Pub Date : 2024-11-13DOI: 10.1177/00220345241281698
M. Jevdjevic, S. Listl
The recent World Health Organization (WHO) Oral Health Resolution and the subsequent WHO Global Oral Health Action Plan highlight the key relevance of providing information on the economic impacts of oral conditions. The purpose of this study was to provide updated estimates for the global, regional, and country-level economic impacts of oral conditions in 2019. Extending previously established methods, dental expenditures (costs for treatments) and productivity losses for 5 oral conditions (caries in deciduous and permanent teeth, periodontitis, edentulism, other oral diseases) were estimated for the year 2019. The estimated total worldwide economic impacts of oral conditions in 2019 were US $710B, of which US $387B (US $327B to US $404B) was due to direct costs and US $323B (US $186 to US $460) was due to productivity losses for the 5 main oral conditions. Low-income countries spent an average of US $0.52 (US $0.22 to US $0.96) per capita on dental care, while high-income countries spent an average of US $260 (US $257 to US $268) per capita—a 500-fold difference. These findings suggest that oral conditions continue to substantiate an enormous economic burden to individuals and society. The comprehensiveness of estimates supersedes that of previous work as the primary information on direct costs was identified for a larger number of countries. The need for more and better routine reporting and monitoring of the economic impact of oral conditions is emphasized. The relevance of such information is also highlighted by its inclusion in the first-ever WHO Global Oral Health Status Report and Global Strategy on Oral health 2023 to 2030. Given the persistently high economic burden of oral conditions, there is a key role for better prioritization of cost-efficient oral health programs as well as needs-responsive capacity planning.
{"title":"Global, Regional, and Country-Level Economic Impacts of Oral Conditions in 2019","authors":"M. Jevdjevic, S. Listl","doi":"10.1177/00220345241281698","DOIUrl":"https://doi.org/10.1177/00220345241281698","url":null,"abstract":"The recent World Health Organization (WHO) Oral Health Resolution and the subsequent WHO Global Oral Health Action Plan highlight the key relevance of providing information on the economic impacts of oral conditions. The purpose of this study was to provide updated estimates for the global, regional, and country-level economic impacts of oral conditions in 2019. Extending previously established methods, dental expenditures (costs for treatments) and productivity losses for 5 oral conditions (caries in deciduous and permanent teeth, periodontitis, edentulism, other oral diseases) were estimated for the year 2019. The estimated total worldwide economic impacts of oral conditions in 2019 were US $710B, of which US $387B (US $327B to US $404B) was due to direct costs and US $323B (US $186 to US $460) was due to productivity losses for the 5 main oral conditions. Low-income countries spent an average of US $0.52 (US $0.22 to US $0.96) per capita on dental care, while high-income countries spent an average of US $260 (US $257 to US $268) per capita—a 500-fold difference. These findings suggest that oral conditions continue to substantiate an enormous economic burden to individuals and society. The comprehensiveness of estimates supersedes that of previous work as the primary information on direct costs was identified for a larger number of countries. The need for more and better routine reporting and monitoring of the economic impact of oral conditions is emphasized. The relevance of such information is also highlighted by its inclusion in the first-ever WHO Global Oral Health Status Report and Global Strategy on Oral health 2023 to 2030. Given the persistently high economic burden of oral conditions, there is a key role for better prioritization of cost-efficient oral health programs as well as needs-responsive capacity planning.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"72 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601244","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}
Pub Date : 2024-10-25DOI: 10.1177/00220345241279369
C. Duan, Y. Abola, J. Zhao, Y. Wang
