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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 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。
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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 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。
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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 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。
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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 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
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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 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,&nbsp;Anja Reck,&nbsp;Michela De Pellegrin,&nbsp;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 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 ,&nbsp;Xiaohu Lin ,&nbsp;Yuanyuan Cao ,&nbsp;Zhang Zhao ,&nbsp;Xiaoge Zhang ,&nbsp;Yang Zhao ,&nbsp;Songge Liu ,&nbsp;Bo Hu ,&nbsp;Wei Cao ,&nbsp;Wei Li ,&nbsp;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 &lt; 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
Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation 应激对持续性颞下颌关节炎症大鼠模型疼痛敏感性和情绪反应的影响
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-19 DOI: 10.1016/j.archoralbio.2025.106463
Jardel Francisco Mazzi-Chaves , Ana Paula Ribeiro Novaes , Glauce Crivelaro Nascimento , Christie Ramos Andrade Leite-Panissi

Objective

Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impact of acute and chronic stress on the progression of temporomandibular joint (TMJ) pain, secondary hyperalgesia, and stress-induced affective disturbances.

Design

Using a well-established preclinical model, Wistar-Hannover rats underwent persistent TMJ inflammation via intra-articular administration of Freund’s complete adjuvant (CFA). Orofacial mechanical allodynia and secondary hyperalgesia were assessed using von Frey test in the orofacial region and hot plate test in the hind paw. To evaluate the influence of stress on affective behaviors, Acute stress (AS), chronic restraint stress (CRS) and Unpredictable chronic stress (UCS) paradigms were implemented, followed by behavioral assessments using the elevated plus maze (EPM), open field (OF), and sucrose preference tests.

Results

Results demonstrated that chronic stress exacerbated CFA-induced orofacial allodynia. TMJ inflammation induced secondary hyperalgesia, with AS partially restoring baseline nociception, while UCS amplified central sensitization. Notably, CRS did not influence hind paw nociception in CFA-injected rats. Behavioral analyses revealed that CFA injection heightened anxiety-like behavior by decreased open-arm exploration. Acute stress further intensified anxiety and impaired exploratory activity, whereas chronic stresses significantly worsened both anxiety- and depression-like behaviors.

