首页 > 最新文献

Journal of dental research最新文献

英文 中文
Improved Visualization of Oral Microbial Consortia. 改进口腔微生物群的可视化。
Pub Date : 2024-06-03 DOI: 10.1177/00220345241251784
S T Ramirez-Puebla, J L Mark Welch, G G Borisy

Bacteria on the tongue dorsum (TD) form consortia tens to hundreds of microns in diameter organized around a core of epithelial cells. Whole-mount preparations have been instrumental in revealing their organization and specific microbial associations. However, their thickness and intricate 3-dimensional complexity present challenges for a comprehensive spatial analysis. To overcome these challenges, we employed a complementary approach: embedding in hydrophilic plastic followed by sectioning and postsectioning labeling. Samples were labeled by hybridization with multiplexed fluorescent oligonucleotide probes and visualized by spectral imaging and linear unmixing. Application of this strategy to TD biofilms improved the visualization of bacteria that were difficult to resolve in whole-mount imaging. Actinomyces, previously detected as patches, became resolved at the single-cell level. The filamentous taxa Leptotrichia and Lachnospiraceae, located at the core of the consortium, were regularly visualized whereas previously they were rarely detected when using whole mounts. Streptococcus salivarius, heterogeneously detected in whole mounts, were regularly and homogenously observed. Two-dimensional images provide valuable information about the organization of bacterial biofilms. However, they offer only a single plane of view for objects that can extend to hundreds of microns in thickness, and information obtained from such images may not always reflect the complexity of a 3-dimensional object. We combined serial physical sectioning with optical sectioning to facilitate the 3-dimensional reconstruction of consortia, spanning over 100 µm in thickness. Our work showcases the use of hydrophilic plastic embedding and sectioning for examining the structure of TD biofilms through spectral imaging fluorescence in situ hybridization. The result was improved visualization of important members of the human oral microbiome. This technique serves as a complementary method to the previously employed whole-mount analysis, offering its own set of advantages and limitations. Addressing the spatial complexity of bacterial consortia demands a multifaceted approach for a comprehensive and effective analysis.

舌背(TD)上的细菌围绕上皮细胞核心形成直径数十到数百微米的联合体。整片制备有助于揭示它们的组织和特定的微生物关联。然而,它们的厚度和错综复杂的三维复杂性给全面的空间分析带来了挑战。为了克服这些挑战,我们采用了一种补充方法:将样本包埋在亲水性塑料中,然后进行切片和切片后标记。样品通过与多重荧光寡核苷酸探针杂交进行标记,并通过光谱成像和线性非混合成像进行可视化。将这一策略应用于 TD 生物膜,可改善整片成像中难以分辨的细菌的可视化。以前检测到的片状放线菌,现在可以在单细胞水平上分辨出来。位于菌群核心的丝状类群 Leptotrichia 和 Lachnospiraceae 也能经常被观察到,而以前在使用全装片时很少能检测到它们。唾液链球菌(Streptococcus salivarius)在整片装片中检测不均一,而在二维图像中则可以定期观察到。二维图像提供了有关细菌生物膜组织的宝贵信息。然而,对于厚度可达数百微米的物体,二维图像只能提供单一视角,而且从二维图像中获得的信息并不总能反映三维物体的复杂性。我们将序列物理切片与光学切片相结合,促进了厚度超过 100 微米的联合体的三维重建。我们的工作展示了如何利用亲水性塑料包埋和切片技术,通过光谱成像荧光原位杂交技术检查 TD 生物膜的结构。结果改善了人类口腔微生物群重要成员的可视化。这项技术是对之前采用的整片分析方法的补充,有其自身的优势和局限性。要解决细菌群的空间复杂性问题,需要采用多方面的方法进行全面有效的分析。
{"title":"Improved Visualization of Oral Microbial Consortia.","authors":"S T Ramirez-Puebla, J L Mark Welch, G G Borisy","doi":"10.1177/00220345241251784","DOIUrl":"10.1177/00220345241251784","url":null,"abstract":"<p><p>Bacteria on the tongue dorsum (TD) form consortia tens to hundreds of microns in diameter organized around a core of epithelial cells. Whole-mount preparations have been instrumental in revealing their organization and specific microbial associations. However, their thickness and intricate 3-dimensional complexity present challenges for a comprehensive spatial analysis. To overcome these challenges, we employed a complementary approach: embedding in hydrophilic plastic followed by sectioning and postsectioning labeling. Samples were labeled by hybridization with multiplexed fluorescent oligonucleotide probes and visualized by spectral imaging and linear unmixing. Application of this strategy to TD biofilms improved the visualization of bacteria that were difficult to resolve in whole-mount imaging. <i>Actinomyces</i>, previously detected as patches, became resolved at the single-cell level. The filamentous taxa <i>Leptotrichia</i> and Lachnospiraceae, located at the core of the consortium, were regularly visualized whereas previously they were rarely detected when using whole mounts. <i>Streptococcus salivarius</i>, heterogeneously detected in whole mounts, were regularly and homogenously observed. Two-dimensional images provide valuable information about the organization of bacterial biofilms. However, they offer only a single plane of view for objects that can extend to hundreds of microns in thickness, and information obtained from such images may not always reflect the complexity of a 3-dimensional object. We combined serial physical sectioning with optical sectioning to facilitate the 3-dimensional reconstruction of consortia, spanning over 100 µm in thickness. Our work showcases the use of hydrophilic plastic embedding and sectioning for examining the structure of TD biofilms through spectral imaging fluorescence in situ hybridization. The result was improved visualization of important members of the human oral microbiome. This technique serves as a complementary method to the previously employed whole-mount analysis, offering its own set of advantages and limitations. Addressing the spatial complexity of bacterial consortia demands a multifaceted approach for a comprehensive and effective analysis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study. 牙髓再生管模型中 DPSC-ECs 的血管新生研究。
Pub Date : 2024-06-01 Epub Date: 2024-05-08 DOI: 10.1177/00220345241236392
Y Zhang, J Liu, I J de Souza Araujo, L Bahammam, L L Munn, G T J Huang

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.

