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Advances in Precision Oral Health Research. 口腔精密保健研究进展
Q1 Medicine Pub Date : 2019-11-01 DOI: 10.1177/0022034519879059
M E Ryan, R Garcia
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引用次数: 0
Searching Deep and Wide: Advances in the Molecular Understanding of Dental Caries and Periodontal Disease. 深入和广泛的探索:龋病和牙周病的分子认识进展
Q1 Medicine Pub Date : 2019-11-01 DOI: 10.1177/0022034519877387
K Divaris

During the past decades, remarkable progress has been made in the understanding of the molecular basis of the 2 most common oral diseases, dental caries and periodontal disease. Improvements in our knowledge of the diseases' underlying biology have illuminated previously unrecognized aspects of their pathogenesis. Importantly, the key role of the oral (supragingival and subgingival) microbiome is now well recognized, and both diseases are now best understood as dysbiotic. From a host susceptibility standpoint, some progress has been made in dissecting the "hyperinflammatory" trait and other pathways of susceptibility underlying periodontitis, and novel susceptibility loci have been reported for dental caries. Nevertheless, there is a long road to the translation of these findings and the realization of precision oral health. There is promise and hope that the rapidly increasing capacity of generating multiomics data layers and the aggregation of study samples and cohorts comprising thousands of participants will accelerate the discovery and translation processes. A first key element in this process has been the identification and interrogation of biologically informed disease traits-these "deep" or "precise" traits have the potential of revealing biologically homogeneous disease signatures and genetic susceptibility loci that might present with overlapping or heterogeneous clinical signs. A second key element has been the formation of international consortia with the goals of combining and harmonizing oral health data of thousands of individuals from diverse settings-these "wide" collaborative approaches leverage the power of large sample sizes and are aimed toward the discovery or validation of genetic influences that would otherwise be impossible to detect. Importantly, advancements via these directions require an unprecedented engagement of systems biology and team science models. The article highlights novel insights into the molecular basis of dental caries and chronic periodontitis that have been gained from recent and ongoing studies involving "deep" and "wide" analytical approaches.

在过去的几十年里,人们对龋齿和牙周病这两种最常见的口腔疾病的分子基础的了解取得了显著的进展。我们对这些疾病的潜在生物学知识的改进已经阐明了以前未被认识到的发病机制方面。重要的是,口腔(龈上和龈下)微生物组的关键作用现在得到了很好的认识,这两种疾病现在都被最好地理解为益生菌失调。从宿主易感性的角度来看,在分析牙周炎的“高炎症”特征和其他易感性途径方面取得了一些进展,并且已经报道了龋齿的新易感性位点。然而,这些发现的翻译和实现精确口腔健康还有很长的路要走。产生多组学数据层的能力迅速增加,研究样本和由数千名参与者组成的队列的聚集将加速发现和翻译过程,这是有希望的。这个过程的第一个关键因素是识别和询问生物学上已知的疾病特征——这些“深层”或“精确”的特征有可能揭示生物学上同质的疾病特征和可能呈现重叠或异质临床症状的遗传易感位点。第二个关键因素是国际联盟的形成,其目标是结合和协调来自不同环境的成千上万个人的口腔健康数据——这些“广泛”的合作方法利用了大样本的力量,旨在发现或验证遗传影响,否则就不可能检测到。重要的是,通过这些方向的进步需要前所未有的系统生物学和团队科学模型的参与。这篇文章强调了对龋齿和慢性牙周炎分子基础的新见解,这些见解来自于最近和正在进行的涉及“深度”和“广泛”分析方法的研究。
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引用次数: 0
Precision Reengineering of the Oral Microbiome for Caries Management. 口腔微生物组的精确再造用于龋齿管理
Q1 Medicine Pub Date : 2019-11-01 DOI: 10.1177/0022034519877386
J L Baker, X He, W Shi