Conclusion

These findings underscore the complex interplay between stress and pain processing in TMDs, highlighting the detrimental role of chronic stress in exacerbating pain sensitivity and emotional dysregulation. Understanding these mechanisms could lead to more effective, targeted treatments, improving patient outcomes.
目的颞下颌疾病(TMDs)常伴有焦虑、抑郁等心理困扰,可调节疼痛感知和敏感性。本研究探讨了急性和慢性应激对颞下颌关节(TMJ)疼痛、继发性痛觉过敏和应激性情感障碍进展的影响。设计采用成熟的临床前模型,Wistar-Hannover大鼠通过关节内给予Freund 's完全佐剂(CFA)进行持续性TMJ炎症。采用von Frey试验和后爪热板试验对大鼠口面部机械异常性痛和继发性痛觉过敏进行评估。为了评估应激对情感行为的影响,本研究采用急性应激(AS)、慢性约束应激(CRS)和不可预测慢性应激(UCS)范式,并采用升高+迷宫(EPM)、开阔场(of)和蔗糖偏好测试进行行为评估。结果慢性应激加重cfa诱导的口面部异常痛。颞下颌关节炎症引起继发性痛觉过敏,AS部分恢复基线痛觉,而UCS放大中枢致敏。值得注意的是,CRS对注射cfa的大鼠后爪痛觉没有影响。行为分析显示,CFA注射通过减少张开臂探查而增加焦虑样行为。急性应激进一步加剧了焦虑和探索性活动,而慢性应激显著恶化了焦虑和抑郁样行为。结论这些发现强调了应激与疼痛加工之间复杂的相互作用,强调了慢性应激在加剧疼痛敏感性和情绪失调中的有害作用。了解这些机制可以带来更有效、更有针对性的治疗,改善患者的预后。
{"title":"Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation","authors":"Jardel Francisco Mazzi-Chaves ,&nbsp;Ana Paula Ribeiro Novaes ,&nbsp;Glauce Crivelaro Nascimento ,&nbsp;Christie Ramos Andrade Leite-Panissi","doi":"10.1016/j.archoralbio.2025.106463","DOIUrl":"10.1016/j.archoralbio.2025.106463","url":null,"abstract":"<div><h3>Objective</h3><div>Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impact of acute and chronic stress on the progression of temporomandibular joint (TMJ) pain, secondary hyperalgesia, and stress-induced affective disturbances.</div></div><div><h3>Design</h3><div>Using a well-established preclinical model, Wistar-Hannover rats underwent persistent TMJ inflammation via intra-articular administration of Freund’s complete adjuvant (CFA). Orofacial mechanical allodynia and secondary hyperalgesia were assessed using von Frey test in the orofacial region and hot plate test in the hind paw. To evaluate the influence of stress on affective behaviors, Acute stress (AS), chronic restraint stress (CRS) and Unpredictable chronic stress (UCS) paradigms were implemented, followed by behavioral assessments using the elevated plus maze (EPM), open field (OF), and sucrose preference tests.</div></div><div><h3>Results</h3><div>Results demonstrated that chronic stress exacerbated CFA-induced orofacial allodynia. TMJ inflammation induced secondary hyperalgesia, with AS partially restoring baseline nociception, while UCS amplified central sensitization. Notably, CRS did not influence hind paw nociception in CFA-injected rats. Behavioral analyses revealed that CFA injection heightened anxiety-like behavior by decreased open-arm exploration. Acute stress further intensified anxiety and impaired exploratory activity, whereas chronic stresses significantly worsened both anxiety- and depression-like behaviors.</div></div><div><h3>Conclusion</h3><div>These findings underscore the complex interplay between stress and pain processing in TMDs, highlighting the detrimental role of chronic stress in exacerbating pain sensitivity and emotional dysregulation. Understanding these mechanisms could lead to more effective, targeted treatments, improving patient outcomes.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106463"},"PeriodicalIF":2.1,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621367","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
Growing new teeth: A systematic review of functional whole-tooth regeneration in orthotopic animal models 生长新牙:原位动物模型全牙功能再生的系统综述。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106461
Pei-Jung Wu, Mar Jovani-Sancho

Objective

To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential.

Design

A systematic review of in vivo studies involving orthotopic implantation of generated tooth constructs, analyzing experimental design, cell sources, scaffolding materials, implantation techniques, and outcome measures including histological, radiological, and functional evaluations.

Results

Considerable heterogeneity was observed in animal models, developmental stages at implantation, and cellular components. Polycaprolactone (PCL) membranes were often associated with improved eruption and reduced ankylosis, suggesting enhanced periodontal integration.

Conclusions

PCL-based scaffolding systems may facilitate functional tooth regeneration, but further standardized in vivo research is needed to validate translational potential.
目的:确定和评估目前具有高转化潜力的原位动物模型的功能全牙再生策略。设计:系统回顾体内研究,包括生成的牙齿构建体的原位种植,分析实验设计、细胞来源、支架材料、种植技术和结果测量,包括组织学、放射学和功能评估。结果:在动物模型、着床发育阶段和细胞成分中观察到相当大的异质性。聚己内酯(PCL)膜通常与改善出疹和减少强直有关,表明牙周整合增强。结论:基于pcl的支架系统可能促进功能性牙齿再生,但需要进一步标准化的体内研究来验证其转化潜力。
{"title":"Growing new teeth: A systematic review of functional whole-tooth regeneration in orthotopic animal models","authors":"Pei-Jung Wu,&nbsp;Mar Jovani-Sancho","doi":"10.1016/j.archoralbio.2025.106461","DOIUrl":"10.1016/j.archoralbio.2025.106461","url":null,"abstract":"<div><h3>Objective</h3><div>To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential.</div></div><div><h3>Design</h3><div>A systematic review of <em>in vivo</em> studies involving orthotopic implantation of generated tooth constructs, analyzing experimental design, cell sources, scaffolding materials, implantation techniques, and outcome measures including histological, radiological, and functional evaluations.</div></div><div><h3>Results</h3><div>Considerable heterogeneity was observed in animal models, developmental stages at implantation, and cellular components. Polycaprolactone (PCL) membranes were often associated with improved eruption and reduced ankylosis, suggesting enhanced periodontal integration.</div></div><div><h3>Conclusions</h3><div>PCL-based scaffolding systems may facilitate functional tooth regeneration, but further standardized <em>in vivo</em> research is needed to validate translational potential.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106461"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566602","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
Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition 桑叶中的活性成分四甲木犀草素通过抑制NF-κB促进牙周炎微环境下颌骨骨髓间充质干细胞成骨。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106459
Yuning Xia , Chao Shan , Zeyu Wu , Jin Zhao