基于细胞的牙髓再生过程中的血管新生过程很难研究。在此,我们开发了一种模拟根管空间的试管模型,可直接观察体外血管化过程。我们使用的内皮样细胞(ECs)来源于表达内皮细胞标记CD144、vWF、VEGFR1和VEGFR2的引导性人类牙髓干细胞(DPSCs)。人微血管内皮细胞(hMVECs)作为阳性对照。DPSC-ECs 在 Matrigel 上形成的小管与 hMVECs 相似。将细胞与纤维蛋白原/凝血酶原或小鼠血液混合,然后播种到 96 孔板的孔中,或注射到锥形塑料管(长 14 毫米,顶端开口直径 1 或 2 毫米)中,大端用 MTA 密封,以模拟根管空间。将孔或管中的细胞/凝胶在体外培养不同时间,并在显微镜下观察形态变化。然后将样本固定并进行组织学分析,以确定血管的形成。在细胞播种后 1 到 3 d 的培养过程中可观察到血管样网络。从组织学角度看,96 孔板或管中的 hMVEC 和 DPSC-EC 都显示出细胞内空泡的形成。一些细胞显示出合并的大液泡,这表明细胞有腔化。还观察到类似血管的管状结构。除了冠状三分之一处的一些样本(顶端直径 1 毫米)外,整个管内的细胞看起来都很健康。hMVECs 形成的血管腔比 DPSC-ECs 大,而后者的管腔和管状结构数量更多。我们的结论是,DPSC-ECs 可在体外三维纤维蛋白凝胶系统中形成血管结构并持续生长。该管状模型似乎是模拟根管空间进行血管形成和牙髓再生研究的一个适当而简单的系统。
{"title":"Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study.","authors":"Y Zhang, J Liu, I J de Souza Araujo, L Bahammam, L L Munn, G T J Huang","doi":"10.1177/00220345241236392","DOIUrl":"10.1177/00220345241236392","url":null,"abstract":"<p><p>The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11122093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA Technology to Regenerate and Repair Alveolar Bone Defects. 用于牙槽骨缺损再生和修复的 RNA 技术。
Pub Date : 2024-06-01 Epub Date: 2024-05-07 DOI: 10.1177/00220345241242047
D Su, S Swearson, S Eliason, K G Rice, B A Amendt

microRNA-200a (miR-200a) targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of miR-200a overexpression and miR-200a inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration. Inhibition of miR-200a using PMIS-miR-200a significantly increased osteogenic biomarkers of human embryonic palatal mesenchyme cells and promoted bone regeneration in rat tooth socket defects. In rat maxillary M1 molar extractions, the supporting tooth structures were removed with an implant drill to yield a 3-mm defect in the alveolar bone. A collagen sponge was inserted into the open alveolar defect and PMIS-miR-200a plasmid DNA was added to the sponge and the wound sutured to protect the sponge and close the defect. It was important to remove the existing tooth supporting structure, which can influence alveolar bone regeneration. The alveolar bone was regenerated in 4 wk. The collagen sponge acts to stabilize and deliver the PMIS-miR-200a DNA to cells entering the sponge in the bone defect. We show that mesenchymal stem cells expressing CD90 and Stro-1 enter the sponges, take up the DNA, and express PMIS-miR-200a. PMIS-miR-200a initiates a bone regeneration program in transformed cells in vivo. In vitro inhibition of miR-200a was found to upregulate Wnt and BMP signaling activity as well as Runx2, OCN, Lef-1, Msx2, and Dlx5 associated with osteogenesis. Liver and blood toxicity testing of PMIS-miR-200a-treated rats showed no increase in several biomarkers of liver disease. These results demonstrate the therapeutic function of PMIS-miR-200a for rapid bone regeneration. Furthermore, the studies were designed to demonstrate the ease of use of PMIS-miR-200a in solution and applied using a syringe in the clinic through a simple one-time application.

