阐明牙周炎的免疫机制。
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引用次数: 0
Upregulated expressions of caspase-4 and -5 upon challenging with periodontal microorganisms in human gingival epithelial cells 人牙龈上皮细胞中牙周微生物侵袭后caspase-4和-5的表达上调
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-27 DOI: 10.1016/j.archoralbio.2026.106526
Anupong Makeudom, Ekapong Dechtham, Nutthapong Kantrong, Pimphorn Meekhantong, Khuanchanok Laongnualpanich, Suttichai Krisanaprakornkit

Objectives

Gram-negative periodontal microorganisms may be recognized by caspase-4/-5, lipopolysaccharide sensors, in human gingival epithelial cells (HGECs). This study aimed to determine expressions of inflammasomal biomolecules and to elucidate their signaling in epithelial cells upon challenging with cell wall extract of Porphyromonas gingivalis, Prevotella intermedia, or Fusobacterium nucleatum.

Design

HGECs were stimulated with 1 or 5 μg/ml of each extract for 24 h. Expressions of caspase-1, caspase-4/-5, and gasdermin D were assayed by RT-qPCR and immunoblotting. Interleukin (IL)-1β and IL-18 levels in conditioned medium were measured by ELISA. Apoptosis was analyzed by immunoblotting for caspase-3, BCL-2, and BAX expressions and by flow cytometry for annexin V and propidium iodide staining. Upon stimulation, phosphorylation of receptor-interacting serine/threonine-protein 2 (RIP2) kinase and localization of the p50 and p65 subunits of NF-kappaB were determined.

Results

Significantly upregulated expressions of caspase-4/-5 proteins, but not their gene, upon challenging with each extract were found (p < 0.05). However, gene and protein expressions of caspase-1 or gasdermin D were not significantly altered in the extract-stimulated HGECs, consistent with unchanged levels of IL-1β or IL-18, unaltered expressions of caspase-3, BCL-2, BAX, and non-differences in the percentages of apoptosis. Enhancement of phosphorylated RIP2 kinase and nuclear expression of the p50 and p65 subunits were instead observed in HGECs stimulated with each extract.

Conclusion

The cell wall extract of Porphyromonas gingivalis, Prevotella intermedia, or Fusobacterium nucleatum upregulated expressions of caspase-4/-5 proteins in HGECs and activated RIP2 kinase that led to induced expression of NF-kappaB, without any sign of pyroptotic cell death.
目的研究革兰氏阴性牙周微生物在人牙龈上皮细胞(HGECs)中可能被脂多糖传感器caspase-4/-5识别。本研究旨在确定炎症体生物分子的表达,并阐明它们在牙龈卟啉单胞菌、中间普雷沃氏菌或核梭杆菌细胞壁提取物刺激上皮细胞时的信号传导。每一种提取物分别以1或5 μg/ml刺激hges 24 h。采用RT-qPCR和免疫印迹法检测caspase-1、caspase-4/-5、gasdermin D的表达。ELISA法检测条件培养基中白细胞介素(IL)-1β和IL-18水平。免疫印迹法检测caspase-3、BCL-2和BAX的表达,流式细胞术检测膜联蛋白V和碘化丙啶染色。刺激后,测定受体相互作用丝氨酸/苏氨酸蛋白2 (RIP2)激酶的磷酸化和NF-kappaB的p50和p65亚基的定位。结果caspase-4/-5蛋白表达显著上调,而caspase-4/-5基因表达不上调(p <; 0.05)。然而,在提取物刺激的hgec中,caspase-1或gasdermin D的基因和蛋白质表达没有显著改变,与IL-1β或IL-18水平不变、caspase-3、BCL-2、BAX表达不变以及凋亡百分比无差异一致。相反,在每一种提取物刺激的hgec中,观察到磷酸化的RIP2激酶和p50和p65亚基的核表达增强。结论牙龈卟啉单胞菌、中间普氏菌和核梭杆菌细胞壁提取物可上调HGECs中caspase-4/-5蛋白的表达,激活RIP2激酶,诱导NF-kappaB表达,无细胞热亡迹象。
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引用次数: 0
Mouthrinses differentially rewire salivary virus-microbiome interaction dynamics in COVID-19 patients: A randomized controlled trial 一项随机对照试验:漱口水在COVID-19患者中差异地重新连接唾液病毒-微生物组相互作用动力学
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-23 DOI: 10.1016/j.archoralbio.2026.106524
Armelia Sari Widyarman , Rika Bur , Nadeeka S. Udawatte , Prika Maulina Agaristi , Intan Razari , Syukrini Bahri , Mario Richi , Tri Erri Astoeti , Chaminda Jayampath Seneviratne

Objective

In this randomized clinical trial (RCT) we evaluated the efficacy of mouthrinses containing sodium chlorite (NaClO2), povidone iodine (PVP-I), cetylpyridinium chloride (CPC) compared to sterile water control in modulating salivary SARS-CoV-2 viral load and the oral microbiome in COVID-19 patients.

