Archives of oral biology最新文献_第2页

Prevalence and eradication of mixed biofilms of Streptococcus mutans and Candida albicans using naringin: In vitro and in silico investigations 柚皮苷对变形链球菌和白色念珠菌混合生物膜的流行和根除：体外和计算机研究

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

Archives of oral biology

Pub Date : 2025-12-13 DOI: 10.1016/j.archoralbio.2025.106482

Chevuru Sai Shreya Reddy , Lekha Sree Venkatesan , Dhanraj Ganapathy, Palanivel Sathishkumar

Objective

To identify a potential natural therapeutic agent to treat the mixed biofilms of Streptococcus mutans and Candida albicans, thereby preventing dental caries.

Design

The coexisting S. mutans and C. albicans was isolated from dental caries. Antimicrobial activity of various natural components was assessed against S. mutans and C. albicans. Antibiofilm efficacy of naringin was assessed against the biofilm of mixed S. mutans and C. albicans. The cell viability in mixed biofilm was determined using MTT assay and CLSM investigations. The molecular docking analysis of naringin with secreted aspartic proteinase (SAP2) of C. albicans and glucosyltransferase-I (GtfB) of S. mutans was performed using AutoDock and PyMOL tools. The biocompatibility of naringin was determined on human RBCs and HGF cells.

Results

The natural components such as curcumin, naringin, quercetin, morin, rutin, and hesperetin shows the antimicrobial effects against the clinical isolates S. mutans and C. albicans. Among these, naringin exhibits the significant antimicrobial effect against S. mutans (MIC:183 ± 5.70 µM), C. albicans (MIC:196 ± 0.00 µM), and their mixed culture (MIC:200 ± 10.00 µM). The MTT and CLSM results indicates that 2xMIC (400 µM) of naringin demonstrates the potential eradication of mature biofilm of mixed S. mutans and C. albicans. Naringin establishes the strong binding interaction with enzymes GtfB of S. mutans and SAP2 of C. albicans. The IC₅₀ value of naringin towards HGF cells was noted as 711.5 µM.

Conclusions

The flavonoid naringin demonstrates the effective and safe therapeutic potential to treat coexisting S. mutans and C. albicans biofilm virulence to prevent the dental caries.

目的寻找一种治疗变形链球菌和白色念珠菌混合生物膜的潜在天然治疗剂，以预防龋病的发生。设计从龋中分离出变形链球菌和白色念珠菌。评估了各种天然成分对变形链球菌和白色念珠菌的抑菌活性。研究了柚皮苷对变形链球菌和白色念珠菌混合生物膜的抗菌效果。采用MTT法和CLSM法测定混合生物膜中的细胞活力。利用AutoDock和PyMOL工具对柚皮苷与白念珠菌分泌的天冬氨酸蛋白酶（SAP2）和变形链球菌的葡萄糖基转移酶（GtfB）进行分子对接分析。测定柚皮苷在人红细胞和HGF细胞上的生物相容性。结果姜黄素、柚皮素、槲皮素、桑皮素、芦丁、橙皮素等天然成分对临床分离的变形链球菌和白色念珠菌均有抑菌作用。其中,柚皮苷表现出显著的抗菌效应对变形链球菌(麦克风:183 ±5.70  µM),白念珠菌(麦克风:196 ±0.00  µM),及其混合文化(麦克风:200 ±10.00  µM)。MTT和CLSM结果表明，柚皮苷的2xMIC（400 µM）显示出对混合变形链球菌和白色念珠菌成熟生物膜的潜在根除作用。柚皮苷与变形链球菌的GtfB酶和白色念珠菌的SAP2酶有较强的结合作用。柚皮素对HGF细胞的IC50值为711.5 µM。结论黄酮类柚皮苷对变形链球菌和白色念珠菌共存的生物膜毒力具有安全有效的治疗作用。

{"title":"Prevalence and eradication of mixed biofilms of Streptococcus mutans and Candida albicans using naringin: In vitro and in silico investigations","authors":"Chevuru Sai Shreya Reddy , Lekha Sree Venkatesan , Dhanraj Ganapathy, Palanivel Sathishkumar","doi":"10.1016/j.archoralbio.2025.106482","DOIUrl":"10.1016/j.archoralbio.2025.106482","url":null,"abstract":"<div><h3>Objective</h3><div>To identify a potential natural therapeutic agent to treat the mixed biofilms of <em>Streptococcus mutans</em> and <em>Candida albicans</em>, thereby preventing dental caries.</div></div><div><h3>Design</h3><div>The coexisting <em>S. mutans</em> and <em>C. albicans</em> was isolated from dental caries. Antimicrobial activity of various natural components was assessed against <em>S. mutans</em> and <em>C. albicans</em>. Antibiofilm efficacy of naringin was assessed against the biofilm of mixed <em>S. mutans</em> and <em>C. albicans</em>. The cell viability in mixed biofilm was determined using MTT assay and CLSM investigations. The molecular docking analysis of naringin with secreted aspartic proteinase (SAP2) of <em>C. albicans</em> and glucosyltransferase-I (GtfB) of <em>S. mutans</em> was performed using AutoDock and PyMOL tools. The biocompatibility of naringin was determined on human RBCs and HGF cells.</div></div><div><h3>Results</h3><div>The natural components such as curcumin, naringin, quercetin, morin, rutin, and hesperetin shows the antimicrobial effects against the clinical isolates <em>S. mutans</em> and <em>C. albicans</em>. Among these, naringin exhibits the significant antimicrobial effect against <em>S. mutans</em> (MIC:183 ± 5.70 µM), <em>C. albicans</em> (MIC:196 ± 0.00 µM), and their mixed culture (MIC:200 ± 10.00 µM). The MTT and CLSM results indicates that 2xMIC (400 µM) of naringin demonstrates the potential eradication of mature biofilm of mixed <em>S. mutans</em> and <em>C. albicans</em>. Naringin establishes the strong binding interaction with enzymes GtfB of <em>S. mutans</em> and SAP2 of <em>C. albicans</em>. The IC<sub>50</sub> value of naringin towards HGF cells was noted as 711.5 µM.</div></div><div><h3>Conclusions</h3><div>The flavonoid naringin demonstrates the effective and safe therapeutic potential to treat coexisting <em>S. mutans</em> and <em>C. albicans</em> biofilm virulence to prevent the dental caries.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"183 ","pages":"Article 106482"},"PeriodicalIF":2.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799797","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

Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang’s therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis 探讨肠道菌群代谢物轴与加味丹宣口康治疗口腔黏膜下纤维化雄性大鼠疗效的关系：多组学分析

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

Archives of oral biology

Pub Date : 2025-12-11 DOI: 10.1016/j.archoralbio.2025.106480

Chenwei Wang , Yuzhe Dai , Yao Ye , Qianqi Zeng , Jin Tan

Objective

This work aims to explore how Jiawei Danxuan Koukang (JDK) ameliorates Oral Submucous Fibrosis (OSF) via regulating the gut microbiota and its metabolites.

Design

We established an OSF rat model via oral mucosal arecoline injection. Rats were randomly divided into five groups: control, model, lycopene-treated, quercetin-treated, and JDK-treated. After intervention, we analyzed: serum metabolites by Liquid Chromatography-Mass Spectrometry -based untargeted metabolomics; gut microbiota profiling via 16S rDNA sequencing; oral mucosal histopathology and fibrosis using hematoxylin-eosin and Masson trichrome staining; expressions of fibrosis-related proteins (Transforming Growth Factor-β1 (TGF-β1), Collagen Type I Alpha 1 Chain (COL1A1)) by western blot; and cytokines (Interleukin-1β, Interleukin-6, Interleukin-10) in serum, oral and colon tissues via enzyme-linked immunosorbent assay.

Results

In the OSF model group, 120 serum metabolites were upregulated and 39 were down-regulated. When comparing the JDK group with the model group, 83 metabolites were upregulated and 132 were downregulated in the JDK group. Specifically, JDK targeted key metabolites: prostaglandins, leukotrienes, lysophosphatidylcholine, and 4-hydroxyproline. JDK also regulated two critical metabolic pathways: gly-cine-serine-threonine metabolism and tryptophan metabolism. JDK reduces the pro-inflammatory Ruminococcus and restores the butyrate-producing Lachnospiraceae_NK4A136_group. JDK downregulated Interleukin-1β and Interleukin-6 levels systemically and locally, concurrently increasing Interleukin-10, and reduced the expression of fibrosis-related proteins (TGF-β1, COL1A1) in the oral mucosa.

Conclusions

JDK alleviates OSF by normalizing inflammation and fibrosis-related metabolic pathways, linking gut microbiota remodeling to metabolic homeostasis.

目的：探讨加味丹宣口康（JDK）通过调节肠道菌群及其代谢产物改善口腔黏膜下纤维化（OSF）的机制。设计：通过口腔黏膜注射槟榔碱建立OSF大鼠模型。将大鼠随机分为5组：对照组、模型组、番茄红素组、槲皮素组和jdk组。干预后，我们通过液相色谱-质谱法分析血清代谢物的非靶向代谢组学；通过16S rDNA测序分析肠道微生物群；苏木精-伊红和马松三色染色法观察口腔黏膜组织病理学和纤维化；western blot检测纤维化相关蛋白（转化生长因子-β1 （TGF-β1）、ⅰ型胶原α 1链（COL1A1））的表达；以及血清、口腔和结肠组织中的细胞因子（白细胞介素-1β、白细胞介素-6、白细胞介素-10）。结果：OSF模型组血清代谢物上调120个，下调39个。与模型组比较，JDK组代谢产物上调83个，下调132个。具体来说，JDK针对的是关键代谢物：前列腺素、白三烯、溶血磷脂酰胆碱和4-羟基脯氨酸。JDK还调节了两个关键的代谢途径：甘氨酸-丝氨酸-苏氨酸代谢和色氨酸代谢。JDK降低了促炎瘤胃球菌，恢复了产丁酸酯Lachnospiraceae_NK4A136_group。JDK全系统和局部下调白介素-1β和白介素-6水平，同时升高白介素-10，降低口腔黏膜纤维化相关蛋白（TGF-β1, COL1A1）的表达。结论：JDK通过使炎症和纤维化相关的代谢途径正常化，将肠道微生物群重塑与代谢稳态联系起来，从而减轻OSF。

{"title":"Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang’s therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis","authors":"Chenwei Wang , Yuzhe Dai , Yao Ye , Qianqi Zeng , Jin Tan","doi":"10.1016/j.archoralbio.2025.106480","DOIUrl":"10.1016/j.archoralbio.2025.106480","url":null,"abstract":"<div><h3>Objective</h3><div>This work aims to explore how Jiawei Danxuan Koukang (JDK) ameliorates Oral Submucous Fibrosis (OSF) via regulating the gut microbiota and its metabolites.</div></div><div><h3>Design</h3><div>We established an OSF rat model via oral mucosal arecoline injection. Rats were randomly divided into five groups: control, model, lycopene-treated, quercetin-treated, and JDK-treated. After intervention, we analyzed: serum metabolites by Liquid Chromatography-Mass Spectrometry -based untargeted metabolomics; gut microbiota profiling via 16S rDNA sequencing; oral mucosal histopathology and fibrosis using hematoxylin-eosin and Masson trichrome staining; expressions of fibrosis-related proteins (Transforming Growth Factor-β1 (TGF-β1), Collagen Type I Alpha 1 Chain (COL1A1)) by western blot; and cytokines (Interleukin-1β, Interleukin-6, Interleukin-10) in serum, oral and colon tissues via enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>In the OSF model group, 120 serum metabolites were upregulated and 39 were down-regulated. When comparing the JDK group with the model group, 83 metabolites were upregulated and 132 were downregulated in the JDK group. Specifically, JDK targeted key metabolites: prostaglandins, leukotrienes, lysophosphatidylcholine, and 4-hydroxyproline. JDK also regulated two critical metabolic pathways: gly-cine-serine-threonine metabolism and tryptophan metabolism. JDK reduces the pro-inflammatory Ruminococcus and restores the butyrate-producing Lachnospiraceae_NK4A136_group. JDK downregulated Interleukin-1β and Interleukin-6 levels systemically and locally, concurrently increasing Interleukin-10, and reduced the expression of fibrosis-related proteins (TGF-β1, COL1A1) in the oral mucosa.</div></div><div><h3>Conclusions</h3><div>JDK alleviates OSF by normalizing inflammation and fibrosis-related metabolic pathways, linking gut microbiota remodeling to metabolic homeostasis.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106480"},"PeriodicalIF":2.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770178","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

