Background
The global burden of periodontal diseases remains high. Population growth trends, changes in risk factors and improved tooth retention will increase the socio‐economic burden of ...periodontitis that is responsible for 3.5 million years lived with disability, 54 billion USD/year in lost productivity and a major portion of the 442 billion USD/year cost for oral diseases.
Methods
In the context of the Milan World Exhibition 2015 “Feeding the Planet, Energy for Life,” a green paper was developed and offered for global consultation by the European Federation of Periodontology. The final draft was endorsed by professional organizations around the world and is presented to stakeholders as a call for global action.
Results
Specific actions for the public, policymakers, educators and professional organizations have been identified in the areas of prevention, detection and care. These actions align public interest and knowledge, need for self‐care, professional intervention and policies to the best scientific evidence to proactively promote periodontal health and effectively manage the global burden of periodontal diseases, in accordance with WHO/UN priorities and strategies for tackling common non‐communicable diseases via the Common Risk Factor Approach.
Conclusions
A strong and coherent body of evidence allows identification of actionable preventive, diagnostic and therapeutic strategies to effectively promote periodontal health and general wellbeing, and better manage the socio‐economic consequences. Action requires consideration of the specific national scenarios.
SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality
. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use ...as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC
= 0.69 µM) and DNA-unwinding (IC
= 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.
Microbial persisters are the featured tiny sub-population of microorganisms that are highly tolerant to multiple antimicrobials. Currently, studies on persisters remain a considerable challenge owing ...to technical limitations. Here, we explored the application of single-cell Raman spectroscopy (SCRS) in the investigation of persisters.
Escherichia coli
(ATCC 25922) cells were treated with a lethal dosage of ampicillin (100 μg/mL, 32 × MIC, 4 h) for the formation of persisters. The biochemical characters of
E. coli
and its persisters were assessed by SCRS, and their metabolic activities were labeled and measured with D
2
O-based single-cell Raman spectroscopy (D
2
O-Ramanometry). Notable differences in the intensity of Raman bands related to major cellular components and metabolites were observed between
E. coli
and its ampicillin-treated persisters. Based on their distinct Raman spectra,
E. coli
and its persister cells were classified into different projective zones through the principal component analysis and t-distributed stochastic neighbor embedding. According to the D
2
O absorption rate,
E. coli
persisters exhibited higher metabolic activities than those of untreated
E. coli
. Importantly, after the termination of ampicillin exposure, these persister cells showed a temporal pattern of D
2
O intake that was distinct from non-persister cells. To our knowledge, this is the first report on identifying
E. coli
persisters and assessing their metabolic activities through the integrated SCRS and D
2
O-Ramanometry approach. These novel findings enhance our understanding of the phenotypes and functionalities of microbial persister cells. Further investigations could be extended to other pathogens by disclosing microbial pathogenicity mechanisms for developing novel therapeutic strategies and approaches.
Background
A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly ...prevalent and often associated with hypersensitivity, the development of caries and non‐carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations.
Methods
Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants.
Results
Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon‐Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm‐induced inflammation (such as neoplastic diseases); 2) diabetes‐associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking – now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues – is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non‐carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm‐induced gingival inflammation and loss of periodontal supporting tissues.
Conclusion
An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented.
Background
A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly ...prevalent and often associated with hypersensitivity, the development of caries and non‐carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations.
Methods
Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants.
Results
Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon‐Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm‐induced inflammation (such as neoplastic diseases); 2) diabetes‐associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking – now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues – is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non‐carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm‐induced gingival inflammation and loss of periodontal supporting tissues.
Conclusion
An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented.
Securing an adequate blood supply for the survival of cell transplants is critical for a successful outcome in tissue engineering. Interactions between endothelial and progenitor/stem cells are ...important for vascularization of regenerating tissue. Recently, self-assembling peptide nanofibers were described as a promising environment for pulp regeneration due to their synthetic nature and controlled physicochemical properties. In this study, the peptide hydrogel PuraMatrix™ was used as a scaffold system to investigate the role of dental pulp stem cells (DPSCs) in triggering angiogenesis and the potential for regenerating vascularized pulp in vivo. Human umbilical vein endothelial cells (HUVECs), DPSCs, or cocultures of both cell types were encapsulated in three-dimensional PuraMatrix. The peptide nanofiber microenvironment supported cell survival, cell migration, and capillary network formation in the absence of exogenous growth factors. DPSCs increased early vascular network formation by facilitating the migration of HUVECs and by increasing vascular endothelial growth factor (VEGF) expression. Both the DPSC-monoculture and coculture groups exhibited vascularized pulp-like tissue with patches of osteodentin after transplantation in mice. The cocultured groups exhibited more extracellular matrix, vascularization, and mineralization than the DPSC-monocultures in vivo. The DPSCs play a critical role in initial angiogenesis, whereas coordinated efforts by the HUVECs and DPSCs are required to achieve a balance between extracellular matrix deposition and mineralization. The findings of this study also highlighted the importance of a microenvironment that supports cell-cell interactions and cell migration, which contribute to successful dental pulp regeneration.
Dental caries (tooth decay) is an infectious disease. Its etiology is not fully understood from the microbiological perspective. This study characterizes the diversity of microbial flora in the ...saliva of children with and without dental caries. Children (3-4 years old) with caries (
= 20) and without caries (
= 20) were recruited. Unstimulated saliva (2 mL) was collected from each child and the total microbial genomic DNA was extracted. DNA amplicons of the V3-V4 hypervariable region of the bacterial 16S rRNA gene were generated and subjected to Illumina Miseq sequencing. A total of 17 phyla, 26 classes, 40 orders, 80 families, 151 genera, and 310 bacterial species were represented in the saliva samples. There was no significant difference in the microbiome diversity between caries-affected and caries-free children (
> 0.05). The relative abundance of several species (
,
,
sp.
