Thomas George Kallarakkal, B S M S Siriwardena, Ariyapala Samaranayaka, R P Ekanayaka, W M Tilakaratne
Background: Cervical lymph node metastasis is one of the most important prognosticators in oral squamous cell carcinoma (OSCC). The presence of extranodal extension (ENE) in metastatic nodes further worsens the prognosis. The primary objective of this study was to develop a simple model to predict ENE in OSCC using demographic and clinicopathological parameters that are easily available in a preoperative clinical setting.
Methods: All patients who underwent surgery for the treatment of primary OSCC of the tongue or buccal mucosa with neck dissection (ND) between 1998 and 2020 from two oral pathology diagnostic units were included in the study. Chi-square tests were utilised to analyse the presence/absence of associations between each input parameter and ENE. The strengths of these associations were assessed using univariable and multivariable logistic regressions and indicated as odds ratios.
Results: Among the 1098 OSCC patients included in the study, 185 (16.85%) patients exhibited ENE. In the multivariable logistic regression model the odds for ENE were greater in females and tongue OSCC. Similarly, increasing T category and DOI as well as a dyscohesive WPOI were associated with a greater odds ratio for ENE. The AUCs from the 10-fold cross-validations to assess the predictive ability of the newly developed model ranged from 0.655 to 0.842 with a 95% CI of 0.663-0.744, indicating that the diagnostic accuracy of our model was acceptable.
Conclusion: Our model confirms that a higher risk of ENE is associated with female gender, tumours of the tongue, increasing tumour size as well as DOI and a dyscohesive WPOI.
{"title":"Prediction of Extranodal Extension in Oral Squamous Cell Carcinoma Using Demographic and Clinicopathological Variables-Evidence From a Multicentre Study.","authors":"Thomas George Kallarakkal, B S M S Siriwardena, Ariyapala Samaranayaka, R P Ekanayaka, W M Tilakaratne","doi":"10.1111/jop.70086","DOIUrl":"https://doi.org/10.1111/jop.70086","url":null,"abstract":"<p><strong>Background: </strong>Cervical lymph node metastasis is one of the most important prognosticators in oral squamous cell carcinoma (OSCC). The presence of extranodal extension (ENE) in metastatic nodes further worsens the prognosis. The primary objective of this study was to develop a simple model to predict ENE in OSCC using demographic and clinicopathological parameters that are easily available in a preoperative clinical setting.</p><p><strong>Methods: </strong>All patients who underwent surgery for the treatment of primary OSCC of the tongue or buccal mucosa with neck dissection (ND) between 1998 and 2020 from two oral pathology diagnostic units were included in the study. Chi-square tests were utilised to analyse the presence/absence of associations between each input parameter and ENE. The strengths of these associations were assessed using univariable and multivariable logistic regressions and indicated as odds ratios.</p><p><strong>Results: </strong>Among the 1098 OSCC patients included in the study, 185 (16.85%) patients exhibited ENE. In the multivariable logistic regression model the odds for ENE were greater in females and tongue OSCC. Similarly, increasing T category and DOI as well as a dyscohesive WPOI were associated with a greater odds ratio for ENE. The AUCs from the 10-fold cross-validations to assess the predictive ability of the newly developed model ranged from 0.655 to 0.842 with a 95% CI of 0.663-0.744, indicating that the diagnostic accuracy of our model was acceptable.</p><p><strong>Conclusion: </strong>Our model confirms that a higher risk of ENE is associated with female gender, tumours of the tongue, increasing tumour size as well as DOI and a dyscohesive WPOI.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reema Shehadeh, Mor Bar Ilan, Sara Dovrat, Ronit Yerushalmi, Michal Tepperberg Oikawa, Evangelia Piperi, Nikolaos G Nikitakis, Noam Yarom
Objective: Acyclovir-resistant herpes simplex virus infections pose a significant challenge in immunosuppressed patients. This study aimed to characterize the clinical features, treatment outcomes, and mortality associated with acyclovir-resistant herpes simplex virus infection.
Materials and methods: A retrospective analysis was conducted on 18 patients diagnosed with acyclovir-resistant herpes simplex virus. Diagnosis was confirmed via plaque reduction assay. Data on demographics, underlying conditions, oral and systemic manifestations, management, and outcomes were retrieved and analyzed.