Small nucleolar RNAs (snoRNAs), a distinct class of noncoding RNAs, encompass highly diverse structures and have a range of 60 to 300 nucleotides in length. About 90% of human snoRNAs are intronic and embedded within introns of their host gene transcripts. Most snoRNAs enriched in specific tissue correlate in abundance with their parental host genes. Advancements in high-throughput sequencing have facilitated the discovery of dysregulated snoRNA expression in numerous human malignancies including head and neck squamous cell carcinoma (HNSCC). Hundreds of differentially expressed snoRNAs have been identified in HNSCC tissues. Among 1,524 snoRNA genes in a 567 HNSCC cohort, 113 snoRNAs were found to be survival related. As for snoRNA’s roles in HNSCC, based on the available evidence, dysregulated snoRNAs are closely associated with the carcinogenesis and development of HNSCC. Upregulated snoRNAs have been shown to augment the expression of other oncogenes or activate the Wnt/β-catenin signaling pathway, thereby promoting tumor cell viability, glycolysis, migration, and the epithelial-mesenchymal transition while inhibiting apoptosis in vitro. In vivo animal studies have further elucidated the functional roles of snoRNAs. Knockdown of host genes of these snoRNAs suppressed the Wnt/β-catenin signaling pathway and restrained tumor proliferation and aggressiveness in mice. The putative mechanisms underlying these observations are associated with the biological functions of snoRNAs, primarily involving microRNA-like functions through the generation of microRNA-like fragments and regulation of alternative splicing to yield diverse transcripts. While most of the snoRNAs are upregulated in HNSCC, 4 downregulated snoRNAs have been identified and annotated. SNORA36B (implicated in the regulation of DNA templates) and U3 (chr17, influencing cell proliferation) may serve as protective factors associated with prolonged overall survival. This review describes the viable structures of snoRNAs, endeavors to refine snoRNA sequencing technology, and summarizes snoRNAs’ expression profile as well as their role in HNSCC progression for potential diagnostic and therapeutic strategies for HNSCC management.
{"title":"Small Nucleolar RNAs in Head and Neck Squamous Cell Carcinomas","authors":"C. Duan, Y. Abola, J. Zhao, Y. Wang","doi":"10.1177/00220345241279369","DOIUrl":"https://doi.org/10.1177/00220345241279369","url":null,"abstract":"Small nucleolar RNAs (snoRNAs), a distinct class of noncoding RNAs, encompass highly diverse structures and have a range of 60 to 300 nucleotides in length. About 90% of human snoRNAs are intronic and embedded within introns of their host gene transcripts. Most snoRNAs enriched in specific tissue correlate in abundance with their parental host genes. Advancements in high-throughput sequencing have facilitated the discovery of dysregulated snoRNA expression in numerous human malignancies including head and neck squamous cell carcinoma (HNSCC). Hundreds of differentially expressed snoRNAs have been identified in HNSCC tissues. Among 1,524 snoRNA genes in a 567 HNSCC cohort, 113 snoRNAs were found to be survival related. As for snoRNA’s roles in HNSCC, based on the available evidence, dysregulated snoRNAs are closely associated with the carcinogenesis and development of HNSCC. Upregulated snoRNAs have been shown to augment the expression of other oncogenes or activate the Wnt/β-catenin signaling pathway, thereby promoting tumor cell viability, glycolysis, migration, and the epithelial-mesenchymal transition while inhibiting apoptosis in vitro. In vivo animal studies have further elucidated the functional roles of snoRNAs. Knockdown of host genes of these snoRNAs suppressed the Wnt/β-catenin signaling pathway and restrained tumor proliferation and aggressiveness in mice. The putative mechanisms underlying these observations are associated with the biological functions of snoRNAs, primarily involving microRNA-like functions through the generation of microRNA-like fragments and regulation of alternative splicing to yield diverse transcripts. While most of the snoRNAs are upregulated in HNSCC, 4 downregulated snoRNAs have been identified and annotated. SNORA36B (implicated in the regulation of DNA templates) and U3 (chr17, influencing cell proliferation) may serve as protective factors associated with prolonged overall survival. This review describes the viable structures of snoRNAs, endeavors to refine snoRNA sequencing technology, and summarizes snoRNAs’ expression profile as well as their role in HNSCC progression for potential diagnostic and therapeutic strategies for HNSCC management.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490435","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}
