Xinjia Cai, Heyu Zhang, Yanjin Wang, Jianyun Zhang, Tiejun Li
{"title":"Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts","authors":"Xinjia Cai, Heyu Zhang, Yanjin Wang, Jianyun Zhang, Tiejun Li","doi":"10.1038/s41368-024-00287-y","DOIUrl":"https://doi.org/10.1038/s41368-024-00287-y","url":null,"abstract":"<p>Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898–0.973) and prognosis (AUC = 0.840, 95%CI: 0.751–0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"35 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis","authors":"Xiao Yang, Hui Zhao, Rui Li, Yang Chen, Zhi Xu, Zhengjun Shang","doi":"10.1038/s41368-024-00286-z","DOIUrl":"https://doi.org/10.1038/s41368-024-00286-z","url":null,"abstract":"<p>A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqiao Xu, Xuyan Gong, Lei Zhang, Han Zhang, Yao Sun
{"title":"PRX1-positive mesenchymal stem cells drive molar morphogenesis.","authors":"Xiaoqiao Xu, Xuyan Gong, Lei Zhang, Han Zhang, Yao Sun","doi":"10.1038/s41368-024-00277-0","DOIUrl":"10.1038/s41368-024-00277-0","url":null,"abstract":"<p><p>Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1<sup>+</sup> cells within M1. These PRX1<sup>+</sup> cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1<sup>+</sup> cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"15"},"PeriodicalIF":14.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Gunter Hartel, Roberto A Barrero, Touraj Taheri, Liz Kenny, Sarju Vasani, Martin Batstone, Omar Breik, Chamindie Punyadeera
{"title":"A novel saliva-based miRNA profile to diagnose and predict oral cancer.","authors":"Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Gunter Hartel, Roberto A Barrero, Touraj Taheri, Liz Kenny, Sarju Vasani, Martin Batstone, Omar Breik, Chamindie Punyadeera","doi":"10.1038/s41368-023-00273-w","DOIUrl":"10.1038/s41368-023-00273-w","url":null,"abstract":"<p><p>Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n = 50), OPMD (n = 52), and controls (n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"14"},"PeriodicalIF":14.9,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuan Zhou, Xinjia Cai, Fengyang Jing, Xuefen Li, Jianyun Zhang, Heyu Zhang, Tiejun Li
{"title":"Genomic alterations in oral multiple primary cancers.","authors":"Xuan Zhou, Xinjia Cai, Fengyang Jing, Xuefen Li, Jianyun Zhang, Heyu Zhang, Tiejun Li","doi":"10.1038/s41368-023-00265-w","DOIUrl":"10.1038/s41368-023-00265-w","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"13"},"PeriodicalIF":14.9,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression.","authors":"Wen Wang, Qian Wang, Shiying Sun, Pengfei Zhang, Yuyu Li, Weimin Lin, Qiwen Li, Xiao Zhang, Zhe Ma, Haiyan Lu","doi":"10.1038/s41368-023-00272-x","DOIUrl":"10.1038/s41368-023-00272-x","url":null,"abstract":"<p><p>Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"12"},"PeriodicalIF":14.9,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10838930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment","authors":"Jiang Lin, Chengshuo Wang, Xiangdong Wang, Faming Chen, Wei Zhang, Hongchen Sun, Fuhua Yan, Yaping Pan, Dongdong Zhu, Qintai Yang, Shaohua Ge, Yao Sun, Kuiji Wang, Yuan Zhang, Mu Xian, Ming Zheng, Anchun Mo, Xin Xu, Hanguo Wang, Xuedong Zhou, Luo Zhang","doi":"10.1038/s41368-024-00278-z","DOIUrl":"https://doi.org/10.1038/s41368-024-00278-z","url":null,"abstract":"<p>Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnesium promotes vascularization and osseointegration in diabetic states","authors":"Linfeng Liu, Feiyu Wang, Wei Song, Danting Zhang, Weimin Lin, Qi Yin, Qian Wang, Hanwen Li, Quan Yuan, Shiwen Zhang","doi":"10.1038/s41368-023-00271-y","DOIUrl":"https://doi.org/10.1038/s41368-023-00271-y","url":null,"abstract":"<p>Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg<sup>2+</sup> promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg<sup>2+</sup> promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg<sup>2+</sup> promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"36 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139644015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma.","authors":"Zheqi Liu, Zhen Zhang, Yu Zhang, Wenkai Zhou, Xu Zhang, Canbang Peng, Tong Ji, Xin Zou, Zhiyuan Zhang, Zhenhu Ren","doi":"10.1038/s41368-023-00267-8","DOIUrl":"10.1038/s41368-023-00267-8","url":null,"abstract":"<p><p>Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"9"},"PeriodicalIF":10.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bob T Rosier, William Johnston, Miguel Carda-Diéguez, Annabel Simpson, Elena Cabello-Yeves, Krystyna Piela, Robert Reilly, Alejandro Artacho, Chris Easton, Mia Burleigh, Shauna Culshaw, Alex Mira
{"title":"Publisher Correction: Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability.","authors":"Bob T Rosier, William Johnston, Miguel Carda-Diéguez, Annabel Simpson, Elena Cabello-Yeves, Krystyna Piela, Robert Reilly, Alejandro Artacho, Chris Easton, Mia Burleigh, Shauna Culshaw, Alex Mira","doi":"10.1038/s41368-024-00283-2","DOIUrl":"10.1038/s41368-024-00283-2","url":null,"abstract":"","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"8"},"PeriodicalIF":10.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10811215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}