Results: The cohort was comprised of 10 women and eight men with a median age of 41.5 years. Acute myeloid leukemia was the most common underlying medical condition (n = 5), and 17 patients had undergone allogeneic hematopoietic cell transplantation. Oral lesions were observed in all 18 cases, primarily on the tongue (n = 12) and lips (n = 11). Acyclovir resistance was detected after a median of 151.5 days (range: 30-1736 days), after which foscarnet became the primary treatment. Despite therapy, 11 patients died after a median survival of 3 months post-diagnosis.
Conclusions: Acyclovir-resistant herpes simplex virus infections are associated with considerable morbidity and mortality in immunocompromised patients. These findings highlight the need for heightened awareness, alternative antiviral therapies, and improved prophylactic strategies to manage these patients more effectively.
Clinical relevance: Dentists play a key role in detecting acyclovir resistance through persistent oral HSV lesions, emphasizing early recognition, referral, and supportive care.
{"title":"Characteristics of Acyclovir-Resistant Herpes Simplex Virus Infection in Hematological Patients.","authors":"Reema Shehadeh, Mor Bar Ilan, Sara Dovrat, Ronit Yerushalmi, Michal Tepperberg Oikawa, Evangelia Piperi, Nikolaos G Nikitakis, Noam Yarom","doi":"10.1111/jop.70078","DOIUrl":"https://doi.org/10.1111/jop.70078","url":null,"abstract":"<p><strong>Objective: </strong>Acyclovir-resistant herpes simplex virus infections pose a significant challenge in immunosuppressed patients. This study aimed to characterize the clinical features, treatment outcomes, and mortality associated with acyclovir-resistant herpes simplex virus infection.</p><p><strong>Materials and methods: </strong>A retrospective analysis was conducted on 18 patients diagnosed with acyclovir-resistant herpes simplex virus. Diagnosis was confirmed via plaque reduction assay. Data on demographics, underlying conditions, oral and systemic manifestations, management, and outcomes were retrieved and analyzed.</p><p><strong>Results: </strong>The cohort was comprised of 10 women and eight men with a median age of 41.5 years. Acute myeloid leukemia was the most common underlying medical condition (n = 5), and 17 patients had undergone allogeneic hematopoietic cell transplantation. Oral lesions were observed in all 18 cases, primarily on the tongue (n = 12) and lips (n = 11). Acyclovir resistance was detected after a median of 151.5 days (range: 30-1736 days), after which foscarnet became the primary treatment. Despite therapy, 11 patients died after a median survival of 3 months post-diagnosis.</p><p><strong>Conclusions: </strong>Acyclovir-resistant herpes simplex virus infections are associated with considerable morbidity and mortality in immunocompromised patients. These findings highlight the need for heightened awareness, alternative antiviral therapies, and improved prophylactic strategies to manage these patients more effectively.</p><p><strong>Clinical relevance: </strong>Dentists play a key role in detecting acyclovir resistance through persistent oral HSV lesions, emphasizing early recognition, referral, and supportive care.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme Iani Pontes, Anna Luíza Damaceno Araújo, Andresa Borges Soares, Saman Warnakulasuriya, André Luis Santana de Freitas, Caroline Gennari Stevão, Marcelo Sperandio, Matheus Cardoso Moraes
Background: Oral leukoplakia (OL) is a potentially malignant disorder of the oral mucosa. Accurate prediction of malignant transformation (MT) remains a clinical challenge. This study aimed to develop and evaluate a machine learning model that integrates histopathological, demographic, and DNA content features to predict MT risk in OL.
Methods: We conducted a retrospective cohort study of 97 OL cases-18 with confirmed MT and 79 non-transformed controls-selected from a larger series. Each case included clinicopathological features, and DNA content data obtained by flow cytometry for cell cycle phases (G1, S-phase, G2 and excess DNA beyond the tetraploid region [4cER]). All cases had a minimum 5-year follow-up or histologically confirmed transformation. A multilayer perceptron (MLP) model was trained on 27 features. Stratified five-fold cross-validation and minority class oversampling (positive filling) were used to improve learning and mitigate data imbalance. Performance was evaluated using accuracy, sensitivity, specificity, F1-score, AUC, and Kaplan-Meier survival analysis.
