Pub Date : 2025-10-14DOI: 10.1016/j.archoralbio.2025.106425
Yingshun Yang , Kaicheng Yang , Shixiong Peng , Shasha Man , He Chen
Objective
To investigate the molecular mechanisms underlying how Twinfilin actin-binding protein 1 (TWF1) drives the malignant progression of head and neck squamous cell carcinoma (HNSCC).
Design
A pan-cancer analysis of TCGA datasets was performed to evaluate TWF1 expression and prognostic significance, followed by validation using quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in clinical HNSCC specimens. Functional assays (CCK-8, colony formation, wound healing, and Transwell invasion) were conducted following siRNA-mediated TWF1 knockdown in SCC9 cells. Additionally, the same functional assays were conducted in an HSC3 cell model overexpressing TWF1 to further evaluate its oncogenic function. The involvement of the AKT signaling pathway was examined by Western blot and validated through rescue experiments with the AKT activator SC79.
Results
TWF1 was found to be upregulated in 13 cancer types, including HNSCC. Elevated TWF1 expression, advanced T stage, and lymph node metastasis were identified as independent prognostic indicators in HNSCC. qPCR confirmed increased TWF1 expression, and IHC showed higher TWF1 protein levels in HNSCC tissues. TWF1 knockdown suppressed SCC9 cell proliferation, migration, and invasion, and reduced phosphorylated AKT levels. Conversely, TWF1 overexpression in HSC3 cells promoted proliferation, migration, and invasion while enhancing AKT phosphorylation. SC79 treatment partially reversed the malignant phenotypes suppressed by TWF1 knockdown, supporting TWF1’s regulatory role through AKT phosphorylation.
Conclusion
TWF1 acts as an oncogenic driver in HNSCC, promoting tumor progression through the AKT signaling pathway. It may serve as a potential therapeutic target in precision medicine for HNSCC.
目的:探讨Twinfilin actin-binding protein 1 (TWF1)驱动头颈部鳞状细胞癌(HNSCC)恶性进展的分子机制。设计:对TCGA数据集进行泛癌分析,评估TWF1的表达和预后意义,随后使用定量实时PCR (qPCR)和免疫组织化学(IHC)对临床HNSCC标本进行验证。在SCC9细胞中sirna介导的TWF1敲除后进行功能测定(CCK-8、菌落形成、伤口愈合和Transwell侵袭)。此外,在过表达TWF1的HSC3细胞模型中进行了相同的功能测定,以进一步评估其致癌功能。通过Western blot检测AKT信号通路的参与情况,并通过AKT激活剂SC79的拯救实验进行验证。结果:在包括HNSCC在内的13种癌症类型中发现TWF1表达上调。TWF1表达升高、T分期晚期和淋巴结转移被确定为HNSCC的独立预后指标。qPCR证实TWF1表达升高,IHC显示HNSCC组织中TWF1蛋白水平升高。TWF1敲除抑制SCC9细胞增殖、迁移和侵袭,降低磷酸化AKT水平。相反,在HSC3细胞中,TWF1过表达促进增殖、迁移和侵袭,同时增强AKT磷酸化。SC79治疗部分逆转了TWF1敲低抑制的恶性表型,支持了TWF1通过AKT磷酸化的调节作用。结论:TWF1在HNSCC中发挥致癌驱动作用,通过AKT信号通路促进肿瘤进展。它可能成为HNSCC精准医学的潜在治疗靶点。
{"title":"TWF1 promotes tumor progression in head and neck squamous cell carcinoma via AKT phosphorylation","authors":"Yingshun Yang , Kaicheng Yang , Shixiong Peng , Shasha Man , He Chen","doi":"10.1016/j.archoralbio.2025.106425","DOIUrl":"10.1016/j.archoralbio.2025.106425","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the molecular mechanisms underlying how Twinfilin actin-binding protein 1 (TWF1) drives the malignant progression of head and neck squamous cell carcinoma (HNSCC).</div></div><div><h3>Design</h3><div>A pan-cancer analysis of TCGA datasets was performed to evaluate <em>TWF1</em> expression and prognostic significance, followed by validation using quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in clinical HNSCC specimens. Functional assays (CCK-8, colony formation, wound healing, and Transwell invasion) were conducted following siRNA-mediated TWF1 knockdown in SCC9 cells. Additionally, the same functional assays were conducted in an HSC3 cell model overexpressing TWF1 to further evaluate its oncogenic function. The involvement of the AKT signaling pathway was examined by Western blot and validated through rescue experiments with the AKT activator SC79.</div></div><div><h3>Results</h3><div><em>TWF1</em> was found to be upregulated in 13 cancer types, including HNSCC. Elevated <em>TWF1</em> expression, advanced T stage, and lymph node metastasis were identified as independent prognostic indicators in HNSCC. qPCR confirmed increased <em>TWF1</em> expression, and IHC showed higher TWF1 protein levels in HNSCC tissues. TWF1 knockdown suppressed SCC9 cell proliferation, migration, and invasion, and reduced phosphorylated AKT levels. Conversely, TWF1 overexpression in HSC3 cells promoted proliferation, migration, and invasion while enhancing AKT phosphorylation. SC79 treatment partially reversed the malignant phenotypes suppressed by TWF1 knockdown, supporting TWF1’s regulatory role through AKT phosphorylation.</div></div><div><h3>Conclusion</h3><div>TWF1 acts as an oncogenic driver in HNSCC, promoting tumor progression through the AKT signaling pathway. It may serve as a potential therapeutic target in precision medicine for HNSCC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106425"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357221","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 : 2025-10-14DOI: 10.1016/j.archoralbio.2025.106427
Thaysa Fernandes Pinto Mendes , Adrianne Caroline Pereira dos Santos Lima , Eva Aline Costa Cutrim , Paulo Sérgio de Araújo Sousa , Durcilene Alves da Silva , Lucas Antonio Duarte Nicolau , Leily Macedo Firoozmand
Objective
To evaluate, in vitro, the topical effect of polysaccharide cashew gum (PLS-cg) on dentine subjected to erosive cycles that simulate refluxate contact in the oral cavity.