Technological advancements have revolutionized our understanding of the complexity and importance of the human microbiome. This progress has also emphasized the need for precision therapeutics, as it has underscored the dilemmas, such as dysbiosis and increasing antibiotic resistance, associated with current, broad-spectrum treatment modalities. Dental caries remains the most common chronic disease worldwide, accompanied by a tremendous financial and social burden, despite widespread and efficacious fluoride and hygienic regimens. Over the past several decades, various precision approaches to combat dental caries, including vaccines, probiotics, and antimicrobial compounds, have been pursued. Despite the distinct overall conceptual strengths of each approach, for various reasons, there are currently no approved precision antibiotic therapeutics to prevent dental caries. Specifically targeted antimicrobial peptides (STAMPs) are synthetic molecules that combine the antibiotic moiety of a traditional antimicrobial peptide with a targeting domain to provide specificity against a particular organism. Conjoining the killing domain from the antimicrobial, novispirin G10, and a targeting domain derived from the Streptococcus mutans pheromone, CSP, the STAMP C16G2 was designed to provide targeted killing of S. mutans, widely considered the keystone species in dental caries pathogenesis. C16G2 was able to selectively eliminate S. mutans from complex ecosystems while leaving closely related, yet health-associated, oral species unharmed. This remodeling of the dental plaque community is expected to have significant advantages compared to conventional broad-spectrum mouthwashes, as the intact, surviving community is apt to prevent reinfection by pathogens. Following successful phase I clinical trials that evaluated the safety and basic microbiology of C16G2 treatments, the phase II trials of several C16G2 formulations are currently in progress. C16G2 represents an exciting advance in precision therapeutics, and the STAMP platform provides vast opportunities for both the development of additional therapeutics and the overall study of microbial ecology.

技术进步彻底改变了我们对人类微生物组复杂性和重要性的理解。这一进展也强调了精准治疗的必要性,因为它强调了与当前广谱治疗模式相关的困境,如生态失调和抗生素耐药性增加。龋齿仍然是世界上最常见的慢性疾病,伴随着巨大的经济和社会负担,尽管有广泛有效的氟化物和卫生方案。在过去的几十年里,人们一直在寻求各种精确的方法来对抗龋齿,包括疫苗、益生菌和抗菌化合物。尽管每种方法的总体概念优势不同,但由于各种原因,目前还没有批准的预防龋齿的精确抗生素疗法。特异性靶向抗微生物肽(STAMP)是将传统抗微生物肽的抗生素部分与靶向结构域结合以提供针对特定生物体的特异性的合成分子。STAMP C16G2结合了来自抗菌药物诺维Spirin G10的杀伤结构域和来自变形链球菌信息素CSP的靶向结构域,旨在提供对变形链球菌的靶向杀伤,变形链球菌被广泛认为是龋齿发病机制中的关键物种。C16G2能够选择性地从复杂的生态系统中清除变异链球菌,同时使密切相关但与健康相关的口腔物种免受伤害。与传统的广谱漱口水相比,这种牙菌斑群落的重塑有望具有显著的优势,因为完整的、存活的群落易于防止病原体的再次感染。在成功评估C16G2治疗的安全性和基本微生物学的I期临床试验之后,几种C16G2制剂的II期试验目前正在进行中。C16G2代表了精准治疗的一个令人兴奋的进步,STAMP平台为开发额外的治疗方法和微生物生态学的整体研究提供了巨大的机会。
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引用次数: 0
Oral Rehabilitation of Patients Sustaining Orofacial Injuries: The UPenn Initiative 口腔康复对口腔颌面损伤患者的影响:UPenn倡议
Q1 Medicine Pub Date : 2019-10-21 DOI: 10.1177/0022034519877400
Qunzhou Zhang, Chider Chen, M. B. Chang, R. Shanti, R. Shanti, Steven B. Cannady, Bert W. O'Malley, S. Shi, A. D. Le, A. D. Le
Tissue injuries in the oral and maxillofacial structures secondary to trauma, warfare, ablative cancer, and benign tumor surgery result in significant losses of speech, masticatory and swallowing functions, aesthetic deformities, and overall psychological stressors and compromise. Optimal oral rehabilitation remains a formidable challenge and an unmet clinical need due to the influence of multiple factors related to the physiologic limitations of tissue repair, the lack of site and function-specific donor tissues and constructs, and an integrated team of multidisciplinary professionals. The advancements in stem cell biology, biomaterial science, and tissue engineering technologies, particularly the 3-dimensional bioprinting technology, together with digital imaging and computer-aided design and manufacturing technologies, have paved the path for personalized/precision regenerative medicine. At the University of Pennsylvania, we have launched the initiative to integrate multidisciplinary health professionals and translational/clinical scientists in medicine, dentistry, stem cell biology, tissue engineering, and regenerative medicine to develop a comprehensive, patient-centered approach for precision and personalized reconstruction, as well as oral rehabilitation of patients sustaining orofacial tissue injuries and defects, especially oral cancer patients.
