Pub Date : 2026-01-11DOI: 10.1016/j.archoralbio.2025.106493
Leonardo Moreira Teodosio , Ana Flavia Simões Barbosa , Alexandra Mussolino de Queiroz , Harley Francisco de Oliveira , Camila Andrade Zamperini , Jardel Francisco Mazzi-Chaves , Manoel D. Sousa-Neto , Yara Teresinha Corrêa Silva-Sousa , Fuad Jacob Abi Rached-Junior , Edson Alfredo , Fabiane Carneiro Lopes-Olhê
Objective
This study evaluated a novel methodology for assessing dentin wear resistance and morphological changes in teeth submitted to conventional (CR) or hypofractionated radiotherapy (HR).
Design
Fifteen maxillary canines were divided into three groups: control, CR (60 Gy, 2 Gy/day) and HR (55 Gy, 2.75 Gy/day). The roots were sectioned 3 mm from the apex and 3 mm above and fixed in acrylic resin and tested on a universal testing machine by measuring the force required to wear away the dentin. The specimens were submitted to microhardness analysis with indentations at 50, 100 and 150 µm from the radicular canal surface, scanning electron microscopy (SEM) to identify cracks and energy dispersive X-ray spectroscopy (EDS-X) to quantify calcium (Ca) and phosphorus (P) and analyze the Ca/P ratio.
Results
No significant difference in wear resistance (MPa) was detected between the irradiated groups (CR: 0.102 ± 0.01, HR: 0.111 ± 0.01) and the control group (0.114 ± 0.02) (p > 0.05). Lower microhardness values were observed in the irradiated groups (CR: 37.92 ± 5.78, HR: 32.71 ± 4.37) compared to the control (50.00 ± 3.31), with no difference between them (p > 0.05). The irradiated groups had a higher number of cracks compared to the control, and there was no statistically significant difference in the Ca/P ratio values between the groups tested (p > 0.05).
Conclusions
The new method assessed the wear resistance of dentin after radiotherapy reliably. Although wear resistance and the Ca/P ratio were not altered, both radiotherapy protocols reduced dentin microhardness.
{"title":"Evaluation of the effects induced by radiotherapy on dentin during endodontic instrumentation using a novel methodology for assessing wear resistance","authors":"Leonardo Moreira Teodosio , Ana Flavia Simões Barbosa , Alexandra Mussolino de Queiroz , Harley Francisco de Oliveira , Camila Andrade Zamperini , Jardel Francisco Mazzi-Chaves , Manoel D. Sousa-Neto , Yara Teresinha Corrêa Silva-Sousa , Fuad Jacob Abi Rached-Junior , Edson Alfredo , Fabiane Carneiro Lopes-Olhê","doi":"10.1016/j.archoralbio.2025.106493","DOIUrl":"10.1016/j.archoralbio.2025.106493","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluated a novel methodology for assessing dentin wear resistance and morphological changes in teeth submitted to conventional (CR) or hypofractionated radiotherapy (HR).</div></div><div><h3>Design</h3><div>Fifteen maxillary canines were divided into three groups: control, CR (60 Gy, 2 Gy/day) and HR (55 Gy, 2.75 Gy/day). The roots were sectioned 3 mm from the apex and 3 mm above and fixed in acrylic resin and tested on a universal testing machine by measuring the force required to wear away the dentin. The specimens were submitted to microhardness analysis with indentations at 50, 100 and 150 µm from the radicular canal surface, scanning electron microscopy (SEM) to identify cracks and energy dispersive X-ray spectroscopy (EDS-X) to quantify calcium (Ca) and phosphorus (P) and analyze the Ca/P ratio.</div></div><div><h3>Results</h3><div>No significant difference in wear resistance (MPa) was detected between the irradiated groups (CR: 0.102 ± 0.01, HR: 0.111 ± 0.01) and the control group (0.114 ± 0.02) (p > 0.05). Lower microhardness values were observed in the irradiated groups (CR: 37.92 ± 5.78, HR: 32.71 ± 4.37) compared to the control (50.00 ± 3.31), with no difference between them (p > 0.05). The irradiated groups had a higher number of cracks compared to the control, and there was no statistically significant difference in the Ca/P ratio values between the groups tested (p > 0.05).</div></div><div><h3>Conclusions</h3><div>The new method assessed the wear resistance of dentin after radiotherapy reliably. Although wear resistance and the Ca/P ratio were not altered, both radiotherapy protocols reduced dentin microhardness.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106493"},"PeriodicalIF":2.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000155","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}
Pub Date : 2026-01-10DOI: 10.1016/j.archoralbio.2026.106516
Drisya Soman , Jayanthi P , Mahesh CM , Rahul Radhakrishnan
Background
Antimicrobial peptides are integral components of the innate immune system and play a vital role in maintaining oral homeostasis. LL-37, the only human cathelicidin antimicrobial peptide, has gained increasing attention due to its broad-spectrum antimicrobial activity and diverse immunomodulatory functions within the oral cavity.
Objective
This narrative review aims to characterise the molecular structure, biological functions, and clinical relevance of LL-37 in oral health and disease.