Design
Human dentine blocks were prepared, standardized, and randomly assigned to one of three treatment groups (n = 10): control group (C) without treatment, commercial dental varnish (CDV) 5 % NaF fluoride varnish, and PLS-cg extract (experimental group). The baseline enamel superficial microhardness (HK) and roughness (Ra) were assessed. The dentin was subjected to erosive cycles (6 × 5 min/day for 9 days) using a hydrochloric acid–pepsin solution (pH 2; 0.75-mg/mL pepsin). Surface roughness (Ra), microhardness (HK), percentage surface hardness loss (%SHL), and topographic analysis with scanning electron microscopy (SEM) were used to evaluate the protective heteropolysaccharide effect. Predictive molecular docking simulations were used to investigate possible interactions between PLS-cg and metalloproteinases (MMP2 and MMP9). The data were analyzed with two-way analysis of variance, t test, Pearson’s correlation, and Tukey’s test (p < 0.05).
Results
PLS-cg preserved HK significantly better than the control group (p < 0.001), with the lowest %SHL (-14.04 ± 8.22) and minimal Ra changes (0.124 ± 0.005). Pearson’s correlation between Ra and %SHL was significant and positive (0.7740, p < 0.001). SEM analysis revealed more prominent dentinal tubule openings in the control group, whereas CDV and PLS-cg showed tubule obliteration. Molecular docking identified possible interactions between PLS-cg and MMPs.
Conclusion
The findings indicate that PLS-cg may reduce dentine erosion caused by supraesophageal manifestations of gastroesophageal reflux disease.
{"title":"Topical effect of polysaccharide cashew gum on the mitigation of dentin erosion progression under in vitro supraesophageal reflux simulation","authors":"Thaysa Fernandes Pinto Mendes , Adrianne Caroline Pereira dos Santos Lima , Eva Aline Costa Cutrim , Paulo Sérgio de Araújo Sousa , Durcilene Alves da Silva , Lucas Antonio Duarte Nicolau , Leily Macedo Firoozmand","doi":"10.1016/j.archoralbio.2025.106427","DOIUrl":"10.1016/j.archoralbio.2025.106427","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate, <em>in vitro</em>, the topical effect of polysaccharide cashew gum (PLS-cg) on dentine subjected to erosive cycles that simulate refluxate contact in the oral cavity.</div></div><div><h3>Design</h3><div>Human dentine blocks were prepared, standardized, and randomly assigned to one of three treatment groups (<em>n</em> = 10): control group (C) without treatment, commercial dental varnish (CDV) 5 % NaF fluoride varnish, and PLS-cg extract (experimental group). The baseline enamel superficial microhardness (HK) and roughness (Ra) were assessed. The dentin was subjected to erosive cycles (6 × 5 min/day for 9 days) using a hydrochloric acid–pepsin solution (pH 2; 0.75-mg/mL pepsin). Surface roughness (Ra), microhardness (HK), percentage surface hardness loss (%SHL), and topographic analysis with scanning electron microscopy (SEM) were used to evaluate the protective heteropolysaccharide effect. Predictive molecular docking simulations were used to investigate possible interactions between PLS-cg and metalloproteinases (MMP2 and MMP9). The data were analyzed with two-way analysis of variance, <em>t</em> test, Pearson’s correlation, and Tukey’s test (<em>p</em> < 0.05).</div></div><div><h3>Results</h3><div>PLS-cg preserved HK significantly better than the control group (<em>p</em> < 0.001), with the lowest %SHL (-14.04 ± 8.22) and minimal Ra changes (0.124 ± 0.005). Pearson’s correlation between Ra and %SHL was significant and positive (0.7740, <em>p</em> < 0.001). SEM analysis revealed more prominent dentinal tubule openings in the control group, whereas CDV and PLS-cg showed tubule obliteration. Molecular docking identified possible interactions between PLS-cg and MMPs.</div></div><div><h3>Conclusion</h3><div>The findings indicate that PLS-cg may reduce dentine erosion caused by supraesophageal manifestations of gastroesophageal reflux disease.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106427"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318937","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 : 2025-10-14DOI: 10.1016/j.archoralbio.2025.106428
Kai Wang , Aiguo Wang , Liewang Qiu , Ling Xu , Jingjing Wei
Objective
To identify m1A-modified genes with diagnostic potential linking periodontitis and type 2 diabetes mellitus (T2DM) by integrating bioinformatics and experimental validation.