Methods

Forty PCR-confirmed COVID-19 patients were randomly allocated to four groups (n = 10 each) and rinsed with 10 ml of their assigned solution for 30 s. Saliva was collected pre-rinse and at 5-min, 3-hour, and 6-hour post-rinse. Viral load was quantified via RT-qPCR targeting N and ORF1ab genes, and oral microbiome was analyzed using 16S rRNA sequencing.

Results

CPC reduced viral load by 1.5-fold (P = 0.12), PVP-I by 1.2-fold (P = 0.18), and NaClO2 by 1.1-fold (P = 0.34) at 6-hour, though not statistically significant. Overall oral microbiome diversity and composition remained stable (P = 0.67), although CPC and PVP-I significantly altered specific taxa such as Leptotrichia sp. and Lautropia mirabilis. Moreover, CPC and PVP-I disrupted the salivary microbiome network with SARS-CoV-2 genes, namely N and ORF1ab genes.

Conclusion

This study to provide new insight into the modulation dynamics of mouthrinses on salivary SARS CoV-2 and oral microbiome, suggesting that CPC and PVP-I may provide potential health benefits by reducing viral load and modulating microbiome–virus networks.
目的通过随机临床试验(RCT),比较含亚氯酸钠(NaClO2)、聚维酮碘(PVP-I)、氯化十六烷基吡啶(CPC)漱口水与无菌对照水对COVID-19患者唾液SARS-CoV-2病毒载量和口腔微生物群的调节作用。方法40例pcr确诊的COVID-19患者随机分为4组(每组 = 10例),分别用指定溶液10 ml冲洗30 s。冲洗前、冲洗后5分钟、3小时和6小时收集唾液。采用靶向N和ORF1ab基因的RT-qPCR定量病毒载量,采用16S rRNA测序分析口腔微生物组。结果scpc在6小时降低病毒载量1.5倍(P = 0.12),降低PVP-I 1.2倍(P = 0.18),降低NaClO2 1.1倍(P = 0.34),但差异无统计学意义。总体口腔微生物群落多样性和组成保持稳定(P = 0.67),尽管CPC和PVP-I显著改变了特定的类群,如纤毛菌和奇迹Lautropia mirabilis。此外,CPC和PVP-I破坏了带有SARS-CoV-2基因(即N和ORF1ab基因)的唾液微生物组网络。结论本研究为漱口水对唾液SARS - CoV-2和口腔微生物组的调节动力学提供了新的见解,提示CPC和PVP-I可能通过降低病毒载量和调节微生物-病毒网络提供潜在的健康益处。
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引用次数: 0
Genetic polymorphisms in headache attributed to temporomandibular disorder: A case-control study 颞下颌紊乱所致头痛的遗传多态性:一项病例对照研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-22 DOI: 10.1016/j.archoralbio.2026.106523
Camilla Porto Campello , Cleidiel Aparecido Araujo Lemos , Elker Lene Santos de Lima , Renata Silva Melo Fernandes , Maria Tereza Cartaxo Muniz

Objective

The aim of this study was to examine the relationship between three single nucleotide polymorphisms (SNPs): −308 G/A TNF-α, −174 G/C IL-6, and C677T MTHFR and the presence of headache attributed to temporomandibular disorder (HATMD).

Design

This case-control study included a total of 68 patients with HATMD and 200 controls, aged 18 years and older. Both sets of participants included both genders. The diagnosis followed the diagnostic criteria for temporomandibular disorders (DC/TMD). The temporomandibular disorder pain screen was also applied. The −308 G/A TNF-α and 677 C/T MTHFR SNPs were genotyped using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP), and −174 G/C IL-6 SNP was performed by PCR. Allele frequencies and logistic regression analysis were used to assess the association between HATMD and genotypes.

Results

The results revealed that the AA genotype of −308 G/A TNF-α SNP (ORGG/AA= 0.20, 95 % CI: 0.0568–0.7724,p = 0.0290) and the CT genotype of C677T MTHFR SNP (ORCC/CT = 0.40, 95 % CI: 0.2224–0.7350, p = 0.0042) were protective factors for HATMD risk. No significant association was found between -174G/C IL-6 SNP and the risk of HATMD (ORGG/CC = 0.58, 95 % CI: 0.2122–1.6367, p = 0.45).

