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Role of Fusobacterium nucleatum in the pathogenesis of oral squamous cell carcinoma: A systematic review of molecular mechanisms and signalling pathways 核梭杆菌在口腔鳞状细胞癌发病机制中的作用:分子机制和信号通路的系统综述
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-08-06 DOI: 10.1016/j.archoralbio.2025.106369
Bara’a El-Dwaikat , Ikhlas El Karim , Daniel B. Longley , Paul N. Moynagh , Fionnuala T. Lundy

Objectives

To evaluate the mechanisms and signalling pathways involved in the pathogenesis of oral squamous cell carcinoma (OSCC) that are promoted by Fusobacterium nucleatum infection across human participant, in vivo and in vitro studies.

Design

This systematic review was conducted in accordance with the PRISMA guidelines to address the question: What mechanisms and potential signalling pathways are implicated in the pathogenesis of OSCC facilitated by F. nucleatum infection, compared with non-infected controls? Searches were performed across three electronic databases: Scopus, Web of Science, and MEDLINE.

Results

Sixty-three studies met the inclusion criteria for the systematic review. Studies involving human participants revealed alterations in bacterial genes related to lipopolysaccharide (LPS) synthesis, bacterial mobility and flagellar assembly. Additionally, alteration in host genes including DNA repair, tumour protein P53 (TP53), toll-like receptors and proinflammatory genes such as interleukin (IL)1β, IL8, and IL6 were reported. In vivo studies reported upregulation of cyclin D1 and IL6 following F. nucleatum infection. In vitro studies demonstrated changes in epithelial-mesenchymal transition markers such as E-cadherin, N-cadherin, vimentin, and zinc finger E-box binding homeobox (ZEB)1/2, along with increased expression of inflammatory markers, including IL-8 and IL-6 following F. nucleatum infection.

Conclusion

The findings from this systematic review highlight a significant molecular response to F. nucleatum infection in oral cancer. The results underscore the complex interaction between F. nucleatum and host molecular pathways, offering valuable insights into how this bacterium may contribute to oral cancer development and progression.
目的探讨口腔鳞状细胞癌(OSCC)的发病机制和信号通路,探讨口腔鳞状细胞癌(OSCC)在人体内和体外研究中受核梭杆菌感染的影响。根据PRISMA指南,本系统综述旨在解决以下问题:与未感染对照相比,核胞梭菌感染诱发OSCC的发病机制和潜在信号通路涉及哪些机制和潜在信号通路?通过三个电子数据库进行搜索:Scopus、Web of Science和MEDLINE。结果63项研究符合系统评价的纳入标准。涉及人类参与者的研究揭示了与脂多糖(LPS)合成、细菌流动性和鞭毛组装相关的细菌基因的改变。此外,宿主基因的改变包括DNA修复、肿瘤蛋白P53 (TP53)、toll样受体和促炎基因,如白细胞介素(IL)1β、IL8和IL6。体内研究报告了核胞梭菌感染后细胞周期蛋白D1和il - 6的上调。体外研究表明,上皮-间质转化标记物如e -钙粘蛋白、n -钙粘蛋白、vimentin和锌指E-box结合同源盒(ZEB)1/2的变化,以及炎症标记物,包括IL-8和IL-6的表达增加。结论本系统综述的研究结果强调了口腔癌对具核梭菌感染的显著分子反应。结果强调了核梭菌与宿主分子途径之间复杂的相互作用,为这种细菌如何促进口腔癌的发展和进展提供了有价值的见解。
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引用次数: 0
The salivary and GCF AGE/sRAGE-IL-17 axis in periodontitis and diabetes: A pathophysiological perspective on disease progression and inflammation 牙周炎和糖尿病患者的唾液和GCF AGE/ sage - il -17轴:疾病进展和炎症的病理生理学视角
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-08-06 DOI: 10.1016/j.archoralbio.2025.106370
Alper Aydoğdu , Yagmur Deniz Yıldırım , Banu Ertürk , Begüm Cicek , Deniz Cagdas , Uğur Ünlütürk , Ezel Berker

Objective

Diabetes, if uncontrolled, increases the risk of periodontal disease and associated tooth loss. While AGE and sRAGE levels have been explored in diabetes, their role in localized inflammation in periodontium is poorly understood. The aim of this study was to investigate AGE/sRAGE ratio and IL-17 in saliva&gingival crevicular fluid in the presence of periodontitis in diabetic patients which may underlie disease development or progression.