Design
Transcriptomic data for periodontitis and T2DM patients were integrated from the GEO database to analyze m1A-related gene expression. A diagnostic model was constructed using ridge and logistic regression. Gene function enrichment, immune infiltration, and protein-protein interaction analyses explored m1A regulatory mechanisms based on m1A scoring and patient clustering models. Gingival tissue samples were collected from periodontitis patients and healthy controls, and a streptozotocin-induced diabetic β-cell model was established. qRT-PCR was performed to validate candidate genes (RRP8, ALKBH3, MAK16, and DDX18). Statistical comparisons were conducted using the non-parametric Mann–Whitney U test.
Results
Several m1A-related genes were differentially expressed in both periodontitis and T2DM. RRP8 and ALKBH3 had high predictive value, with area under the curve (AUC) values of 0.80 (periodontitis) and 0.72 (T2DM). m1A scoring and patient clustering models effectively distinguished patient groups with distinct transcriptomic and immune profiles. Hub genes MAK16 and DDX18 showed consistent expression patterns and strong correlations with immune infiltration. qRT-PCR confirmed significant downregulation of RRP8, ALKBH3, MAK16, and DDX18 in inflamed gingival tissues, and upregulation in the diabetic cell model (p < 0.05), supporting the bioinformatics findings.
Conclusions
This integrative study identifies key m1A-modified genes potentially linking periodontitis and diabetes. The combination of bioinformatics analysis and experimental validation highlights their potential as diagnostic biomarkers and provides novel insights into shared molecular mechanisms of these comorbid conditions.
{"title":"Combined bioinformatics and experimental validation identifies m1A-modified genes as potential diagnostic biomarkers in periodontitis and diabetes","authors":"Kai Wang , Aiguo Wang , Liewang Qiu , Ling Xu , Jingjing Wei","doi":"10.1016/j.archoralbio.2025.106428","DOIUrl":"10.1016/j.archoralbio.2025.106428","url":null,"abstract":"<div><h3>Objective</h3><div>To identify m1A-modified genes with diagnostic potential linking periodontitis and type 2 diabetes mellitus (T2DM) by integrating bioinformatics and experimental validation.</div></div><div><h3>Design</h3><div>Transcriptomic data for periodontitis and T2DM patients were integrated from the GEO database to analyze m1A-related gene expression. A diagnostic model was constructed using ridge and logistic regression. Gene function enrichment, immune infiltration, and protein-protein interaction analyses explored m1A regulatory mechanisms based on m1A scoring and patient clustering models. Gingival tissue samples were collected from periodontitis patients and healthy controls, and a streptozotocin-induced diabetic β-cell model was established. qRT-PCR was performed to validate candidate genes (<em>RRP8</em>, <em>ALKBH3</em>, <em>MAK16</em>, and <em>DDX18</em>). Statistical comparisons were conducted using the non-parametric Mann–Whitney U test.</div></div><div><h3>Results</h3><div>Several m1A-related genes were differentially expressed in both periodontitis and T2DM. <em>RRP8</em> and <em>ALKBH3</em> had high predictive value, with area under the curve (AUC) values of 0.80 (periodontitis) and 0.72 (T2DM). m1A scoring and patient clustering models effectively distinguished patient groups with distinct transcriptomic and immune profiles. Hub genes <em>MAK16</em> and <em>DDX18</em> showed consistent expression patterns and strong correlations with immune infiltration. qRT-PCR confirmed significant downregulation of <em>RRP8</em>, <em>ALKBH3</em>, <em>MAK16</em>, and <em>DDX18</em> in inflamed gingival tissues, and upregulation in the diabetic cell model (<em>p</em> < 0.05), supporting the bioinformatics findings.</div></div><div><h3>Conclusions</h3><div>This integrative study identifies key m1A-modified genes potentially linking periodontitis and diabetes. The combination of bioinformatics analysis and experimental validation highlights their potential as diagnostic biomarkers and provides novel insights into shared molecular mechanisms of these comorbid conditions.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106428"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314167","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}
This systematic review and meta-analysis aimed to investigate the potential of fucose as a biomarker for oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC).
Design
Relevant articles were searched across multiple databases, including PubMed, Scopus, Google Scholar, Science Direct, and Clinical Key. Twenty-three studies that met the eligibility criteria were included for qualitative review; out of which, 20 studies that provided data for comparison between study and control groups were further subjected to meta-analysis.