创伤、战争、癌症消融和良性肿瘤手术导致的口腔和颌面部结构的组织损伤导致言语、咀嚼和吞咽功能的显著丧失、审美畸形以及整体心理压力源和妥协。由于组织修复的生理限制、缺乏特定部位和功能的供体组织和构建体以及多学科专业人员的综合团队等多种因素的影响,最佳口腔康复仍然是一项艰巨的挑战,也是一项未满足的临床需求。干细胞生物学、生物材料科学和组织工程技术的进步,特别是三维生物打印技术,以及数字成像和计算机辅助设计和制造技术,为个性化/精确再生医学铺平了道路。在宾夕法尼亚大学,我们发起了一项倡议,整合医学、牙科、干细胞生物学、组织工程和再生医学领域的多学科健康专业人员和转化/临床科学家,以开发一种全面的、以患者为中心的精确和个性化重建方法,以及口面部组织损伤和缺损患者、尤其是口腔癌症患者的口腔康复。
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引用次数: 8
Precision Health: Bringing Oral Health into the Context of Overall Health 精准健康:将口腔健康纳入全面健康的范畴
Q1 Medicine Pub Date : 2019-10-21 DOI: 10.1177/0022034519877392
L. Tabak, E. Green, S. Devaney, M. Somerman
Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease—including the human genome, microbiome, epigenome, proteome, and others.
基因组学、数据科学和生物技术的空前进步开创了医疗保健的新时代,在这个时代,干预措施越来越适合个体患者。基于精确性的方法扩展到口腔健康,这对整体健康至关重要。充分利用精准口腔健康的潜力将取决于研究,以更全面地了解健康的基础和导致疾病的因素,包括人类基因组、微生物组、表观基因组、蛋白质组等。
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引用次数: 4
Looking Back and Ahead: The Food and Drug Administration's Regulation of the Tobacco Industry and Next-Generation Products. 回顾和展望:美国食品药品监督管理局对烟草行业和下一代产品的监管。
Q1 Medicine Pub Date : 2019-10-01 DOI: 10.1177/0022034519872472
M Jacob

Regulatory policy toward tobacco significantly affects oral health because tobacco use is a driver of diseases that manifest themselves in or near the oral cavity. Tobacco use in the United States has been associated with millions of cases of periodontal disease. Researchers have identified the role of combusted and noncombusted tobacco products in promoting cancers of the head and neck, leading to disease and premature death. Tobacco companies have moved increasingly toward so-called next-generation products (NGPs)-products that may emit fewer toxins than combustible forms of tobacco. Although NGPs may negatively affect the lungs and other bodily systems, they shift the injection site of nicotine from the lungs to the oral cavity and oral tissues. Because the long-term effects of NGPs are unknown, this tobacco marketing development has profound implications for oral disease. The US Food and Drug Administration exercises regulatory authority over tobacco products. The tobacco industry has avoided meaningful regulation of its products, especially smokeless forms. By publishing new research, oral health scientists can meaningfully shape the climate in which the administration's policy making occurs.