Escitalopram exposure compromises osteogenic potential of human osteoblastic cells 艾司西酞普兰暴露会损害人成骨细胞的成骨潜能。

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

Archives of oral biology

Pub Date : 2025-12-11 DOI: 10.1016/j.archoralbio.2025.106481

Augusto Del Pintor Pasotti , Rodrigo Mendes Ferreiro Girondo , Bruno Haddad , Marcelo Franchin , Bruna Benso , Rogerio Heládio Lopes Motta , Henrique Ballassini Abdalla

Objective

This study aimed to assess the impact of escitalopram on bone metabolism by evaluating its effects on cell viability and proliferation, wound-healing capacity, osteogenic activity, bone formation markers, and collagen deposition.

Design

The effects of escitalopram were studied on human osteoblastic SAOS-2 cells. Escitalopram (1–1000 µM) was tested in a dose–response curve. Cell viability was measured by MTT assay, and proliferation by hemocytometer counting. Cell migration was examined with the Scratch assay over 72 h. Osteogenic differentiation was assessed by gene expression of RUNX2, Osterix (Osx), bone sialoprotein (BSP), type I collagen (COL1), and osteocalcin (OCN) using RT-qPCR. Alkaline phosphatase (ALP) activity was analyzed at 4 and 8 days. Mineralization was determined by Alizarin Red staining (days 10, 14, 21). For last, Immunofluorescence was carried out for collagen 1 staining (days 3, 7 and 10).

Results

Escitalopram induced cytotoxicity in doses greater than 100 µM, reducing cell viability within 24 h. At non-toxic concentrations (≤30 µM), proliferation was enhanced in 30 µM after 7 days. Conversely, escilalopram reduced the migration capacity in a concentration-dependent manner. Moreover, the gene expression of RUNX2, OSX, BSP, COL1, and OCN were diminished when exposed to escitalopram. In the functional tests, escitalopram significantly decreases ALP activity at day 4, but not at day 8. Mineralization was dose-dependently impaired at 14 and 21 days. Collagen type I immunofluorescence exhibit weaker staining when escitalopram exposure.

Conclusion

Escitalopram compromises osteoblast differentiation, extracellular matrix formation, and migratory potential. These results provide mechanistic insight into the adverse skeletal effects of SSRIs and suggest the need for monitoring bone health in long-term users.

目的：本研究旨在通过评价艾司西酞普兰对细胞活力和增殖、创面愈合能力、成骨活性、骨形成标志物和胶原沉积的影响来评估艾司西酞普兰对骨代谢的影响。设计：研究艾司西酞普兰对人成骨细胞SAOS-2的影响。以依西酞普兰（1-1000 µM）为剂量-反应曲线。MTT法测定细胞活力，血细胞计数法测定细胞增殖。在72 h内用Scratch法检测细胞迁移。采用RT-qPCR检测RUNX2、Osterix （Osx）、骨涎蛋白（BSP）、I型胶原（COL1）、骨钙素（OCN）的基因表达，评估成骨分化程度。在第4天和第8天分析碱性磷酸酶（ALP）的活性。用茜素红染色测定矿化（第10、14、21天）。最后免疫荧光法对胶原蛋白1进行染色（第3、7、10天）。结果：艾司西酞普兰在剂量大于100 µM时诱导细胞毒性，在24 h内降低细胞活力。在无毒浓度（≤30 µM）下，7天后，30 µM浓度的细胞增殖增强。相反，依西酞普兰以浓度依赖的方式降低了迁移能力。此外，暴露于艾司西酞普兰后，RUNX2、OSX、BSP、COL1和OCN的基因表达减少。在功能测试中，艾司西酞普兰在第4天显著降低ALP活性，但在第8天没有。矿化在第14和21天呈剂量依赖性受损。依西酞普兰暴露后，I型胶原免疫荧光染色较弱。结论：艾司西酞普兰影响成骨细胞分化、细胞外基质形成和迁移潜能。这些结果为SSRIs对骨骼的不良影响提供了机制上的见解，并建议有必要监测长期使用者的骨骼健康。