Materials and methods
A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Google Scholar, to identify relevant in vitro, in vivo, and clinical studies evaluating the expression, mechanisms of action, and pathological implications of LL-37 in oral tissues.
Results
LL-37 is expressed by various oral tissues, including the gingival epithelium, salivary glands, and inflammatory cells, contributing to host defence against microbial challenges. In addition to its direct antimicrobial effects, LL-37 modulates inflammatory responses, promotes wound healing, and influences cellular proliferation and angiogenesis. Altered expression of LL-37 has been associated with the pathogenesis of several oral diseases, such as periodontitis, dental caries, endodontic infections, and oral squamous cell carcinoma.
Conclusion
LL-37 plays a multifaceted role in oral immunity by integrating antimicrobial, immunomodulatory, and tissue-regenerative functions. Enhanced understanding of its molecular characterisation and biological activities may support the development of LL-37 as a diagnostic biomarker and a potential therapeutic target in oral pathology.
{"title":"LL-37 antimicrobial peptide: Molecular characterisation and its role in oral health and disease–A narrative review","authors":"Drisya Soman , Jayanthi P , Mahesh CM , Rahul Radhakrishnan","doi":"10.1016/j.archoralbio.2026.106516","DOIUrl":"10.1016/j.archoralbio.2026.106516","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial peptides are integral components of the innate immune system and play a vital role in maintaining oral homeostasis. LL-37, the only human cathelicidin antimicrobial peptide, has gained increasing attention due to its broad-spectrum antimicrobial activity and diverse immunomodulatory functions within the oral cavity.</div></div><div><h3>Objective</h3><div>This narrative review aims to characterise the molecular structure, biological functions, and clinical relevance of LL-37 in oral health and disease.</div></div><div><h3>Materials and methods</h3><div>A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Google Scholar, to identify relevant in vitro, in vivo, and clinical studies evaluating the expression, mechanisms of action, and pathological implications of LL-37 in oral tissues.</div></div><div><h3>Results</h3><div>LL-37 is expressed by various oral tissues, including the gingival epithelium, salivary glands, and inflammatory cells, contributing to host defence against microbial challenges. In addition to its direct antimicrobial effects, LL-37 modulates inflammatory responses, promotes wound healing, and influences cellular proliferation and angiogenesis. Altered expression of LL-37 has been associated with the pathogenesis of several oral diseases, such as periodontitis, dental caries, endodontic infections, and oral squamous cell carcinoma.</div></div><div><h3>Conclusion</h3><div>LL-37 plays a multifaceted role in oral immunity by integrating antimicrobial, immunomodulatory, and tissue-regenerative functions. Enhanced understanding of its molecular characterisation and biological activities may support the development of LL-37 as a diagnostic biomarker and a potential therapeutic target in oral pathology.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106516"},"PeriodicalIF":2.1,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973708","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}
Pub Date : 2026-01-09DOI: 10.1016/j.archoralbio.2026.106515
Seok Bin Yang , Kyu Hwan Kwack , Jae-Hyung Lee , Ji-Hoi Moon
Objectives
Oral live microbial therapeutics (LMTs) show promise for halitosis, caries, and adjunctive periodontal care, yet benefits often fade after dosing stops. We synthesized evidence across indications and reframed development around quantifying and engineering persistence at intraoral sites, while outlining safety-by-design and delivery considerations for the oral niche.
Design
This narrative review integrated randomized trials, observational studies, and in vitro/ex vivo investigations to characterize clinical outcomes, persistence-related metrics, and engineering principles relevant to oral LMT development. Sources included PubMed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, with backward/forward citation tracking. We included studies on LMTs in oral or gut contexts when mechanistically informative for oral applications (e.g., persistence, delivery, or biocontainment). Eligibility required clinical outcomes or persistence-related readouts. Two reviewers screened records and resolved disagreements by consensus. Reporting and assay principles were informed by STORMS and MIQE to support transparent, reproducible methods.
Results
Across indications, effects typically peak during dosing and attenuate after cessation, varying with strain, delivery format, and co-interventions (e.g., tongue dorsum debridement; standardized periodontal care). Persistence is rarely co-measured with clinical endpoints, limiting mechanistic interpretation. We outline a site-resolved measurement set, including time above the limit-of-detection, colonization area under the curve, apparent half-life (t½), and t½ under oral-mimetic shear, together with an engineering toolkit combining mucoadhesive/enamel-interactive carriers, single-cell coatings, and multilayer biocontainment (e.g., logic-gated/CRISPR kill switches, synthetic auxotrophy), and chemistry, manufacturing, and controls considerations.
Conclusions
Embedding persistence metrics and safety-by-design into study protocols may support more durable outcomes, and standardized, site-resolved reporting will be essential for clinical translation.