Design

This cross-sectional study included 64 patients, divided into 4 groups as healthy (H), periodontitis without diabetes(P), periodontitis patients with controlled diabetes(DP), periodontitis patients with poorly controlled diabetes(PDP). Periodontal clinical parameters were recorded. AGE, sRAGE, IL-17 levels in GCF and saliva samples were measured with ELISA and AGE/sRAGE ratio was determined.

Results

GCF AGE/sRAGE ratio and IL-17 levels of periodontitis groups were significantly higher than H group, while sRAGE levels were significantly lower (p < 0.05). In addition, AGE/sRAGE ratio of PDP group were significantly higher than DP group in GCF and saliva (p < 0.05). ROC curve analysis showed significantly discriminative performance of the parameters in both GCF and saliva. HbA1c levels were positively correlated with AGE/sRAGE ratio in GCF and saliva(p < 0.05).

Conclusions

This study demonstrated that GCF and salivary biomarkers, particularly IL-17 and AGE/sRAGE ratio, may have diagnostic potential in distinguishing periodontal disease severity in relation to glycemic status. ROC analysis supported the discriminative ability of these markers, especially in GCF, with satisfactory sensitivity and specificity. The AGE/sRAGE ratio in both GCF and saliva showed promise as a non-invasive biomarker, especially in patients with poorly controlled diabetes.
糖尿病如果不加以控制,会增加牙周病和相关牙齿脱落的风险。虽然AGE和sRAGE水平已经在糖尿病中得到了探讨,但它们在牙周组织局部炎症中的作用却知之甚少。本研究的目的是调查糖尿病患者牙周炎患者唾液和龈沟液中AGE/sRAGE比值和IL-17,这可能是疾病发生或进展的基础。设计本横断面研究纳入64例患者,分为健康(H)、无糖尿病牙周炎(P)、糖尿病控制牙周炎(DP)、糖尿病控制不佳牙周炎(PDP) 4组。记录牙周临床参数。ELISA法测定GCF和唾液中AGE、sRAGE、IL-17水平,并测定AGE/sRAGE比值。结果牙周炎组gcf AGE/sRAGE比值及IL-17水平显著高于H组,sRAGE水平显著低于H组(p <; 0.05)。GCF和唾液中,PDP组的AGE/sRAGE比值显著高于DP组(p <; 0.05)。ROC曲线分析显示GCF和唾液的参数具有显著的判别性。HbA1c水平与GCF和唾液中AGE/sRAGE比值呈正相关(p <; 0.05)。本研究表明GCF和唾液生物标志物,特别是IL-17和AGE/sRAGE比值,可能在区分牙周病严重程度与血糖状态的关系方面具有诊断潜力。ROC分析支持这些标记的鉴别能力,特别是在GCF中,具有令人满意的敏感性和特异性。GCF和唾液中的AGE/sRAGE比值显示出作为一种非侵入性生物标志物的前景,特别是在糖尿病控制不良的患者中。
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引用次数: 0
Oral microecological community- Streptococcus mutans dysbiosis and interaction provide therapeutic perspectives for dental caries 口腔微生态群落-变形链球菌生态失调及其相互作用为龋病的治疗提供了新的思路
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-08-06 DOI: 10.1016/j.archoralbio.2025.106367
Yue Zhou, Chenchen Zhang, Yalan Deng, Lei Lei, Tao Hu

Objective

This review aims to provide an overview of the dysbiosis and interaction between Streptococcus mutans (S. mutans) and other Streptococci, Veillonella spp., Lactobacillus spp., and Candida albicans in the oral cavity, which is a major driver of cariogenicity.

Design

The search for this narrative review was conducted in databases including PubMed, Web of Science, and Google Scholar, employing keywords like "Dental caries," "Streptococcus mutans," "Commensal Streptococci," "Veillonella," "Lactobacillus," "Candida albicans," and "Interaction" while manually retrieving the reference lists of journal articles.

Results

Dental caries has a high prevalence and low treatment rate in the population, which poses a great burden to public health and the social economy. The etiology of dental caries is closely linked to the imbalance of oral microbial communities. S. mutans is the major pathogen of dental caries. The cariogenic mechanism of S. mutans is primarily related to acid production and acid resistance, as well as polysaccharide production, adhesion, colonization, and the formation of cariogenic biofilm. However, there are complex interactions between S. mutans and other symbiotic microorganisms in the oral cavity, which synergistically or antagonistically affect the pathogenicity of microorganisms.