Results
The analysis revealed significantly high fucose levels in the saliva of OPMD patients (p = 0.013) and OSCC patients (p = 0.003) compared to healthy controls. Additionally, fucose levels were elevated in the serum of patients with OSCC (p < 0.001) and oral leukoplakia (p = 0.027) compared to controls.
Conclusion
The findings of this meta-analysis suggest that fucose could serve as a potential biomarker for OPMDs and OSCC. However, the presence of significant heterogeneity in serum evaluation and the limited studies focusing on saliva indicate the need for further investigation.
{"title":"Fucose as a biomarker in oral potentially malignant disorders and oral squamous cell carcinoma: A systematic review and meta-analysis","authors":"Shruti Gupta , Deepti Sharma , Anita Hooda , Mala Kamboj","doi":"10.1016/j.archoralbio.2025.106423","DOIUrl":"10.1016/j.archoralbio.2025.106423","url":null,"abstract":"<div><h3>Objectives</h3><div>This systematic review and meta-analysis aimed to investigate the potential of fucose as a biomarker for oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC).</div></div><div><h3>Design</h3><div>Relevant articles were searched across multiple databases, including PubMed, Scopus, Google Scholar, Science Direct, and Clinical Key. Twenty-three studies that met the eligibility criteria were included for qualitative review; out of which, 20 studies that provided data for comparison between study and control groups were further subjected to meta-analysis.</div></div><div><h3>Results</h3><div>The analysis revealed significantly high fucose levels in the saliva of OPMD patients (p = 0.013) and OSCC patients (p = 0.003) compared to healthy controls. Additionally, fucose levels were elevated in the serum of patients with OSCC (p < 0.001) and oral leukoplakia (p = 0.027) compared to controls.</div></div><div><h3>Conclusion</h3><div>The findings of this meta-analysis suggest that fucose could serve as a potential biomarker for OPMDs and OSCC. However, the presence of significant heterogeneity in serum evaluation and the limited studies focusing on saliva indicate the need for further investigation.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106423"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318955","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}
Dental caries is a significant global issue, which affects approximately 44 % of the global population. The objective of this research is to extract crude phytochemicals from Psidium guajava, Acacia nilotica, Syzygium aromaticum, and Salvadora persica and also optimizing using RSM. Therefore, this aims to maximize the antibacterial potential of the extracts at effective inhibition of dental caries
Method
The crude extracts from the plants samples, with varying extraction parameters, such as ethanol concentrations, temperatures, and solid-solvent ratios was done using Soxhlet method and antibacterial activity was determined through well and disc diffusion methods along with optimization was performed by Response Surface Methodology (RSM).
Results
The results depict that Psidium guajava exhibited the strongest antibacterial activity against S. mutans and Lactobacillus, with inhibition zones of 36 mm & 20 mm and 32 mm & 24 mm for both well and disc diffusion. Similarly, Syzygium aromaticum also shows slight stronger inhibition zones, Acacia nilotica exhibited moderate activity and in contrast, Salvadora persica showed limited activity. RSM optimization was validated and with well fitted quadratic models R² values ranging from 0.69 to 0.79. Predicted and experimental values are in close agreement between with differences below 0.5 %.
Conclusion
These findings suggest that P. guajava, S. aromaticum and A. nilotica have strong potential as natural antibacterial agents in oral care formulations.
{"title":"Optimization and evaluation of antibacterial extracts from Acacia nilotica, Psidium guajava, Syzygium aromaticum, and Salvadora persica to inhibit dental caries","authors":"Chamundeswari Kandasamy , Arunadevi Baladhandapani , Renuka Devi Ponnuswamy , Hemananthan Eswaran , Vinodhini Karthikeyan , Saranya Rajendran","doi":"10.1016/j.archoralbio.2025.106426","DOIUrl":"10.1016/j.archoralbio.2025.106426","url":null,"abstract":"<div><h3>Objective</h3><div>Dental caries is a significant global issue, which affects approximately 44 % of the global population. The objective of this research is to extract crude phytochemicals from <em>Psidium guajava</em>, <em>Acacia nilotica</em>, <em>Syzygium aromaticum</em>, and <em>Salvadora persica</em> and also optimizing using RSM. Therefore, this aims to maximize the antibacterial potential of the extracts at effective inhibition of dental caries</div></div><div><h3>Method</h3><div>The crude extracts from the plants samples, with varying extraction parameters, such as ethanol concentrations, temperatures, and solid-solvent ratios was done using Soxhlet method and antibacterial activity was determined through well and disc diffusion methods along with optimization was performed by Response Surface Methodology (RSM).</div></div><div><h3>Results</h3><div>The results depict that <em>Psidium guajava</em> exhibited the strongest antibacterial activity against <em>S. mutans</em> and <em>Lactobacillus</em>, with inhibition zones of 36 mm & 20 mm and 32 mm & 24 mm for both well and disc diffusion. Similarly, <em>Syzygium aromaticum</em> also shows slight stronger inhibition zones, <em>Acacia nilotica</em> exhibited moderate activity and in contrast, <em>Salvadora persica</em> showed limited activity. RSM optimization was validated and with well fitted quadratic models R² values ranging from 0.69 to 0.79. Predicted and experimental values are in close agreement between with differences below 0.5 %.</div></div><div><h3>Conclusion</h3><div>These findings suggest that <em>P. guajava</em>, <em>S. aromaticum</em> and <em>A. nilotica</em> have strong potential as natural antibacterial agents in oral care formulations.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"181 ","pages":"Article 106426"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575031","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}
Previous articles have shown that tooth loss is associated with cognitive decline in animal and human studies. Additionally, poor nutritional status including low-protein diet is associated with dementia. The evidence of the association of tooth loss and nutritional status is uncertain. The purpose of this study was to investigate the relationship between low-protein diet intake and cognitive decline following tooth loss in mice.