microRNA-200a(miR-200a)靶向参与成骨分化和骨发育的多种信号通路。然而,它在成骨和骨再生中的治疗功能仍然未知。在本研究中,我们利用体外和体内模型研究了 miR-200a 过表达和使用基于质粒的 miR 抑制剂系统(PMIS)抑制 miR-200a 对成骨分化和骨再生的分子功能。利用PMIS-miR-200a抑制miR-200a能显著增加人胚胎腭间充质细胞的成骨生物标志物,并促进大鼠牙槽缺损的骨再生。在大鼠上颌 M1 磨牙拔除术中,用种植钻去除支撑牙齿的结构,在牙槽骨上形成 3 毫米的缺损。在打开的牙槽骨缺损中插入胶原蛋白海绵,并在海绵中加入 PMIS-miR-200a 质粒 DNA,然后缝合伤口以保护海绵并关闭缺损。重要的是要去除可能影响牙槽骨再生的现有牙齿支撑结构。牙槽骨在 4 周后再生。海绵胶原起到了稳定的作用,并将 PMIS-miR-200a DNA 传递给进入骨缺损海绵中的细胞。我们发现,表达 CD90 和 Stro-1 的间充质干细胞进入海绵,吸收 DNA 并表达 PMIS-miR-200a。PMIS-miR-200a 启动了体内转化细胞的骨再生程序。研究发现,体外抑制 miR-200a 能上调 Wnt 和 BMP 信号活性以及与成骨相关的 Runx2、OCN、Lef-1、Msx2 和 Dlx5。对 PMIS-miR-200a 处理过的大鼠进行的肝脏和血液毒性测试表明,几种肝病生物标志物没有增加。这些结果证明了 PMIS-miR-200a 在快速骨再生方面的治疗功能。此外,这些研究旨在证明 PMIS-miR-200a 溶液的易用性,在临床上使用注射器进行一次性简单应用即可。
{"title":"RNA Technology to Regenerate and Repair Alveolar Bone Defects.","authors":"D Su, S Swearson, S Eliason, K G Rice, B A Amendt","doi":"10.1177/00220345241242047","DOIUrl":"10.1177/00220345241242047","url":null,"abstract":"<p><p><i>microRNA-200a</i> (<i>miR-200a</i>) targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of <i>miR-200a</i> overexpression and <i>miR-200a</i> inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration. Inhibition of <i>miR-200a</i> using <i>PMIS-miR-200a</i> significantly increased osteogenic biomarkers of human embryonic palatal mesenchyme cells and promoted bone regeneration in rat tooth socket defects. In rat maxillary M1 molar extractions, the supporting tooth structures were removed with an implant drill to yield a 3-mm defect in the alveolar bone. A collagen sponge was inserted into the open alveolar defect and <i>PMIS-miR-200a</i> plasmid DNA was added to the sponge and the wound sutured to protect the sponge and close the defect. It was important to remove the existing tooth supporting structure, which can influence alveolar bone regeneration. The alveolar bone was regenerated in 4 wk. The collagen sponge acts to stabilize and deliver the <i>PMIS-miR-200a</i> DNA to cells entering the sponge in the bone defect. We show that mesenchymal stem cells expressing CD90 and Stro-1 enter the sponges, take up the DNA, and express <i>PMIS-miR-200a. PMIS-miR-200a</i> initiates a bone regeneration program in transformed cells in vivo. In vitro inhibition of <i>miR-200a</i> was found to upregulate Wnt and BMP signaling activity as well as <i>Runx2, OCN, Lef-1, Msx2</i>, and <i>Dlx5</i> associated with osteogenesis. Liver and blood toxicity testing of <i>PMIS-miR-200a</i>-treated rats showed no increase in several biomarkers of liver disease. These results demonstrate the therapeutic function of <i>PMIS-miR-200a</i> for rapid bone regeneration. Furthermore, the studies were designed to demonstrate the ease of use of <i>PMIS-miR-200a</i> in solution and applied using a syringe in the clinic through a simple one-time application.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11122091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mouse Models for Head and Neck Squamous Cell Carcinoma. 头颈部鳞状细胞癌小鼠模型
Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1177/00220345241240997
J Zhou, C Liu, P Amornphimoltham, S C Cheong, J S Gutkind, Q Chen, Z Wang

The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.

头颈部鳞状细胞癌(HNSCC)的预后和存活率多年来一直未变,其发病机制仍未完全明了,需要进一步研究。目前迫切需要一种理想的动物模型来准确复制 HNSCC 复杂的微环境。在所有用于临床前癌症研究的动物模型中,肿瘤小鼠模型因其与人类高度相似而最为人熟知和广泛使用。目前,HNSCC 的小鼠模型大致可分为化学诱导模型、基因工程小鼠模型(GEMMs)和移植小鼠模型,每种模型都有其独特的优势和局限性。在化学物质诱导模型中,致癌物质通过多步骤过程自发形成肿瘤。这种模型与人类致癌过程相似,是研究 HNSCC 从癌前病变开始和发展的理想临床前平台。其主要缺点是这些模型耗时较长,而且与人类癌症一样,在时间、位置和病变数量方面难以预测。GEMM涉及基因修饰的转基因和基因敲除小鼠,导致肿瘤微环境中的恶性转化,这种微环境再现了体内的肿瘤发生过程,包括它们与免疫系统的相互作用。然而,大多数 HNSCC GEMMs 的肿瘤发病率较低,在临床研究中的预后意义有限。移植小鼠模型因其一致性、可用性和高效性而在癌症研究中得到最广泛的应用。根据供体和受体物种的匹配情况,移植小鼠模型可分为异种移植模型和同种异体模型。在后者中,移植细胞和宿主来自同一品系,因此共生模型与研究功能性免疫系统相关。在这篇综述中,我们全面总结了这些不同的 HNSCC 小鼠模型的特点、建立方法和潜在应用,旨在帮助研究人员选择合适的动物模型进行研究。
{"title":"Mouse Models for Head and Neck Squamous Cell Carcinoma.","authors":"J Zhou, C Liu, P Amornphimoltham, S C Cheong, J S Gutkind, Q Chen, Z Wang","doi":"10.1177/00220345241240997","DOIUrl":"10.1177/00220345241240997","url":null,"abstract":"<p><p>The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ENAM Mutations Can Cause Hypomaturation Amelogenesis Imperfecta. ENAM突变可导致成髓细胞发育不全。
Pub Date : 2024-06-01 Epub Date: 2024-05-08 DOI: 10.1177/00220345241236695
Y-L Wang, H-C Lin, T Liang, J C-Y Lin, J P Simmer, J C-C Hu, S-K Wang

Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.