Conclusion

The interactions between S. mutans and oral commensal microorganisms on the microecology provide an in-depth understanding of the etiology of cariogenicity and new pathways for multiple caries prevention and treatment, such as hydrogen peroxide, arginine, farnesol, and probiotics.
目的本文旨在综述变形链球菌(S. mutans)与其他链球菌、细孔菌、乳杆菌和白色念珠菌在口腔内的生态失调和相互作用,这是导致龋齿的主要原因。在PubMed、Web of Science和谷歌Scholar等数据库中搜索这篇叙叙性综述,使用关键词如“龋齿”、“变形链球菌”、“共生链球菌”、“细纹菌”、“乳酸菌”、“白色念珠菌”和“相互作用”,同时手动检索期刊文章的参考文献列表。结果龋病在人群中发病率高,治愈率低,给公共卫生和社会经济造成了巨大负担。龋齿的病因与口腔微生物群落的失衡密切相关。变形链球菌是龋齿的主要病原体。变形链球菌的蛀牙机制主要与产酸和耐酸有关,也与多糖的产生、粘附、定植和蛀牙生物膜的形成有关。然而,变形链球菌与口腔内其他共生微生物之间存在复杂的相互作用,协同或拮抗影响微生物的致病性。结论变形链球菌与口腔共生微生物在微生态上的相互作用,为深入了解龋齿的致病机理提供了新的途径,如过氧化氢、精氨酸、法尼醇、益生菌等。
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引用次数: 0
Transplanted mesenchymal stem cells isolated from the bone marrow ameliorate the histological alterations in the parotid glands of hypothyroid male rats 骨髓间充质干细胞移植可改善甲状腺功能减退雄性大鼠腮腺的组织学改变
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-08-06 DOI: 10.1016/j.archoralbio.2025.106368
Hanan El-Hemedy , Mohamed Badawy , Mary Moheb , Maha El Shahawy

Objective

To elucidate the possible outcome of mesenchymal stem cells extracted from the bone marrow (BM-MSCs) on the altered histological structure of the parotid gland of male rats with induced hypothyroidism.

Design

24 adult male Wistar rats were used. The rats were divided into 3 groups, each containing 8 animals. The control group contained the sham-operated animals. The hypothyroid rat group (HT group) contained animals receiving carbimazole at a dose of 20 mg/kg per day up to 6 weeks to induce hypothyroidism. The third group contained rats with induced hypothyroidism and were administered BM-MSCs via the tail vein (HT-MSC) group. BM-MSCs were extracted from 3-week-old rats and were immunophenotyped prior to injection to the HT-MSC group. The parotid glands were dissected 6 weeks post injection and processed to assess PKH67-labelled cells, histomorphometry and staining with Haematoxylin and Eosin (H and E).

Results

Rats with induced hypothyroidism depicted a significant decrease in the thyroid hormones´ serum levels. Extracted BM-MSCs were CD105 + , CD90 + and CD45-. The parotid gland of HT group depicted an abnormal structure of the acini, intercalated, striated and excretory ducts including nuclear alterations, vacuolization and indistinct boundaries compared to their controls. In addition, the area and perimeter of the acini were diminished. The HT-MSCs group depicted green PKH67+-labelled MSCs, restoration of the normal acinar and ductal configuration, and regular area and perimeter of the acini.

Conclusion

Transplanted BM-MSCs resumed the normal parotid gland acinar, intercalated, striated and excretory duct structure in the hypothyroid male rats, suggesting restored tissue function.
目的探讨骨髓间充质干细胞(bmscs)对雄性甲状腺功能减退大鼠腮腺组织结构改变的影响。设计选用24只成年雄性Wistar大鼠。将大鼠分为3组,每组8只。对照组包含假手术的动物。甲状腺功能减退大鼠组(HT组)给予卡马唑20 mg/kg /天,连续6周诱导甲状腺功能减退。第三组为诱导甲状腺功能减退大鼠,经尾静脉给药(HT-MSC)组。从3周龄大鼠中提取BM-MSCs,并在注射HT-MSC组前进行免疫表型分析。注射后6周切除腮腺,进行pkh67标记细胞、组织形态测定和血红素和伊红染色(H和E)。结果诱导甲状腺功能减退大鼠血清甲状腺激素 水平显著降低。提取的BM-MSCs为CD105 + 、CD90 + 和CD45-。腮腺HT组描述了一个异常的腺泡结构,夹层的,有条纹的和排泄管道包括核改变,液泡化和模糊边界相比,他们的控制。此外,腺泡的面积和周长都缩小了。HT-MSCs组描绘了绿色PKH67+标记的MSCs,恢复了正常的腺泡和导管结构,以及腺泡的规则面积和周长。结论移植的骨髓间充质干细胞恢复了甲状腺功能减退雄性大鼠正常的腮腺腺泡、插层、条纹和排泄管结构,提示组织功能恢复。
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引用次数: 0
Association between electronic nicotine delivery systems and dental caries: A systematic review with meta-analysis 电子尼古丁传递系统与龋齿之间的关系:一项荟萃分析的系统综述
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-26 DOI: 10.1016/j.archoralbio.2025.106366
Matheus dos Santos Fernandez , Francisco Wilker Mustafa Gomes Muniz , Felipe Gomes Dallepiane , Nathalia Ribeiro Jorge da Silva-Garcia , Mateus Andrade Rocha , Andreia Morales Cascaes , Ariadne Cristiane Cabral Cruz , Maísa Casarin