Results: Significant predictors of MT included 4cER (p = 0.005), G2 phase (p = 0.04), dysplasia grading (p = 0.003), and inflammatory infiltrate (p = 0.01). The optimized model yielded 72% sensitivity, 96% specificity, and an AUC of 85.4%. Survival analysis showed significantly poorer outcomes in the high-risk cases predicted by the model (p < 0.0001).
Conclusion: Integrating DNA content analysis with machine learning provides an objective and clinically useful model to stratify malignant risk in OL, complementing conventional histopathology and supporting personalized patient management.
{"title":"Predicting Malignant Transformation in Oral Leukoplakia: A Multilayer Perceptron Approach Incorporating Clinicopathological Features and DNA Content.","authors":"Guilherme Iani Pontes, Anna Luíza Damaceno Araújo, Andresa Borges Soares, Saman Warnakulasuriya, André Luis Santana de Freitas, Caroline Gennari Stevão, Marcelo Sperandio, Matheus Cardoso Moraes","doi":"10.1111/jop.70084","DOIUrl":"https://doi.org/10.1111/jop.70084","url":null,"abstract":"<p><strong>Background: </strong>Oral leukoplakia (OL) is a potentially malignant disorder of the oral mucosa. Accurate prediction of malignant transformation (MT) remains a clinical challenge. This study aimed to develop and evaluate a machine learning model that integrates histopathological, demographic, and DNA content features to predict MT risk in OL.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 97 OL cases-18 with confirmed MT and 79 non-transformed controls-selected from a larger series. Each case included clinicopathological features, and DNA content data obtained by flow cytometry for cell cycle phases (G1, S-phase, G2 and excess DNA beyond the tetraploid region [4cER]). All cases had a minimum 5-year follow-up or histologically confirmed transformation. A multilayer perceptron (MLP) model was trained on 27 features. Stratified five-fold cross-validation and minority class oversampling (positive filling) were used to improve learning and mitigate data imbalance. Performance was evaluated using accuracy, sensitivity, specificity, F1-score, AUC, and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>Significant predictors of MT included 4cER (p = 0.005), G2 phase (p = 0.04), dysplasia grading (p = 0.003), and inflammatory infiltrate (p = 0.01). The optimized model yielded 72% sensitivity, 96% specificity, and an AUC of 85.4%. Survival analysis showed significantly poorer outcomes in the high-risk cases predicted by the model (p < 0.0001).</p><p><strong>Conclusion: </strong>Integrating DNA content analysis with machine learning provides an objective and clinically useful model to stratify malignant risk in OL, complementing conventional histopathology and supporting personalized patient management.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Trigeminal neuralgia is a common neuropathic pain of the oral and maxillofacial region. P2X7 receptor, a neural mediator, P2X7 receptor is closely related to this condition. Despite several studies on the role of Jujuboside A in sleep, few reports are available on its effects on chronic neuropathic pain.
Methods: In this study, a rat trigeminal neuralgia model was established by chronic constriction injury of the infraorbital nerve. Rats were intervened with Jujuboside A and P2X7 shRNA. For the behavioral aspect, the changes in the facial mechanical pain withdrawal threshold of the rats were measured. Molecular biology techniques such as Western Blotting, Real-Time Quantitative PCR, Immunohistochemistry and Enzyme-Linked Immunosorbent Assay were used to determine the changes in the P2X7 receptor, pyroptosis pathway, and inflammatory factors.
Results: The facial mechanical withdrawal threshold showed a significantly greater reduction in the trigeminal neuralgia group than in the sham group at 14 days post-operation. Jujuboside A therapy could alleviate the facial allodynia and inhibit the up-regulation of P2X7 expression in the spinal trigeminal subnucleus caudalis. Additionally, the expression of P2X7, nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3 caspase-1 and interleukin-1β was significantly greater in the trigeminal neuralgia group than in the sham group, suggesting activation of the pyroptosis cascade; this could be reversed by Jujuboside A application. Moreover, Jujuboside A administration downregulated the phosphorylation of ERK1/2 in the spinal trigeminal subnucleus caudalis of the trigeminal neuralgia group. Molecular docking demonstrated a high binding force between Jujuboside A and P2X7. Furthermore, the P2X7 knockdown treatments effectively increased the facial mechanical withdrawal threshold of trigeminal neuralgia rats.