釉质发育不全症(AI)是一组遗传性疾病,其特点是釉质形成的不同阶段受到干扰而导致不同表现的釉质畸形。发育不全性釉质发育不全(hypoplastic AI)是指釉质在釉质形成的分泌阶段出现异常而导致的釉质厚度缺陷,而釉质发育不全性釉质发育不全(hypomaturation AI)则是指釉质在成熟阶段出现矿化和硬度不足。ENAM编码最大的釉质基质蛋白--釉质素,ENAM的突变已被证实可导致全身性或局部性发育不全AI。在这里,我们鉴定了两个具有不同的发育不全和釉质发育不全缺陷的人工智能家族,并在ENAM的同一位置发现了两个不同的吲哚突变,即c588+1del和c.588+1dup。微型基因剪接试验表明,这两个突变分别导致了ENAM蛋白的帧移位和截断,即p.Asn197Ilefs*81和p.Asn197Glufs*25。对小鼠下颌门牙上的ENAM进行原位杂交证实,ENAM在分泌期成髓细胞中的表达受到限制,这也提示了AI发育不全的间接致病机制。硅学分析表明,这两种截短的ENAM可能会形成淀粉样结构,并通过其C端添加的异常区域导致自身和野生型蛋白聚集。同样,蛋白质分泌试验表明,截短蛋白不能正常分泌,并阻碍了野生型ENAM的分泌。此外,与野生型相比,过量表达突变体蛋白会显著增加内质网应激,并上调未折叠蛋白反应(UPR)相关基因和 UPR 控制的促凋亡基因 TNFRSF10B 的表达。Caspase、末端脱氧核苷酸转移酶UTP缺口末端标记(TUNEL)和3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-溴化四氮唑(MTT)检测进一步表明,这两种截短蛋白,尤其是p.Asn197Ilefs*81,可诱导细胞凋亡并降低细胞存活率,这表明这两种ENAM突变是通过成髓细胞病理变化和死亡而非简单的功能缺失引起人工智能的。这项研究表明,ENAM突变可导致全身釉质发育不全,并提示蛋白病是ENAM相关性人工智能的潜在发病机制。
{"title":"<i>ENAM</i> Mutations Can Cause Hypomaturation Amelogenesis Imperfecta.","authors":"Y-L Wang, H-C Lin, T Liang, J C-Y Lin, J P Simmer, J C-C Hu, S-K Wang","doi":"10.1177/00220345241236695","DOIUrl":"10.1177/00220345241236695","url":null,"abstract":"<p><p>Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in <i>ENAM</i>, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of <i>ENAM</i>, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of <i>Enam</i> on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and <i>TNFRSF10B</i>, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 <i>ENAM</i> mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an <i>ENAM</i> mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for <i>ENAM</i>-associated AI.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11122092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harold C. Slavkin: A Transformative Leader of Our Times. 哈罗德-斯拉夫金我们时代的变革领袖。
Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1177/00220345241247784
D V Kleinman, M C Alfano, Y Chai, R N D'Souza

Harold (Hal) C. Slavkin, DDS, the 22nd president of the American Association for Dental, Oral, and Craniofacial Research (1993 to 1994), died on December 22, 2023. During a career that spanned almost 6 decades, Hal distinguished himself as an international authority on craniofacial biology and an advocate for oral health equity. He served as dean of the University of Southern California's dental school, founded the school's Center for Craniofacial Molecular Biology, created the nation's first PhD program in craniofacial biology, and served as the sixth director of the National Institute of Dental and Craniofacial Research. Hal's studies of the molecular and cellular underpinnings of craniofacial malformations prepared him to champion translational research later in his career, when his work with patient advocates revealed the importance of applying new discoveries to clinical practice. A visionary thinker, skilled administrator, progressive educator, compelling communicator, researcher, scholar, and mentor, Hal was known as a Renaissance leader. He rejoiced in fostering collaborative synergies among people and organizations. Throughout his life, family was his central grounding force. He and his wife, Lois, advanced a wide range of social and community initiatives and took great pride in their children, grandchildren, and great-grandchildren. We remember Hal for his indelible spirit, unflappable enthusiasm for science, fierce advocacy for social justice, and infectious zest for life. Here, we outline his multidimensional accomplishments through the lenses of academia, government, and nonprofit organizations. Although it is with heavy hearts that we bid goodbye to this remarkable man, our spirits are lightened by the many gifts he left behind.