目的:口服活微生物疗法(LMTs)显示出对口臭、龋齿和辅助牙周护理的希望,但在停止给药后,效果往往会消失。我们综合了适应症的证据,并围绕口腔内部位的量化和工程持久性重新制定了发展,同时概述了口腔生态位的安全性设计和交付考虑。设计:本综述综合了随机试验、观察性研究和体外/离体研究,以表征临床结果、持久性相关指标和与口服LMT开发相关的工程原理。来源包括PubMed/MEDLINE, Web of Science, Embase和ClinicalTrials.gov,具有向后/向前引文跟踪。我们纳入了在口服或肠道环境下的LMTs的研究,当机械信息用于口服应用时(例如,持久性,递送或生物遏制)。资格要求临床结果或持久性相关读数。两名审稿人筛选记录,并通过协商一致的方式解决分歧。报告和分析原则由STORMS和MIQE告知,以支持透明、可重复的方法。结果:在适应症中,效果通常在给药期间达到峰值,停药后减弱,随张力、给药形式和联合干预(如舌背清创、标准化牙周护理)而变化。持续性很少与临床终点同时测量,限制了机制解释。我们概述了一个位点分辨率的测量集,包括超过检测限的时间、曲线下的定植面积、表观半衰期(t1 / 2)和口腔模拟剪切下的t1 / 2,以及一个工程工具包,该工具包结合了粘接/搪膜相互作用载体、单细胞涂层和多层生物防护(例如逻辑门控/CRISPR终止开关、合成缺陷),以及化学、制造和控制方面的考虑。将持续性指标和安全性设计纳入研究方案可能会支持更持久的结果,标准化、现场解决的报告对临床翻译至关重要。
{"title":"Oral live microbial therapeutics: A synthetic biology roadmap toward durable oral microbiome-based therapies","authors":"Seok Bin Yang , Kyu Hwan Kwack , Jae-Hyung Lee , Ji-Hoi Moon","doi":"10.1016/j.archoralbio.2026.106515","DOIUrl":"10.1016/j.archoralbio.2026.106515","url":null,"abstract":"<div><h3>Objectives</h3><div>Oral live microbial therapeutics (LMTs) show promise for halitosis, caries, and adjunctive periodontal care, yet benefits often fade after dosing stops. We synthesized evidence across indications and reframed development around quantifying and engineering persistence at intraoral sites, while outlining safety-by-design and delivery considerations for the oral niche.</div></div><div><h3>Design</h3><div>This narrative review integrated randomized trials, observational studies, and <em>in vitro/ex vivo</em> investigations to characterize clinical outcomes, persistence-related metrics, and engineering principles relevant to oral LMT development. Sources included PubMed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, with backward/forward citation tracking. We included studies on LMTs in oral or gut contexts when mechanistically informative for oral applications (<em>e.g</em>., persistence, delivery, or biocontainment). Eligibility required clinical outcomes or persistence-related readouts. Two reviewers screened records and resolved disagreements by consensus. Reporting and assay principles were informed by STORMS and MIQE to support transparent, reproducible methods.</div></div><div><h3>Results</h3><div>Across indications, effects typically peak during dosing and attenuate after cessation, varying with strain, delivery format, and co-interventions (<em>e.g</em>., tongue dorsum debridement; standardized periodontal care). Persistence is rarely co-measured with clinical endpoints, limiting mechanistic interpretation. We outline a site-resolved measurement set, including time above the limit-of-detection, colonization area under the curve, apparent half-life (t½), and t½ under oral-mimetic shear, together with an engineering toolkit combining mucoadhesive/enamel-interactive carriers, single-cell coatings, and multilayer biocontainment (<em>e.g</em>., logic-gated/CRISPR kill switches, synthetic auxotrophy), and chemistry, manufacturing, and controls considerations.</div></div><div><h3>Conclusions</h3><div>Embedding persistence metrics and safety-by-design into study protocols may support more durable outcomes, and standardized, site-resolved reporting will be essential for clinical translation.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106515"},"PeriodicalIF":2.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973209","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}
In this study, we examine the role of the leucine-rich pentatricopeptide repeat-containing gene (LRPPRC) as a new m6A reader in head and neck squamous cell carcinoma (HNSCC). We also analyze its expression pattern, prognostic significance, and response to immunotherapy.
Design
LRPPRC expression was comprehensively analyzed in HNSCC using data from The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) and then validated in an independent patient cohort using real-time qPCR. The study further investigated the correlations between LRPPRC expression and methylation status, as well as their associations with clinicopathological features, patient prognosis, and immune profiles. Additionally, the impact of LRPPRC expression on the response to immunotherapy was assessed.
Results
We found that LRPPRC is significantly upregulated in HNSCC tissues and correlates with advanced clinicopathological features, nodal metastasis, and poor survival outcomes. In contrast, the DNA methylation level of LRPPRC was found to be reduced in HNSCC. Furthermore, LRPPRC expression is significantly correlated with infiltration of immune cells, specifically in CD4⁺ T cells, macrophages, and dendritic cells. Importantly, the expression of LRPPRC has been found to be a predictor of resistance to immunotherapy in patients with HNSCC.
Conclusion
Our findings suggest that LRPPRC may serve as a promising biomarker for HNSCC prognosis and a therapeutic target for controlling cancer metastases and enhancing patient outcomes, while being a predictor for immune therapy response as well.