Design
Male senescence-accelerated mouse-prone 8 mice were randomly allocated into sham-operated control and tooth loss groups with extracted maxillary molars: control with normal-protein diet; control with low-protein diet; bilateral maxillary molar extraction with normal-protein diet; and bilateral maxillary molar extraction with low-protein diet. After 6 months, a behavioral test was conducted, and mRNA expression and immunohistochemistry in the brain were analyzed.
Results
Behavioral test revealed no effect of the interaction between tooth loss and low-protein diet intake on cognitive decline; however, tooth loss had a marked effect on cognitive decline. Real-time polymerase chain reaction showed no interaction between tooth loss and low-protein intake for Bax/Bcl-2 mRNA expression; however, tooth loss had a significant effect on Bax/Bcl-2 mRNA expression. Immunohistochemical analysis showed that the effect of tooth loss in neuronal inflammation and neuronal loss were observed in CA1 and DG region, but the effect of low-protein diet was limited in CA3.
Conclusion
The present study revealed that the impact of tooth loss on cognitive decline was not dependent on the low-protein diet condition.
{"title":"Tooth loss induces cognitive decline independent of low-protein diet intake in male mice","authors":"Rie Hatakeyama , Hiroshi Oue , Miyuki Yokoi , Eri Ishida , Takayasu Kubo , Kazuhiro Tsuga","doi":"10.1016/j.archoralbio.2025.106421","DOIUrl":"10.1016/j.archoralbio.2025.106421","url":null,"abstract":"<div><h3>Objectives</h3><div>Previous articles have shown that tooth loss is associated with cognitive decline in animal and human studies. Additionally, poor nutritional status including low-protein diet is associated with dementia. The evidence of the association of tooth loss and nutritional status is uncertain. The purpose of this study was to investigate the relationship between low-protein diet intake and cognitive decline following tooth loss in mice.</div></div><div><h3>Design</h3><div>Male senescence-accelerated mouse-prone 8 mice were randomly allocated into sham-operated control and tooth loss groups with extracted maxillary molars: control with normal-protein diet; control with low-protein diet; bilateral maxillary molar extraction with normal-protein diet; and bilateral maxillary molar extraction with low-protein diet. After 6 months, a behavioral test was conducted, and mRNA expression and immunohistochemistry in the brain were analyzed.</div></div><div><h3>Results</h3><div>Behavioral test revealed no effect of the interaction between tooth loss and low-protein diet intake on cognitive decline; however, tooth loss had a marked effect on cognitive decline. Real-time polymerase chain reaction showed no interaction between tooth loss and low-protein intake for <em>Bax/Bcl-2</em> mRNA expression; however, tooth loss had a significant effect on <em>Bax/Bcl-2</em> mRNA expression. Immunohistochemical analysis showed that the effect of tooth loss in neuronal inflammation and neuronal loss were observed in CA1 and DG region, but the effect of low-protein diet was limited in CA3.</div></div><div><h3>Conclusion</h3><div>The present study revealed that the impact of tooth loss on cognitive decline was not dependent on the low-protein diet condition.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106421"},"PeriodicalIF":2.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310278","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 : 2025-10-10DOI: 10.1016/j.archoralbio.2025.106420
Lisa Danielly Curcino Araujo , Ana Paula Gomes-Moura , Raquel Assed Bezerra da Silva , Michel Reis Messora , Flávia Aparecida Chaves Furlaneto , Sérgio Luis de Souza Salvador , Allan Radaic , Pachiyappan Kamarajan , Yvonne L. Kapila , Paulo Nelson-Fillho , Higinio Arzate , Samin Sirous , Geeta Bhuvanagiri , Léa Assed Bezerra da Silva
Objective
To investigate the effect of the HN019 probiotic on the modulation of inflammation and the resorption of mineralized tissues in experimentally induced periapical lesions in an animal model, evaluating its impact on the expression of cementum protein 1 (CEMP-1).
