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  • 1.

    【2hr】Changes in Caries Risk in a Practice-Based Randomized ControlledTrial

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    机译 在基于实践的随机对照中龋齿风险的变化试用版
    摘要：To demonstrate that Caries Management by Risk Assessment (CAMBRA) can be successfully implemented in dental practice, 30 dentists were recruited to perform a 2-y CAMBRA trial. Twenty-one dentists (18 private practices, 3 community clinics) participated in a randomized, controlled, parallel-arm, double-blind clinical trial with individual-level assignment of 460 participants to standard of care (control) versus active CAMBRA treatment (intervention). Control or active antimicrobial and remineralizing agents were dispensed at baseline and 6-, 12-, 18-, and 24-mo recall visits according to risk level and assigned treatment arm. Primary outcome measure was dentist-determined caries risk level at recall. Among initially high-risk participants, secondary outcomes were recorded disease indicators. Generalized estimating equations were used to fit log-linear models for each outcome while accounting for repeated measurements. At 24 mo, follow-up rates were 34.3% for high-risk participants (32.1% intervention, 37.1% control) and 44.2% for low-risk participants (38.7% intervention, 49.5% control). Among 242 participants classified as high caries risk at baseline (137 intervention, 105 control), a lower percentage of participants remained at high risk in the intervention group (statistically significant at all time points). At 24 mo, 25% in the intervention group and 54% in the control group remained at high risk (P = 0.003). Among 192participants initially classified as low risk (93 intervention, 99 control), mostparticipants remained at low risk. At 24 mo, 89% in the intervention group and 71% in thecontrol group were low caries risk (P = 0.18). Thepercentage of initially high-risk participants with recorded disease indicators decreasedover time in both intervention and control groups, being always lower for the interventiongroup (statistically significant at the 12- and 18-mo time point). In this practice-basedclinical trial, a significantly greater percentage of high-caries-risk participants wereclassified at a lower risk level after CAMBRA preventive therapies were provided. Mostparticipants initially assessed at low caries risk stayed at low risk (ClinicalTrials.gov).
  • 2.

    【2hr】Rebalancing the Caries Microbiome Dysbiosis: Targeted Treatment and Sugar Alcohols

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    机译 重新平衡龋齿微生物组的营养不良：靶向治疗和糖醇
    • 作者：L. Zhan
    • 刊名：Advances in Dental Research
    • 2018年第1期
    摘要：Dental caries is a disease that results from microbiome dysbiosis with the involvement of multiple cariogenic species, including mutans streptococci (MS), lactobacilli, Scardovia wiggsiae, and several Actinomyces species that have the cariogenic traits of acid production and acid tolerance. Sugar consumption also plays an important role interacting with microbiome dysbiosis, determining the fate of caries development. In addition, the MS transmission that encompasses multiple sources can have long-term impacts on the oral microbiome and caries development in children. Intervention in MS transmission in early childhood may promote effective long-term caries prevention. Anticaries regimens aimed against the above mechanisms will be important for successful caries management. Xylitol and erythritol may serve as good components of anticaries regimens as oral microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in early childhood with both oral and systemic benefits. Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol and erythritol with consideration of their impacts on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health. On the other hand, the anticaries agent C16G2, specifically targeting Streptococcus mutans, the most common cariogenic bacterial species, has shown good safety for short-term oral topical use and promising effects in reducing S. mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future study on its anticaries effect will need to include its long-term impact on the oral microbiome and effects on other important cariogenic bacteria.
  • 3.

    【2hr】Fluoride Use in Health Care Settings: Association with Children’s Caries Risk