{"title":"High expression of a novel m6A reader LRPPRC predicts immunotherapy response and prognosis in head and neck cancer","authors":"Karpakavinayakam Gopalakrishnan , Balachander Kannan , Vijayashree Priyadharsini Jayaseelan , Paramasivam Arumugam","doi":"10.1016/j.archoralbio.2026.106514","DOIUrl":"10.1016/j.archoralbio.2026.106514","url":null,"abstract":"<div><h3>Objective</h3><div>In this study, we examine the role of the leucine-rich pentatricopeptide repeat-containing gene (LRPPRC) as a new m6A reader in head and neck squamous cell carcinoma (HNSCC). We also analyze its expression pattern, prognostic significance, and response to immunotherapy.</div></div><div><h3>Design</h3><div>LRPPRC expression was comprehensively analyzed in HNSCC using data from The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) and then validated in an independent patient cohort using real-time qPCR. The study further investigated the correlations between LRPPRC expression and methylation status, as well as their associations with clinicopathological features, patient prognosis, and immune profiles. Additionally, the impact of LRPPRC expression on the response to immunotherapy was assessed.</div></div><div><h3>Results</h3><div>We found that LRPPRC is significantly upregulated in HNSCC tissues and correlates with advanced clinicopathological features, nodal metastasis, and poor survival outcomes. In contrast, the DNA methylation level of <em>LRPPRC</em> was found to be reduced in HNSCC. Furthermore, <em>LRPPRC</em> expression is significantly correlated with infiltration of immune cells, specifically in CD4⁺ T cells, macrophages, and dendritic cells. Importantly, the expression of LRPPRC has been found to be a predictor of resistance to immunotherapy in patients with HNSCC.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that LRPPRC may serve as a promising biomarker for HNSCC prognosis and a therapeutic target for controlling cancer metastases and enhancing patient outcomes, while being a predictor for immune therapy response as well.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106514"},"PeriodicalIF":2.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973210","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}
Pub Date : 2026-01-08DOI: 10.1016/j.archoralbio.2026.106511
Rawan Yassin Nimir , Homa Darmani
Objective(s)
We compared the antimicrobial and antivirulence activities of juglone, a plant-derived naphthoquinone, with chlorhexidine (CHX), a widely used dental antiseptic, against Enterococcus faecalis, a pathogen associated with persistent oral and endodontic infections.
Design
Antimicrobial efficacy was evaluated using well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Possible interactions between juglone and CHX were investigated using well diffusion and checkerboard methods. Antivirulence activity was assessed by measuring secreted enzymes (caseinase, gelatinase, and hemolysin), biofilm formation, metabolic activity, extracellular polymeric substance (EPS) production, and disruption of mature biofilms. Oxidative stress responses were examined through lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC).
Results
Juglone showed antibacterial activity with MICs in a similar range to CHX; however, no synergistic interaction between the two agents was observed. Juglone strongly inhibited caseinase, gelatinase, and hemolysin, whereas CHX showed no effect on caseinase and weaker inhibition of the others. CHX more effectively reduced early biofilm formation, metabolic activity, and mature biomass, whereas both agents similarly decreased EPS production and viability during biofilm development. Notably, in preformed biofilms, juglone at 16 ×MIC caused greater killing (∼4-log10 CFU) than CHX (∼2-log10). Both compounds increased LDH release and reduced SOD activity and T-AOC, while juglone uniquely decreased MDA levels, indicating additional redox-modulating effects.
Conclusions
Juglone impairs E. faecalis virulence by reducing enzymatic activity, oxidative stress tolerance, and biofilm viability, with stronger effects on established biofilms, highlighting its potential for further investigation in oral infection management.
{"title":"Antibacterial and anti-virulence activity of juglone against Enterococcus faecalis compared with chlorhexidine","authors":"Rawan Yassin Nimir , Homa Darmani","doi":"10.1016/j.archoralbio.2026.106511","DOIUrl":"10.1016/j.archoralbio.2026.106511","url":null,"abstract":"<div><h3>Objective(s)</h3><div>We compared the antimicrobial and antivirulence activities of juglone, a plant-derived naphthoquinone, with chlorhexidine (CHX), a widely used dental antiseptic, against <em>Enterococcus faecalis</em>, a pathogen associated with persistent oral and endodontic infections.</div></div><div><h3>Design</h3><div>Antimicrobial efficacy was evaluated using well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Possible interactions between juglone and CHX were investigated using well diffusion and checkerboard methods. Antivirulence activity was assessed by measuring secreted enzymes (caseinase, gelatinase, and hemolysin), biofilm formation, metabolic activity, extracellular polymeric substance (EPS) production, and disruption of mature biofilms. Oxidative stress responses were examined through lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC).</div></div><div><h3>Results</h3><div>Juglone showed antibacterial activity with MICs in a similar range to CHX; however, no synergistic interaction between the two agents was observed. Juglone strongly inhibited caseinase, gelatinase, and hemolysin, whereas CHX showed no effect on caseinase and weaker inhibition of the others. CHX more effectively reduced early biofilm formation, metabolic activity, and mature biomass, whereas both agents similarly decreased EPS production and viability during biofilm development. Notably, in preformed biofilms, juglone at 16 ×MIC caused greater killing (∼4-log<sub>10</sub> CFU) than CHX (∼2-log<sub>10</sub>). Both compounds increased LDH release and reduced SOD activity and T-AOC, while juglone uniquely decreased MDA levels, indicating additional redox-modulating effects.</div></div><div><h3>Conclusions</h3><div>Juglone impairs <em>E. faecalis</em> virulence by reducing enzymatic activity, oxidative stress tolerance, and biofilm viability, with stronger effects on established biofilms, highlighting its potential for further investigation in oral infection management.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106511"},"PeriodicalIF":2.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954223","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}
HOXD10 is implicated in the carcinogenesis and progression of various cancers, including oral cancer. However, its regulatory mechanism and functional role remain unclear.