{"title":"Escitalopram exposure compromises osteogenic potential of human osteoblastic cells","authors":"Augusto Del Pintor Pasotti , Rodrigo Mendes Ferreiro Girondo , Bruno Haddad , Marcelo Franchin , Bruna Benso , Rogerio Heládio Lopes Motta , Henrique Ballassini Abdalla","doi":"10.1016/j.archoralbio.2025.106481","DOIUrl":"10.1016/j.archoralbio.2025.106481","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess the impact of escitalopram on bone metabolism by evaluating its effects on cell viability and proliferation, wound-healing capacity, osteogenic activity, bone formation markers, and collagen deposition.</div></div><div><h3>Design</h3><div>The effects of escitalopram were studied on human osteoblastic SAOS-2 cells. Escitalopram (1–1000 µM) was tested in a dose–response curve. Cell viability was measured by MTT assay, and proliferation by hemocytometer counting. Cell migration was examined with the Scratch assay over 72 h. Osteogenic differentiation was assessed by gene expression of RUNX2, Osterix (Osx), bone sialoprotein (BSP), type I collagen (COL1), and osteocalcin (OCN) using RT-qPCR. Alkaline phosphatase (ALP) activity was analyzed at 4 and 8 days. Mineralization was determined by Alizarin Red staining (days 10, 14, 21). For last, Immunofluorescence was carried out for collagen 1 staining (days 3, 7 and 10).</div></div><div><h3>Results</h3><div>Escitalopram induced cytotoxicity in doses greater than 100 µM, reducing cell viability within 24 h. At non-toxic concentrations (≤30 µM), proliferation was enhanced in 30 µM after 7 days. Conversely, escilalopram reduced the migration capacity in a concentration-dependent manner. Moreover, the gene expression of RUNX2, OSX, BSP, COL1, and OCN were diminished when exposed to escitalopram. In the functional tests, escitalopram significantly decreases ALP activity at day 4, but not at day 8. Mineralization was dose-dependently impaired at 14 and 21 days. Collagen type I immunofluorescence exhibit weaker staining when escitalopram exposure.</div></div><div><h3>Conclusion</h3><div>Escitalopram compromises osteoblast differentiation, extracellular matrix formation, and migratory potential. These results provide mechanistic insight into the adverse skeletal effects of SSRIs and suggest the need for monitoring bone health in long-term users.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106481"},"PeriodicalIF":2.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783949","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

Oral green and red propolis attenuate bone resorption and inflammation in experimental apical periodontitis 口腔绿色和红色蜂胶可减弱实验性根尖牙周炎患者的骨吸收和炎症

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

Archives of oral biology

Pub Date : 2025-12-09 DOI: 10.1016/j.archoralbio.2025.106479

José Alex da Silva , Letícia Cabrera Capalbo , Renan Dal-Fabbro , Romulo de Oliveira Sales-Junior , Bharbara de Moura Pereira , Edilson Ervolino , João Eduardo Gomes-Filho , Leopoldo Cosme-Silva

Objective

To test whether systemic green or red propolis modulates inflammation and bone resorption in rat apical periodontitis (AP).

Design

Twenty-four male Wistar rats received AP induction in the first mandibular molars and were randomized to Control, Green propolis, or Red propolis (n = 8/group). Propolis (100 mg/kg in water) or vehicle was administered daily by gavage for 30 days. On day 30, periapical tissues were evaluated by micro-CT, histology (inflammatory score), and immunohistochemistry for RANKL, OPG, and TRAP-positive osteoclasts. Data were analyzed with Shapiro-Wilk, Kruskal-Wallis/Dunn, or one-way ANOVA/Tukey (α=0.05).

Results

Both propolis groups showed significantly less periapical bone resorption than the control group on micro-CT analysis (p < 0.05). Histological evaluation revealed predominantly chronic inflammatory infiltrates, with significantly lower inflammation scores in the propolis-treated groups (p < 0.05). Immunohistochemical analysis demonstrated a significant reduction in RANKL expression, an increase in OPG levels, and fewer TRAP-positive multinucleated cells in both propolis groups compared to the control (p < 0.05). No significant differences were observed between green and red propolis.

Conclusion

Thirty days of systemic green or red propolis similarly attenuated periapical inflammation and osteoclast-mediated bone resorption in experimental AP, reflected by lower resorption volumes, reduced RANKL/TRAP, and higher OPG, indicating that propolis may serve as a host-modulatory adjunct to preserve periapical bone.

目的观察全身绿色蜂胶和红色蜂胶对大鼠根尖牙周炎（AP）炎症和骨吸收的调节作用。设计24只雄性Wistar大鼠在第一下颌磨牙进行AP诱导，随机分为对照组、绿色蜂胶组和红色蜂胶组（ = 8只/组）。蜂胶（100 mg/kg水）或载药，每天灌胃30天。第30天，通过显微ct、组织学（炎症评分）和免疫组织化学对根尖周围组织进行RANKL、OPG和trap阳性破骨细胞的评估。采用Shapiro-Wilk、Kruskal-Wallis/Dunn或单因素方差分析/Tukey分析（α=0.05）。结果微ct分析显示，蜂胶组和蜂胶组根尖周骨吸收明显低于对照组（p <； 0.05）。组织学评估显示慢性炎症浸润为主，蜂胶治疗组炎症评分明显降低（p <； 0.05）。免疫组织化学分析显示，与对照组相比，两个蜂胶组的RANKL表达显著降低，OPG水平升高，trap阳性多核细胞减少（p <； 0.05）。绿色蜂胶和红色蜂胶之间无显著差异。结论在实验性AP中，连续30天系统使用绿色或红色蜂胶同样可以减轻根尖周炎症和破骨细胞介导的骨吸收，表现为吸收体积降低、RANKL/TRAP降低、OPG升高，表明蜂胶可能是一种宿主调节剂，可以保护根尖周骨。