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    机译 在医疗机构中使用氟化物：与儿童龋齿风险相关
    摘要：Expanded partnership with the medical community is an important strategy for reducing dental caries disparities. The purpose of this study was to assess the relationship between fluoride (F) “in office” (drops/tablets and/or varnish), as prescribed or applied by a health care professional by age 1 y, and 1) caries development and 2) presence of other caries risk factors or mediators (e.g., socioeconomic status). Child–primary caregiver (PCG) pairs (N = 1,325) were recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort study to validate a caries risk tool for primary health care settings. PCGs completed a caries risk questionnaire, while children received caries examinations per the criteria of the International Caries Detection and Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding children’s history of F in office were tested for association with other caries risk variables and caries experience at ages 2.5 and 4 y via generalized estimating equation models applied to logistic regression. The sample was 48% female, and many children (61%) were Medicaid enrolled. The prevalence of cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y. Children who received F in office were likely deemed at higher caries risk and indeed were significantly (P < 0.01) more likely to develop cavitated caries lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3, respectively). Factors significantly associated with receiving F included the following: child being Medicaid enrolled, not having an employed adult in the household, child and PCG often consuming sugary drinks and snacks, and PCG having recent caries experience. Increased F in office from a health care provider by age 1 y was associated with known caries risk factors. Most (69%) children had never been to the dentist, suggesting that risk factors could be alerting medical providers and/or parents, thereby affecting in-office F recommendations. Differences among states could also be related to state-specific F-varnish reimbursement policies (ClinicalTrials.gov ).
  • 4.

    【2hr】Getting to Know “The Known Unknowns”: Heterogeneity in the OralMicrobiome

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    机译 认识“已知的未知数”：口腔中的异质性微生物组
    • 作者：R.A. Burne
    • 刊名：Advances in Dental Research
    • 2018年第1期
    摘要：Technological advances in DNA sequencing have provided unprecedented insights into the composition of the oral microbiome in health and disease, and RNA-sequencing and metabolomics-related technologies are beginning to yield information on the activities of these organisms. Importantly, progress in this area has brought the scientific community closer to an understanding of what constitutes a health-associated microbiome and is supporting the notion that the microbiota in healthy sites assumes an active role in promoting health and suppressing the acquisition, persistence, and activities of overt and opportunistic pathogens. It is also becoming clear that a significant impediment to developing a conclusive body of evidence that defines a healthy microbiome and the mechanisms by which beneficial bacteria promote health is that an inherent characteristic of the most abundant members of the oral flora, those that potentially play the greatest roles in health and disease, is intraspecies genomic diversity. In particular, individual isolates of abundant commensal and pathogenic streptococci show tremendous variability in gene content, and this variability manifests in tremendous phenotypic heterogeneity. Analysis of the consequences of this diversity has been complicated by the exquisite sensitivity these bacteria have evolved to environmental inputs, inducing rapid and substantial fluctuations in behaviors, and often only within subpopulations of theorganisms. Thus, the conditions under which the oral microbiota is studied can producewidely different results within and between species. Fortunately, continually diminishingcosts and ongoing refinements in sequencing and metabolomics are making it practical tostudy the oral microbiome at a level that will create a sufficiently robust understandingof the functions of individual organisms and reveal the complex interrelationships ofthese microbes (“the known unknowns”) in a way that researchers will be able to engage inthe rational design of reliable and economical risk assessments and preventivetherapies.
  • 5.

    【2hr】Silver Fluoride as a Treatment for Dental Caries

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    机译 氟化银治疗龋齿
    • 作者：J.A. Horst
    • 刊名：Advances in Dental Research
    • 2018年第1期
    摘要：Medical management of caries is a distinct treatment philosophy that employs topical minimally invasive therapies that treat the disease and is not merely prevention. This strategy is justified as an alternative or supplement to traditional care by significant disease recurrence rates following comprehensive operative treatment under general anesthesia. Silver diamine fluoride (SDF) is one agent to enable effective noninvasive treatment. The announcement of breakthrough therapy designation by the Food and Drug Administration (FDA) suggests that SDF may become the first FDA-approved drug for treating caries. Since our systematic review performed in April 2015, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety in young children, start patients with high disease severity on an intensive regimen of multiple applications over the first few weeks, and continue with semiannual maintenance doses as previously suggested. Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome inform potential opportunities for understanding caries arrest. SDF can be added to the set of evidence-based noninvasive methods to treat caries lesions in primary teeth, such as the Hall crown technique and sealing lesions with accessible margins.
  • 6.