Design
Matched normal and oral cancer tissue samples from patients stratified into oral potentially malignant disorders (OPMD, n = 25), lymph-node negative (LN(-), n = 25), and lymph-node positive (LN(+), n = 25) groups were analysed along with a panel of oral cancer cell lines. Expression was quantified by qRT-PCR and DNA methylation was profiled by methyl-capture sequencing followed by correlation analysis with expression. The DNA methyltransferase inhibitor(DNMTi): Decitabine(5-Aza-CdR) and histone deacetylase inhibitors(HDACi) – suberoylanilide hydroxamic acid(SAHA) and sodium butyrate(NaB) were used to evaluate epigenetic regulation in SCC9 cells. Promoter regions were characterized by dual luciferase assay and sodium butyrate effects on cell proliferation, migration and cell cycle were assessed.
Results
HOXD10 was significantly upregulated in OPMD and LN(+) groups and oral cancer cell lines but not in the LN(-) samples or across cancer stages/grades compared with normal controls. Promoter hypermethylation correlated positively, though not significantly, with expression. 5-Aza-CdR treatment did not alter HOXD10 levels, while HDACi treatment reduced expression. Two promoter regions were identified as active regulatory elements modulated by histone acetylation. Functionally, NaB impaired cell proliferation, migration and induced G2-M arrest. Survival analysis demonstrated modest prognostic value of HOXD10 alone but improved predictive accuracy for disease recurrence when integrated with tumor stage and grade.
Conclusion
HOXD10 expression in oral cancer is regulated predominantly via histone acetylation. These findings highlight its epigenetic regulation and suggest potential clinical relevance with tumor stage and grade although further studies are needed to confirm diagnostic or prognostic value.
目的:hoxd10参与多种癌症的发生和发展,包括口腔癌。但其调控机制和功能作用尚不清楚。设计将匹配的正常和口腔癌组织样本分为口腔潜在恶性疾病(OPMD, n = 25)、淋巴结阴性(LN(-), n = 25)和淋巴结阳性(LN(+), n = 25)组,并对一组口腔癌细胞系进行分析。通过qRT-PCR定量表达,通过甲基捕获测序分析DNA甲基化,然后进行与表达的相关性分析。采用DNA甲基转移酶抑制剂(DNMTi):地西他滨(5-Aza-CdR)和组蛋白去乙酰化酶抑制剂(HDACi) -亚eroylanilide羟肟酸(SAHA)和丁酸钠(NaB)评估SCC9细胞的表观遗传调控。用双荧光素酶法对启动子区域进行了表征,并评估了丁酸钠对细胞增殖、迁移和细胞周期的影响。结果与正常对照相比,OPMD组、LN(+)组和口腔癌细胞系中shoxd10表达显著上调,而LN(-)组和不同癌症分期/分级中shoxd10表达均不上调。启动子超甲基化与表达呈正相关,但不显著。5-Aza-CdR治疗没有改变HOXD10水平,而HDACi治疗降低了HOXD10的表达。两个启动子区域被确定为由组蛋白乙酰化调节的活性调控元件。功能上,NaB损害细胞增殖、迁移和诱导G2-M阻滞。生存分析显示HOXD10单独的预后价值不大,但当结合肿瘤分期和分级时,疾病复发的预测准确性提高。结论hoxd10在口腔癌组织中的表达主要受组蛋白乙酰化调控。这些发现强调了其表观遗传调控,并提示与肿瘤分期和分级的潜在临床相关性,尽管需要进一步的研究来确认诊断或预后价值。
{"title":"HOXD10 expression in oral cancer is driven by histone acetylation rather than promoter DNA methylation","authors":"Dhanraj Salur Basavarajappa , U Sangeetha Shenoy , Naveena Kumar AN , Shama Prasada Kabekkodu , Sanjiban Chakrabarty , Raghu Radhakrishnan","doi":"10.1016/j.archoralbio.2026.106512","DOIUrl":"10.1016/j.archoralbio.2026.106512","url":null,"abstract":"<div><h3>Objective</h3><div><em>HOXD10</em> is implicated in the carcinogenesis and progression of various cancers, including oral cancer. However, its regulatory mechanism and functional role remain unclear.</div></div><div><h3>Design</h3><div>Matched normal and oral cancer tissue samples from patients stratified into oral potentially malignant disorders (OPMD, n = 25), lymph-node negative (LN(-), n = 25), and lymph-node positive (LN(+), n = 25) groups were analysed along with a panel of oral cancer cell lines. Expression was quantified by qRT-PCR and DNA methylation was profiled by methyl-capture sequencing followed by correlation analysis with expression. The DNA methyltransferase inhibitor(DNMTi): Decitabine(5-Aza-CdR) and histone deacetylase inhibitors(HDACi) – suberoylanilide hydroxamic acid(SAHA) and sodium butyrate(NaB) were used to evaluate epigenetic regulation in SCC9 cells. Promoter regions were characterized by dual luciferase assay and sodium butyrate effects on cell proliferation, migration and cell cycle were assessed.</div></div><div><h3>Results</h3><div><em>HOXD10</em> was significantly upregulated in OPMD and LN(+) groups and oral cancer cell lines but not in the LN(-) samples or across cancer stages/grades compared with normal controls. Promoter hypermethylation correlated positively, though not significantly, with expression. 5-Aza-CdR treatment did not alter <em>HOXD10</em> levels, while HDACi treatment reduced expression. Two promoter regions were identified as active regulatory elements modulated by histone acetylation. Functionally, NaB impaired cell proliferation, migration and induced G2-M arrest. Survival analysis demonstrated modest prognostic value of <em>HOXD10</em> alone but improved predictive accuracy for disease recurrence when integrated with tumor stage and grade.</div></div><div><h3>Conclusion</h3><div><em>HOXD10</em> expression in oral cancer is regulated predominantly via histone acetylation. These findings highlight its epigenetic regulation and suggest potential clinical relevance with tumor stage and grade although further studies are needed to confirm diagnostic or prognostic value.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106512"},"PeriodicalIF":2.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973208","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}