Pub Date : 2024-10-18DOI: 10.1177/00220345241272052
S E Uribe,J Issa,F Sohrabniya,A Denny,N N Kim,A F Dayo,A Chaurasia,A Sofi-Mahmudi,M Büttner,F Schwendicke
The development of artificial intelligence (AI) in dentistry requires large and well-annotated datasets. However, the availability of public dental imaging datasets remains unclear. This study aimed to provide a comprehensive overview of all publicly available dental imaging datasets to address this gap and support AI development. This observational study searched all publicly available dataset resources (academic databases, preprints, and AI challenges), focusing on datasets/articles from 2020 to 2023, with PubMed searches extending back to 2011. We comprehensively searched for dental AI datasets containing images (intraoral photos, scans, radiographs, etc.) using relevant keywords. We included datasets of >50 images obtained from publicly available sources. We extracted dataset characteristics, patient demographics, country of origin, dataset size, ethical clearance, image details, FAIRness metrics, and metadata completeness. We screened 131,028 records and extracted 16 unique dental imaging datasets. The datasets were obtained from Kaggle (18.8%), GitHub, Google, Mendeley, PubMed, Zenodo (each 12.5%), Grand-Challenge, OSF, and arXiv (each 6.25%). The primary focus was tooth segmentation (62.5%) and labeling (56.2%). Panoramic radiography was the most common imaging modality (58.8%). Of the 13 countries, China contributed the most images (2,413). Of the datasets, 75% contained annotations, whereas the methods used to establish labels were often unclear and inconsistent. Only 31.2% of the datasets reported ethical approval, and 56.25% did not specify a license. Most data were obtained from dental clinics (50%). Intraoral radiographs had the highest findability score in the FAIR assessment, whereas cone-beam computed tomography datasets scored the lowest in all categories. These findings revealed a scarcity of publicly available imaging dental data and inconsistent metadata reporting. To promote the development of robust, equitable, and generalizable AI tools for dental diagnostics, treatment, and research, efforts are needed to address data scarcity, increase diversity, mandate metadata completeness, and ensure FAIRness in AI dental imaging research.
{"title":"Publicly Available Dental Image Datasets for Artificial Intelligence.","authors":"S E Uribe,J Issa,F Sohrabniya,A Denny,N N Kim,A F Dayo,A Chaurasia,A Sofi-Mahmudi,M Büttner,F Schwendicke","doi":"10.1177/00220345241272052","DOIUrl":"https://doi.org/10.1177/00220345241272052","url":null,"abstract":"The development of artificial intelligence (AI) in dentistry requires large and well-annotated datasets. However, the availability of public dental imaging datasets remains unclear. This study aimed to provide a comprehensive overview of all publicly available dental imaging datasets to address this gap and support AI development. This observational study searched all publicly available dataset resources (academic databases, preprints, and AI challenges), focusing on datasets/articles from 2020 to 2023, with PubMed searches extending back to 2011. We comprehensively searched for dental AI datasets containing images (intraoral photos, scans, radiographs, etc.) using relevant keywords. We included datasets of >50 images obtained from publicly available sources. We extracted dataset characteristics, patient demographics, country of origin, dataset size, ethical clearance, image details, FAIRness metrics, and metadata completeness. We screened 131,028 records and extracted 16 unique dental imaging datasets. The datasets were obtained from Kaggle (18.8%), GitHub, Google, Mendeley, PubMed, Zenodo (each 12.5%), Grand-Challenge, OSF, and arXiv (each 6.25%). The primary focus was tooth segmentation (62.5%) and labeling (56.2%). Panoramic radiography was the most common imaging modality (58.8%). Of the 13 countries, China contributed the most images (2,413). Of the datasets, 75% contained annotations, whereas the methods used to establish labels were often unclear and inconsistent. Only 31.2% of the datasets reported ethical approval, and 56.25% did not specify a license. Most data were obtained from dental clinics (50%). Intraoral radiographs had the highest findability score in the FAIR assessment, whereas cone-beam computed tomography datasets scored the lowest in all categories. These findings revealed a scarcity of publicly available imaging dental data and inconsistent metadata reporting. To promote the development of robust, equitable, and generalizable AI tools for dental diagnostics, treatment, and research, efforts are needed to address data scarcity, increase diversity, mandate metadata completeness, and ensure FAIRness in AI dental imaging research.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"44 1","pages":"220345241272052"},"PeriodicalIF":7.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449335","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}
Pub Date : 2024-10-17DOI: 10.1177/00220345241253191
D. Proaño, H. Huang, S. Allin, B.M. Essue, S. Singhal, C. Quiñonez
The objective of this study is to characterize how financial hardship related to oral health care (OHC) out-of-pocket (OOP) spending has been conceptualized, defined, and measured in the literature and to identify evidence gaps in this area. This scoping review follows Arksey and O’Malley’s framework and synthesizes financial hardship from OHC concepts, methodologies, and evidence gaps. We searched Ovid-Medline, Ovid-Embase, PubMed, Web of Science, Scopus, EconLit, Business Source Premier, and the Cochrane Library. Gray literature was sourced from institutional websites (World Health Organization, United Nations, World Bank Group, Organisation for Economic Co-operation and Development, and governmental health agencies) as well as ProQuest Dissertations and Thesis Global. We used defined inclusion and exclusion criteria to select studies published between 2000 and 2023. Of the 1,876 records, 65 met our criteria. The studies conceptualized financial hardship as catastrophic spending, impoverishment, negative coping strategies, bankruptcy, financial burden, food insecurity, and personal financial hardship experience. We found heterogeneity in defining OHC OOP payments and services. Also, financial hardship was frequently measured as catastrophic health expenditure using cross-sectional designs and national household spending surveys from high-income and to a lesser extent lower-middle-income countries. We identify and discuss challenges in terms of conceptualizing financial hardship, study designs, and measurement instruments in the OHC context. Some of the common evidence gaps identified include studying the causal relationship in financial hardship from OHC, assessing the financial hardship and unmet dental needs due to cost relationship, and distinguishing the effect between pain/discomfort and esthetic/cosmetic dental treatments on financial hardship. Financial hardship in OHC needs further exploration and the use of consistent definitions as well must distinguish between treatments alleviating pain/discomfort from esthetic/cosmetic treatments. Our study is relevant for policy makers and researchers aiming to monitor financial protection of OOP payments on OHC in the wake of universal health coverage for oral health.
本研究的目的是描述与口腔健康护理（OHC）自付（OOP）支出相关的经济困难在文献中是如何被概念化、定义和衡量的，并找出该领域的证据差距。本范围界定综述遵循 Arksey 和 O'Malley 的框架，从口腔健康护理的概念、方法和证据差距方面综合了经济困难。我们检索了 Ovid-Medline、Ovid-Embase、PubMed、Web of Science、Scopus、EconLit、Business Source Premier 和 Cochrane 图书馆。灰色文献来自机构网站（世界卫生组织、联合国、世界银行集团、经济合作与发展组织和政府卫生机构）以及 ProQuest Dissertations and Thesis Global。我们采用明确的纳入和排除标准来选择 2000 年至 2023 年间发表的研究。在 1,876 条记录中，有 65 条符合我们的标准。这些研究将经济困难概念化为灾难性支出、贫困化、消极应对策略、破产、经济负担、粮食不安全和个人经济困难经历。我们发现，对老年健康保险自付费用和服务的定义存在差异。此外，通过横截面设计和高收入国家的全国家庭支出调查，经济困难经常被衡量为灾难性医疗支出，中低收入国家的情况较少。我们确定并讨论了在老年保健背景下，经济困难的概念化、研究设计和测量工具方面所面临的挑战。一些常见的证据缺口包括：研究OHC经济困难的因果关系，评估经济困难和因费用关系而未满足的牙科需求，以及区分疼痛/不适和美学/美容牙科治疗对经济困难的影响。口腔健康方面的经济困难需要进一步探讨，并使用一致的定义，同时必须区分减轻疼痛/不适的治疗和美容/整容治疗。我们的研究对政策制定者和研究人员很有意义，他们的目标是在口腔健康全民医保之后，监测口腔健康方面的自费项目支付的经济保护情况。