Conclusion: These findings suggest the potential benefits of Jujuboside A in trigeminal neuralgia treatment through suppression of pyroptosis by inhibition of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3/caspase-1 pathway mediated by the P2X7 receptor in the spinal trigeminal subnucleus caudalis.
{"title":"Jujuboside A Alleviates Facial Allodynia of CCI-ION Rats by Inhibiting the Expression of P2X7 Receptor in the Spinal Trigeminal Subnucleus Caudalis.","authors":"Min Zhou, Wei Han, Yangyuan Wu, Zhiqiang Ouyang, Yuhan Zhou, Lijuan Liu, Yanting Qiu, Yuanyi Zhang, Jingyan Zhang, Xinyue Pu, Yun Gao, Wei Xiong","doi":"10.1111/jop.70085","DOIUrl":"https://doi.org/10.1111/jop.70085","url":null,"abstract":"<p><strong>Background: </strong>Trigeminal neuralgia is a common neuropathic pain of the oral and maxillofacial region. P2X7 receptor, a neural mediator, P2X7 receptor is closely related to this condition. Despite several studies on the role of Jujuboside A in sleep, few reports are available on its effects on chronic neuropathic pain.</p><p><strong>Methods: </strong>In this study, a rat trigeminal neuralgia model was established by chronic constriction injury of the infraorbital nerve. Rats were intervened with Jujuboside A and P2X7 shRNA. For the behavioral aspect, the changes in the facial mechanical pain withdrawal threshold of the rats were measured. Molecular biology techniques such as Western Blotting, Real-Time Quantitative PCR, Immunohistochemistry and Enzyme-Linked Immunosorbent Assay were used to determine the changes in the P2X7 receptor, pyroptosis pathway, and inflammatory factors.</p><p><strong>Results: </strong>The facial mechanical withdrawal threshold showed a significantly greater reduction in the trigeminal neuralgia group than in the sham group at 14 days post-operation. Jujuboside A therapy could alleviate the facial allodynia and inhibit the up-regulation of P2X7 expression in the spinal trigeminal subnucleus caudalis. Additionally, the expression of P2X7, nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3 caspase-1 and interleukin-1β was significantly greater in the trigeminal neuralgia group than in the sham group, suggesting activation of the pyroptosis cascade; this could be reversed by Jujuboside A application. Moreover, Jujuboside A administration downregulated the phosphorylation of ERK1/2 in the spinal trigeminal subnucleus caudalis of the trigeminal neuralgia group. Molecular docking demonstrated a high binding force between Jujuboside A and P2X7. Furthermore, the P2X7 knockdown treatments effectively increased the facial mechanical withdrawal threshold of trigeminal neuralgia rats.</p><p><strong>Conclusion: </strong>These findings suggest the potential benefits of Jujuboside A in trigeminal neuralgia treatment through suppression of pyroptosis by inhibition of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3/caspase-1 pathway mediated by the P2X7 receptor in the spinal trigeminal subnucleus caudalis.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: CBD holds substantial promise in medical applications. This review aims to comprehensively analyse the current status of cannabidiol (CBD) in dentistry.
Methods: A systematic search of databases including PubMed-MEDLINE, Scopus, Embase, Cochrane Library, World Intellectual Property Organization (WIPO), European Patent Office (EPO), and the United States Patent and Trademark Office (USPTO) was conducted. Peer-reviewed journal manuscripts focusing on cell studies, clinical trials, and registered patents related to CBD and its derivatives in dentistry were summarised. Inclusion criteria were studies on CBD in dentistry, including original research and patents, published in English between 2013 and mid-2023 (articles) or early 2024 (patents), with full-text availability. Excluded were non-dentistry studies, unpublished or non-peer-reviewed reports, and duplicates using Microsoft Excel. The risk of bias was evaluated using the Cochrane RoB 2 tool. Two observers independently screened the articles for inclusion in the present study to mitigate bias. Cohen's kappa was used to measure inter-rater agreement.