美国牙科、口腔和颅面研究协会第 22 任主席(1993-1994 年)、牙科博士哈罗德-斯拉夫金(Harold (Hal) C. Slavkin)于 2023 年 12 月 22 日去世。在将近 60 年的职业生涯中,哈尔作为颅面生物学方面的国际权威和口腔健康公平的倡导者表现突出。他曾担任南加州大学牙科学院院长,创建了该学院的颅面分子生物学中心,创立了美国第一个颅面生物学博士项目,并担任美国国家牙科和颅面研究所第六任所长。哈尔对颅颌面畸形的分子和细胞基础的研究为他在职业生涯后期倡导转化研究做好了准备,他与患者权益倡导者的合作揭示了将新发现应用于临床实践的重要性。作为一位富有远见的思想家、娴熟的管理者、进步的教育者、令人信服的沟通者、研究者、学者和导师,哈尔被誉为文艺复兴时期的领导者。他乐于促进人与人之间、组织与组织之间的协作协同。在他的一生中,家庭是他的核心支柱。他和妻子露易丝推动了广泛的社会和社区活动,并为他们的子女、孙子女和曾孙子女感到自豪。我们缅怀哈尔,是因为他那永不磨灭的精神、对科学的不懈热情、对社会正义的积极倡导以及对生活的感染力。在此,我们从学术界、政府和非营利组织的角度概述了他多方面的成就。虽然我们怀着沉重的心情向这位杰出的人告别,但他留下的许多礼物让我们的心情更加轻松。
{"title":"Harold C. Slavkin: A Transformative Leader of Our Times.","authors":"D V Kleinman, M C Alfano, Y Chai, R N D'Souza","doi":"10.1177/00220345241247784","DOIUrl":"10.1177/00220345241247784","url":null,"abstract":"<p><p>Harold (Hal) C. Slavkin, DDS, the 22nd president of the American Association for Dental, Oral, and Craniofacial Research (1993 to 1994), died on December 22, 2023. During a career that spanned almost 6 decades, Hal distinguished himself as an international authority on craniofacial biology and an advocate for oral health equity. He served as dean of the University of Southern California's dental school, founded the school's Center for Craniofacial Molecular Biology, created the nation's first PhD program in craniofacial biology, and served as the sixth director of the National Institute of Dental and Craniofacial Research. Hal's studies of the molecular and cellular underpinnings of craniofacial malformations prepared him to champion translational research later in his career, when his work with patient advocates revealed the importance of applying new discoveries to clinical practice. A visionary thinker, skilled administrator, progressive educator, compelling communicator, researcher, scholar, and mentor, Hal was known as a Renaissance leader. He rejoiced in fostering collaborative synergies among people and organizations. Throughout his life, family was his central grounding force. He and his wife, Lois, advanced a wide range of social and community initiatives and took great pride in their children, grandchildren, and great-grandchildren. We remember Hal for his indelible spirit, unflappable enthusiasm for science, fierce advocacy for social justice, and infectious zest for life. Here, we outline his multidimensional accomplishments through the lenses of academia, government, and nonprofit organizations. Although it is with heavy hearts that we bid goodbye to this remarkable man, our spirits are lightened by the many gifts he left behind.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis. AZGP1 会加剧牙周炎中巨噬细胞 M1 的极化和脓毒血症。
Pub Date : 2024-06-01 Epub Date: 2024-03-15 DOI: 10.1177/00220345241235616
S Yang, Y Yin, Y Sun, D Ai, X Xia, X Xu, J Song

Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of Azgp1 in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while Azgp1-/- mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of Azgp1 markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from Azgp1-overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by Azgp1 overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.

牙周炎中的牙周组织破坏是宿主对牙周病原体的炎症反应的结果,而这种反应在 2 型糖尿病(T2DM)的情况下可能会加剧。越来越多的证据表明,巨噬细胞介导的炎症与正常和 T2DM 条件下牙周炎的发病机制密切相关。然而,其根本机制仍然难以捉摸。甲型-2-糖蛋白 1(AZGP1)是一种具有 MHC-I 结构域的糖蛋白,与炎症和代谢紊乱都有关系。在这项研究中,我们发现 AZGP1 主要与牙周炎组织中的巨噬细胞共定位。与对照组相比,AZGP1在牙周炎中增高,在伴有T2DM时进一步增高。在牙周炎和 T2DM 相关牙周炎的小鼠模型中,腺相关病毒介导的 Azgp1 在牙周中的过表达显著增强了牙周炎症和牙槽骨丧失,并伴随着 M1 巨噬细胞的升高和热蛋白沉积,而 Azgp1-/- 小鼠则表现出相反的效应。在受到脂多糖(LPS)或 LPS 和棕榈酸(PA)刺激的原发性骨髓衍生巨噬细胞中,Azgp1 的过表达或基因敲除分别显著上调或抑制了巨噬细胞 M1 标记和 NLR 家族含吡林域 3(NLRP3)/caspase-1 信号转导的关键成分的表达。此外,在LPS或LPS+PA刺激下,Azgp1表达的巨噬细胞的条件培养基诱导了人牙周韧带干细胞(hPDLSCs)更高的炎症激活和更低的成骨分化。此外,NLRP3或caspase-1抑制剂可挽救Azgp1过表达诱导的巨噬细胞M1极化和脓毒症升高以及对hPDLSCs的相关不利影响。总之,我们的研究阐明了AZGP1可通过NLRP3/casapse-1途径促进巨噬细胞M1极化和热凋亡,从而加重牙周炎,而这在T2DM相关牙周炎中表现得更为明显。这一发现加深了人们对AZGP1在牙周炎发病机制中作用的认识,并表明AZGP1是糖尿病对牙周炎症产生不良影响的关键环节。
{"title":"AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis.","authors":"S Yang, Y Yin, Y Sun, D Ai, X Xia, X Xu, J Song","doi":"10.1177/00220345241235616","DOIUrl":"10.1177/00220345241235616","url":null,"abstract":"<p><p>Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of <i>Azgp1</i> in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while <i>Azgp1</i><sup>-/-</sup> mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of <i>Azgp1</i> markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from <i>Azgp1</i>-overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by <i>Azgp1</i> overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic Review of Prognosis Models in Predicting Tooth Loss in Periodontitis. 预测牙周炎牙齿脱落的预后模型的系统性回顾。
Pub Date : 2024-06-01 Epub Date: 2024-05-10 DOI: 10.1177/00220345241237448
D Y Chow, J R H Tay, G G Nascimento