{"title":"Oral Health Care Out-of-Pocket Costs and Financial Hardship: A Scoping Review","authors":"D. Proaño, H. Huang, S. Allin, B.M. Essue, S. Singhal, C. Quiñonez","doi":"10.1177/00220345241253191","DOIUrl":"https://doi.org/10.1177/00220345241253191","url":null,"abstract":"The objective of this study is to characterize how financial hardship related to oral health care (OHC) out-of-pocket (OOP) spending has been conceptualized, defined, and measured in the literature and to identify evidence gaps in this area. This scoping review follows Arksey and O’Malley’s framework and synthesizes financial hardship from OHC concepts, methodologies, and evidence gaps. We searched Ovid-Medline, Ovid-Embase, PubMed, Web of Science, Scopus, EconLit, Business Source Premier, and the Cochrane Library. Gray literature was sourced from institutional websites (World Health Organization, United Nations, World Bank Group, Organisation for Economic Co-operation and Development, and governmental health agencies) as well as ProQuest Dissertations and Thesis Global. We used defined inclusion and exclusion criteria to select studies published between 2000 and 2023. Of the 1,876 records, 65 met our criteria. The studies conceptualized financial hardship as catastrophic spending, impoverishment, negative coping strategies, bankruptcy, financial burden, food insecurity, and personal financial hardship experience. We found heterogeneity in defining OHC OOP payments and services. Also, financial hardship was frequently measured as catastrophic health expenditure using cross-sectional designs and national household spending surveys from high-income and to a lesser extent lower-middle-income countries. We identify and discuss challenges in terms of conceptualizing financial hardship, study designs, and measurement instruments in the OHC context. Some of the common evidence gaps identified include studying the causal relationship in financial hardship from OHC, assessing the financial hardship and unmet dental needs due to cost relationship, and distinguishing the effect between pain/discomfort and esthetic/cosmetic dental treatments on financial hardship. Financial hardship in OHC needs further exploration and the use of consistent definitions as well must distinguish between treatments alleviating pain/discomfort from esthetic/cosmetic treatments. Our study is relevant for policy makers and researchers aiming to monitor financial protection of OOP payments on OHC in the wake of universal health coverage for oral health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"78 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448655","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}
Pub Date : 2024-10-14DOI: 10.1177/00220345241280026
J M Richman,W L Siqueira
{"title":"Colin Dawes In Memoriam: JDR Editor Emeritus and Pioneer in Salivary Research.","authors":"J M Richman,W L Siqueira","doi":"10.1177/00220345241280026","DOIUrl":"https://doi.org/10.1177/00220345241280026","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"55 1","pages":"220345241280026"},"PeriodicalIF":7.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436115","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}
Pub Date : 2024-10-14DOI: 10.1177/00220345241274354
J Wang,X Dong,J Lei,Y Zhang,S Chen,Y He
The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA.
{"title":"β-catenin Orchestrates Gli1+ Cell Fate in Condylar Development and TMJOA.","authors":"J Wang,X Dong,J Lei,Y Zhang,S Chen,Y He","doi":"10.1177/00220345241274354","DOIUrl":"https://doi.org/10.1177/00220345241274354","url":null,"abstract":"The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"229 1","pages":"220345241274354"},"PeriodicalIF":7.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436156","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}
Pub Date : 2024-10-12DOI: 10.1177/00220345241280257
D. Yang, D. Yang, Y. Song, J. Liu, Y. Wang, X. Feng, X. Zeng, Q. Chen, J. Li, H. Dan
Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)–induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.