    【2hr】The Evidence for Caries Management by Risk Assessment (CAMBRA®)

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    机译 通过风险评估（CAMBRA®）进行龋齿管理的证据
    摘要：A system for Caries Management by Risk Assessment (CAMBRA®) has been developed in California. The purpose of this article is to summarize the science behind the methodology, the history of the development of CAMBRA, and the outcomes of clinical application. The CAMBRA caries risk assessment (CRA) tool for ages 6 y through adult has been used at the University of California, San Francisco (UCSF), for 14 y, and outcome studies involving thousands of patients have been conducted. Three outcomes assessments, each on different patient cohorts, demonstrated a clear relationship between CAMBRA-CRA risk levels of low, moderate, high, and extreme with cavitation or lesions into dentin (by radiograph) at follow-up. This validated risk prediction tool has been updated with time and is now routinely used at UCSF and in other settings worldwide as part of normal clinical practice. The CAMBRA-CRA tool for 0- to 5-y-olds has demonstrated similar predictive validity and is in routine use. The addition of chemical therapy (antibacterial plus fluoride) to the traditional restorative treatment plan, based on caries risk status, has been shown to reduce the caries increment by about 20% to 38% in high-caries-risk adult patients. The chemical therapy used for high-risk patients is a combination of daily antibacterial therapy (0.12% w/v chlorhexidine gluconate mouth rinse) and twice-daily high-concentration fluoride toothpaste (5,000 ppm F), both for home use. These outcomes assessments provide the evidence to use these CRA tools with confidence. Caries can be managed by adding chemical therapy, based on the assessed caries risk level, coupled with necessary restorative procedures. For high- and extreme-risk patients, a combination of antibacterial and fluoride therapy is necessary. The fluoride therapy must be supplemented by antibacterial therapy to reduce the bacterial challenge, modify the biofilm, and provide prevention rather than continued caries progression.
  • 7.

    【2hr】Therapeutic Strategies Targeting Cariogenic Biofilm Microenvironment

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    机译 针对致癌生物膜微环境的治疗策略
    摘要：Cariogenic biofilms are highly structured microbial communities embedded in an extracellular matrix, a multifunctional scaffold that is essential for the existence of the biofilm lifestyle and full expression of virulence. The extracellular matrix provides the physical and biological properties that enhance biofilm adhesion and cohesion, as well as create a diffusion-modulating milieu, protecting the resident microbes and facilitating the formation of localized acidic pH niches. These biochemical properties pose significant challenges for the development of effective antibiofilm therapeutics to control dental caries. Conventional approaches focusing solely on antimicrobial activity or enhancing remineralization may not achieve maximal efficacy within the complex biofilm microenvironment. Recent approaches disrupting the biofilm microbial community and the microenvironment have emerged, including specific targeting of cariogenic pathogens, modulation of biofilm pH, and synergistic combination of bacterial killing and matrix degradation. Furthermore, new “smart” nanotechnologies that trigger drug release or activation in response to acidic pH are being developed that could enhance the efficacy of current and prospective chemical modalities. Therapeutic strategies that can locally disrupt the pathogenic niche by targeting the biofilm structure and its microenvironment to eliminate the embedded microorganism and facilitate the action of remineralizing agents may lead to enhanced and precise anticaries approaches.
  • 8.

    【2hr】Potential Uses of Arginine in Dentistry

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    机译 牙科中精氨酸的潜在用途
    • 作者：M.M. Nascimento
    • 刊名：Advances in Dental Research
    • 2018年第1期
    摘要：Carious lesions develop in tooth surfaces where there is an imbalance of the processes of acid and alkali production by supragingival biofilms. Since low pH is the main driving factor in the development of carious lesions, most efforts to identify an effective anticaries therapy have focused on targeting the acid-producing bacteria and their mechanisms of acid production. An expanding area of oral microbiology has now been devoted to explore microbial metabolic activities that help to neutralize biofilm pH and thus inhibit the caries process. Arginine metabolism via the arginine deiminase pathway (ADS) produces alkali in the form of ammonia that counteracts the effects of biofilm acidification from bacterial glycolysis. ADS also functions as an adaptive strategy used by certain bacteria to thrive in oral biofilms. Substantial evidence accumulated from laboratory and clinical observations supports the hypotheses that measurements of arginine metabolism via ADS may serve as an important caries risk assessment criterion and that providing arginine regularly to supragingival biofilms can be an effective therapy for caries intervention. This article reviews the potential of arginine-based therapies such as the use of arginine as prebiotic, ADS+ strains as probiotics, and oral care formulations containing arginine for prevention and management of dental caries.
  • 9.