Conclusion

The −308 G/A TNF-α and C677T MTHFR SNPs were identified as protective factors against the development of HATMD.
目的本研究的目的是研究三个单核苷酸多态性(snp):−308 G/A TNF-α,−174 G/C IL-6和C677T MTHFR与颞下颌疾病(HATMD)引起的头痛之间的关系。本病例对照研究共纳入68例HATMD患者和200例对照组,年龄在18岁及以上。两组参与者都包括男女。诊断符合颞下颌疾患诊断标准(DC/TMD)。颞下颌紊乱疼痛筛查也被应用。采用聚合酶链反应-限制性片段多态性(PCR- rflp)对−308 G/A TNF-α和677 C/T MTHFR SNP进行基因分型,采用PCR对−174 G/C IL-6 SNP进行基因分型。采用等位基因频率和logistic回归分析来评估HATMD与基因型之间的相关性。结果显示,−308 G/A TNF-α SNP的AA基因型(ORGG/AA= 0.20, 95 % CI: 0.0568 ~ 0.7724,p = 0.0290)和C677T MTHFR SNP的CT基因型(ORCC/CT = 0.40, 95 % CI: 0.2224 ~ 0.7350, p = 0.0042)是HATMD发病的保护因素。-174G/C IL-6 SNP与HATMD风险无显著相关性(ORGG/CC = 0.58, 95 % CI: 0.2122-1.6367, p = 0.45)。结论−308 G/A TNF-α和C677T MTHFR snp是抑制HATMD发生的保护因子。
{"title":"Genetic polymorphisms in headache attributed to temporomandibular disorder: A case-control study","authors":"Camilla Porto Campello ,&nbsp;Cleidiel Aparecido Araujo Lemos ,&nbsp;Elker Lene Santos de Lima ,&nbsp;Renata Silva Melo Fernandes ,&nbsp;Maria Tereza Cartaxo Muniz","doi":"10.1016/j.archoralbio.2026.106523","DOIUrl":"10.1016/j.archoralbio.2026.106523","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to examine the relationship between three single nucleotide polymorphisms (SNPs): −308 G/A <em>TNF-α</em>, −174 G/C <em>IL-6</em>, and C677T <em>MTHFR</em> and the presence of headache attributed to temporomandibular disorder (HATMD).</div></div><div><h3>Design</h3><div>This case-control study included a total of 68 patients with HATMD and 200 controls, aged 18 years and older. Both sets of participants included both genders. The diagnosis followed the diagnostic criteria for temporomandibular disorders (DC/TMD). The temporomandibular disorder pain screen was also applied. The −308 G/A <em>TNF-α</em> and 677 C/T <em>MTHFR</em> SNPs were genotyped using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP), and −174 G/C <em>IL-6</em> SNP was performed by PCR. Allele frequencies and logistic regression analysis were used to assess the association between HATMD and genotypes.</div></div><div><h3>Results</h3><div>The results revealed that the AA genotype of −308 G/A <em>TNF-α</em> SNP (OR<sub>GG/AA</sub>= 0.20, 95 % CI: 0.0568–0.7724,p = 0.0290) and the CT genotype of C677T <em>MTHFR</em> SNP (OR<sub>CC/CT</sub> = 0.40, 95 % CI: 0.2224–0.7350, p = 0.0042) were protective factors for HATMD risk. No significant association was found between -174G/C <em>IL-6</em> SNP and the risk of HATMD (OR<sub>GG/CC</sub> = 0.58, 95 % CI: 0.2122–1.6367, p = 0.45).</div></div><div><h3>Conclusion</h3><div>The −308 G/A <em>TNF-α</em> and C677T <em>MTHFR</em> SNPs were identified as protective factors against the development of HATMD.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106523"},"PeriodicalIF":2.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075572","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
Experts' narrative review “Mastication, Hippocampal Structure Changes and Cognition” 专家述评《咀嚼、海马结构变化与认知》
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-21 DOI: 10.1016/j.archoralbio.2026.106522
Maria Grazia Piancino

Objective

Recent evidence highlights a fundamental link between masticatory function and brain health. Once regarded solely as a peripheral motor activity for food processing and occlusal balance, mastication is now recognized as a key factor in maintaining and enhancing cognitive function across the lifespan.

Design

This narrative review was conducted using relevant keywords through searches in PubMed, Scopus, and Web of Science, as well as manual searching of the bibliographies of journal articles.

Results

Basic research has shown that chewing stimulates neurogenesis in the hippocampus, resulting in increased neuronal and synaptic density, as well as the upregulation of brain-derived neurotrophic factor (BDNF), which leads to improvements in memory and cognition. This effect has been documented in both animal and clinical research, particularly among the elderly, and is supported by data from national health programs, which indicate that adequate prosthodontic rehabilitation can help preserve cognitive function. Etiopathogenetic insights suggest that loss of posterior teeth, rather than overall tooth count, is particularly detrimental, as these teeth are essential for effective mastication. Proposed mechanisms involve exercise-induced myokines, such as Cathepsin B, and chewing-induced neprilysin production, which may mediate hippocampal neuroprotection.