{"title":"Oral green and red propolis attenuate bone resorption and inflammation in experimental apical periodontitis","authors":"José Alex da Silva , Letícia Cabrera Capalbo , Renan Dal-Fabbro , Romulo de Oliveira Sales-Junior , Bharbara de Moura Pereira , Edilson Ervolino , João Eduardo Gomes-Filho , Leopoldo Cosme-Silva","doi":"10.1016/j.archoralbio.2025.106479","DOIUrl":"10.1016/j.archoralbio.2025.106479","url":null,"abstract":"<div><h3>Objective</h3><div>To test whether systemic green or red propolis modulates inflammation and bone resorption in rat apical periodontitis (AP).</div></div><div><h3>Design</h3><div>Twenty-four male Wistar rats received AP induction in the first mandibular molars and were randomized to Control, Green propolis, or Red propolis (n = 8/group). Propolis (100 mg/kg in water) or vehicle was administered daily by gavage for 30 days. On day 30, periapical tissues were evaluated by micro-CT, histology (inflammatory score), and immunohistochemistry for RANKL, OPG, and TRAP-positive osteoclasts. Data were analyzed with Shapiro-Wilk, Kruskal-Wallis/Dunn, or one-way ANOVA/Tukey (α=0.05).</div></div><div><h3>Results</h3><div>Both propolis groups showed significantly less periapical bone resorption than the control group on micro-CT analysis (p < 0.05). Histological evaluation revealed predominantly chronic inflammatory infiltrates, with significantly lower inflammation scores in the propolis-treated groups (p < 0.05). Immunohistochemical analysis demonstrated a significant reduction in RANKL expression, an increase in OPG levels, and fewer TRAP-positive multinucleated cells in both propolis groups compared to the control (p < 0.05). No significant differences were observed between green and red propolis.</div></div><div><h3>Conclusion</h3><div>Thirty days of systemic green or red propolis similarly attenuated periapical inflammation and osteoclast-mediated bone resorption in experimental AP, reflected by lower resorption volumes, reduced RANKL/TRAP, and higher OPG, indicating that propolis may serve as a host-modulatory adjunct to preserve periapical bone.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106479"},"PeriodicalIF":2.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733278","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

Effect of phenotype switched Candida auris mono-culture and co-culture biofilms on the morphology, viability, and adhesion of hTERT TIGKs and ORL-48 cell lines 表型转换耳念珠菌单培养和共培养生物膜对hTERT TIGKs和ORL-48细胞株形态、活力和粘附的影响

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

Archives of oral biology

Pub Date : 2025-12-09 DOI: 10.1016/j.archoralbio.2025.106478

Mukarramah Zainal , Nurul ‘Izzah Mohd Sarmin , Mohammad Johari Ibrahim , Nicola Cirillo , Stuart G. Dashper , Mohd Hafiz Arzmi

Objectives

This study aims to determine the paracrine effects of Candida auris phenotypic switching in mono- and co-culture with Staphylococcus aureus on oral epithelial homeostasis and oncogenic progression in phenotypically normal (hTERT TIGKs) and malignant (ORL-48) oral keratinocytes.

Design

C. auris switched phenotype was scored using Phloxine B, and mono- and co-culture biofilms with S. aureus were developed. hTERT TIGKs and ORL-48 cell lines were independently seeded into 6-well and 96-well plates for dispase and viability test, respectively. The oral cell lines were exposed to phenotypically switched C. auris mono- and co-culture biofilm test cell growth medium (TCGM) for 24 h. Outcomes included cell morphology, metabolic activity/viability (CCK-8), and cell–cell adhesion (dispase assay).

Results

Microscopic observation revealed that the biofilm induced damage and disrupted epithelial cell integrity in a paracrine manner. The mono- and co-culture TCGM suppressed the growth of normal cells while promoting the metabolic activity of cancer cells. The adhesion analysis of hTERT TIGKs indicated a strong intercellular cohesion, while ORL-48 cells downregulated intercellular adhesion and compromised cell-cell cohesion.

Conclusion

C. auris biofilms promote the development of a malignant phenotype by regulating cell viability, promoting epithelial-mesenchymal transition, and adhesion in a switched generation-dependent manner.

目的：本研究旨在确定金黄色葡萄球菌单培养和共培养时耳念珠菌表型转换对口腔上皮稳态和表型正常（hTERT TIGKs）和恶性（ORL-48）口腔角质形成细胞的癌性进展的旁分泌作用。设计：利用苯氧辛B对金黄色葡萄球菌的开关表型进行评分，并与金黄色葡萄球菌进行单培养和共培养生物膜的制备。hTERT TIGKs和ORL-48细胞系分别独立接种于6孔和96孔板中进行疾病和活力检测。将口腔细胞系暴露于表型切换的耳念珠菌单一和共培养生物膜试验细胞生长培养基（TCGM）中24 h。结果包括细胞形态、代谢活性/活力（CCK-8）和细胞-细胞粘附（疾病测定）。结果：显微镜观察显示，生物膜以旁分泌方式诱导上皮细胞损伤和破坏细胞完整性。单独培养和共培养的TCGM抑制正常细胞的生长，同时促进癌细胞的代谢活性。hTERT TIGKs的粘附分析表明，细胞间黏附较强，而ORL-48细胞的细胞间黏附下调，细胞间黏附受损。结论：耳念珠菌生物膜通过调节细胞活力、促进上皮-间质转化和粘附，以一种世代依赖的方式促进恶性表型的发展。