Results: The total number of included studies was 57. Cell-based studies demonstrated CBD's effectiveness in modulating cellular responses and anti-inflammatory properties, especially in oral-origin cells, and its impact on osteogenic differentiation. Research, including clinical trials and patents, has shown CBD's benefits in treating pain and inflammation in the maxillofacial area, notably in conditions such as radiation-induced mucositis. CBD research in dental pain and inflammation is advanced, but studies on CBD's role in regenerative dentistry remain limited.
Conclusion: More studies on the mineralisation of oro-facial structures are necessary to fully understand CBD's role in regenerative dentistry. This study was supported by the Faculty of Dentistry, Chulalongkorn University. This study was registered in the PROSPERO (ID: CRD4201055832) and Open Science Framework (OSF) database (osf.io/z3bd8). The PRISMA guideline was followed to include the relevant full-text papers.
背景:CBD在医学应用方面有着巨大的前景。本文旨在全面分析大麻二酚(CBD)在牙科中的现状。方法:系统检索PubMed-MEDLINE、Scopus、Embase、Cochrane Library、世界知识产权组织(WIPO)、欧洲专利局(EPO)、美国专利商标局(USPTO)等数据库。总结了与牙科CBD及其衍生物相关的细胞研究、临床试验和注册专利的同行评审期刊手稿。纳入标准是2013年至2023年中期(文章)或2024年初(专利)期间以英文发表的CBD在牙科领域的研究,包括原创研究和专利,并提供全文。排除非牙科研究,未发表或未经同行评议的报告,以及使用Microsoft Excel重复的报告。使用Cochrane RoB 2工具评估偏倚风险。两名观察员独立筛选纳入本研究的文章,以减轻偏倚。科恩kappa被用来衡量评分者之间的一致性。结果:纳入的研究总数为57项。基于细胞的研究证明了CBD在调节细胞反应和抗炎特性方面的有效性,特别是在口腔来源的细胞中,以及它对成骨分化的影响。包括临床试验和专利在内的研究表明,CBD在治疗颌面疼痛和炎症方面有好处,尤其是在辐射引起的粘膜炎等疾病中。CBD在牙痛和炎症方面的研究取得了进展,但关于CBD在再生牙科中的作用的研究仍然有限。结论:为了充分了解CBD在再生牙科中的作用,需要对口腔-面部结构的矿化进行更多的研究。这项研究得到了朱拉隆功大学牙科学院的支持。本研究已在PROSPERO (ID: CRD4201055832)和开放科学框架(OSF)数据库(OSF .io/z3bd8)中注册。按照PRISMA指南纳入了相关的全文论文。
{"title":"Therapeutic Potential of Cannabidiol in Dentistry: A Systematic Review From Cellular Mechanisms to Clinical Trials.","authors":"Chatvadee Kornsuthisopon, Ajjima Chansaenroj, Sornkanok Vimolmangkang, Lakshman P Samaranayake, Thanaphum Osathanon","doi":"10.1111/jop.70081","DOIUrl":"https://doi.org/10.1111/jop.70081","url":null,"abstract":"<p><strong>Background: </strong>CBD holds substantial promise in medical applications. This review aims to comprehensively analyse the current status of cannabidiol (CBD) in dentistry.</p><p><strong>Methods: </strong>A systematic search of databases including PubMed-MEDLINE, Scopus, Embase, Cochrane Library, World Intellectual Property Organization (WIPO), European Patent Office (EPO), and the United States Patent and Trademark Office (USPTO) was conducted. Peer-reviewed journal manuscripts focusing on cell studies, clinical trials, and registered patents related to CBD and its derivatives in dentistry were summarised. Inclusion criteria were studies on CBD in dentistry, including original research and patents, published in English between 2013 and mid-2023 (articles) or early 2024 (patents), with full-text availability. Excluded were non-dentistry studies, unpublished or non-peer-reviewed reports, and duplicates using Microsoft Excel. The risk of bias was evaluated using the Cochrane RoB 2 tool. Two observers independently screened the articles for inclusion in the present study to mitigate bias. Cohen's kappa was used to measure inter-rater agreement.</p><p><strong>Results: </strong>The total number of included studies was 57. Cell-based studies demonstrated CBD's effectiveness in modulating cellular responses and anti-inflammatory properties, especially in oral-origin cells, and its impact on osteogenic differentiation. Research, including clinical trials and patents, has shown CBD's benefits in treating pain and inflammation in the maxillofacial area, notably in conditions such as radiation-induced mucositis. CBD research in dental pain and inflammation is advanced, but studies on CBD's role in regenerative dentistry remain limited.</p><p><strong>Conclusion: </strong>More studies on the mineralisation of oro-facial structures are necessary to fully understand CBD's role in regenerative dentistry. This study was supported by the Faculty of Dentistry, Chulalongkorn University. This study was registered in the PROSPERO (ID: CRD4201055832) and Open Science Framework (OSF) database (osf.io/z3bd8). The PRISMA guideline was followed to include the relevant full-text papers.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by high metastatic potential and poor prognosis. Previous studies have focused on the correlation between hypermethylated ZNF582 and HNSCC prognosis, particularly in diagnostic contexts, but the underlying molecular mechanisms remain poorly understood. This study explored the biological function and underlying mechanisms of ZNF582 in HNSCC.