Pub Date : 2026-01-08DOI: 10.1016/j.archoralbio.2026.106504
Luis Limo , Justin Donovan , Stephanie Frisbee , Noha Gomaa
Objectives
To map and synthesise current evidence on how lifelong biological, environmental, and social exposures, collectively conceptualised as the exposome, interact with the human oral microbiome to influence oral disease development and progression within a One Health framework.
Design
A scoping review was conducted to identify peer-reviewed studies published in English that examined the relationships between the exposome and the human oral microbiome. The review followed the Arksey and O’Malley framework, applying its five-stage methodological approach. Comprehensive searches were performed in MEDLINE, Embase, PsycInfo, Scopus, Web of Science, and CINAHL. Study quality was assessed using the Joanna Briggs Institute (JBI) tools, and results were reported in accordance with PRISMA-ScR guidelines.
Results
A total of twenty-nine studies were included in this review. These showed that health status, non-communicable diseases, medication use, and psychosocial factors influence the biodiversity, abundance, and function of the human oral microbiome. Other studies suggested that animal interactions and physical and chemical exposures can alter host-microbiome interactions, as well as microbial community dynamics within the oral cavity. While the studies reviewed used reliable methods and standardized protocols, they were of moderate quality due to small sample sizes, potential reverse causality, and limited control for confounding and multiple testing.
Conclusion
This review highlights the complexity of the human oral microbiome and its interactions with the various components of the exposome, emphasizing the focus on disease impact and health behaviours, while noting a gap in research on non-bacterial communities, interaction mechanisms, and long-term effects on dysbiosis.
目标:绘制和综合目前的证据,说明终身生物、环境和社会暴露(统称为暴露者)如何与人类口腔微生物群相互作用,从而影响“同一个健康”框架下口腔疾病的发展和进展。设计:进行了一项范围审查,以确定发表的同行评议的英文研究,这些研究检查了暴露体与人类口腔微生物群之间的关系。该评估遵循Arksey和O'Malley框架,采用其五阶段方法方法。在MEDLINE、Embase、PsycInfo、Scopus、Web of Science和CINAHL中进行综合检索。使用Joanna Briggs Institute (JBI)工具评估研究质量,并根据PRISMA-ScR指南报告结果。结果:本综述共纳入29项研究。这些研究表明,健康状况、非传染性疾病、药物使用和社会心理因素会影响人类口腔微生物群的生物多样性、丰度和功能。其他研究表明,动物相互作用和物理和化学暴露可以改变宿主-微生物组相互作用,以及口腔内微生物群落动态。虽然回顾的研究使用了可靠的方法和标准化的方案,但由于样本量小,潜在的反向因果关系,以及对混杂和多重测试的控制有限,它们的质量一般。结论:本综述强调了人类口腔微生物群的复杂性及其与暴露体各组成部分的相互作用,强调了疾病影响和健康行为的重点,同时指出了非细菌群落、相互作用机制和对生态失调的长期影响的研究空白。
{"title":"The exposome and the human oral microbiome through the one health lens","authors":"Luis Limo , Justin Donovan , Stephanie Frisbee , Noha Gomaa","doi":"10.1016/j.archoralbio.2026.106504","DOIUrl":"10.1016/j.archoralbio.2026.106504","url":null,"abstract":"<div><h3>Objectives</h3><div>To map and synthesise current evidence on how lifelong biological, environmental, and social exposures, collectively conceptualised as the exposome, interact with the human oral microbiome to influence oral disease development and progression within a One Health framework.</div></div><div><h3>Design</h3><div>A scoping review was conducted to identify peer-reviewed studies published in English that examined the relationships between the exposome and the human oral microbiome. The review followed the Arksey and O’Malley framework, applying its five-stage methodological approach. Comprehensive searches were performed in MEDLINE, Embase, PsycInfo, Scopus, Web of Science, and CINAHL. Study quality was assessed using the Joanna Briggs Institute (JBI) tools, and results were reported in accordance with PRISMA-ScR guidelines.</div></div><div><h3>Results</h3><div>A total of twenty-nine studies were included in this review. These showed that health status, non-communicable diseases, medication use, and psychosocial factors influence the biodiversity, abundance, and function of the human oral microbiome. Other studies suggested that animal interactions and physical and chemical exposures can alter host-microbiome interactions, as well as microbial community dynamics within the oral cavity. While the studies reviewed used reliable methods and standardized protocols, they were of moderate quality due to small sample sizes, potential reverse causality, and limited control for confounding and multiple testing.</div></div><div><h3>Conclusion</h3><div>This review highlights the complexity of the human oral microbiome and its interactions with the various components of the exposome, emphasizing the focus on disease impact and health behaviours, while noting a gap in research on non-bacterial communities, interaction mechanisms, and long-term effects on dysbiosis.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106504"},"PeriodicalIF":2.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020982","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}