{"title":"Ferroptosis Induction Enhances Photodynamic Therapy Efficacy for OLK","authors":"D. Yang, D. Yang, Y. Song, J. Liu, Y. Wang, X. Feng, X. Zeng, Q. Chen, J. Li, H. Dan","doi":"10.1177/00220345241280257","DOIUrl":"https://doi.org/10.1177/00220345241280257","url":null,"abstract":"Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)–induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"2 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430419","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}
Pub Date : 2024-10-12DOI: 10.1177/00220345241271943
C. Graves, E. Babikow, N. Ghaltakhchyan, T.Q. Ngo, C. Li, S. Wang, A. Shoji, C. Bocklage, S.T. Phillips, M. Markovetz, S.A. Frazier-Bowers, K. Divaris, M. Freire, S. Wallet, D. Wu, L.A. Jacox
Tissue-specific immune responses are critical determinants of health-maintaining homeostasis and disease-related dysbiosis. In the context of COVID-19, oral immune responses reflect local host-pathogen dynamics near the site of infection and serve as important “windows to the body,” reflecting systemic responses to the invading SARS-CoV-2 virus. This study leveraged multiplex technology to characterize the salivary SARS-CoV-2–specific immunological landscape (37 cytokines/chemokines and 11 antibodies) during early infection. Cytokine/immune profiling was performed on unstimulated cleared whole saliva collected from 227 adult SARS-CoV-2+ participants and 37 controls. Statistical analysis and modeling revealed significant differential abundance of 25 cytokines (16 downregulated, 9 upregulated). Pathway analysis demonstrated early SARS-CoV-2 infection is associated with local suppression of oral type I/III interferon and blunted natural killer–/T-cell responses, reflecting a potential novel immune-evasion strategy enabling infection. This virus-associated immune suppression occurred concomitantly with significant upregulation of proinflammatory pathways including marked increases in the acute phase proteins pentraxin-3 and chitinase-3-like-1. Irrespective of SARS-CoV-2 infection, prior vaccination was associated with increased total α-SARS-CoV-2-spike (trimer), -S1 protein, -RBD, and -nucleocapsid salivary antibodies, highlighting the importance of COVID-19 vaccination in eliciting mucosal responses. Altogether, our findings highlight saliva as a stable and accessible biofluid for monitoring host responses to SARS-CoV-2 over time and suggest that oral-mucosal immune dysregulation is a hallmark of early SARS-CoV-2 infection, with possible implications for viral evasion mechanisms.
{"title":"Immune Dysregulation in the Oral Cavity during Early SARS-CoV-2 Infection","authors":"C. Graves, E. Babikow, N. Ghaltakhchyan, T.Q. Ngo, C. Li, S. Wang, A. Shoji, C. Bocklage, S.T. Phillips, M. Markovetz, S.A. Frazier-Bowers, K. Divaris, M. Freire, S. Wallet, D. Wu, L.A. Jacox","doi":"10.1177/00220345241271943","DOIUrl":"https://doi.org/10.1177/00220345241271943","url":null,"abstract":"Tissue-specific immune responses are critical determinants of health-maintaining homeostasis and disease-related dysbiosis. In the context of COVID-19, oral immune responses reflect local host-pathogen dynamics near the site of infection and serve as important “windows to the body,” reflecting systemic responses to the invading SARS-CoV-2 virus. This study leveraged multiplex technology to characterize the salivary SARS-CoV-2–specific immunological landscape (37 cytokines/chemokines and 11 antibodies) during early infection. Cytokine/immune profiling was performed on unstimulated cleared whole saliva collected from 227 adult SARS-CoV-2+ participants and 37 controls. Statistical analysis and modeling revealed significant differential abundance of 25 cytokines (16 downregulated, 9 upregulated). Pathway analysis demonstrated early SARS-CoV-2 infection is associated with local suppression of oral type I/III interferon and blunted natural killer–/T-cell responses, reflecting a potential novel immune-evasion strategy enabling infection. This virus-associated immune suppression occurred concomitantly with significant upregulation of proinflammatory pathways including marked increases in the acute phase proteins pentraxin-3 and chitinase-3-like-1. Irrespective of SARS-CoV-2 infection, prior vaccination was associated with increased total α-SARS-CoV-2-spike (trimer), -S1 protein, -RBD, and -nucleocapsid salivary antibodies, highlighting the importance of COVID-19 vaccination in eliciting mucosal responses. Altogether, our findings highlight saliva as a stable and accessible biofluid for monitoring host responses to SARS-CoV-2 over time and suggest that oral-mucosal immune dysregulation is a hallmark of early SARS-CoV-2 infection, with possible implications for viral evasion mechanisms.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"9 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430416","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}