Objective

This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment.

Design

Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using Porphyromonas gingivalis-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11–7082.

Results

TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11–7082.

Conclusion

TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.
目的:研究桑叶生物活性物质四甲木犀草素(TML)对牙周炎微环境下颌骨骨髓间充质干细胞(JBMMSCs)的影响及其机制。设计:采用网络药理学和分子对接的方法,鉴定桑叶的有效成分及其治疗牙周炎的靶点。采用牙龈卟啉单胞菌脂多糖(5 μg/mL)建立JBMMSCs炎症模型。通过CCK-8和ELISA法确定TML的最佳浓度。采用ALP/ARS染色、RT-PCR和Western blot (WB)检测成骨分化、炎症标志物和NF-κB通路活性。建立大鼠结扎性牙周炎模型,通过组织病理学染色、显微ct、RT-PCR和WB评价TML的作用。从每个动物实验组中分离JBMMSCs进行体外成骨验证。通过比较TML与NF-κB抑制剂BAY11-7082,阐明其作用机制。结果:TML是靶向NF-κB和炎症介质(IL-6、IL-1β、TNF-α)的关键成分。5 μM TML显著抑制JBMMSCs炎症因子,促进成骨分化,抑制NF-κB活化。在大鼠中,30 mg/kg TML显著减少炎症和牙槽骨丢失,其疗效与吲哚美辛相当,TML处理组的JBMMSCs表现出增强的成骨作用。TML对NF-κB的抑制作用与BAY11-7082相似。结论:TML通过抑制NF-κB通路,减轻牙周炎症,增强JBMMSCs成骨潜能,为牙周炎相关骨再生提供了一种新的策略。
{"title":"Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition","authors":"Yuning Xia ,&nbsp;Chao Shan ,&nbsp;Zeyu Wu ,&nbsp;Jin Zhao","doi":"10.1016/j.archoralbio.2025.106459","DOIUrl":"10.1016/j.archoralbio.2025.106459","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment.</div></div><div><h3>Design</h3><div>Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using <em>Porphyromonas gingivalis</em>-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11–7082.</div></div><div><h3>Results</h3><div>TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11–7082.</div></div><div><h3>Conclusion</h3><div>TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106459"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is there geometric morphometric evidence for the selection against impaction? A comparative cross-sectional study of specific tooth-agenesis patterns 是否有几何形态计量学证据证明选择不受撞击?特定牙齿发育模式的比较横断面研究。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106462
Sarah Boussali , Anaïs Cavaré

Objectives

Reductions in tooth number and facial prognathism may reflect shared genetic and evolutionary mechanisms but have been inconsistently reported by traditional cephalometric analyses. This study aimed to assess whether common patterns of dental agenesis are associated with craniofacial morphology using geometric morphometric methods.

Design

This retrospective comparative cross-sectional study included 538 patients aged 10–19 years from a French orthodontic population. Individuals with hypodontia (n = 269), restricted to third molars, maxillary lateral incisors, or second premolars, were matched by age and sex with controls without agenesis (n = 269). Craniofacial morphology was assessed on lateral cephalograms using 18 landmarks and 87 semilandmarks. Multiple linear regression and Procrustes MANOVA were applied to evaluate differences in size and shape, adjusting for sex and age.