This study reviews and appraises the methodological and reporting quality of prediction models for tooth loss in periodontitis patients, including the use of regression and machine learning models. Studies involving prediction modeling for tooth loss in periodontitis patients were screened. A search was performed in MEDLINE via PubMed, Embase, and CENTRAL up to 12 February 2022, with citation chasing. Studies exploring model development or external validation studies for models assessing tooth loss in periodontitis patients for clinical use at any time point, with all prediction horizons in English, were considered. Studies were excluded if models were not developed for use in periodontitis patients, were not developed or validated on any data set, predicted outcomes other than tooth loss, or were prognostic factor studies. The CHARMS checklist was used for data extraction, TRIPOD to assess reporting quality, and PROBAST to assess the risk of bias. In total, 4,661 records were screened, and 45 studies were included. Only 26 studies reported any kind of performance measure. The median C-statistic reported was 0.671 (range, 0.57-0.97). All studies were at a high risk of bias due to inappropriate handling of missing data (96%), inappropriate evaluation of model performance (92%), and lack of accounting for model overfitting in evaluating model performance (68%). Many models predicting tooth loss in periodontitis are available, but studies evaluating these models are at a high risk of bias. Model performance measures are likely to be overly optimistic and might not be replicated in clinical use. While this review is unable to recommend any model for clinical practice, it has collated the existing models and their model performance at external validation and their associated sample sizes, which would be helpful to identify promising models for future external validation studies.

本研究回顾并评估了牙周炎患者牙齿缺失预测模型的方法和报告质量,包括回归模型和机器学习模型的使用。研究筛选了涉及牙周炎患者牙齿缺失预测模型的研究。截至 2022 年 2 月 12 日,通过 PubMed、Embase 和 CENTRAL 在 MEDLINE 中进行了检索,并进行了引文追逐。这些研究探讨了牙周炎患者在任何时间点用于临床的牙齿缺失评估模型的开发或外部验证研究,所有预测范围均为英语。如果所开发的模型不是用于牙周炎患者、未在任何数据集上开发或验证、预测的结果不是牙齿脱落,或者是预后因素研究,则排除这些研究。CHARMS 检查表用于数据提取,TRIPOD 用于评估报告质量,PROBAST 用于评估偏倚风险。共筛选出 4,661 条记录,并纳入了 45 项研究。只有 26 项研究报告了任何类型的绩效衡量标准。报告的 C 统计量中位数为 0.671(范围为 0.57-0.97)。由于对缺失数据的处理不当(96%)、对模型性能的评估不当(92%)以及在评估模型性能时没有考虑模型的过度拟合(68%),所有研究都存在较高的偏倚风险。目前有许多预测牙周炎患者牙齿脱落的模型,但评估这些模型的研究存在较高的偏倚风险。模型的性能指标可能过于乐观,在临床使用中可能无法复制。虽然本综述无法向临床实践推荐任何模型,但它整理了现有模型及其在外部验证中的模型性能以及相关样本量,这将有助于为未来的外部验证研究确定有前途的模型。
{"title":"Systematic Review of Prognosis Models in Predicting Tooth Loss in Periodontitis.","authors":"D Y Chow, J R H Tay, G G Nascimento","doi":"10.1177/00220345241237448","DOIUrl":"10.1177/00220345241237448","url":null,"abstract":"<p><p>This study reviews and appraises the methodological and reporting quality of prediction models for tooth loss in periodontitis patients, including the use of regression and machine learning models. Studies involving prediction modeling for tooth loss in periodontitis patients were screened. A search was performed in MEDLINE via PubMed, Embase, and CENTRAL up to 12 February 2022, with citation chasing. Studies exploring model development or external validation studies for models assessing tooth loss in periodontitis patients for clinical use at any time point, with all prediction horizons in English, were considered. Studies were excluded if models were not developed for use in periodontitis patients, were not developed or validated on any data set, predicted outcomes other than tooth loss, or were prognostic factor studies. The CHARMS checklist was used for data extraction, TRIPOD to assess reporting quality, and PROBAST to assess the risk of bias. In total, 4,661 records were screened, and 45 studies were included. Only 26 studies reported any kind of performance measure. The median C-statistic reported was 0.671 (range, 0.57-0.97). All studies were at a high risk of bias due to inappropriate handling of missing data (96%), inappropriate evaluation of model performance (92%), and lack of accounting for model overfitting in evaluating model performance (68%). Many models predicting tooth loss in periodontitis are available, but studies evaluating these models are at a high risk of bias. Model performance measures are likely to be overly optimistic and might not be replicated in clinical use. While this review is unable to recommend any model for clinical practice, it has collated the existing models and their model performance at external validation and their associated sample sizes, which would be helpful to identify promising models for future external validation studies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Performance Dental Resins Containing a Starburst Monomer. 含星爆单体的高性能牙科树脂。
Pub Date : 2024-05-01 Epub Date: 2024-03-28 DOI: 10.1177/00220345241232312
S Q Dai, W Zhou, L Y Duan, K Tang, Z Y Yang, R J Cao, F R Tay, L N Niu, J H Chen