{"title":"Effect of phenotype switched Candida auris mono-culture and co-culture biofilms on the morphology, viability, and adhesion of hTERT TIGKs and ORL-48 cell lines","authors":"Mukarramah Zainal , Nurul ‘Izzah Mohd Sarmin , Mohammad Johari Ibrahim , Nicola Cirillo , Stuart G. Dashper , Mohd Hafiz Arzmi","doi":"10.1016/j.archoralbio.2025.106478","DOIUrl":"10.1016/j.archoralbio.2025.106478","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to determine the paracrine effects of <em>Candida auris</em> phenotypic switching in mono- and co-culture with <em>Staphylococcus aureus</em> on oral epithelial homeostasis and oncogenic progression in phenotypically normal (hTERT TIGKs) and malignant (ORL-48) oral keratinocytes.</div></div><div><h3>Design</h3><div><em>C. auris</em> switched phenotype was scored using Phloxine B, and mono- and co-culture biofilms with <em>S. aureus</em> were developed. hTERT TIGKs and ORL-48 cell lines were independently seeded into 6-well and 96-well plates for dispase and viability test, respectively. The oral cell lines were exposed to phenotypically switched <em>C. auris</em> mono- and co-culture biofilm test cell growth medium (TCGM) for 24 h. Outcomes included cell morphology, metabolic activity/viability (CCK-8), and cell–cell adhesion (dispase assay).</div></div><div><h3>Results</h3><div>Microscopic observation revealed that the biofilm induced damage and disrupted epithelial cell integrity in a paracrine manner. The mono- and co-culture TCGM suppressed the growth of normal cells while promoting the metabolic activity of cancer cells. The adhesion analysis of hTERT TIGKs indicated a strong intercellular cohesion, while ORL-48 cells downregulated intercellular adhesion and compromised cell-cell cohesion.</div></div><div><h3>Conclusion</h3><div><em>C. auris</em> biofilms promote the development of a malignant phenotype by regulating cell viability, promoting epithelial-mesenchymal transition, and adhesion in a switched generation-dependent manner.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106478"},"PeriodicalIF":2.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783979","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

BBI608 induces apoptosis in mucoepidermoid carcinoma cells by targeting a post-transcriptional regulatory mechanisms of myeloid cell leukemia-1 BBI608通过靶向髓细胞白血病-1的转录后调控机制诱导黏液表皮样癌细胞凋亡

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

Archives of oral biology

Pub Date : 2025-12-04 DOI: 10.1016/j.archoralbio.2025.106467

Da-In Choi , Hyun-Ji Kim , Dong-Guk Park , Jae-Han Lee , Thantrira Porntaveetus , Sung-Dae Cho

Objectives

BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines.

Design

The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4′,6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR.

Results

BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively.

Conclusion

These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.

目的bbi608在几种人类癌症中显示出抗肿瘤活性。然而，其对黏液表皮样癌（MEC）的疗效尚不清楚。本研究考察了BBI608在MEC细胞系中的抗肿瘤作用。设计采用台盼蓝排斥法、活/死法和球形法检测BBI608对MC3和jd -15黏液表皮样癌（MEC）细胞株的抗肿瘤活性。通过免疫印迹、4′，6-二氨基-2-苯基吲哚（DAPI）染色、膜联蛋白v -异硫氰酸荧光素/碘化丙啶（V-FITC/PI）双染色和逆转录定量PCR研究凋亡效应。结果bbi608对MEC细胞株有抑制生长作用，降低细胞活力和成球能力，增加细胞死亡。cleaved caspase-3和PARP表达增加，细胞核凋亡形态学改变，Annexin V阳性增加，证实bbi608诱导细胞凋亡。BBI608显著下调Mcl-1表达，促进MEC细胞凋亡。Mcl-1下调似乎分别由MC3和YD-15细胞中的蛋白酶体依赖性蛋白降解和翻译调节机制介导。结论BBI608通过诱导mcl -1依赖性细胞凋亡，有效抑制MEC细胞体外增殖。这表明BBI608作为MEC的潜在治疗剂值得进一步研究。

{"title":"BBI608 induces apoptosis in mucoepidermoid carcinoma cells by targeting a post-transcriptional regulatory mechanisms of myeloid cell leukemia-1","authors":"Da-In Choi , Hyun-Ji Kim , Dong-Guk Park , Jae-Han Lee , Thantrira Porntaveetus , Sung-Dae Cho","doi":"10.1016/j.archoralbio.2025.106467","DOIUrl":"10.1016/j.archoralbio.2025.106467","url":null,"abstract":"<div><h3>Objectives</h3><div>BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines.</div></div><div><h3>Design</h3><div>The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4′,6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR.</div></div><div><h3>Results</h3><div>BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106467"},"PeriodicalIF":2.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681572","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

Third-molar agenesis shifts mandibular second-molar mineralisation timeline: An orthopantomographic study in South Indian children 第三磨牙发育移位下颌第二磨牙矿化时间：南印度儿童的骨断层研究

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

Archives of oral biology

Pub Date : 2025-12-03 DOI: 10.1016/j.archoralbio.2025.106466

Subramanyeswara Swamy Chinni , Nallan CSK Chaitanya , Waheeda Shahnaz , Usha Gangavarapu , Shivani Ramesh Mungala , Sudheer B. Balla

Background and objective

In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associated with differences in the mineralisation stage of the mandibular second molar in South Indian children.

Design

Orthopantomograms from 570 children (240 males, 330 females; 10–14.99 years) were staged using Demirjian A to H criteria. Descriptive comparisons were supplemented with a proportional-odds ordinal logistic regression, modelling second-molar stage as the ordered outcome, with agenesis extent, age, and sex as predictors. Results are reported as adjusted odds ratios (aORs).

Results

Each additional year of age was associated with substantially higher odds of being in a more advanced second-molar stage (aOR 5.41, 95 % CI 4.47–6.56). Males had lower odds than females of being in a higher stage (aOR 0.58, 95 % CI 0.41–0.81). Relative to children with no third-molar agenesis, the odds of being in a higher second-molar stage were progressively lower with greater agenesis: one missing (aOR 0.53, 95 % CI 0.31–0.91), two missing (aOR 0.39, 95 % CI 0.24–0.62), three missing (aOR 0.26, 95 % CI 0.11–0.62), and all four missing (aOR 0.04, 95 % CI 0.02–0.09).

Conclusion

Third-molar agenesis was associated with less advanced mandibular second-molar stages after accounting for age and sex. Agenesis status and extent may be relevant for the 14-year threshold. Future work should develop and externally validate prediction models that integrate third molar agenesis to improve accuracy and minimise misclassification.