Methods: ZNF582 expression was analyzed in HNSCC and non-tumor tissues. Functional assays, including colony formation, wound healing, Transwell, TUNEL assays, and xenograft models, were performed in HNSCC cell lines with or without ZNF582 overexpression. To assess cancer stemness, fluorescence-activated cell sorting, tumorsphere formation assay, extreme limiting dilution assay, and an orthotopic model were used. High-throughput RNA sequencing was performed to identify the altered signaling pathways.
Results: Bioinformatics analysis revealed that low ZNF582 expression in HNSCC correlated with poor prognosis. Overexpression of ZNF582 suppressed HNSCC proliferation, migration, and invasion, while promoting apoptosis both in vitro and in vivo. ZNF582 also reduced cancer stem cell activity and metastasis in HNSCC. Mechanically, ZNF582 overexpression inhibited the MAPK and PI3K/AKT signaling pathways.
Conclusion: Our findings suggested that ZNF582 overexpression inhibits HNSCC progression via the MAPK and PI3K/AKT signaling pathways, highlighting ZNF582 as a potential therapeutic target gene for HNSCC treatment.
{"title":"ZNF582 Inhibits Head and Neck Squamous Cell Carcinoma Progression and Stemness via MAPK and PI3K/AKT Signaling Pathways.","authors":"Yaqing Mao, Shuo Liu, Zhen Qin, Wenbo Zhang, Lingfei Jia, Xin Peng","doi":"10.1111/jop.70079","DOIUrl":"https://doi.org/10.1111/jop.70079","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by high metastatic potential and poor prognosis. Previous studies have focused on the correlation between hypermethylated ZNF582 and HNSCC prognosis, particularly in diagnostic contexts, but the underlying molecular mechanisms remain poorly understood. This study explored the biological function and underlying mechanisms of ZNF582 in HNSCC.</p><p><strong>Methods: </strong>ZNF582 expression was analyzed in HNSCC and non-tumor tissues. Functional assays, including colony formation, wound healing, Transwell, TUNEL assays, and xenograft models, were performed in HNSCC cell lines with or without ZNF582 overexpression. To assess cancer stemness, fluorescence-activated cell sorting, tumorsphere formation assay, extreme limiting dilution assay, and an orthotopic model were used. High-throughput RNA sequencing was performed to identify the altered signaling pathways.</p><p><strong>Results: </strong>Bioinformatics analysis revealed that low ZNF582 expression in HNSCC correlated with poor prognosis. Overexpression of ZNF582 suppressed HNSCC proliferation, migration, and invasion, while promoting apoptosis both in vitro and in vivo. ZNF582 also reduced cancer stem cell activity and metastasis in HNSCC. Mechanically, ZNF582 overexpression inhibited the MAPK and PI3K/AKT signaling pathways.</p><p><strong>Conclusion: </strong>Our findings suggested that ZNF582 overexpression inhibits HNSCC progression via the MAPK and PI3K/AKT signaling pathways, highlighting ZNF582 as a potential therapeutic target gene for HNSCC treatment.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aims to investigate the relationship between the expression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and the development of oral squamous cell carcinoma (OSCC).