Conclusions

Collectively, these findings support a paradigm shift: mastication should be promoted as a preventive strategy for both oral and neural health. Public health efforts and clinical practices should integrate education on maintaining posterior dentition, promoting diets with adequate texture, and supporting prosthetic rehabilitation to sustain neuromuscular activity, thereby protecting cognitive function from early development through old age.
最近的证据强调了咀嚼功能和大脑健康之间的基本联系。咀嚼曾经仅仅被认为是一种用于食物加工和咬合平衡的外周运动活动,现在被认为是维持和增强认知功能的关键因素。设计本叙述性综述通过PubMed、Scopus和Web of Science检索相关关键词,以及手工检索期刊文章的参考书目进行。结果基础研究表明,咀嚼刺激海马神经发生,导致神经元和突触密度增加,以及脑源性神经营养因子(BDNF)的上调,从而改善记忆和认知。这种效果在动物和临床研究中都有记录,特别是在老年人中,并且得到了国家卫生计划数据的支持,这些数据表明,适当的修复康复可以帮助保持认知功能。从病因学的角度来看,后牙的损失,而不是整个牙齿的数量,是特别有害的,因为这些牙齿是必不可少的有效咀嚼。提出的机制包括运动诱导的肌肉因子,如组织蛋白酶B和咀嚼诱导的神经球蛋白产生,它们可能介导海马神经保护。总的来说,这些发现支持了一种范式转变:咀嚼应该作为一种预防口腔和神经健康的策略来推广。公共卫生工作和临床实践应结合教育,维护后牙列,促进适当质地的饮食,支持假肢康复以维持神经肌肉活动,从而保护认知功能从早期发展到老年。
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引用次数: 0
Cellular passages modulate pre-osteoblast responses to bisphosphonate in high-passage cell models 在高传代细胞模型中,细胞传代调节成骨前细胞对二膦酸盐的反应
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-19 DOI: 10.1016/j.archoralbio.2026.106521
Charukrit Lilakhunakon , Somying Patntirapong

Objective

This study examined the effects of cell passages, drug treatment, or interaction between cell passage and drug treatment on pre-osteoblast growth and activities.

Design

Pre-osteoblasts, MC3T3-E1, were subcultured until reaching high passages (passage 42; P42) and late passages (passage 62; P62). Cells were treated with oral bisphosphonate (BP), alendronate (ALN), at concentrations 1 and 5 μM. Cells were evaluated and compared for cell survival, migration, adhesion, actin cytoskeleton, cell spreading, and gene expressions.

Results

Two-way ANOVA showed that cell migration, cytoskeleton, nuclear condensation, and Intβ1 gene expression were impacted by the interaction between cell passage and ALN, while cell growth, death, adhesion, and spreading were affected by either cell passage or ALN. Cell growth was inhibited by cell passage and ALN. ALN at 5 μM (A5) increased cell death in P42. Cell adhesion was reduced in P62 compared to P42 in A1 condition. Higher cell passage and ALN promoted detachment under mechanical stress. Cell spreading was also disrupted by ALN. Adhesion-related gene expressions such as Intβ1 and FAK were downregulated by cell passage in A5 treatment.

Conclusion

These findings demonstrated differential cellular responses to BPs based on cell passage and interaction between cell passage and ALN. High and late passage cells exhibited distinct sensitivities and behaviors. This underscores the importance of using higher-passage cell models to better mimic aged osteoblasts in vitro when evaluating preclinical studies.
目的探讨细胞传代、药物治疗或细胞传代与药物治疗相互作用对成骨前细胞生长和活性的影响。设计将前成骨细胞MC3T3-E1传代至高传代(传代42;P42)和晚期传代(传代62;P62)。用浓度为1和5 μM的口服双膦酸盐(BP)、阿仑膦酸盐(ALN)处理细胞。评估和比较细胞的存活、迁移、粘附、肌动蛋白细胞骨架、细胞扩散和基因表达。结果双因素方差分析显示,细胞传代和ALN相互作用影响细胞迁移、细胞骨架、核凝聚和in - β1基因表达,细胞生长、死亡、粘附和扩散均受细胞传代和ALN的影响。细胞传代和ALN均抑制细胞生长。ALN在5 μM (A5)时增加P42细胞死亡。A1条件下,P62细胞粘附性较P42降低。较高的细胞传代和ALN促进机械应力下的脱离。细胞扩散也被ALN破坏。在A5处理下,粘附相关基因如in - β1和FAK的表达通过细胞传代下调。结论基于细胞传代和细胞传代与ALN的相互作用,细胞对bp的反应存在差异。高传代和晚传代细胞表现出不同的敏感性和行为。这强调了在评估临床前研究时,使用高传代细胞模型更好地模拟体外衰老成骨细胞的重要性。
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引用次数: 0
A functional axis of mastication and respiration in cognitive function: A narrative review 认知功能中咀嚼和呼吸的功能轴:述评
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-15 DOI: 10.1016/j.archoralbio.2026.106517
Jun Hosomichi, Takashi Ono

Objective

This review presents an integrative framework of the "Mastication–Respiration Axis," proposing that the masticatory and respiratory systems interact to form a functional axis essential for the development and maintenance of cognitive health in brain circuits.