Pub Date : 2026-01-06DOI: 10.1016/j.archoralbio.2025.106496
Zhonghua Wang , Zhenli Liu , Sai Ma , Xiaohui Jia , Xu Zhang , Zhiyi Zhang , Chao Li , Jinping Xiao , Yan Si
Background
Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues. Berberine (BBR), a natural alkaloid with anti-inflammatory and antioxidant properties, has shown potential in treating inflammatory diseases.
Methods
Differentially expressed genes (DEGs) between periodontitis and healthy gingival tissues were identified using the GSE23586 and GSE173078 datasets, while chronic periodontitis-related genes were retrieved from the GeneCards database. Key genes were screened through support vector machine (SVM) and random forest (RF) algorithms, molecular docking, and normal mode analysis. In vitro, human gingival fibroblast-1 (HGF-1) cells were treated with lipopolysaccharide (LPS) to simulate periodontitis.
Results
Six key genes (KRT14, IGFBP6, LRG1, MZB1, DEFB103A, and CD79A) were identified by both SVM and RF algorithms. LRG1 was selected for further study due to its significant downregulation after BBR treatment in LPS-treated HGF-1 cells. LPS treatment increased LRG1 expression and the p-p38/p38 ratio, whereas these effects reversed by BBR treatment. Overexpression of LRG1 diminished BBR’s inhibitory effect on p-p38/p38, while the p38 MAPK pathway inhibitor restored BBR’s efficacy. BBR treatment suppressed LPS-induced inflammatory response, oxidative stress, and ECM degradation, but these effects were relieved by ectopic LRG1 expression.
Conclusion
BBR alleviated LPS-induced periodontitis by inhibiting inflammation, oxidative stress, and ECM degradation through inactivation of the LRG1/p38 MAPK signaling pathway. These findings highlight BBR’s potential as a therapeutic agent for periodontitis, offering a novel molecular target for clinical intervention. Further in vivo studies are warranted to validate its clinical application.
{"title":"Investigating the mechanism of berberine in inhibiting periodontitis progression using machine learning, molecular docking, and experimental validation","authors":"Zhonghua Wang , Zhenli Liu , Sai Ma , Xiaohui Jia , Xu Zhang , Zhiyi Zhang , Chao Li , Jinping Xiao , Yan Si","doi":"10.1016/j.archoralbio.2025.106496","DOIUrl":"10.1016/j.archoralbio.2025.106496","url":null,"abstract":"<div><h3>Background</h3><div>Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues. Berberine (BBR), a natural alkaloid with anti-inflammatory and antioxidant properties, has shown potential in treating inflammatory diseases.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) between periodontitis and healthy gingival tissues were identified using the GSE23586 and GSE173078 datasets, while chronic periodontitis-related genes were retrieved from the GeneCards database. Key genes were screened through support vector machine (SVM) and random forest (RF) algorithms, molecular docking, and normal mode analysis. In vitro, human gingival fibroblast-1 (HGF-1) cells were treated with lipopolysaccharide (LPS) to simulate periodontitis.</div></div><div><h3>Results</h3><div>Six key genes (KRT14, IGFBP6, LRG1, MZB1, DEFB103A, and CD79A) were identified by both SVM and RF algorithms. LRG1 was selected for further study due to its significant downregulation after BBR treatment in LPS-treated HGF-1 cells. LPS treatment increased LRG1 expression and the p-p38/p38 ratio, whereas these effects reversed by BBR treatment. Overexpression of LRG1 diminished BBR’s inhibitory effect on p-p38/p38, while the p38 MAPK pathway inhibitor restored BBR’s efficacy. BBR treatment suppressed LPS-induced inflammatory response, oxidative stress, and ECM degradation, but these effects were relieved by ectopic LRG1 expression.</div></div><div><h3>Conclusion</h3><div>BBR alleviated LPS-induced periodontitis by inhibiting inflammation, oxidative stress, and ECM degradation through inactivation of the LRG1/p38 MAPK signaling pathway. These findings highlight BBR’s potential as a therapeutic agent for periodontitis, offering a novel molecular target for clinical intervention. Further in vivo studies are warranted to validate its clinical application.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106496"},"PeriodicalIF":2.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973709","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}
Pub Date : 2025-12-31DOI: 10.1016/j.archoralbio.2025.106495
Renata de Oliveira Alves , José Roberto Vergínio de Matos , Matheus Henrique Faccioli Ragghianti , Isabela Maria Passarela Gomes , Isabela dos Santos de Deus , Pamela Barbosa dos Santos , Marcelle Danelon , Gabriel Pereira Nunes
Objective
This systematic review and meta-analysis (SRM) investigated the potential of garlic (Allium sativum) against cariogenic oral microorganisms.