Design
Periapical lesion was induced in 45 Wistar rats. The animals were divided into groups according to the irrigating solution used. Root canals were irrigated on days 7 and 14. After 21 days, the animals were euthanized, and mandibles were processed for histological analysis. Descriptive and semi-quantitative evaluations of the inflammatory infiltrate, periodontal ligament, bone and cementum resorption, as well as counts of inflammatory cells were performed using HE staining. Also, to assess cementum formation, tissue sections were stained with an antibody for CEMP-1 and analyzed by immunohistochemistry.
Results
In the Infection + Probiotic Group, the inflammatory infiltrate was mixed and diffuse, ranging from mild to severe, with no statistically significant difference compared to the Control Group (p > 0.05). However, in the Infection + Probiotic Group, cementum resorption was significantly lower compared to Control Group (p < 0.001). Moreover, CEMP-1 expression was significantly higher in Infection + Probiotic-Group compared with all other groups (p < 0.0001).
Conclusion
The probiotic HN019 significantly increased CEMP-1 expression, indicating cementum formation in periapical lesions in vivo. These findings suggest that B. lactis HN019 may have regenerative potential in clinical scenarios. Furthermore, this strain appears to modulate the inflammatory state of periapical lesions toward a reparative phenotype, characterized by reduced bone resorption. Also, inflammatory infiltrate was like control group.
{"title":"B. lactis HN019 modulates periapical inflammation and enhances cementum repair by increasing CEMP-1 expression in an animal model","authors":"Lisa Danielly Curcino Araujo , Ana Paula Gomes-Moura , Raquel Assed Bezerra da Silva , Michel Reis Messora , Flávia Aparecida Chaves Furlaneto , Sérgio Luis de Souza Salvador , Allan Radaic , Pachiyappan Kamarajan , Yvonne L. Kapila , Paulo Nelson-Fillho , Higinio Arzate , Samin Sirous , Geeta Bhuvanagiri , Léa Assed Bezerra da Silva","doi":"10.1016/j.archoralbio.2025.106420","DOIUrl":"10.1016/j.archoralbio.2025.106420","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effect of the HN019 probiotic on the modulation of inflammation and the resorption of mineralized tissues in experimentally induced periapical lesions in an animal model, evaluating its impact on the expression of cementum protein 1 (CEMP-1).</div></div><div><h3>Design</h3><div>Periapical lesion was induced in 45 Wistar rats. The animals were divided into groups according to the irrigating solution used. Root canals were irrigated on days 7 and 14. After 21 days, the animals were euthanized, and mandibles were processed for histological analysis. Descriptive and semi-quantitative evaluations of the inflammatory infiltrate, periodontal ligament, bone and cementum resorption, as well as counts of inflammatory cells were performed using HE staining. Also, to assess cementum formation, tissue sections were stained with an antibody for CEMP-1 and analyzed by immunohistochemistry.</div></div><div><h3>Results</h3><div>In the Infection + Probiotic Group, the inflammatory infiltrate was mixed and diffuse, ranging from mild to severe, with no statistically significant difference compared to the Control Group (p > 0.05). However, in the Infection + Probiotic Group, cementum resorption was significantly lower compared to Control Group (p < 0.001). Moreover, CEMP-1 expression was significantly higher in Infection + Probiotic-Group compared with all other groups (p < 0.0001).</div></div><div><h3>Conclusion</h3><div>The probiotic HN019 significantly increased CEMP-1 expression, indicating cementum formation in periapical lesions in vivo. These findings suggest that <em>B. lactis</em> HN019 may have regenerative potential in clinical scenarios. Furthermore, this strain appears to modulate the inflammatory state of periapical lesions toward a reparative phenotype, characterized by reduced bone resorption. Also, inflammatory infiltrate was like control group.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106420"},"PeriodicalIF":2.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294648","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 : 2025-10-09DOI: 10.1016/j.archoralbio.2025.106410
Yajie Wu , Zhifei Su , Bowen Zhang , Lei Cheng , Ziyou Wang , He Yuan , Jiyao Li
Objectives
The long noncoding RNA (lncRNA) myocardial infarction–associated transcript 2 (Mirt2) has been confirmed to affect several inflammatory diseases. This study was conducted to explore the functional mechanism of Mirt2 in inflammatory alveolar bone loss and its possibility of being a therapeutic target.
Design
The expression level and potential role of Mirt2 in chronic inflammatory alveolar bone loss in mouse models of periodontitis and periapical periodontitis were investigated using micro-CT and qPCR. The characteristics of Mirt2 were evaluated by FISH, qPCR, ELISA, and alkaline phosphatase staining to confirm its function and mechanism of action in inflammatory response.
Results
Mirt2 expression was significantly enriched in inflammatory alveolar bone diseases. Mirt2 expression increased upon LPS stimulation in MC3T3-E1 cells (P < 0.05), located at the cell cytoplasm. Mirt2 knockdown exacerbated the LPS-stimulated inflammatory response in MC3T3-E1 cells, whereas Mirt2 overexpression attenuated this effect and rescued LPS-impaired osteogenic differentiation.