    【2hr】Implant Surface Design Regulates Mesenchymal Stem Cell Differentiation and Maturation

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    机译 植入物表面设计调节间充质干细胞的分化和成熟
    摘要：Changes in dental implant materials, structural design, and surface properties can all affect biological response. While bulk properties are important for mechanical stability of the implant, surface design ultimately contributes to osseointegration. This article reviews the surface parameters of dental implant materials that contribute to improved cell response and osseointegration. In particular, we focus on how surface design affects mesenchymal cell response and differentiation into the osteoblast lineage. Surface roughness has been largely studied at the microscale, but recent studies have highlighted the importance of hierarchical micron/submicron/nanosurface roughness, as well as surface roughness in combination with surface wettability. Integrins are transmembrane receptors that recognize changes in the surface and mediate downstream signaling pathways. Specifically, the noncanonical Wnt5a pathway has been implicated in osteoblastic differentiation of cells on titanium implant surfaces. However, much remains to be elucidated. Only recently have studies been conducted on the differences in biological response to implants based on sex, age, and clinical factors; these all point toward differences that advocate for patient-specific implant design. Finally, challenges in implant surface characterization must be addressed to optimize and compare data across studies. An understanding of both the science and the biology of the materials is crucial for developing novel dental implant materials and surface modifications for improved osseointegration.
  • 10.

    【2hr】Oral Mucosal Expression of HIV-1 Receptors, Co-receptors, and α-defensins: Tableau of Resistance or Susceptibility to HIV Infection?

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    机译 HIV-1受体，共受体和α-防御素的口腔粘膜表达：对HIV感染的抗药性或敏感性的表象？
    摘要：
  • 11.

    【2hr】Alveolar Bone Loss: Mechanisms, Potential Therapeutic Targets, andInterventions

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    机译 牙槽骨丢失：机制，潜在的治疗目标和干预措施
    摘要：This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to peri-odontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca2+ oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone andperiodontal regeneration. The existence of craniofacial bone-specific SSCs is suggestedbased on existing studies. The effects of calcium, vitamin D, and soy isoflavonesupplementation on alveolar and skeletal bone loss in post-menopausal women wereinvestigated. Supplementation resulted in stabilization of forearm bone mass density and areduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontalattachment levels were also well-maintained and alveolar bone loss suppressed during 24 wkof supplementation.
  • 12.

    【2hr】Novel Inflammatory Pathways in Periodontitis

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    机译 牙周炎的新型炎症途径
    摘要：New insights into the biological mechanisms involved in modulating periodontal inflammation and alveolar bone loss are paving the way for novel therapeutic strategies for periodontitis. The neutrophil adhesion cascade for transmigration in response to infection or inflammation is a key paradigm in immunity. Developmental endothelial locus-1 (Del-1) is one of several newly identified endogenous inhibitors of the leukocyte adhesion cascade. Del-1 competes with intercellular adhesion mole-cule-1 (ICAM-1) on endothelial cells for binding to the LFA-1 integrin on neutrophils, thereby regulating neutrophil recruitment and local inflammation. In animal periodontitis models, Del-1 deficiency resulted in severe inflammation and alveolar bone loss, but local treatment with recombinant Del-1 prevented neutrophil infiltration and bone loss. The expression of Del-1 is inhibited by the pro-inflammatory cytokine IL-17. Nucleic-acid-receptor-mediated inflammatory responses may be important in periodontal disease pathogenesis. Bacterial nucleic acids released during inflammation are detected by host microbial DNA sensors, e.g., Toll-like receptor-9 (TLR-9), leading to the activation of pro- and/or anti-inflammatory signaling pathways. DNA from periodontitis-associated bacteria induced pro-inflammatory cytokine production in human macrophage-like cells through the TLR-9 and NF-κB signaling pathways, but had less effect on human osteoblasts. Inhibition of TLR-9signaling in human macrophages reduced cytokine production in response to P. gingivalis DNA. Differential expression of a polymorphic sitein the TLR-9 gene promoter region and increased TLR-9 gene and protein expression werereported in chronic periodontitis. Further research to confirm that periodontal bacterialDNA contributes to destructive inflammation in vivo couldprovide alternative therapeutic targets to control periodontitis.
  • 13.