Design
The SRM was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251133140). Randomized clinical trials (RCTs) evaluating garlic or garlic-derived compounds on cariogenic oral microorganisms were included. A literature search was performed in the main scientific databases. Meta-analyses were performed using RevMan software, with standardized mean difference (SMD) as the effect measure, and a random-effects model was applied with 95 % confidence intervals. Risk of bias was assessed using the Cochrane tool, and the certainty of evidence was graded according to the GRADE approach.
Results
Nine RCTs fulfilled the inclusion criteria, predominantly assessing S. mutans, followed by Lactobacillus spp. and C. albicans. All included trials employed garlic-based mouthwashes as the intervention and consistently demonstrated significant antimicrobial activity. In meta-analysis, compared to chlorhexidine, garlic reduced S. mutans at 1 week (SMD = −0.73, 95 % CI = −1.39 to −0.07, I² = 73 %; p = 0.03), had a slightly lower effect at 2 weeks (SMD = 1.27, 95 % CI = 0.09–2.44, I² = 90 %; p = 0.03), and showed no difference at 1 month (SMD = −0.54, 95 % CI = −2.78–1.70, I² = 96 %; p = 0.64). Compared to sodium fluoride, it demonstrated superior activity at 2 weeks (SMD = −0.79, 95 % CI = −1.22 to −0.36, I² = 0 %; p = 0.0003). Most studies had a low risk of bias, and the certainty of the evidence was rated low.
Conclusions
Garlic-based mouthrinses show significant antimicrobial activity against cariogenic microorganisms, supporting their potential as a phytotherapeutic strategy for biofilm control. However, the evidence remains limited, demonstrating the need for further high-quality clinical trials to confirm long-term efficacy.
{"title":"Antimicrobial effect of garlic-based mouthwash on dental caries-related oral microorganisms: A systematic review and meta-analysis","authors":"Renata de Oliveira Alves , José Roberto Vergínio de Matos , Matheus Henrique Faccioli Ragghianti , Isabela Maria Passarela Gomes , Isabela dos Santos de Deus , Pamela Barbosa dos Santos , Marcelle Danelon , Gabriel Pereira Nunes","doi":"10.1016/j.archoralbio.2025.106495","DOIUrl":"10.1016/j.archoralbio.2025.106495","url":null,"abstract":"<div><h3>Objective</h3><div>This systematic review and meta-analysis (SRM) investigated the potential of garlic (<em>Allium sativum</em>) against cariogenic oral microorganisms.</div></div><div><h3>Design</h3><div>The SRM was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251133140). Randomized clinical trials (RCTs) evaluating garlic or garlic-derived compounds on cariogenic oral microorganisms were included. A literature search was performed in the main scientific databases. Meta-analyses were performed using RevMan software, with standardized mean difference (SMD) as the effect measure, and a random-effects model was applied with 95 % confidence intervals. Risk of bias was assessed using the Cochrane tool, and the certainty of evidence was graded according to the GRADE approach.</div></div><div><h3>Results</h3><div>Nine RCTs fulfilled the inclusion criteria, predominantly assessing <em>S. mutans</em>, followed by <em>Lactobacillus spp</em>. and <em>C. albicans</em>. All included trials employed garlic-based mouthwashes as the intervention and consistently demonstrated significant antimicrobial activity. In meta-analysis, compared to chlorhexidine, garlic reduced <em>S. mutans</em> at 1 week (SMD = −0.73, 95 % CI = −1.39 to −0.07, I² = 73 %; p = 0.03), had a slightly lower effect at 2 weeks (SMD = 1.27, 95 % CI = 0.09–2.44, I² = 90 %; p = 0.03), and showed no difference at 1 month (SMD = −0.54, 95 % CI = −2.78–1.70, I² = 96 %; p = 0.64). Compared to sodium fluoride, it demonstrated superior activity at 2 weeks (SMD = −0.79, 95 % CI = −1.22 to −0.36, I² = 0 %; p = 0.0003). Most studies had a low risk of bias, and the certainty of the evidence was rated low.</div></div><div><h3>Conclusions</h3><div>Garlic-based mouthrinses show significant antimicrobial activity against cariogenic microorganisms, supporting their potential as a phytotherapeutic strategy for biofilm control. However, the evidence remains limited, demonstrating the need for further high-quality clinical trials to confirm long-term efficacy.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106495"},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901753","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}