Design

We narratively synthesized studies identified by structured searches of PubMed from inception to September 1, 2025, using predefined keywords related to mastication/chewing, nasal respiration/breathing, and cognition, and including peer-reviewed human and animal studies published in English.

Results

Evidence shows that mastication and respiration are coordinated at the brainstem through central pattern generators. Dysfunction in this axis—such as reduced chewing or oral breathing—activates stress and inflammatory pathways. The prefrontal cortex, hippocampus, and cerebellum depend on rhythmic inputs from both systems, with nasal respiration acting as a cortical pacemaker. Animal studies demonstrate that masticatory deficiency impairs hippocampal memory, while respiratory disruption during critical developmental periods causes long-lasting cerebellar and affective–motor deficits, offering a neurobiological basis for clinical links between oral breathing and neurodevelopmental disorders.

Conclusions

Mastication and respiration are not merely peripheral functions but are deeply integrated with the central nervous system, forming a critical axis for brain development, plasticity, and function. Dysfunction in this axis, particularly during sensitive developmental windows, may lead to long-term impairments in memory, motor control, and affective regulation. This integrated model highlights the clinical importance of early interventions in dental, orthodontic, and respiratory health to support lifelong neurological well-being.
目的:本文综述了“咀嚼-呼吸轴”的整体框架,提出咀嚼和呼吸系统相互作用形成一个功能轴,对大脑回路中认知健康的发展和维持至关重要。我们使用与咀嚼/咀嚼、鼻呼吸/呼吸和认知相关的预定义关键词,叙述性地综合了PubMed从成立到2025年9月1日的结构化搜索所确定的研究,并包括同行评议的英文发表的人类和动物研究。结果有证据表明,咀嚼和呼吸是通过中枢模式发生器在脑干协调的。这个轴的功能障碍——比如咀嚼或口腔呼吸减少——会激活压力和炎症途径。前额叶皮质、海马体和小脑依赖于这两个系统的节律性输入,鼻呼吸起皮层起搏器的作用。动物研究表明,咀嚼缺陷会损害海马记忆,而关键发育时期的呼吸中断会导致长期的小脑和情感运动缺陷,这为口腔呼吸和神经发育障碍之间的临床联系提供了神经生物学基础。结论咀嚼和呼吸不仅是外周功能,而且与中枢神经系统深度融合,构成了大脑发育、可塑性和功能的关键轴。这个轴的功能障碍,特别是在敏感的发育窗口期,可能导致记忆、运动控制和情感调节的长期损伤。这个综合模型强调了早期干预牙科、正畸和呼吸健康的临床重要性,以支持终身神经系统健康。
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引用次数: 0
Comparative analysis of patient-derived organoids among oral squamous cell carcinoma and mucosa identifies the distinct features 比较分析口腔鳞状细胞癌和粘膜患者来源的类器官,确定其独特的特征
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-15 DOI: 10.1016/j.archoralbio.2026.106520
Jianguo Gan , Wanrong Meng , Dan Yang , Xiaodong Feng , Guiquan Zhu

Objective

This study aimed to establish matched patient-derived organoids from oral squamous cell carcinoma (PDO-T) and adjacent normal mucosa (PDO-N), characterize their distinct features, and evaluate their impact on drug response.

Design

PDOs were generated from primary OSCC tissues and matched adjacent normal mucosa obtained from 18 patients. Morphological and histological characteristics were assessed using brightfield microscopy and phalloidin staining. Immunohistochemistry was performed to evaluate differential marker expression. Drug response assays were conducted in paired PDO-T and PDO-N to assess chemotherapeutic sensitivity.

Results

We successfully established 5 PDO-T and 15 PDO-N lines, with PDO-N exhibiting a higher success rate (∼80 %). Morphological analysis showed that PDO-N formed spherical structures with a central cavity and polarity, while PDO-T displayed irregular structures with heterogeneous cell arrangements. Immunohistochemistry revealed broad distribution of Ki-67, p63 and YAP/TAZ in PDO-T, contrasting with their basal layer restriction in PDO-N. p53 was strongly positive in PDO-T. CK5 and CK13 exhibited a stratified pattern in PDO-N. Importantly, drug testing in paired PDO-T and PDO-N revealed divergent responses, with PDO-N generally more resistant and able to maintain morphological integrity under high-dose treatment.