Objective

To explore the association between the electronic nicotine-delivery systems (ENDS) use and dental caries in adolescents and adults.

Material and methods

Two researchers independently conducted the search across six databases, study selection, data extraction, and assessment of risk of bias and certainty of evidence. Included studies involved participants ≥ 16 years old, assessed ENDS use, and employed clinical and/or radiographic methods for caries diagnosis. Risk of bias was evaluated using the Joanna Briggs Institute Checklist and the Newcastle–Ottawa Scale. A meta-analysis was performed to calculate the mean difference (MD) in caries severity between ENDS users and non-users. The GRADE approach was used to assess the certainty of the evidence.

Results

Of the 559 eligible studies, four were included (three cross-sectional and one was a prospective cohort). Three studies identified a potential association between the ENDS use and either the experience or risk of dental caries, as well as the prevalence of untreated teeth. Three studies were classified as having a high risk of bias. The quantitative analysis of the pooled effects (2 studies) showed no significant MD between the history of dental caries among those who did or did not use ENDS (MD: 0.72, 95 % confidence interval: −1.70–3.15).

Conclusion

It was showed a potential association between ENDS use and increased severity and risk of dental caries in both population groups. However, quantitative analysis showed disease severity is not associated with the use of these devices among adults. The certainty of evidence for qualitative and quantitative analyses was very low.
目的探讨青少年和成人使用电子尼古丁传递系统(ENDS)与龋病的关系。材料和方法两名研究人员独立进行了六个数据库的检索、研究选择、数据提取、偏倚风险评估和证据确定性评估。纳入的研究涉及≥ 16岁的参与者,评估ENDS的使用,并采用临床和/或放射学方法进行龋齿诊断。偏倚风险采用乔安娜布里格斯研究所检查表和纽卡斯尔渥太华量表进行评估。进行荟萃分析以计算ENDS使用者和非使用者之间龋齿严重程度的平均差异(MD)。GRADE方法用于评估证据的确定性。结果在559项符合条件的研究中,纳入了4项(3项是横断面研究,1项是前瞻性队列研究)。三项研究确定了终端使用与龋齿经历或风险以及未经治疗的牙齿患病率之间的潜在关联。三项研究被归类为具有高偏倚风险。综合效应(2项研究)的定量分析显示,使用ENDS或未使用ENDS的龋齿史之间没有显著的MD (MD: 0.72, 95 %置信区间:−1.70-3.15)。结论在两组人群中,ENDS的使用与龋病严重程度和风险增加之间存在潜在关联。然而,定量分析显示,在成年人中,疾病严重程度与这些装置的使用无关。定性和定量分析证据的确定性非常低。
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引用次数: 0
Taiwanese green propolis suppresses NLRP3 inflammasome activation and induces Nrf2/HO-1 pathway to reduce periodontal pathogen-induced endothelial inflammation 台湾绿蜂胶抑制NLRP3炎性体激活,诱导Nrf2/HO-1通路,减少牙周病原体诱导的内皮炎症
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-26 DOI: 10.1016/j.archoralbio.2025.106364
Yi-Jen Lai , Yin-Chu Chuang , Yung-Li Wang , Ming-Tse Li , Emily Sunny Lee , Wei-Ju Lee , Wei-Ning Lin , Yuh-Lien Chen , Ching-Shuen Wang , Thi Thuy Tien Vo , Yue-Wen Chen , I-Ta Lee

Objective

Periodontitis is a chronic inflammatory disease associated with systemic conditions, including cardiovascular diseases. Porphyromonas gingivalis (Pg), a key periodontal pathogen, contributes to vascular endothelial dysfunction through its virulence factors. This study aimed to investigate the protective effects of Taiwanese green propolis (TGP) against Pg-derived lipopolysaccharide (Pg-LPS)-induced endothelial inflammation, focusing on its modulation of the NLRP3 inflammasome and Nrf2/HO-1 signaling pathways.