Dimethacrylate-based chemistries feature extensively as resin monomers in dental resin-based materials due to their distinguished overall performance. However, challenges endure, encompassing inadequate mechanical attributes, volumetric shrinkage, and estrogenicity. Herein, we first synthesized a novel resin monomer, 9-armed starburst polyurethane acrylate (NPUA), via the grafting-onto approach. Compared to the primary commercial dental monomer 2,2-bis [p-(2'-hydroxy-3'-methacryloxypropoxy) phenyl] propane (Bis-GMA) (with a viscosity of 1,174 ± 3 Pa·s and volumetric shrinkage of 4.7% ± 0.1%), the NPUA monomer achieves the lower viscosity (158 ± 1 Pa·s), volumetric shrinkage (2.5% ± 0.1%), and cytotoxicity (P < 0.05). The NPUA-based resins exhibit the higher flexural strength, flexural modulus, hardness, and hydrophobicity and lower volumetric shrinkage, water absorption, and solubility compared to the Bis-GMA (70 wt%)/TEGDMA (30 wt%) resins. The NPUA-based composites exhibit significantly higher flexural strength, flexural modulus, and hardness and lower volumetric shrinkage (171.4 ± 3.0 MPa, 12.6 ± 0.5 GPa, 2.0 ± 0.2 GPa, and 3.4% ± 0.2%, respectively) compared to the Bis-GMA group (120.3 ± 4.7 MPa, 9.4 ± 0.7 GPa, 1.5 ± 0.1 GPa, and 4.7% ± 0.2%, respectively; P < 0.05). This work presents a viable avenue for augmenting the physicochemical attributes of dental resins.

基于二甲基丙烯酸酯的化学物质因其卓越的综合性能而被广泛用作牙科树脂基材料的树脂单体。然而,它也面临着机械性能不足、体积收缩和雌激素性等挑战。在此,我们首先通过接枝-本体法合成了一种新型树脂单体--9-臂星形聚氨酯丙烯酸酯(NPUA)。与主要的商用牙科单体 2,2-双[对-(2'-羟基-3'-甲基丙烯酰氧基丙氧基)苯基]丙烷(Bis-GMA)(粘度为 1,174 ± 3 Pa-s,体积收缩率为 4.7% ± 0.1%)相比,NPUA 单体的粘度(158 ± 1 Pa-s)、体积收缩率(2.5% ± 0.1%)和细胞毒性(P < 0.05)都更低。与 Bis-GMA(70 wt%)/TEGDMA(30 wt%)树脂相比,NPUA 基树脂具有更高的抗弯强度、抗弯模量、硬度和疏水性,以及更低的体积收缩率、吸水性和溶解性。与 Bis-GMA 组(分别为 120.3 ± 4.7 MPa、9.4 ± 0.7 GPa、1.5 ± 0.1 GPa 和 4.7% ± 0.2%;P < 0.05)相比,NPUA 基复合材料的抗弯强度、抗弯模量和硬度明显更高,体积收缩率更低(分别为 171.4 ± 3.0 MPa、12.6 ± 0.5 GPa、2.0 ± 0.2 GPa 和 3.4% ± 0.2%)。这项研究为提高牙科树脂的物理化学属性提供了一条可行的途径。
{"title":"High-Performance Dental Resins Containing a Starburst Monomer.","authors":"S Q Dai, W Zhou, L Y Duan, K Tang, Z Y Yang, R J Cao, F R Tay, L N Niu, J H Chen","doi":"10.1177/00220345241232312","DOIUrl":"10.1177/00220345241232312","url":null,"abstract":"<p><p>Dimethacrylate-based chemistries feature extensively as resin monomers in dental resin-based materials due to their distinguished overall performance. However, challenges endure, encompassing inadequate mechanical attributes, volumetric shrinkage, and estrogenicity. Herein, we first synthesized a novel resin monomer, 9-armed starburst polyurethane acrylate (NPUA), via the grafting-onto approach. Compared to the primary commercial dental monomer 2,2-bis [p-(2'-hydroxy-3'-methacryloxypropoxy) phenyl] propane (Bis-GMA) (with a viscosity of 1,174 ± 3 Pa·s and volumetric shrinkage of 4.7% ± 0.1%), the NPUA monomer achieves the lower viscosity (158 ± 1 Pa·s), volumetric shrinkage (2.5% ± 0.1%), and cytotoxicity (<i>P</i> < 0.05). The NPUA-based resins exhibit the higher flexural strength, flexural modulus, hardness, and hydrophobicity and lower volumetric shrinkage, water absorption, and solubility compared to the Bis-GMA (70 wt%)/TEGDMA (30 wt%) resins. The NPUA-based composites exhibit significantly higher flexural strength, flexural modulus, and hardness and lower volumetric shrinkage (171.4 ± 3.0 MPa, 12.6 ± 0.5 GPa, 2.0 ± 0.2 GPa, and 3.4% ± 0.2%, respectively) compared to the Bis-GMA group (120.3 ± 4.7 MPa, 9.4 ± 0.7 GPa, 1.5 ± 0.1 GPa, and 4.7% ± 0.2%, respectively; <i>P</i> < 0.05). This work presents a viable avenue for augmenting the physicochemical attributes of dental resins.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Social Disadvantage and Multimorbidity Including Oral Conditions in the United States. 美国的社会劣势和包括口腔疾病在内的多病症。
Pub Date : 2024-05-01 Epub Date: 2024-03-19 DOI: 10.1177/00220345241228834
A Mirza, R G Watt, A Heilmann, M Stennett, A Singh