Conclusions
lncRNA Mirt2 suggests a potential role in chronic inflammation–related bone loss, providing potential therapeutic target worthy of future investigation for inflammation-related bone loss.
{"title":"Mirt2 alleviates LPS-induced inflammation of osteoblasts in alveolar bone destruction","authors":"Yajie Wu , Zhifei Su , Bowen Zhang , Lei Cheng , Ziyou Wang , He Yuan , Jiyao Li","doi":"10.1016/j.archoralbio.2025.106410","DOIUrl":"10.1016/j.archoralbio.2025.106410","url":null,"abstract":"<div><h3>Objectives</h3><div>The long noncoding RNA (lncRNA) myocardial infarction–associated transcript 2 (Mirt2) has been confirmed to affect several inflammatory diseases. This study was conducted to explore the functional mechanism of Mirt2 in inflammatory alveolar bone loss and its possibility of being a therapeutic target.</div></div><div><h3>Design</h3><div>The expression level and potential role of Mirt2 in chronic inflammatory alveolar bone loss in mouse models of periodontitis and periapical periodontitis were investigated using micro-CT and qPCR. The characteristics of Mirt2 were evaluated by FISH, qPCR, ELISA, and alkaline phosphatase staining to confirm its function and mechanism of action in inflammatory response.</div></div><div><h3>Results</h3><div>Mirt2 expression was significantly enriched in inflammatory alveolar bone diseases. Mirt2 expression increased upon LPS stimulation in MC3T3-E1 cells (<em>P < 0.05</em>), located at the cell cytoplasm. Mirt2 knockdown exacerbated the LPS-stimulated inflammatory response in MC3T3-E1 cells, whereas Mirt2 overexpression attenuated this effect and rescued LPS-impaired osteogenic differentiation.</div></div><div><h3>Conclusions</h3><div>lncRNA Mirt2 suggests a potential role in chronic inflammation–related bone loss, providing potential therapeutic target worthy of future investigation for inflammation-related bone loss.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106410"},"PeriodicalIF":2.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264037","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 : 2025-10-08DOI: 10.1016/j.archoralbio.2025.106419
Liang Ren , Linlin He , Runyu Zhang , Xiaoyi Li , Shimeng Xiao , Shujuan Guo , Chengcheng Liu , Yi Ding
Objectives
Human gingival fibroblasts (HGFs) are important cells that maintain the structure and integrity of periodontal tissues. Circular RNAs (circRNAs) play critical roles in cellular processes of periodontitis; however, their roles in HGFs remain unclear. This study aimed to elucidate the function and mechanism of a novel circRNA, hsa_circ_0007349, in periodontitis progression by validating its existence, establishing its role in a ceRNA network (targeting miR-127–5p/GLUL), assessing its regulatory effects on HGF functions in vitro, and confirming its pathological impact in a murine periodontitis model.
Design
We performed circRNA sequencing to identify differentially expressed circRNAs between periodontitis and healthy gingival tissues. We selected hsa_circ_0007349, and confirmed its circular structure by Sanger sequencing, RNase R and actinomycin D assays. hsa_circ_0007349/miR-127–5p/glutamate-ammonia ligase (GLUL) interactions were explored using bioinformatics analysis, dual-luciferase reporter assays, RT-qPCR, and western blotting, and their effects on HGF functions were assessed via transcriptome sequencing, Cell Counting Kit-8, cell scratch, and Transwell assays. To further investigate the pathogenic mechanisms, we established a standardized murine periodontitis model using female C57BL/6 mice, followed by histopathological evaluation of periodontal tissue destruction.
Results
Hsa_circ_0007349 expression significantly increased in gingival tissues of patients with periodontitis and in HGFs treated with Porphyromonas gingivalis lipopolysaccharide. hsa_circ_0007349 regulates miR-127–5p to affect cell proliferation, migration, and wound healing, and affects extracellular matrix metabolism and periodontal tissue damage via GLUL.
Conclusion
Hsa_circ_0007349 acts as a competing endogenous RNA to promote HGF proliferation, migration, wound healing and extracellular matrix turnover by targeting miR-127–5p and GLUL.