Design

Human aortic endothelial cells (HAECs) were stimulated with Pg-LPS in the presence or absence of TGP. The expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) was assessed using real-time PCR and ELISA. ROS production was evaluated using fluorescence-based assays, while NF-κB activation and Nrf2 transcriptional activity were analyzed via luciferase reporter assays. Pharmacological inhibitors were used to confirm the involvement of these pathways.

Results

TGP significantly reduced Pg-LPS-induced IL-1β, TNF-α, and IL-6 expression in HAECs. It inhibited NF-κB activation, suppressed ROS generation, and attenuated NLRP3 inflammasome activation. Additionally, TGP upregulated HO-1 expression and enhanced Nrf2 transcriptional activity, as evidenced by ARE-driven luciferase reporter assays. Pharmacological inhibition of Nrf2 and HO-1 reversed TGP’s anti-inflammatory effects, confirming that the Nrf2/HO-1 axis is critical for its protective function.

Conclusions

These findings demonstrate that TGP exerts anti-inflammatory and cytoprotective effects by suppressing NLRP3 inflammasome activation and enhancing the Nrf2/HO-1 pathway, reducing Pg-LPS-induced endothelial inflammation. This study suggests that TGP could be a promising natural therapeutic agent for mitigating periodontal pathogen-induced systemic inflammation.
目的牙周炎是一种与全身疾病相关的慢性炎症性疾病,包括心血管疾病。牙龈卟啉单胞菌(Porphyromonas gingivalis, Pg)是一种重要的牙周病原体,通过其毒力因子导致血管内皮功能障碍。本研究旨在探讨台湾绿蜂胶(TGP)对Pg-derived脂多糖(Pg-LPS)诱导的内皮细胞炎症的保护作用,重点研究其对NLRP3炎性体和Nrf2/HO-1信号通路的调节作用。在存在或不存在TGP的情况下,用Pg-LPS刺激人主动脉内皮细胞(HAECs)。采用real-time PCR和ELISA检测促炎因子(IL-1β、IL-6、TNF-α)的表达。采用荧光法评估ROS生成,采用荧光素酶报告基因法分析NF-κB激活和Nrf2转录活性。药理抑制剂被用来证实这些途径的参与。结果stgp显著降低了pg - lps诱导的haec中IL-1β、TNF-α和IL-6的表达。抑制NF-κB活化,抑制ROS生成,减弱NLRP3炎性体活化。此外,TGP上调HO-1的表达,增强Nrf2的转录活性,这一点得到了驱动荧光素酶报告基因检测的证实。Nrf2和HO-1的药理抑制逆转了TGP的抗炎作用,证实Nrf2/HO-1轴对其保护功能至关重要。结论TGP通过抑制NLRP3炎性小体激活,增强Nrf2/HO-1通路,减轻pg - lps诱导的内皮细胞炎症,发挥抗炎和细胞保护作用。本研究提示TGP可能是一种很有前景的天然治疗药物,可以减轻牙周病原体引起的全身炎症。
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引用次数: 0
The early wear susceptibility of dentine following exposure to citric acid: In vitro study 柠檬酸对牙本质早期磨损敏感性的体外研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-25 DOI: 10.1016/j.archoralbio.2025.106363
B.D. Murchie, M.J. German, P.J. Waterhouse, F. Mullan

Objective

This study investigated the effect of early erosion on the mechanical and structural properties of dentine, while comparing the influence of different citric acid pH and concentration levels.

Design

Twenty dentine specimens were randomly allocated into five groups, according to the citric acid (CA) solution: non-eroded; 1 % buffered CA (pH=3.8); 1 % unbuffered CA (pH=2.55); 6 % buffered CA (pH=3.8); and 6 % unbuffered CA (pH=2.06). Specimen numbers were determined from a sample size power calculation. Erosion groups were subjected to 6x cycles, each lasting 20 s, giving a total exposure of 2 min. Surface alterations were determined by atomic force microscopy (at nanoscale) after each cycle. Erosive changes were also assessed qualitatively/quantitatively with scanning electron microscopy and energy dispersive x-ray spectroscopy. Data were analysed by repeated measures ANOVA with Bonferroni correction.

Results

All erosion groups showed significant structural and mechanical changes after a 20 s exposure interval. Specimens exposed to 6 % unbuffered CA, revealed a significant reduction of modulus of elasticity (p < 0.01), and greater changes to topography and morphology, compared with other groups. The 1 % buffered group had the least erosive changes (p < 0.05). Dentine exposed to 1 % unbuffered CA had a comparably greater rate of erosion, compared with the 6 % buffered solution, as exposure times progressed.