    【2hr】Saliva-Microbe Interactions and Salivary Gland Dysfunction

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    机译 唾液-微生物相互作用与唾液腺功能障碍
    摘要：Adequate salivary secretion is crucial to both oral and general health, since it provides a complex milieu for support of the microbial populations of the mouth, while at the same time containing antimicrobial products that help control these microbial populations. This paper summarizes several aspects of salivary component function, gland secretion mechanisms, and immuno-pathogenesis as related to oral health and disease. Salivary components mediate microbial attachment to oral surfaces, and also interact with planktonic microbial surfaces to facilitate agglutination and elimination of pathogens from the oral cavity. Adhesive interactions are often mediated by lectin-like bacterial proteins that bind to glycan motifs on salivary glycoproteins. An important salivary antimicrobial protein is histatin 5 (Hst 5), which shows potent and selective antifungal activity and also susceptibility to proteolytic degradation. Coupling of Hst 5 with the carrier molecule spermidine significantly enhanced killing of C. albicans and resistance to proteolytic degradation, compared with the parent peptide. Loss of salivary secretion may be caused by disorders such as Sjögren's syndrome (SS) or ectodermal dysplasia, or may be a side-effect of radiation therapy. Two new approaches to the treatment of salivary gland dysfunction include the use of resolvins and the creation of differentiated acinar structures to construct an artificial salivarygland. B-cells contribute to the pathogenesis of SS by releasing cytokines andautoantibodies and by influencing T-cell differentiation. CXCL13, a potent B-cellchemokine associated with autoimmune diseases, is elevated locally and systemically in SSand may represent a novel biomarker or therapeutic target in the management and treatmentof SS.
  • 14.

    【2hr】Recent Advances in Host Defense Mechanisms/ Therapies against Oral InfectiousDiseases and Consequences for Systemic Disease

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    机译 针对口腔感染的宿主防御机制/疗法的最新进展疾病和系统性疾病的后果
    摘要：The innate and adaptive immune systems are both crucial to oral disease mechanisms and their impact on systemic health status. Greater understanding of these interrelationships will yield opportunities to identify new therapeutic targets to modulate disease processes and/or increase host resistance to infectious or inflammatory insult. The topics addressed reflect the latest advances in our knowledge of the role of innate and adaptive immune systems and inflammatory mechanisms in infectious diseases affecting the oral cavity, including periodontitis and candidiasis. In addition, several potential links with systemic inflammatory conditions, such as cardiovascular disease, are explored. The findings elucidate some of the defense mechanisms utilized by host tissues, including the role of IL-17 in providing immunity to oral candidiasis, the antimicrobial defense of mucosal epithelial cells, and the pro-resolution effects of the natural inflammatory regulators, proresolvins and lipoxins. They also describe the role of immune cells in mediating pathologic bone resorption in periodontal disease. These insights highlight the potential for therapeutic benefit of immunomodulatory interventions that bolster or modulate host defense mechanisms in both oral and systemic disease. Among the promising new therapeutic approaches discussed here are epithelial cell gene therapy, passive immunization against immune cell targets, and the use of proresolvin agents.
  • 15.

    【2hr】Genetic Characteristics and Pathogenic Mechanisms of PeriodontalPathogens

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    机译 牙周病的遗传特征及致病机理病原体
    摘要：Periodontal disease is caused by a group of bacteria that utilize a variety of strategies and molecular mechanisms to evade or overcome host defenses. Recent research has uncovered new evidence illuminating interesting aspects of the virulence of these bacteria and their genomic variability. This paper summarizes some of the strategies utilized by the major species–Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis – implicated in the pathogenesis of periodontal disease. Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has revealed variations in their genetic content (ranging between 0.4% and 19.5%) and organization. Strikingly, isolates from human periodontal sites showed no genomic changes during persistent colonization. T. forsythia manipulates the cytokine responses of macrophages and monocytes through its surface glycosylation. Studies have revealed that bacterial surface-expressed O-linked glycans modulate T-cell responses during periodontal inflammation. Periodontal pathogens belonging to the “red complex” consortium express neuraminidases, which enables them to scavenge sialic acid from host glycoconjugates. Analysis of recent data has demonstrated that the cleavedsialic acid acts as an important nutrient for bacterial growth and a moleculefor the decoration of bacteria surfaces to help evade the host immune attack. Inaddition, bacterial entry into host cells is also an important prerequisite forthe lifestyle of periodontal pathogens such as P.gingivalis. Studies have shown that, after its entry into the cell,this bacterium uses multiple sorting pathways destined for autophagy, lysosomes,or recycling pathways. In addition, P. gingivalisreleases outer membrane vesicles which enter cells via endocytosis and cause cellular functional impairment.
  • 16.