烟草监管政策严重影响口腔健康,因为烟草使用是口腔内或口腔附近疾病的驱动因素。在美国,吸烟与数百万例牙周病有关。研究人员已经确定了燃烧和未燃烧的烟草制品在促进头颈癌、导致疾病和过早死亡方面的作用。烟草公司越来越多地转向所谓的下一代产品(NGP),这种产品可能比可燃形式的烟草排放更少的毒素。尽管NGPs可能会对肺部和其他身体系统产生负面影响,但它们会将尼古丁的注射部位从肺部转移到口腔和口腔组织。由于NGP的长期影响尚不清楚,这一烟草营销发展对口腔疾病有着深远的影响。美国食品和药物管理局对烟草产品行使监管权。烟草业一直避免对其产品进行有意义的监管,尤其是无烟产品。通过发表新的研究,口腔健康科学家可以有意义地塑造政府政策制定的环境。
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引用次数: 0
Oral Health Effects of Combusted and Smokeless Tobacco Products. 燃烧和无烟烟草制品对口腔健康的影响
Q1 Medicine Pub Date : 2019-10-01 DOI: 10.1177/0022034519872480
S L Tomar, S S Hecht, I Jaspers, R L Gregory, I Stepanov

The oral cavity is usually the first part of a consumer's body exposed to the constituents of tobacco products or their emissions. Consequently, the oral cavity is a frequent site for carcinogenic, microbial, immunologic, and clinical effects of tobacco use. This article summarizes 5 presentations on various aspects of oral health affected by combusted or noncombusted tobacco products from a recent conference, "Oral Health Effects of Tobacco Products: Science and Regulatory Policy," sponsored by the American Association for Dental Research and the Food and Drug Administration.

口腔通常是消费者身体接触烟草产品成分或其排放物的第一部分。因此,口腔是烟草使用致癌、微生物、免疫和临床影响的常见部位。这篇文章总结了由美国牙科研究协会和食品药品监督管理局主办的最近一次会议“烟草制品对口腔健康的影响:科学与监管政策”中关于燃烧或未燃烧烟草制品对牙齿健康影响的各个方面的5篇演讲。
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引用次数: 0
In Vitro Models, Standards, and Experimental Methods for Tobacco Products 烟草制品的体外模型、标准和实验方法
Q1 Medicine Pub Date : 2019-09-20 DOI: 10.1177/0022034519872474
Tara Aghaloo, J. J. Kim, T. Gordon, H. P. Behrsing
Traditional tobacco products have well-known systemic and local oral effects, including inflammation, vasoconstriction, delayed wound healing, and increased severity of periodontal disease. Specifically in the oral cavity and the lung, cigarette smoking produces cancer, increased infectivity, acute and chronic inflammation, changes in gene expression in epithelial lining cells, and microbiome changes. In recent years, cigarette smoking has greatly decreased in the United States, but the use of new tobacco products has gained tremendous popularity. Without significant knowledge of the oral sequelae of products such as electronic cigarettes, researchers must evaluate current in vitro and in vivo methods to study these agents, as well as develop new tools to adequately study their effects. Some in vitro testing has been performed for electronic cigarettes, including toxicologic models and assays, but these mostly study the effect on the respiratory tract. Recently, direct exposure of the aerosol to in vitro 3-dimensional tissue constructs has been performed, demonstrating changes in cell viability and inflammatory cytokines. For in vivo studies, a universal e-cigarette testing machine or standard vaping regime is needed. A standard research electronic cigarette has recently been developed by the National Institute of Drug Abuse, and other devices delivering aerosols with different nicotine concentrations are becoming available. One of the biggest challenges in this research is keeping up with the new products and the rapidly changing technologies in the industry.