Conclusions

Dentine was highly susceptible to early CA erosion, with significant changes occurring after 20 s, regardless of pH or concentration. Alterations to the pH and/or concentration significantly altered the rate and severity of erosion. Although, CA with a lower pH was the most critical factor for early dentine erosion.
目的探讨早期侵蚀对牙本质力学和结构性能的影响,并比较不同柠檬酸pH和浓度对牙本质力学和结构性能的影响。设计将20个牙本质标本随机分为五组,根据柠檬酸(CA)溶液分为:未腐蚀组;1 %缓冲CA (pH=3.8);1 %未缓冲CA (pH=2.55);6 %缓冲CA (pH=3.8);6 %未缓冲CA (pH=2.06)。样本数量由样本容量功率计算确定。侵蚀组进行6次循环,每次持续20 s,总暴露时间为2 min。每个循环后,通过原子力显微镜(纳米级)测定表面变化。利用扫描电子显微镜和能量色散x射线能谱对侵蚀变化进行定性/定量评估。数据分析采用Bonferroni校正的重复测量方差分析。结果各侵蚀组在20 s的暴露时间后均出现了明显的结构和力学变化。与其他组相比,暴露于6 %无缓冲CA的标本显示弹性模量显著降低(p <; 0.01),地形和形态变化更大。1 %缓冲组糜烂变化最小(p <; 0.05)。随着暴露时间的推移,暴露于1 %未缓冲CA的牙本质比暴露于6 %缓冲溶液的牙本质有更大的侵蚀率。结论牙本质对早期CA侵蚀非常敏感,在20 s后发生显著变化,与pH和浓度无关。pH值和/或浓度的改变显著改变了侵蚀的速率和严重程度。然而,较低pH的CA是早期牙本质侵蚀的最关键因素。
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引用次数: 0
Puerarin enhances the efficacy of carboplatin in oral squamous cell carcinoma via dual targeting 葛根素通过双靶向增强卡铂治疗口腔鳞状细胞癌的疗效
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-24 DOI: 10.1016/j.archoralbio.2025.106360
Liping Xie , Yekun Zhuang , Yehua Lai , Jing Guo , Ziqiang Zhu , Hua Tian , Shanqiang Zhang , Fu Liu

Objective

The purpose of this study was to explore the effects and molecular mechanisms by which puerarin, in combination with carboplatin, combats oral squamous cell carcinoma (OSCC).

Design

The effects of puerarin in combination with carboplatin on OSCC cell viability, proliferation, apoptosis, autophagy, DNA damage, and the Phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway were evaluated through molecular biology experiments and bioinformatics analyses. In addition, an OSCC animal model was established to further evaluate the in vivo anti-tumor effects of combination therapy.

Results

Puerarin synergized with carboplatin to inhibit OSCC cell viability and proliferation, induce DNA damage and apoptosis, and trigger autophagosome formation while blocking autophagic flux, thereby further promoting apoptosis. Combination therapy modulated both autophagy and apoptosis through suppression of the PI3K-AKT-mTOR signaling pathway. In addition, combination therapy improved in vivo efficacy and reduced the toxicity of low-dose carboplatin. The in vivo toxicity of puerarin monotherapy was not significant.

Conclusion

Puerarin enhanced the therapeutic effect of carboplatin on OSCC through a dual mechanism: activating the "DNA damage-autophagic flux blockade-damage accumulation-apoptosis activation" positive feedback loop and inhibiting the PI3K-AKT-mTOR pathway to promote autophagosome formation and apoptosis. The synergistic effect significantly improved the efficacy of carboplatin while reducing its toxicity, and puerarin showed no significant toxic side effects, providing a novel strategy for optimizing clinical combination therapy.
目的探讨葛根素联合卡铂治疗口腔鳞状细胞癌的作用及分子机制。设计通过分子生物学实验和生物信息学分析,评价葛根素联合卡铂对OSCC细胞活力、增殖、凋亡、自噬、DNA损伤以及磷酸肌肽3激酶(PI3K)-AKT丝氨酸/苏氨酸激酶(AKT)-哺乳动物雷帕霉素靶蛋白(mTOR)通路的影响。此外,我们还建立了OSCC动物模型,进一步评价联合治疗的体内抗肿瘤作用。结果红素与卡铂协同作用可抑制OSCC细胞活力和增殖,诱导DNA损伤和凋亡,在阻断自噬通量的同时触发自噬体的形成,从而进一步促进细胞凋亡。联合治疗通过抑制PI3K-AKT-mTOR信号通路调节自噬和凋亡。此外,联合治疗提高了体内疗效,降低了低剂量卡铂的毒性。葛根素单药的体内毒性不显著。结论葛根素通过激活“DNA损伤-自噬通量阻断-损伤积累-凋亡激活”正反馈回路和抑制PI3K-AKT-mTOR通路促进自噬体形成和凋亡的双重机制增强卡铂对OSCC的治疗效果。协同作用显著提高了卡铂的疗效,同时降低了其毒性,葛根素无明显毒副作用,为优化临床联合治疗提供了新的策略。
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引用次数: 0
Elucidating the pathogenesis of oral submucous fibrosis: A comprehensive review 口腔黏膜下纤维化的发病机制研究综述
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-24 DOI: 10.1016/j.archoralbio.2025.106362
Disha Sharma , Sarita Pal , Uma Shanker Pal , Narayan Prasad Yadav