Conclusion

Our comparative analysis delineates distinct features between PDO-T and PDO-N in morphology, biomarker expression, and drug response. These findings provide an intuitive framework for their identification, thereby improving the accuracy of drug screening and enhancing the translational value of PDOs.
目的建立口腔鳞状细胞癌(PDO-T)和邻近正常粘膜(PDO-N)患者来源的匹配类器官,表征它们的不同特征,并评估它们对药物反应的影响。从18例患者的原发OSCC组织和匹配的邻近正常粘膜中生成DesignPDOs。使用明场显微镜和phalloidin染色评估形态学和组织学特征。免疫组化评价差异标志物的表达。对PDO-T和PDO-N进行配对药物反应试验,以评估化疗敏感性。结果我们成功建立了5株PDO-T和15株PDO-N细胞系,其中PDO-N的成功率更高(约80 %)。形态学分析表明,PDO-N形成具有中心空腔和极性的球形结构,而PDO-T呈不规则结构,细胞排列不均一。免疫组织化学显示Ki-67、p63和YAP/TAZ在PDO-T中广泛分布,与它们在PDO-N中的基底层限制形成对比。p53在PDO-T中呈强阳性。CK5和CK13在PDO-N中呈分层模式。重要的是,配对的PDO-T和PDO-N的药物测试显示出不同的反应,PDO-N通常更耐药,并能在高剂量治疗下保持形态完整性。结论我们的比较分析揭示了PDO-T和PDO-N在形态、生物标志物表达和药物反应方面的不同特征。这些发现为pdo的鉴定提供了一个直观的框架,从而提高了药物筛选的准确性,增强了pdo的转化价值。
{"title":"Comparative analysis of patient-derived organoids among oral squamous cell carcinoma and mucosa identifies the distinct features","authors":"Jianguo Gan ,&nbsp;Wanrong Meng ,&nbsp;Dan Yang ,&nbsp;Xiaodong Feng ,&nbsp;Guiquan Zhu","doi":"10.1016/j.archoralbio.2026.106520","DOIUrl":"10.1016/j.archoralbio.2026.106520","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to establish matched patient-derived organoids from oral squamous cell carcinoma (PDO-T) and adjacent normal mucosa (PDO-N), characterize their distinct features, and evaluate their impact on drug response.</div></div><div><h3>Design</h3><div>PDOs were generated from primary OSCC tissues and matched adjacent normal mucosa obtained from 18 patients. Morphological and histological characteristics were assessed using brightfield microscopy and phalloidin staining. Immunohistochemistry was performed to evaluate differential marker expression. Drug response assays were conducted in paired PDO-T and PDO-N to assess chemotherapeutic sensitivity.</div></div><div><h3>Results</h3><div>We successfully established 5 PDO-T and 15 PDO-N lines, with PDO-N exhibiting a higher success rate (∼80 %). Morphological analysis showed that PDO-N formed spherical structures with a central cavity and polarity, while PDO-T displayed irregular structures with heterogeneous cell arrangements. Immunohistochemistry revealed broad distribution of Ki-67, p63 and YAP/TAZ in PDO-T, contrasting with their basal layer restriction in PDO-N. p53 was strongly positive in PDO-T. CK5 and CK13 exhibited a stratified pattern in PDO-N. Importantly, drug testing in paired PDO-T and PDO-N revealed divergent responses, with PDO-N generally more resistant and able to maintain morphological integrity under high-dose treatment.</div></div><div><h3>Conclusion</h3><div>Our comparative analysis delineates distinct features between PDO-T and PDO-N in morphology, biomarker expression, and drug response. These findings provide an intuitive framework for their identification, thereby improving the accuracy of drug screening and enhancing the translational value of PDOs.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106520"},"PeriodicalIF":2.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001701","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
Liraglutide enhances bone regeneration in a critical-size calvarial defect model in male rats: A comparative study with autogenous grafts, allografts, and xenografts 利拉鲁肽促进雄性大鼠临界尺寸颅骨缺损模型中的骨再生:自体、同种异体和异种骨移植的比较研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-15 DOI: 10.1016/j.archoralbio.2026.106519
Necati Zavrak , Aysan Lektemur Alpan , Özlem Özmen

Objective

Bone grafting materials are widely used in the treatment of critical-sized bone defects, and pharmacological agents with the potential to enhance their regenerative potential have been of great interest. The purpose of this study was to investigate the effect of the glucagon-like peptide-1 receptor agonist Liraglutide on bone regeneration when combined with different grafting materials.

Design

Critical-sized calvarial defects with a 5 mm diameter were created bilaterally in rats, and eight experimental groups were formed: Control, autogenous graft, allograft, xenograft, and the combination of each graft material with Liraglutide. Bone healing was evaluated through histomorphometric analyses and micro-computed tomography (micro-CT). analyses. Immunohistochemical analyses for β-catenin, BMP-2, osterix, osteoprotegerin, RANKL, and Runx2 were performed.