Pub Date : 2024-10-12DOI: 10.1177/00220345241272011
K. Yama, S. Morishima, K. Tsutsumi, R. Jo, Y. Aita, T. Inokuchi, T. Okuda, D. Watai, K. Ohara, M. Maruyama, T. Chikazawa, T. Iwamoto, Y. Kakizawa, T. Oniki
Childhood is considered crucial in the establishment of future oral microbiota. However, the precise period of oral microbiota development remains unclear. This study aimed to identify the progression of oral microbiota formation in children. We longitudinally investigated the salivary microbiota of 54 children across 13 time points from 1 wk to 60 mo (5 y) old and their parents at 2 time points as a representative sample of the adult microbiota. Using next-generation sequencing, we obtained 10,000 gene sequences of the 16s rRNA V1-V2 region for each sample. The detection rate in children of 110 operational taxonomic units commonly detected in more than 85% of mothers and fathers, defined as the main constituent bacteria, was 25% at 1 wk old, increased to 80% between 6 and 18 mo old, and reached approximately 90% by 36 mo old. Early main constituent bacteria detected at 1 wk old were limited to Streptococcus, Rothia, and Gemella. At 6 to 18 mo old, the detection rates of various main constituent bacteria, including Neisseria, Haemophilus, and Fusobacterium, increased. UniFrac distance analysis showed that the oral microbiota of children approached that of adults at 6 to 18 mo old. In the weighted UniFrac distance index, unlike the unweighted index, there were no significant changes in children between 36 and 60 mo old from adults, and microbiota formation at 60 mo old was sufficiently advanced to be included within the range of adult individual differences. Our findings suggest that the initial 36 mo, particularly the period from 6 to 18 mo old, consists of a time window for oral microbiota maturation. In addition, the development of microbiota during this period may be critical for future oral disease prevention.
{"title":"Oral Microbiota Development in the First 60 Months: A Longitudinal Study","authors":"K. Yama, S. Morishima, K. Tsutsumi, R. Jo, Y. Aita, T. Inokuchi, T. Okuda, D. Watai, K. Ohara, M. Maruyama, T. Chikazawa, T. Iwamoto, Y. Kakizawa, T. Oniki","doi":"10.1177/00220345241272011","DOIUrl":"https://doi.org/10.1177/00220345241272011","url":null,"abstract":"Childhood is considered crucial in the establishment of future oral microbiota. However, the precise period of oral microbiota development remains unclear. This study aimed to identify the progression of oral microbiota formation in children. We longitudinally investigated the salivary microbiota of 54 children across 13 time points from 1 wk to 60 mo (5 y) old and their parents at 2 time points as a representative sample of the adult microbiota. Using next-generation sequencing, we obtained 10,000 gene sequences of the 16s rRNA V1-V2 region for each sample. The detection rate in children of 110 operational taxonomic units commonly detected in more than 85% of mothers and fathers, defined as the main constituent bacteria, was 25% at 1 wk old, increased to 80% between 6 and 18 mo old, and reached approximately 90% by 36 mo old. Early main constituent bacteria detected at 1 wk old were limited to Streptococcus, Rothia, and Gemella. At 6 to 18 mo old, the detection rates of various main constituent bacteria, including Neisseria, Haemophilus, and Fusobacterium, increased. UniFrac distance analysis showed that the oral microbiota of children approached that of adults at 6 to 18 mo old. In the weighted UniFrac distance index, unlike the unweighted index, there were no significant changes in children between 36 and 60 mo old from adults, and microbiota formation at 60 mo old was sufficiently advanced to be included within the range of adult individual differences. Our findings suggest that the initial 36 mo, particularly the period from 6 to 18 mo old, consists of a time window for oral microbiota maturation. In addition, the development of microbiota during this period may be critical for future oral disease prevention.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430440","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}