Materials and methods: Bioinformatics analyzed CIAPIN1 in pan-cancers; IHC detected CIAPIN1 expression in OSCC and healthy samples; qRT-PCR and WB assayed CIAPIN1 mRNA and protein levels in OSCC and normal cells; MTT, scratch, transwell, flow cytometry, and WB evaluated OSCC cell viability, migration, invasion, EMT, and apoptosis after CIAPIN1 knockdown.
Results: CIAPIN1 abnormally expressed in multiple tumors, especially OSCC, is linked to prognosis. IHC showed elevated CIAPIN1 in OSCC tissues (p < 0.001). qRT-PCR and WB results showed CIAPIN1 was upregulated in CAL-27 (qRT-PCR: p < 0.05, WB: p < 0.05), SAS (qRT-PCR: p < 0.05, WB: p < 0.01), and SCC9 (qRT-PCR: p < 0.01, WB: p < 0.001) cells compared to HOK cells. After the knockdown of CIAPIN1 in SAS and SCC9 cells, MTT assays revealed reduced cell viability (SAS: p < 0.001, SCC9: p < 0.001); scratch tests showed suppressed migration ability (SAS: p < 0.01, SCC9: p < 0.001); transwell assays indicated inhibited invasion capability (SAS: p < 0.01, SCC9: p < 0.001); flow cytometry revealed increased apoptosis rates (SAS: p < 0.01, SCC9: p < 0.01); WB analysis showed reduced N-cadherin expression and increased E-cadherin expression (SAS for N-cadherin: p < 0.05, SCC9 for N-cadherin: p < 0.01; SAS for E-cadherin: p < 0.01, SCC9 for E-cadherin: p < 0.05), indicating CIAPIN1 promotes EMT.
Conclusion: CIAPIN1 contributes to the malignant progression of oral squamous cell carcinoma.
{"title":"CIAPIN1 as a Promoter of Oral Squamous Cell Carcinoma Progression.","authors":"Shan Yang, Changsheng Sun, Zhikai Fang, Hui Jin, Chang Li, Hongfeng Zang, Liu Yang, Lili Li, Wuliji Saiyin","doi":"10.1111/jop.70083","DOIUrl":"https://doi.org/10.1111/jop.70083","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the relationship between the expression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and the development of oral squamous cell carcinoma (OSCC).</p><p><strong>Materials and methods: </strong>Bioinformatics analyzed CIAPIN1 in pan-cancers; IHC detected CIAPIN1 expression in OSCC and healthy samples; qRT-PCR and WB assayed CIAPIN1 mRNA and protein levels in OSCC and normal cells; MTT, scratch, transwell, flow cytometry, and WB evaluated OSCC cell viability, migration, invasion, EMT, and apoptosis after CIAPIN1 knockdown.</p><p><strong>Results: </strong>CIAPIN1 abnormally expressed in multiple tumors, especially OSCC, is linked to prognosis. IHC showed elevated CIAPIN1 in OSCC tissues (p < 0.001). qRT-PCR and WB results showed CIAPIN1 was upregulated in CAL-27 (qRT-PCR: p < 0.05, WB: p < 0.05), SAS (qRT-PCR: p < 0.05, WB: p < 0.01), and SCC9 (qRT-PCR: p < 0.01, WB: p < 0.001) cells compared to HOK cells. After the knockdown of CIAPIN1 in SAS and SCC9 cells, MTT assays revealed reduced cell viability (SAS: p < 0.001, SCC9: p < 0.001); scratch tests showed suppressed migration ability (SAS: p < 0.01, SCC9: p < 0.001); transwell assays indicated inhibited invasion capability (SAS: p < 0.01, SCC9: p < 0.001); flow cytometry revealed increased apoptosis rates (SAS: p < 0.01, SCC9: p < 0.01); WB analysis showed reduced N-cadherin expression and increased E-cadherin expression (SAS for N-cadherin: p < 0.05, SCC9 for N-cadherin: p < 0.01; SAS for E-cadherin: p < 0.01, SCC9 for E-cadherin: p < 0.05), indicating CIAPIN1 promotes EMT.</p><p><strong>Conclusion: </strong>CIAPIN1 contributes to the malignant progression of oral squamous cell carcinoma.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COVID-19 Dry Mouth Induced by SARS-CoV-2 Not Binding Directly to ACE2 but Interacting Electrostatically With Lipid Raft in Salivary Glands.","authors":"Hironori Tsuchiya","doi":"10.1111/jop.70082","DOIUrl":"https://doi.org/10.1111/jop.70082","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Ferella, Letizia Nitro, Fabiana Allevi, Federico Biglioli, Matilde Coccapani, Giovanni Felisati, Giorgia Pugliese, Giorgio Ghilardi, Linda Montavoci, Anna Caretti, Alberto Maria Saibene
Background: Chronic graft-versus-host disease (cGVHD) is a significant complication following hematopoietic cell transplantation, often manifesting with oral lesions that severely impact quality of life. Cytokines such as IL-6, IL-1α, and IL-17 are implicated in inflammation and may serve as biomarkers for disease activity and therapeutic response in cGVHD.