Results

Histomorphometric data demonstrated that Liraglutide significantly enhanced the osteogenic performance of the grafts, resulting in greater new bone formation and defect closure (p < 0.05). The Liraglutide-Autogenous graft group showed the highest levels of new bone formation and defect closure. Immunohistochemical results revealed that Liraglutide promoted osteoblastic activity while suppressing osteoclastic activity. Micro-CT findings supported these outcomes, indicating significant improvements in bone volume, trabecular thickness, and structural integrity.

Conclusion

Liraglutide enhances bone healing and exerts a synergistic effect when used in combination with bone grafts. These findings suggest that Liraglutide serves as a promising adjunct in bone tissue engineering and regenerative medicine.
目的骨移植材料被广泛用于治疗临界尺寸骨缺损,而能够增强其再生潜能的药物一直是人们关注的焦点。本研究旨在探讨胰高血糖素样肽-1受体激动剂利拉鲁肽与不同移植材料联合使用对骨再生的影响。设计在大鼠双侧制造直径为5 mm的临界尺寸颅骨缺损,并形成8个实验组:对照组、自体移植物组、同种异体移植物组、异种移植物组以及每种移植物材料与利拉鲁肽的联合组。通过组织形态学分析和显微计算机断层扫描(micro-CT)评估骨愈合。分析。免疫组化分析β-catenin、BMP-2、osterix、osteoprotegerin、RANKL和Runx2。结果同种形态数据显示,利拉鲁肽显著提高了移植物的成骨性能,导致了更大的新骨形成和缺损闭合(p <; 0.05)。利拉鲁肽自体移植物组显示出最高水平的新骨形成和缺损闭合。免疫组化结果显示利拉鲁肽促进成骨细胞活性,抑制破骨细胞活性。显微ct结果支持这些结果,显示骨体积、骨小梁厚度和结构完整性显著改善。结论利拉鲁肽与骨移植联合应用可促进骨愈合,并具有协同作用。这些发现表明利拉鲁肽在骨组织工程和再生医学中具有很好的辅助作用。
{"title":"Liraglutide enhances bone regeneration in a critical-size calvarial defect model in male rats: A comparative study with autogenous grafts, allografts, and xenografts","authors":"Necati Zavrak ,&nbsp;Aysan Lektemur Alpan ,&nbsp;Özlem Özmen","doi":"10.1016/j.archoralbio.2026.106519","DOIUrl":"10.1016/j.archoralbio.2026.106519","url":null,"abstract":"<div><h3>Objective</h3><div>Bone grafting materials are widely used in the treatment of critical-sized bone defects, and pharmacological agents with the potential to enhance their regenerative potential have been of great interest. The purpose of this study was to investigate the effect of the glucagon-like peptide-1 receptor agonist Liraglutide on bone regeneration when combined with different grafting materials.</div></div><div><h3>Design</h3><div>Critical-sized calvarial defects with a 5 mm diameter were created bilaterally in rats, and eight experimental groups were formed: Control, autogenous graft, allograft, xenograft, and the combination of each graft material with Liraglutide. Bone healing was evaluated through histomorphometric analyses and micro-computed tomography (micro-CT). analyses. Immunohistochemical analyses for β-catenin, BMP-2, osterix, osteoprotegerin, RANKL, and Runx2 were performed.</div></div><div><h3>Results</h3><div>Histomorphometric data demonstrated that Liraglutide significantly enhanced the osteogenic performance of the grafts, resulting in greater new bone formation and defect closure (p &lt; 0.05). The Liraglutide-Autogenous graft group showed the highest levels of new bone formation and defect closure. Immunohistochemical results revealed that Liraglutide promoted osteoblastic activity while suppressing osteoclastic activity. Micro-CT findings supported these outcomes, indicating significant improvements in bone volume, trabecular thickness, and structural integrity.</div></div><div><h3>Conclusion</h3><div>Liraglutide enhances bone healing and exerts a synergistic effect when used in combination with bone grafts. These findings suggest that Liraglutide serves as a promising adjunct in bone tissue engineering and regenerative medicine.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106519"},"PeriodicalIF":2.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036887","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
Is salivary melatonin an indicator of periodontal disease severity? A systematic review and meta-analysis 唾液褪黑素是牙周病严重程度的指标吗?系统回顾和荟萃分析
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-01-15 DOI: 10.1016/j.archoralbio.2026.106518
Rodrigo Martins dos Santos , Franciane Duarte Gonçalves , Liliane Moretti Carneiro , Maria Sara de Lima Coutinho Mattera , Ana Carla Thalez Ywabuchi Nobumoto , Bianca Elvira Belardi , Thais Verônica Saori Tsosura , Gabriel Zopolatto Turci Dias , Gestter Willian Lattari Tessarin , Fernando Yamamoto Chiba

Objectives

To evaluate, through a systematic review and meta-analysis, the differences in salivary melatonin (S-MEL) levels between individuals with periodontal disease and healthy individuals.