Pub Date : 2024-10-12DOI: 10.1177/00220345241279555
Y.Y. Zhang, J. Xiang, Y.Y. He, X. Liu, H.Y. Ye, L. Xu, H.L. Bai, H. Zhang, H.M. Zhang, W.Z. Liu, Q.M. Zhai, P. Ji, R.D. Cannon
Nonresolving inflammation causes irreversible damage to periodontal ligament stem cells (PDLSCs) and impedes alveolar bone restoration. The impaired tissue regeneration ability of stem cells is associated with abnormal mitochondrial metabolism. However, the impact of specific metabolic alterations on the differentiation process of PDLSCs remains to be understood. In this study, we found that inflammation altered the metabolic flux of the tricarboxylic acid cycle and induced the accumulation of fumarate through metabolic testing and metabolic flux analysis. Transcriptome sequencing revealed the potential of fumarate in modulating epigenetics. Specifically, histone methylation typically suppresses the expression of genes related to osteogenesis. Fumarate was found to impede the osteogenic differentiation of PDLSCs that exhibited high levels of H3K9me3. Various techniques, including assay for transposase-accessible chromatin with high-throughput sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing, were used to identify the target genes regulated by H3K9me3. Mechanistically, accumulated fumarate inhibited lysine-specific demethylase 4B (KDM4B) activity and increased H3K9 methylation, thus silencing asporin gene transcription. Preventing fumarate from binding to the histone demethylase KDM4B with α-ketoglutarate effectively restored the impaired osteogenic capacity of PDLSCs and improved alveolar bone recovery. Collectively, our research has revealed the significant impact of accumulated fumarate on the regulation of osteogenesis in stem cells, suggesting that inhibiting fumarate production could be a viable therapeutic approach for treating periodontal diseases.
{"title":"Fumarate Restrains Alveolar Bone Restoration via Regulating H3K9 Methylation","authors":"Y.Y. Zhang, J. Xiang, Y.Y. He, X. Liu, H.Y. Ye, L. Xu, H.L. Bai, H. Zhang, H.M. Zhang, W.Z. Liu, Q.M. Zhai, P. Ji, R.D. Cannon","doi":"10.1177/00220345241279555","DOIUrl":"https://doi.org/10.1177/00220345241279555","url":null,"abstract":"Nonresolving inflammation causes irreversible damage to periodontal ligament stem cells (PDLSCs) and impedes alveolar bone restoration. The impaired tissue regeneration ability of stem cells is associated with abnormal mitochondrial metabolism. However, the impact of specific metabolic alterations on the differentiation process of PDLSCs remains to be understood. In this study, we found that inflammation altered the metabolic flux of the tricarboxylic acid cycle and induced the accumulation of fumarate through metabolic testing and metabolic flux analysis. Transcriptome sequencing revealed the potential of fumarate in modulating epigenetics. Specifically, histone methylation typically suppresses the expression of genes related to osteogenesis. Fumarate was found to impede the osteogenic differentiation of PDLSCs that exhibited high levels of H3K9me3. Various techniques, including assay for transposase-accessible chromatin with high-throughput sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing, were used to identify the target genes regulated by H3K9me3. Mechanistically, accumulated fumarate inhibited lysine-specific demethylase 4B (KDM4B) activity and increased H3K9 methylation, thus silencing asporin gene transcription. Preventing fumarate from binding to the histone demethylase KDM4B with α-ketoglutarate effectively restored the impaired osteogenic capacity of PDLSCs and improved alveolar bone recovery. Collectively, our research has revealed the significant impact of accumulated fumarate on the regulation of osteogenesis in stem cells, suggesting that inhibiting fumarate production could be a viable therapeutic approach for treating periodontal diseases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"67 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430424","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}
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