背景与目的在许多司法管辖区，14年刑期是确定刑事责任和相关决定的重要法律因素。我们研究了南印度儿童下颌第二磨牙矿化阶段的差异是否与第三磨牙发育不全有关。设计采用Demirjian A - H标准对570名儿童（男240名，女330名，10-14.99岁）进行骨断层扫描。描述性比较补充了比例-几率有序逻辑回归，将第二磨牙期建模为有序结果，以发育程度、年龄和性别为预测因子。结果以调整优势比（aORs）报告。结果每增加一岁，出现第二磨牙期晚期的几率显著增加（aOR 5.41, 95 % CI 4.47-6.56）。男性处于较高阶段的几率低于女性（aOR 0.58, 95 % CI 0.41-0.81）。相对于没有第三磨牙发育不全的儿童，第二磨牙发育期较高的几率随着发育不全逐渐降低：1个缺失（aOR 0.53, 95 % CI 0.31-0.91）， 2个缺失（aOR 0.39, 95 % CI 0.24-0.62）， 3个缺失（aOR 0.26, 95 % CI 0.11-0.62）， 4个缺失（aOR 0.04, 95 % CI 0.02-0.09）。结论考虑年龄和性别因素后，下颌第三磨牙发育不全与下颌第二磨牙发育较晚有关。发育状态和程度可能与14岁的阈值有关。未来的工作应该开发和外部验证整合第三磨牙发育的预测模型，以提高准确性和减少错误分类。

{"title":"Third-molar agenesis shifts mandibular second-molar mineralisation timeline: An orthopantomographic study in South Indian children","authors":"Subramanyeswara Swamy Chinni , Nallan CSK Chaitanya , Waheeda Shahnaz , Usha Gangavarapu , Shivani Ramesh Mungala , Sudheer B. Balla","doi":"10.1016/j.archoralbio.2025.106466","DOIUrl":"10.1016/j.archoralbio.2025.106466","url":null,"abstract":"<div><h3>Background and objective</h3><div>In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associated with differences in the mineralisation stage of the mandibular second molar in South Indian children.</div></div><div><h3>Design</h3><div>Orthopantomograms from 570 children (240 males, 330 females; 10–14.99 years) were staged using Demirjian A to H criteria. Descriptive comparisons were supplemented with a proportional-odds ordinal logistic regression, modelling second-molar stage as the ordered outcome, with agenesis extent, age, and sex as predictors. Results are reported as adjusted odds ratios (aORs).</div></div><div><h3>Results</h3><div>Each additional year of age was associated with substantially higher odds of being in a more advanced second-molar stage (aOR 5.41, 95 % CI 4.47–6.56). Males had lower odds than females of being in a higher stage (aOR 0.58, 95 % CI 0.41–0.81). Relative to children with no third-molar agenesis, the odds of being in a higher second-molar stage were progressively lower with greater agenesis: one missing (aOR 0.53, 95 % CI 0.31–0.91), two missing (aOR 0.39, 95 % CI 0.24–0.62), three missing (aOR 0.26, 95 % CI 0.11–0.62), and all four missing (aOR 0.04, 95 % CI 0.02–0.09).</div></div><div><h3>Conclusion</h3><div>Third-molar agenesis was associated with less advanced mandibular second-molar stages after accounting for age and sex. Agenesis status and extent may be relevant for the 14-year threshold. Future work should develop and externally validate prediction models that integrate third molar agenesis to improve accuracy and minimise misclassification.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106466"},"PeriodicalIF":2.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681571","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

Retraction notice to “Berberine reduces inflammation of human dental pulp fibroblast via miR-21/KBTBD7 axis” [Archives of Oral Biology 110 (2020) 104630] “小檗碱通过miR-21/KBTBD7轴降低人牙髓成纤维细胞炎症”的撤稿通知[口腔生物学文献110(2020)104630]。

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

Archives of oral biology

Pub Date : 2025-12-03 DOI: 10.1016/j.archoralbio.2025.106464

Song Jia , Wu Qishan , Jiang Jin , Sun Degang , Wang Fang , Xin Bingchang , Cui Qi

引用次数: 0

Inhibition of protein kinase C activity enables mineralization of senescent dental follicle cells with almost no osteogenic differentiation potential 蛋白激酶C活性的抑制使几乎没有成骨分化潜力的衰老牙滤泡细胞矿化

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

Archives of oral biology

Pub Date : 2025-12-02 DOI: 10.1016/j.archoralbio.2025.106468

Christian Morsczeck, Anja Reck, Michela De Pellegrin, Torsten E. Reichert

Objective

Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential.

Design

Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs.

Results

The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH).

Conclusion

Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs.

目的牙滤泡细胞系具有衰老表型，向生物矿化细胞分化的潜力较差。先前的研究表明，蛋白激酶C （PKC）和蛋白激酶B （AKT）调节dfc的分化。本研究探讨PKC和AKT调控在多大程度上促进成骨潜能差的牙滤泡细胞的分化。设计以地塞米松或骨形态发生蛋白（BMP） 2为诱导剂的细胞培养基对成骨分化潜能差的人衰老牙滤泡细胞进行成骨分化。GÖ6976作为PKC抑制剂，MK-2206作为AKT抑制剂。AKT激活剂SC-79也被使用。用AKT活性形式、PKC磷酸化底物和胶原1的特异性抗体进行Western blot分析。采用茜素染色法测定碱性磷酸酶（ALP）活性和生物矿化程度，定量测定成骨分化程度。real-time rt - pcr定量检测SOST和PTHLH基因表达。结果抑制因子MK-2206抑制AKT，激活因子SC-79激活dfc中AKT。抑制AKT仅能轻微但显著地促进成骨分化。虽然PKC活性的抑制明显只发生在分化的第14天，但PKC抑制促进成骨分化并抑制SOST和甲状旁腺激素相关蛋白（PTHLH）的表达。结论添加GÖ6976是诱导衰老dfc生物矿化的有效方法。