Design

A systematic search was conducted in PubMed, EMBASE, SciELO, LILACS, and BIREME following PRISMA 2020 guidelines and PROSPERO registration. Human studies comparing patients with periodontal disease with healthy controls and reporting S-MEL were included. Screening occurred in two phases. Meta-analysis was performed in Jamovi using the MAJOR module, applying the standardized mean difference (SMD) (Hedges g), a random-effects model, heterogeneity statistics, and publication bias tests. Seventeen comparisons were included.

Results

The random-effects model showed significantly lower S-MEL levels in patients with periodontal disease (SMD = –2.04; 95 % confidence interval [CI] –3.44 to –0.63; p = 0.005), with high heterogeneity (I² = 97.8 %). Notably, most studies reported reduced melatonin levels, despite a few positive effects. Funnel plot asymmetry and Begg/Egger tests suggested publication bias, although trim-and-fill revealed no missing studies. The high fail-safe N supported the robustness of the findings.

Conclusions

S-MEL levels were consistently lower in patients with periodontal disease, suggesting a potential biomarker relationship. Despite the substantial heterogeneity, the overall evidence supports this association. However, further standardized studies are needed.
目的通过系统回顾和荟萃分析,评价牙周病患者和健康人群唾液褪黑素(S-MEL)水平的差异。按照PRISMA 2020指南和PROSPERO注册,在PubMed、EMBASE、SciELO、LILACS和BIREME中进行了系统搜索。人类研究将牙周病患者与健康对照进行比较,并报告S-MEL。筛选分两个阶段进行。在Jamovi中使用MAJOR模块进行meta分析,应用标准化平均差(SMD) (Hedges g)、随机效应模型、异质性统计和发表偏倚检验。包括17个比较。结果随机效应模型显示牙周病患者S-MEL水平显著降低(SMD = -2.04; 95 %置信区间[CI] -3.44 ~ -0.63; p = 0.005),异质性较高(I²= 97.8 %)。值得注意的是,尽管有一些积极的影响,但大多数研究都报告了褪黑激素水平的降低。漏斗图不对称和Begg/Egger检验表明发表偏倚,尽管修整和填充没有发现缺失的研究。高故障安全系数支持了研究结果的稳健性。结论牙周病患者ss - mel水平持续降低,提示可能存在生物标志物关系。尽管存在很大的异质性,但总体证据支持这种关联。然而,需要进一步的标准化研究。
{"title":"Is salivary melatonin an indicator of periodontal disease severity? A systematic review and meta-analysis","authors":"Rodrigo Martins dos Santos ,&nbsp;Franciane Duarte Gonçalves ,&nbsp;Liliane Moretti Carneiro ,&nbsp;Maria Sara de Lima Coutinho Mattera ,&nbsp;Ana Carla Thalez Ywabuchi Nobumoto ,&nbsp;Bianca Elvira Belardi ,&nbsp;Thais Verônica Saori Tsosura ,&nbsp;Gabriel Zopolatto Turci Dias ,&nbsp;Gestter Willian Lattari Tessarin ,&nbsp;Fernando Yamamoto Chiba","doi":"10.1016/j.archoralbio.2026.106518","DOIUrl":"10.1016/j.archoralbio.2026.106518","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate, through a systematic review and meta-analysis, the differences in salivary melatonin (S-MEL) levels between individuals with periodontal disease and healthy individuals.</div></div><div><h3>Design</h3><div>A systematic search was conducted in PubMed, EMBASE, SciELO, LILACS, and BIREME following PRISMA 2020 guidelines and PROSPERO registration. Human studies comparing patients with periodontal disease with healthy controls and reporting S-MEL were included. Screening occurred in two phases. Meta-analysis was performed in Jamovi using the MAJOR module, applying the standardized mean difference (SMD) (Hedges g), a random-effects model, heterogeneity statistics, and publication bias tests. Seventeen comparisons were included.</div></div><div><h3>Results</h3><div>The random-effects model showed significantly lower S-MEL levels in patients with periodontal disease (SMD = –2.04; 95 % confidence interval [CI] –3.44 to –0.63; p = 0.005), with high heterogeneity (I² = 97.8 %). Notably, most studies reported reduced melatonin levels, despite a few positive effects. Funnel plot asymmetry and Begg/Egger tests suggested publication bias, although trim-and-fill revealed no missing studies. The high fail-safe N supported the robustness of the findings.</div></div><div><h3>Conclusions</h3><div>S-MEL levels were consistently lower in patients with periodontal disease, suggesting a potential biomarker relationship. Despite the substantial heterogeneity, the overall evidence supports this association. However, further standardized studies are needed.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106518"},"PeriodicalIF":2.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075570","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
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Archives of oral biology
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