Methods: A prospective monocentric study was conducted on 10 patients with oral cGVHD at San Paolo Hospital, Milan, between April 2023 and January 2024. Salivary and serum levels of IL-6, IL-1α, and IL-17 were measured pre- and post- topical clobetasol treatment for the oral mucosa using enzyme-linked immunoassay (ELISA). Patients underwent clinical assessments for oral pain and dryness using visual analog scales (VAS) and the Oral Mucositis Rating Scale (OMRS). Wilcoxon and Spearman correlation tests were used for statistical analysis.
Results: Significant reductions in serum IL-17 (p = 0.006) and trends towards reduced salivary IL-6 (p = 0.066) were observed post-treatment. No significant changes were found in IL-1α levels. Clinical assessments showed significant improvement in pain and OMRS scores post-therapy (p < 0.05). No correlation was found between cytokine levels and clinical symptoms.
Conclusions: While IL-6 and IL-17 play roles in cGVHD, only IL-17 showed significant reduction after topical steroid therapy. This suggests IL-17's potential as a marker for inflammatory activity in cGVHD. Serum IL-17 may serve as a useful biomarker in oral cGVHD. Future studies with larger cohorts are needed to further validate these findings and explore the role of salivary cytokines in disease monitoring.
{"title":"Salivary and Serum Cytokine Levels in Oral Chronic Graft-Versus-Host Disease: A Longitudinal Study on the Role of IL-6, IL-1α, and IL-17.","authors":"Francesco Ferella, Letizia Nitro, Fabiana Allevi, Federico Biglioli, Matilde Coccapani, Giovanni Felisati, Giorgia Pugliese, Giorgio Ghilardi, Linda Montavoci, Anna Caretti, Alberto Maria Saibene","doi":"10.1111/jop.70076","DOIUrl":"https://doi.org/10.1111/jop.70076","url":null,"abstract":"<p><strong>Background: </strong>Chronic graft-versus-host disease (cGVHD) is a significant complication following hematopoietic cell transplantation, often manifesting with oral lesions that severely impact quality of life. Cytokines such as IL-6, IL-1α, and IL-17 are implicated in inflammation and may serve as biomarkers for disease activity and therapeutic response in cGVHD.</p><p><strong>Methods: </strong>A prospective monocentric study was conducted on 10 patients with oral cGVHD at San Paolo Hospital, Milan, between April 2023 and January 2024. Salivary and serum levels of IL-6, IL-1α, and IL-17 were measured pre- and post- topical clobetasol treatment for the oral mucosa using enzyme-linked immunoassay (ELISA). Patients underwent clinical assessments for oral pain and dryness using visual analog scales (VAS) and the Oral Mucositis Rating Scale (OMRS). Wilcoxon and Spearman correlation tests were used for statistical analysis.</p><p><strong>Results: </strong>Significant reductions in serum IL-17 (p = 0.006) and trends towards reduced salivary IL-6 (p = 0.066) were observed post-treatment. No significant changes were found in IL-1α levels. Clinical assessments showed significant improvement in pain and OMRS scores post-therapy (p < 0.05). No correlation was found between cytokine levels and clinical symptoms.</p><p><strong>Conclusions: </strong>While IL-6 and IL-17 play roles in cGVHD, only IL-17 showed significant reduction after topical steroid therapy. This suggests IL-17's potential as a marker for inflammatory activity in cGVHD. Serum IL-17 may serve as a useful biomarker in oral cGVHD. Future studies with larger cohorts are needed to further validate these findings and explore the role of salivary cytokines in disease monitoring.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145390587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}