Objective

Oral submucosal fibrosis (OSMF) is a progressive and potentially malignant disorder of the oral cavity. This review aims to explore the key mechanisms underlying OSMF pathogenesis and its malignant transformation to oral cancer, focusing on the role of associated cells, growth factors, and signaling pathways, by detailing the sequential events within each pathway and their interconnections.

Design

A comprehensive literature search was conducted using databases such as PubMed, Scopus, Google Scholar, and SciFinder to identify affected cells, pathways, and cellular mechanisms associated with OSMF and oral cancer.

Results

This review elaborates the signaling pathways responsible for the progression of OSMF through myofibroblast activation. It highlights the altered functionality of key cellular players, including epithelial, endothelial, immune cells, and fibroblasts. It also enhances the understanding of OSMF pathophysiology by revealing the specific growth factors (TGF-βs, PDGF, FGF, VEGF, CTGF) and signaling pathways such as PI3K/AKT, JAK/STAT, WNT/β-catenin, and NF-кB, that are involved in the initiation and progression of OSMF and its malignant transformation to oral cancer.

Conclusion

This review identifies potential therapeutic targets and biomarkers within signaling pathways, mainly TGF-β and PI3K/AKT, that regulate fibroblast activation, inflammation, reactive oxygen species generation, collagen synthesis, and degradation in OSMF, which further leads to oral cancer development. In order to develop new treatments that target particular biomarkers, a deeper understanding of these signaling cascades is necessary.
目的口腔黏膜下纤维化(OSMF)是一种进行性口腔疾病,具有潜在的恶性。本文旨在探讨OSMF发病机制及其恶性转化为口腔癌的关键机制,重点关注相关细胞、生长因子和信号通路的作用,并详细介绍各通路内的顺序事件及其相互联系。DesignA使用PubMed、Scopus、谷歌Scholar和SciFinder等数据库进行全面的文献检索,以确定与OSMF和口腔癌相关的受影响细胞、途径和细胞机制。结果本文阐述了OSMF通过肌成纤维细胞激活的信号通路。它强调了关键细胞参与者的功能改变,包括上皮细胞、内皮细胞、免疫细胞和成纤维细胞。通过揭示参与OSMF发生、发展及口腔癌恶性转化的特定生长因子(TGF-βs、PDGF、FGF、VEGF、CTGF)和PI3K/AKT、JAK/STAT、WNT/β-catenin、NF-кB等信号通路,增强了对OSMF病理生理的认识。结论本综述在信号通路中发现了潜在的治疗靶点和生物标志物,主要是TGF-β和PI3K/AKT,它们调节OSMF中成纤维细胞的活化、炎症、活性氧的产生、胶原的合成和降解,从而进一步导致口腔癌的发生。为了开发针对特定生物标志物的新疗法,有必要更深入地了解这些信号级联反应。
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引用次数: 0
Mandibular movements and swallowing threshold in older adults with obesity using removable prostheses 使用可移动假体治疗老年肥胖患者的下颌运动和吞咽阈值
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-07-23 DOI: 10.1016/j.archoralbio.2025.106361
Guilherme Fantini Ferreira , Talita Malini Carletti , Ingrid Meira Andrade , Mayara Abreu Pinheiro , Ana Carolina Pero , Renata Cunha Matheus Rodrigues Garcia

Objective

In adults, obesity has been associated with reduced chewing ability. However, evidence for the association of obesity with chewing movements in partially edentate older adults is scarce. This study was conducted to evaluate the influence of obesity on the mandibular movements and swallowing thresholds of obese older adults using removable prostheses.