传统烟草制品具有众所周知的全身和局部口腔作用,包括炎症、血管收缩、伤口愈合延迟和牙周病严重程度增加。特别是在口腔和肺部,吸烟会导致癌症、传染性增加、急性和慢性炎症、上皮衬里细胞基因表达的变化以及微生物组的变化。近年来,吸烟在美国大大减少,但新烟草产品的使用却大受欢迎。在对电子烟等产品的口腔后遗症缺乏深入了解的情况下,研究人员必须评估目前研究这些药物的体外和体内方法,并开发新的工具来充分研究其效果。已经对电子烟进行了一些体外测试,包括毒理学模型和分析,但这些测试主要研究对呼吸道的影响。最近,已经将气溶胶直接暴露于体外三维组织构建体,证明了细胞活力和炎性细胞因子的变化。对于体内研究,需要一台通用的电子烟测试机或标准的电子烟制度。美国国家药物滥用研究所最近开发了一种标准的研究电子烟,其他输送不同尼古丁浓度气溶胶的设备也开始出现。这项研究的最大挑战之一是跟上行业中新产品和快速变化的技术。
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引用次数: 8
Oral Health Effects of Tobacco Products: Science and Regulatory Policy 烟草制品对口腔健康的影响:科学与监管政策
Q1 Medicine Pub Date : 2019-09-20 DOI: 10.1177/0022034519872481
Scott L. Tomar
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引用次数: 2
Novel Nicotine Delivery Systems 新型尼古丁传递系统
Q1 Medicine Pub Date : 2019-09-20 DOI: 10.1177/0022034519872475
Purnima S. Kumar, P. Clark, M. Brinkman, D. Saxena
Electronic nicotine delivery systems (ENDS) are devices that contain a power source, a heating element, and a tank or cartridge containing an “e-liquid,” which is a mixture of nicotine and flavoring in a glycerol–propylene glycol vehicle. Their increasing popularity among adolescents might be attributed to aggressive marketing in physical venues, social media outlets, as well as irreversible changes caused by nicotine in the developing brains of youth and young adults, predisposing them to addictive behaviors. Adolescent ENDS users were 4 times more likely to initiate cigarette smoking, and the odds of quitting smoking were lower and, in many instances, delayed for those using ENDS. ENDS also renormalize cigarette-like behaviors, such as inhaling/exhaling smoke. The oral cavity is the initial point of contact of ENDS and the first affected system in humans. Oral health depends on an intricate balance in the interactions between oral bacteria and the human immune system, and dysbiosis of oral microbial communities underlies the etiology of periodontitis, caries, and oral cancer. Emerging evidence from subjects with periodontitis as well as periodontally healthy subjects demonstrates that e-cigarette use is associated with a compositional and functional shift in the oral microbiome, with an increase in opportunistic pathogens and virulence traits.
电子尼古丁输送系统(ENDS)是一种包含电源、加热元件和含有“电子液体”的容器或药筒的设备,“电子液体”是甘油-丙二醇载体中尼古丁和调味剂的混合物。它们在青少年中越来越受欢迎,可能是由于实体场所和社交媒体的积极营销,以及尼古丁在青少年和年轻人发育中的大脑中引起的不可逆转的变化,使他们容易上瘾。使用电子烟终端的青少年开始吸烟的可能性是使用电子烟终端的青少年的4倍,戒烟的几率较低,在许多情况下,戒烟延迟。ENDS还使类似香烟的行为重新正常化,例如吸入/呼出烟雾。口腔是ENDS的最初接触点,也是人类第一个受影响的系统。口腔健康依赖于口腔细菌和人体免疫系统之间相互作用的复杂平衡,而口腔微生物群落的生态失调是牙周炎、龋齿和口腔癌病因的基础。来自牙周炎患者和牙周健康受试者的新证据表明,电子烟的使用与口腔微生物组的组成和功能变化有关,并伴有机会性病原体和毒力特征的增加。
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引用次数: 24
期刊
Advances in Dental Research
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