Results

No significant association was found between agenesis status and craniofacial size in the overall configuration as well as in the cranial base, maxilla, and mandible. A significant sex effect was detected in the mandible, with smaller centroid size in males (p = 0.012). Multivariate regression on shape confirmed allometric effects across all configurations. Procrustes MANOVA detected a significant effect of sex on overall shape (p = 0.003), but neither age nor hypodontia reached significance.

Conclusion

In this large geometric morphometric study, no generalized or localized alterations in craniofacial morphology were detected, even in third molar agenesis, suggesting that the anthropological significance of hypodontia should be regarded with caution.
目的:牙齿数量减少和面部前突可能反映了共同的遗传和进化机制,但传统的头颅测量分析报告不一致。本研究旨在利用几何形态计量学方法评估牙齿发育不全的常见模式是否与颅面形态相关。设计:这项回顾性比较横断面研究包括538名年龄在10-19岁的法国正畸人群。下颌缺失个体(n = 269),局限于第三磨牙,上颌侧门牙或第二前磨牙,按年龄和性别与无发育的对照组(n = 269)匹配。采用18个标志和87个半标志在侧位脑电图上评估颅面形态。应用多元线性回归和Procrustes方差分析评估大小和形状的差异,并对性别和年龄进行调整。结果:发育不全状态与颅面大小、颅底、上颌骨、下颌骨整体形态无显著相关性。下颌骨存在显著的性别效应,男性的质心尺寸较小(p = 0.012)。形状的多元回归证实了所有构型的异速生长效应。Procrustes MANOVA检测到性别对整体形状有显著影响(p = 0.003),但年龄和下颌畸形均无显著影响。结论:在这项大型几何形态测量学研究中,即使在第三磨牙发育中,也没有发现颅面形态的普遍或局部改变,这表明下颌畸形的人类学意义应该谨慎对待。
{"title":"Is there geometric morphometric evidence for the selection against impaction? A comparative cross-sectional study of specific tooth-agenesis patterns","authors":"Sarah Boussali ,&nbsp;Anaïs Cavaré","doi":"10.1016/j.archoralbio.2025.106462","DOIUrl":"10.1016/j.archoralbio.2025.106462","url":null,"abstract":"<div><h3>Objectives</h3><div>Reductions in tooth number and facial prognathism may reflect shared genetic and evolutionary mechanisms but have been inconsistently reported by traditional cephalometric analyses. This study aimed to assess whether common patterns of dental agenesis are associated with craniofacial morphology using geometric morphometric methods.</div></div><div><h3>Design</h3><div>This retrospective comparative cross-sectional study included 538 patients aged 10–19 years from a French orthodontic population. Individuals with hypodontia (n = 269), restricted to third molars, maxillary lateral incisors, or second premolars, were matched by age and sex with controls without agenesis (n = 269). Craniofacial morphology was assessed on lateral cephalograms using 18 landmarks and 87 semilandmarks. Multiple linear regression and Procrustes MANOVA were applied to evaluate differences in size and shape, adjusting for sex and age.</div></div><div><h3>Results</h3><div>No significant association was found between agenesis status and craniofacial size in the overall configuration as well as in the cranial base, maxilla, and mandible. A significant sex effect was detected in the mandible, with smaller centroid size in males (<em>p</em> = 0.012). Multivariate regression on shape confirmed allometric effects across all configurations. Procrustes MANOVA detected a significant effect of sex on overall shape (p = 0.003), but neither age nor hypodontia reached significance.</div></div><div><h3>Conclusion</h3><div>In this large geometric morphometric study, no generalized or localized alterations in craniofacial morphology were detected, even in third molar agenesis, suggesting that the anthropological significance of hypodontia should be regarded with caution.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106462"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566631","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}
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Archives of oral biology
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