Design

Thirty-eight partially edentulous older adults were assigned to obese (n = 18, 71.11 ± 5.18 years) and control (n = 20, 70.00 ± 5.36 years) groups. All participants received new prostheses. Six months later, their mandibular range of motion, jaw movements during chewing, and swallowing thresholds were assessed using jaw-tracking methods. The data were compared using the independent t test (α = 5 %).

Results

Relative to controls, older adults with obesity had lesser vertical apertures (34.65 mm ± 2.26), and masticatory cycle times (600.53 ms ± 68.05), and longer mandibular closing times (242.15 ms ± 40.05; all p < 0.05). Additionally, the obese group exhibited larger median particle sizes (4.89 ± 0.70) and fewer chewing cycles before swallowing (20.44 ± 4.51; both p < 0.001).

Conclusions

Older adults with obesity wearers of removable dentures had reduced jaw range of motion and mandibular movements during chewing, and impaired masticatory function related to swallowing threshold relative to controls. These findings may contribute to the understanding of the complex relationship between obesity and masticatory function.
目的在成年人中,肥胖与咀嚼能力下降有关。然而,在部分有牙的老年人中,很少有证据表明肥胖与咀嚼运动有关。本研究旨在评估肥胖对使用可移动假体的肥胖老年人下颌运动和吞咽阈值的影响。设计将38名部分无牙老年人分为肥胖组(n = 18,71.11 ± 5.18岁)和对照组(n = 20,70.00 ± 5.36岁)。所有的参与者都接受了新的义肢。6个月后,使用下颌追踪方法评估他们的下颌运动范围、咀嚼时下颌运动和吞咽阈值。资料比较采用独立t检验(α = 5 %)。结果与对照组相比,老年肥胖患者的垂直开口(34.65 mm±2.26)和咀嚼周期次数(600.53 ms±68.05)较少,下颌闭合时间(242.15 ms±40.05)较长;所有p & lt; 0.05)。此外,肥胖组的中位颗粒尺寸更大(4.89 ± 0.70),吞咽前咀嚼周期更少(20.44 ± 4.51;p & lt; 0.001)。结论肥胖成人可摘义齿佩戴者咀嚼时下颌活动范围缩小,吞咽阈相关咀嚼功能受损。这些发现可能有助于理解肥胖与咀嚼功能之间的复杂关系。
{"title":"Mandibular movements and swallowing threshold in older adults with obesity using removable prostheses","authors":"Guilherme Fantini Ferreira ,&nbsp;Talita Malini Carletti ,&nbsp;Ingrid Meira Andrade ,&nbsp;Mayara Abreu Pinheiro ,&nbsp;Ana Carolina Pero ,&nbsp;Renata Cunha Matheus Rodrigues Garcia","doi":"10.1016/j.archoralbio.2025.106361","DOIUrl":"10.1016/j.archoralbio.2025.106361","url":null,"abstract":"<div><h3>Objective</h3><div>In adults, obesity has been associated with reduced chewing ability. However, evidence for the association of obesity with chewing movements in partially edentate older adults is scarce. This study was conducted to evaluate the influence of obesity on the mandibular movements and swallowing thresholds of obese older adults using removable prostheses.</div></div><div><h3>Design</h3><div>Thirty-eight partially edentulous older adults were assigned to obese (<em>n</em> = 18, 71.11 ± 5.18 years) and control (<em>n</em> = 20, 70.00 ± 5.36 years) groups. All participants received new prostheses. Six months later, their mandibular range of motion, jaw movements during chewing, and swallowing thresholds were assessed using jaw-tracking methods. The data were compared using the independent <em>t</em> test (<em>α</em> = 5 %).</div></div><div><h3>Results</h3><div>Relative to controls, older adults with obesity had lesser vertical apertures (34.65 mm ± 2.26), and masticatory cycle times (600.53 ms ± 68.05), and longer mandibular closing times (242.15 ms ± 40.05; all <em>p</em> &lt; 0.05). Additionally, the obese group exhibited larger median particle sizes (4.89 ± 0.70) and fewer chewing cycles before swallowing (20.44 ± 4.51; both <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Older adults with obesity wearers of removable dentures had reduced jaw range of motion and mandibular movements during chewing, and impaired masticatory function related to swallowing threshold relative to controls. These findings may contribute to the understanding of the complex relationship between obesity and masticatory function.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106361"},"PeriodicalIF":2.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714213","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
期刊
Archives of oral biology
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