Existing studies on multimorbidity have largely excluded oral diseases in multimorbidity prevalence estimates. The reason behind this is somewhat unclear, as chronic oral conditions are highly prevalent, affecting over half the global population. To address this gap, we examined the relationship between social disadvantage and multimorbidity, stratifying by the inclusion and exclusion of oral conditions. For participants aged 30 y and over (n = 3,693), cross-sectional analysis was carried out using the US National Health and Nutrition Survey (2013-2014). Multimorbidity was defined as having 2 or more chronic conditions. Five medical conditions were examined: diabetes, asthma, arthritis, cardiovascular disease, and depression, as well as 4 oral health conditions: caries, periodontal disease, number of teeth, and edentulousness. Education and income poverty ratio were selected as measures of social disadvantage. Multimorbidity prevalence estimates according to social disadvantage were analyzed on an absolute and relative scale using inverse probability treatment weighting (IPTW), adjusting for age, sex, and ethnicity. The inclusion of oral health conditions in the assessment of multimorbidity increased the overall prevalence of multimorbidity from 20.8% to 53.4%. Findings from IPTW analysis demonstrated clear social gradients for multimorbidity estimates stratified by the exclusion of oral conditions. Upon inclusion of oral conditions, the prevalence of multimorbidity was higher across all social groups for both education and income. Stratifying by the inclusion of oral conditions, the mean probability of multimorbidity was 27% (95% confidence interval [CI], 23%-30%) higher in the low-education group compared to the high-education group. Similarly, the mean probability of multimorbidity was 44% (95% CI, 40%-48%) higher in the low-income group. On a relative scale, low education was associated with a 1.52 times (95% CI, 1.44-1.61) higher prevalence of multimorbidity compared to high education. Low income was associated with a 2.18 (95% CI, 1.99-2.39) higher prevalence of multimorbidity. This novel study strongly supports the impact of chronic oral conditions on multimorbidity prevalence estimates.

现有的多病症研究在估算多病症患病率时大多不包括口腔疾病。这背后的原因尚不清楚,因为慢性口腔疾病的发病率很高,影响着全球一半以上的人口。为了填补这一空白,我们研究了社会不利条件与多病症之间的关系,并根据口腔疾病的纳入和排除情况进行了分层。我们利用美国国家健康与营养调查(2013-2014 年)对 30 岁及以上的参与者(n = 3,693 人)进行了横断面分析。多病症的定义是患有 2 种或 2 种以上慢性疾病。研究对象包括五种疾病:糖尿病、哮喘、关节炎、心血管疾病和抑郁症,以及四种口腔健康状况:龋齿、牙周病、牙齿数量和无牙。教育程度和收入贫困率被选为衡量社会不利条件的指标。使用反概率处理加权法(IPTW)对社会不利条件下的多病症患病率估计值进行了绝对和相对分析,并对年龄、性别和种族进行了调整。将口腔健康状况纳入多病评估后,多病的总体患病率从 20.8% 增加到 53.4%。IPTW 分析结果显示,在排除口腔疾病的情况下,多病症估计值的社会梯度非常明显。在纳入口腔疾病后,所有社会群体的多病症患病率在教育程度和收入方面都较高。根据口腔状况进行分层,与高学历群体相比,低学历群体的多病患病平均概率高出 27%(95% 置信区间 [CI],23%-30%)。同样,低收入组患多病的平均概率比高学历组高 44%(95% 置信区间,40%-48%)。相对而言,与高学历相比,低学历者的多病症患病率要高出 1.52 倍(95% CI,1.44-1.61)。低收入与多病症患病率高出 2.18 倍(95% CI,1.99-2.39)有关。这项新颖的研究有力地证明了慢性口腔疾病对多病患病率估计的影响。
{"title":"Social Disadvantage and Multimorbidity Including Oral Conditions in the United States.","authors":"A Mirza, R G Watt, A Heilmann, M Stennett, A Singh","doi":"10.1177/00220345241228834","DOIUrl":"10.1177/00220345241228834","url":null,"abstract":"<p><p>Existing studies on multimorbidity have largely excluded oral diseases in multimorbidity prevalence estimates. The reason behind this is somewhat unclear, as chronic oral conditions are highly prevalent, affecting over half the global population. To address this gap, we examined the relationship between social disadvantage and multimorbidity, stratifying by the inclusion and exclusion of oral conditions. For participants aged 30 y and over (<i>n</i> = 3,693), cross-sectional analysis was carried out using the US National Health and Nutrition Survey (2013-2014). Multimorbidity was defined as having 2 or more chronic conditions. Five medical conditions were examined: diabetes, asthma, arthritis, cardiovascular disease, and depression, as well as 4 oral health conditions: caries, periodontal disease, number of teeth, and edentulousness. Education and income poverty ratio were selected as measures of social disadvantage. Multimorbidity prevalence estimates according to social disadvantage were analyzed on an absolute and relative scale using inverse probability treatment weighting (IPTW), adjusting for age, sex, and ethnicity. The inclusion of oral health conditions in the assessment of multimorbidity increased the overall prevalence of multimorbidity from 20.8% to 53.4%. Findings from IPTW analysis demonstrated clear social gradients for multimorbidity estimates stratified by the exclusion of oral conditions. Upon inclusion of oral conditions, the prevalence of multimorbidity was higher across all social groups for both education and income. Stratifying by the inclusion of oral conditions, the mean probability of multimorbidity was 27% (95% confidence interval [CI], 23%-30%) higher in the low-education group compared to the high-education group. Similarly, the mean probability of multimorbidity was 44% (95% CI, 40%-48%) higher in the low-income group. On a relative scale, low education was associated with a 1.52 times (95% CI, 1.44-1.61) higher prevalence of multimorbidity compared to high education. Low income was associated with a 2.18 (95% CI, 1.99-2.39) higher prevalence of multimorbidity. This novel study strongly supports the impact of chronic oral conditions on multimorbidity prevalence estimates.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11047010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of dental research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1