{"title":"Hsa_circ_0007349 upregulates glutamate-ammonia ligase to modulate gingival fibroblast wound healing","authors":"Liang Ren , Linlin He , Runyu Zhang , Xiaoyi Li , Shimeng Xiao , Shujuan Guo , Chengcheng Liu , Yi Ding","doi":"10.1016/j.archoralbio.2025.106419","DOIUrl":"10.1016/j.archoralbio.2025.106419","url":null,"abstract":"<div><h3>Objectives</h3><div>Human gingival fibroblasts (HGFs) are important cells that maintain the structure and integrity of periodontal tissues. Circular RNAs (circRNAs) play critical roles in cellular processes of periodontitis; however, their roles in HGFs remain unclear. This study aimed to elucidate the function and mechanism of a novel circRNA, hsa_circ_0007349, in periodontitis progression by validating its existence, establishing its role in a ceRNA network (targeting miR-127–5p/GLUL), assessing its regulatory effects on HGF functions in vitro, and confirming its pathological impact in a murine periodontitis model.</div></div><div><h3>Design</h3><div>We performed circRNA sequencing to identify differentially expressed circRNAs between periodontitis and healthy gingival tissues. We selected hsa_circ_0007349, and confirmed its circular structure by Sanger sequencing, RNase R and actinomycin D assays. hsa_circ_0007349/miR-127–5p/glutamate-ammonia ligase (GLUL) interactions were explored using bioinformatics analysis, dual-luciferase reporter assays, RT-qPCR, and western blotting, and their effects on HGF functions were assessed via transcriptome sequencing, Cell Counting Kit-8, cell scratch, and Transwell assays. To further investigate the pathogenic mechanisms, we established a standardized murine periodontitis model using female C57BL/6 mice, followed by histopathological evaluation of periodontal tissue destruction.</div></div><div><h3>Results</h3><div>Hsa_circ_0007349 expression significantly increased in gingival tissues of patients with periodontitis and in HGFs treated with <em>Porphyromonas gingivalis</em> lipopolysaccharide. hsa_circ_0007349 regulates miR-127–5p to affect cell proliferation, migration, and wound healing, and affects extracellular matrix metabolism and periodontal tissue damage via GLUL.</div></div><div><h3>Conclusion</h3><div>Hsa_circ_0007349 acts as a competing endogenous RNA to promote HGF proliferation, migration, wound healing and extracellular matrix turnover by targeting miR-127–5p and GLUL.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106419"},"PeriodicalIF":2.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263629","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}
To characterize the oral microbiome of substance users (primarily tobacco, alcohol, and opioids) compared to healthy controls in the high-incidence Mizo tribal community of Northeast India, and to examine their association with food and lifestyle habits.
Methods
Saliva samples from 53 substance users and 35 healthy controls were subjected to 16S rRNA (V3–V4 region) sequencing. Alpha and beta diversity analyses, differential abundance testing, and microbial functional prediction were conducted. Statistical analyses were corrected for multiple comparisons using false discovery rate (FDR) adjustment where applicable. Associations with food and lifestyle habits were also examined.
Results
Substance users exhibited significantly lower alpha diversity, and beta diversity analyses revealed distinct clustering between the two groups. Firmicutes_D, Actinobacteria, Rothia, and Streptococcus were more abundant in substance users, whereas Bacteroidota, Proteobacteria, Neisseria, and Prevotella were enriched in healthy controls. Functional predictions indicated upregulation of biofilm formation and xenobiotic degradation pathways in substance users. Exposure to Jhum cultivation, prenatal smoking, and consumption of fermented pork fat (saum) were correlated with microbial composition.
Conclusions
Substance use and associated environmental exposures were linked to oral microbiome dysbiosis. Certain bacterial taxa may serve as potential microbial biomarkers of substance use in this high-risk tribal population, warranting further investigation.
{"title":"Distinct oral microbiome profiles in substance users in the high-incidence Mizo tribal community, Northeast India","authors":"Lalfak Zuali , Lalchhanhima Ralte , John Zothanzama , Christine Vanlalbiakdiki Sailo , Nachimuthu Senthil Kumar","doi":"10.1016/j.archoralbio.2025.106418","DOIUrl":"10.1016/j.archoralbio.2025.106418","url":null,"abstract":"<div><h3>Objectives</h3><div>To characterize the oral microbiome of substance users (primarily tobacco, alcohol, and opioids) compared to healthy controls in the high-incidence Mizo tribal community of Northeast India, and to examine their association with food and lifestyle habits.</div></div><div><h3>Methods</h3><div>Saliva samples from 53 substance users and 35 healthy controls were subjected to 16S rRNA (V3–V4 region) sequencing. Alpha and beta diversity analyses, differential abundance testing, and microbial functional prediction were conducted. Statistical analyses were corrected for multiple comparisons using false discovery rate (FDR) adjustment where applicable. Associations with food and lifestyle habits were also examined.</div></div><div><h3>Results</h3><div>Substance users exhibited significantly lower alpha diversity, and beta diversity analyses revealed distinct clustering between the two groups. Firmicutes_D, Actinobacteria, <em>Rothia</em>, and <em>Streptococcus</em> were more abundant in substance users, whereas Bacteroidota, Proteobacteria, <em>Neisseria</em>, and <em>Prevotella</em> were enriched in healthy controls. Functional predictions indicated upregulation of biofilm formation and xenobiotic degradation pathways in substance users. Exposure to Jhum cultivation, prenatal smoking, and consumption of fermented pork fat (saum) were correlated with microbial composition.</div></div><div><h3>Conclusions</h3><div>Substance use and associated environmental exposures were linked to oral microbiome dysbiosis. Certain bacterial taxa may serve as potential microbial biomarkers of substance use in this high-risk tribal population, warranting further investigation.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106418"},"PeriodicalIF":2.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304953","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}