{"title":"Inhibition of protein kinase C activity enables mineralization of senescent dental follicle cells with almost no osteogenic differentiation potential","authors":"Christian Morsczeck, Anja Reck, Michela De Pellegrin, Torsten E. Reichert","doi":"10.1016/j.archoralbio.2025.106468","DOIUrl":"10.1016/j.archoralbio.2025.106468","url":null,"abstract":"<div><h3>Objective</h3><div>Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential.</div></div><div><h3>Design</h3><div>Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs.</div></div><div><h3>Results</h3><div>The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH).</div></div><div><h3>Conclusion</h3><div>Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106468"},"PeriodicalIF":2.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681573","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

Evaluation of the correlativity of SOX4 and epithelial-mesenchymal transition markers expression in the prognosis of oral squamous cell carcinoma SOX4与上皮-间质转化标志物表达在口腔鳞状细胞癌预后中的相关性评价

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

Archives of oral biology

Pub Date : 2025-11-28 DOI: 10.1016/j.archoralbio.2025.106465

Pengfei Zhao , Xiaohu Lin , Yuanyuan Cao , Zhang Zhao , Xiaoge Zhang , Yang Zhao , Songge Liu , Bo Hu , Wei Cao , Wei Li , Xianjun Zhang

Objectives

To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC) and to evaluate their functional role.

Design

A total of 250 OSCC tissues and 80 normal oral mucosa specimens were analyzed by immunohistochemistry for SOX4, E-cadherin, N-cadherin, and TWIST1 expression. Kaplan–Meier survival curves with log-rank tests, Cox proportional hazards regression (univariate and multivariate), and Spearman correlation were performed to assess prognostic value and clinicopathological associations. Functional validation was conducted by SOX4 knockdown and overexpression in OSCC cell lines, followed by migration, invasion, and EMT marker analyses.

Results

High SOX4, N-cadherin, and TWIST1 expression correlated with larger tumor size, lymph node metastasis, advanced clinical stage, and poor differentiation (p < 0.05). SOX4 expression showed positive correlation with N-cadherin and TWIST1, and negative correlation with E-cadherin. Kaplan–Meier analysis demonstrated that high SOX4, N-cadherin, and TWIST1 expression were associated with significantly poorer overall survival. Functional assays confirmed that SOX4 overexpression promoted EMT and cell motility, whereas knockdown reversed these effects.

Conclusions

In summary, our study identified SOX4, N-cadherin, TWIST1, E-cadherin, lymph node metastasis, and clinical staging as independent factors influencing the prognosis of OSCC. SOX4 promotes EMT, thereby influencing the progression and prognosis of OSCC.

目的：探讨性别决定区Y-box 4 （SOX4）和上皮-间质转化（EMT）标志物E-cadherin、N-cadherin、TWIST1在口腔鳞状细胞癌（OSCC）中的预后意义，并评价其功能作用。设计：采用免疫组化方法分析250例OSCC组织和80例正常口腔黏膜标本中SOX4、E-cadherin、N-cadherin和TWIST1的表达。采用Kaplan-Meier生存曲线、log-rank检验、Cox比例风险回归（单因素和多因素）和Spearman相关性来评估预后价值和临床病理相关性。通过在OSCC细胞系中敲除和过表达SOX4进行功能验证，然后进行迁移、侵袭和EMT标记分析。结果：SOX4、N-cadherin、TWIST1高表达与肿瘤大小较大、淋巴结转移、临床分期较晚、分化程度较差相关（p ）结论：综上所述，我们的研究发现SOX4、N-cadherin、TWIST1、E-cadherin、淋巴结转移、临床分期是影响OSCC预后的独立因素。SOX4促进EMT，从而影响OSCC的进展和预后。

{"title":"Evaluation of the correlativity of SOX4 and epithelial-mesenchymal transition markers expression in the prognosis of oral squamous cell carcinoma","authors":"Pengfei Zhao , Xiaohu Lin , Yuanyuan Cao , Zhang Zhao , Xiaoge Zhang , Yang Zhao , Songge Liu , Bo Hu , Wei Cao , Wei Li , Xianjun Zhang","doi":"10.1016/j.archoralbio.2025.106465","DOIUrl":"10.1016/j.archoralbio.2025.106465","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC) and to evaluate their functional role.</div></div><div><h3>Design</h3><div>A total of 250 OSCC tissues and 80 normal oral mucosa specimens were analyzed by immunohistochemistry for SOX4, E-cadherin, N-cadherin, and TWIST1 expression. Kaplan–Meier survival curves with log-rank tests, Cox proportional hazards regression (univariate and multivariate), and Spearman correlation were performed to assess prognostic value and clinicopathological associations. Functional validation was conducted by SOX4 knockdown and overexpression in OSCC cell lines, followed by migration, invasion, and EMT marker analyses.</div></div><div><h3>Results</h3><div>High SOX4, N-cadherin, and TWIST1 expression correlated with larger tumor size, lymph node metastasis, advanced clinical stage, and poor differentiation (p < 0.05). SOX4 expression showed positive correlation with N-cadherin and TWIST1, and negative correlation with E-cadherin. Kaplan–Meier analysis demonstrated that high SOX4, N-cadherin, and TWIST1 expression were associated with significantly poorer overall survival. Functional assays confirmed that SOX4 overexpression promoted EMT and cell motility, whereas knockdown reversed these effects.</div></div><div><h3>Conclusions</h3><div>In summary, our study identified SOX4, N-cadherin, TWIST1, E-cadherin, lymph node metastasis, and clinical staging as independent factors influencing the prognosis of OSCC. SOX4 promotes EMT, thereby influencing the progression and prognosis of OSCC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106465"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662044","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