,
, and
) was higher in the caries-affected group than in the caries-free group (
< 0.05).
and
sp.
were more abundant in caries-free children than in caries-affected children (
< 0.05). The salivary microbiome profiles of caries-free and caries-affected children were similar. Salivary counts of certain bacteria such as
and
may be useful for screening/assessing children's risk of developing caries.
Background
Periodontal disease closely links to various systemic diseases. This l8‐year retrospective cohort study investigated whether poor periodontal condition may increase the risk for onset of ...systemic comorbidities.
Methods
A total of 488 individual dental folders from 17 400 dental hospital attendees registered from 1996 to 1998 were randomly selected, and these participants were free of diabetes, cardiovascular disease, chronic obstructive pulmonary disease, cancer, stroke, cognitive impairment, hypertension, and dyslipidemia in the Clinical Management System. The records of periodontal examination and orthopantomogram on the first registration were obtained, and full‐mouth bone level (BL) was measured. Onsets of the eight comorbidities concerned above until 2016 were retrieved from the system.
Results
The participants with worse periodontal status on their first registration had significantly higher numbers of the eight comorbidities/mortality during the 18‐year follow‐ups than their counterparts (P < 0.05). BL presented as bone loss/age was independently correlated to the comorbidity profiles in two multivariate models (0 to 1 versus ≥2; 0 to 2 versus ≥3) after adjusting for age and sex (odds ratio OR = 1.87; OR = 2.18, P < 0.05), highlighting that the individuals with more bone resorption exhibited a greater number of the comorbidities as compared with their counterparts. Moreover, those with onsets of more comorbidities showed worse periodontal conditions according to four parameters employed (community periodontal index, BL, bone loss/age and number of remaining teeth) (P < 0.05).
Conclusions
Within the limitations of this 18‐year retrospective cohort study, our findings provide the first evidence that periodontal disease experience to some extent reflects the host susceptibility to onset of common systemic comorbidities. Further studies with larger sample sizes and appropriate adjustment of critical confounders are highly warranted to substantiate the current observation.
Abstract Introduction Scaffolds often fail to mimic essential functions of the physiologic extracellular matrix (ECM) that regulates cell-cell communication in tissue microenvironments. The ...development of scaffold-free microtissues containing stem cell–derived ECM may serve as a successful alternative to the use of artificial scaffolds. The current study aimed to fabricate 3-dimensional microtissue spheroids of dental pulp cells (DPCs) prevascularized by human umbilical vein endothelial cells (HUVECs) and to characterize these scaffold-free spheroids for the in vitro formation of pulplike tissue constructs. Methods Three-dimensional microtissue spheroids of DPC alone and DPC-HUVEC co-cultures were fabricated using agarose micro-molds. Cellular organization within the spheroids and cell viability (live/dead assay) were assessed at days 1, 7, and 14. Microtissue spheroids were allowed to self-assemble into macrotissues, induced for odontogenic differentiation (21 days), and examined for expression levels of osteo/odontogenic markers: alkaline phosphatase, bone sialoprotein and RUNX2 (Real-time PCR), mineralization (von-Kossa), and prevascularisation (immunohistochemistry for CD31). Results The DPC microtissue microenvironment supported HUVEC survival and capillary network formation in the absence of a scaffolding material and external angiogenic stimulation. Immunohistochemical staining for CD31 showed the capillary network formed by HUVECs did sustain—for a prolonged period—even after the microtissues transformed into a macrotissue. Induced, prevascularized macrotissues showed enhanced differentiation capacity compared with DPC alone macrotissues, as shown by higher osteo/odontogenic gene expression levels and mineralization. Conclusions These findings provide insight into the complex intercellular cross talk occurring between DPCs and HUVECs in the context of angiogenesis and pulp regeneration and highlight the significance of developing a favorable 3-dimensional microenvironment that can, in turn, contribute toward successful pulp regeneration strategies.
Abstract Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. ...The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells. Additionally, shear stress upregulated osteoprotegerin expression in osteocytes, downregulated the effect of IL-17A on RANKL and TNF-α expression, and attenuated IL-17A-activated osteoclastic differentiation in the co-culture system of MLO-Y4 and BMM cells. Furthermore, we explored the signaling pathways that potentially mediate these effects in osteocytes, and found that the extracellular signal-regulated kinase (ERK)1/2 and signal transducer and activator of transcription (STAT3) pathways were suppressed by IL-17A but induced by fluid flow. EphA2 signaling enhances osteoclastogenesis in osteocytes, and the intercellular reversed EphA2-ephrinA2 signaling from osteocytes to BMM play an important role in IL-17A-dependent osteoclastic differentiation. EphB4 signaling inhibits osteoclastogenesis in osteocytes, and the intercellular reversed EphB4-ephrinB2 signaling from osteocytes to BMM could inhibit IL-17A-dependent osteoclastic differentiation. The current findings suggest that IL-17A as a promoter of bone resorption and fluid shear stress critically regulate bone remodeling via osteocyte-specific signaling pathways. IL-17 modulation-based approaches may be developed as a novel therapeutic strategy for enhancing bone remodeling efficiency and stability.
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