    【2hr】Outside-the-(Cavity-prep)-Box Thinking

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    机译 腔外思维
    摘要：Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application.
  • 17.

    【2hr】Targeted Antimicrobial Treatment to Re-establish a Healthy Microbial Flora for Long-term Protection

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    机译 靶向抗菌治疗可重建健康的微生物区系，以提供长期保护
    摘要：Streptococcus mutans has been implicated as the major acid-producing (cariogenic) bacterium. Dietary sugars and other factors may cause an imbalance of oral microflora that enables S. mutans to become dominant in the multi-species biofilms on the tooth surface, which could lead to dental caries. The application of broad-spectrum antimicrobials often results in re-colonization and re-dominance of S. mutans within oral flora, while in contrast, therapies capable of selective elimination of S. mutans from oral microbial communities may help to re-establish the normal flora and provide long-term protection. C16G2, a novel synthetic antimicrobial peptide with specificity for S. mutans, was found to have robust killing efficacy and selectivity for S. mutans in vitro. A subsequent pilot human study found that a single application of C16G2 in the oral cavity (formulated in a mouthrinse vehicle) was associated with a reduction in plaque and salivary S. mutans, lactic acid production, and enamel demineralization during the entire 4-day testing period. C16G2 is now being developed as a new anticaries drug.
  • 18.

    【2hr】Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries

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    机译 用于开发可预防龋齿的药物的战略蛋白质靶点分析
    摘要：Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.
  • 19.

    【2hr】Progress Dissecting the Oral Microbiome in Caries and Health

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    机译 剖析龋齿与健康中口腔微生物组的研究进展
    摘要：Recent rapid advances in “-omics” technologies have yielded new insights into the interaction of the oral microbiome with its host. Associations of species that are usually considered to be acid-tolerant with caries have been confirmed, while some recognized as health-associated are often present in greater proportions in the absence of caries. In addition, some newly identified bacteria have been suggested as potential contributors to the caries process. In spite of this progress, two major challenges remain. The first is that there is a great deal of heterogeneity in the phenotypic capabilities of individual species of oral bacteria. The second is that the most abundant taxa in oral biofilms display remarkable phenotypic plasticity, i.e., the bacteria associated most strongly with health or with caries can morph rapidly in response to alterations in environmental pH, carbohydrate availability and source, and oxygen tension and redox environment. However, new technologic advances coupled with “old-fashioned microbiology” are starting to erode the barriers to a more complete understanding of oral biofilm physiology and ecology, and in doing so are beginning to provide insights for the creation of novel cost-effective caries control therapies.
  • 20.

    【2hr】Fluoride Plus Functionalized β-TCP

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    机译 氟化物加功能化β-TCP
    摘要：With more than 50 years of clinical success, fluoride serves as the gold standard agent for preventing tooth decay. In particular, the action of fluoride facilitates saliva-driven remineralization of demineralized enamel and alters solubility beneficially. Still, tooth decay remains problematic, and one way to address it may be through the development of new mineralizing agents. Laboratory and clinical studies have demonstrated that the combination of fluoride and functionalized β-tricalcium phosphate (fTCP) produces stronger, more acid-resistant mineral relative to fluoride, native β-TCP, or fTCP alone. In contrast to other calcium-based approaches that seem to rely on high levels of calcium and phosphate to drive remineralization, fTCP is a low-dose system designed to fit within existing topical fluoride preparations. The functionalization of β-TCP with organic and/or inorganic molecules provides a barrier that prevents premature fluoride-calcium interactions and aids in mineralization when applied via common preparations and procedures. While additional clinical studies are warranted, supplementing with fTCP to enhance fluoride-based nucleation activity, with subsequent remineralization driven by dietary and salivary calcium and phosphate, appears to be a promising approach.
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