The use of propolis in dentistry,oral health,and medicine: A review

BackgroundPropolis is a resinous product that is collected from plants by bees to cover holes and crevices in their hives. Propolis has potent antibacterial, antiviral, anti-inflammatory, wound healing, and anticancer properties. Propolis has been used therapeutically by humans for centuries, including the treatment of dental caries and mouth infections.HighlightThis review article attempts to analyze the potential use of propolis in general dentistry and oral health management.ConclusionPropolis is potentially useful in dentistry and oral health management based on available in vitro, in vivo, and ex vivo studies, as well as human clinical trials.     

An in vitro study of the effects of Phellodendron bark extract and berberine chloride on periodontal pathogenic bacteria in the oral microbiome

ObjectivesPeriodontal disease is triggered by oral microbiome dysbiosis. Thus, to prevent its onset, it is important to maintain relative abundance of periodontal pathogenic bacteria in the oral microbiome at a low level. While Phellodendron bark extract (PBE) and its active ingredient, berberine, exert antibacterial effects on periodontal pathogenic bacteria, such as Porphyromonas gingivalis, their effects on the oral microbiome as a whole remain unknown. Therefore, we aimed to clarify the potential of PBE and berberine chloride (BC) in regulating the relative abundance of periodontal pathogenic bacteria in the oral microbiome.MethodsSaliva was collected from 20 participants. Each participant's saliva was combined separately with P. gingivalis suspension and either PBE or BC in a modified basal medium. The samples were then incubated under anaerobic conditions for 24 h. After cultivation, we determined the total bacterial concentration using quantitative polymerase chain reaction analysis and the bacterial composition using 16 S ribosomal RNA gene sequencing.ResultsThe total bacterial concentration was reduced because of treatment with PBE and BC. Bacterial 16 S ribosomal RNA gene sequencing confirmed that treatment with PBE and BC significantly reduced the relative abundance of periodontal pathogenic bacteria, including red and orange complex bacteria.ConclusionsOur findings suggest that PBE and BC reduce the relative abundance of periodontal pathogenic bacteria in the oral microbiome. Thus, PBE and BC can aid in preventing periodontal disease, given their ability to regulate the oral microbiome composition and their anti-inflammatory effects.     

The role of sugar-rich diet and salivary proteins in dental plaque formation and oral health

BackgroundDental plaque is a complex colorless film of bacteria that develops on the surfaces of teeth. Different mechanisms of microbial adhesion to tooth surfaces exist. Both non-specific and specific types of adherence have been anticipated.HighlightThe present review evaluated the effect of sugar-rich diet and salivary proteins on oral hygiene and dental plaque development.ConclusionThe oral microbiota is essential for maintaining and reestablishing a healthy oral cavity. Different types of sugars have different effects on the inhibition and formation of dental plaque. The peptides, proteins, and amino acids secreted by parotid glands in the oral cavity facilitate neutralizing the acidity in dental plaque and preventing dental caries. A properly balanced diet is crucial for both a healthy oral cavity and the oral microbiome.     

Toward the use of Boesenbergia rotunda extracts and the chalcone panduratin A to treat periodontitis

Novel affordable medications are needed to treat chronic periodontitis, which is one of the most common dental pathologies worldwide. Extracts prepared from the rhizome of the medicinal plant Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot, are used to treat a variety of human pathologies. These extracts contain potent anti-inflammatory compounds, including the chalcone derivative panduratin A (Pa-A), which is the lead compound of a series of analogues, designated panduratins A to Y. The anti-inflammatory properties of the extracts of B. rotunda and the most abundant bioactive products found in these extracts (including Pa-A, 4-hydroxyoanduratin, isopanduratin, and others) have been reviewed. A standardized extract of the plant has promising utility in the treatment of gingival inflammation. The effects are characterized by three actions: (i) a direct antimicrobial effect against fungi and oral pathogens such as Porphyromonas gingivalis, (ii) a marked anti-inflammatory effect via a reduced production of mediators, like prostaglandin E2 and different interleukins, and (iii) a dual bone-preserving effect, with a reduction in bone resorption and an increase in bone formation. Acting as a protease inhibitor, Pa-A is one of the main active ingredients of the extract, implicated in these actions. A Pa-A-standardized extract of B. rotunda has been used in humans for treating dyspepsia. The product is safe and well-tolerated. The development of panduratin-containing dental products, for the prevention and treatment of periodontitis, has been proposed. The structural analogues, Pa-A to-Y, should also be investigated for the treatment of dental inflammation.     

Nanotechnology-based therapies for the prevention and treatment of Streptococcus mutans-derived dental caries

BackgroundDental caries results from long-term acid production when sugar is metabolized by a bacterial biofilm, resulting in a loss of calcium and phosphate from the enamel. Streptococcus mutans is a type of acid-producing bacteria and a virulent contributor to oral biofilms. Conventional treatment options, such as cefazolin and ampicillin, have significant levels of bacterial resistance. Other topical agents, such as fluoride, tend to be washed away by saliva, resulting in low therapeutic efficacy.HighlightThis review aims to highlight the solubility issues that plague poorly water-soluble therapeutic agents, various novel polymeric, and lipid-based nanotechnology systems that aim to improve the retention of therapeutic agents in the oral cavity.ConclusionIn this review, different formulation types demonstrated improved therapeutic outcomes by enhancing drug solubility, promoting penetration into the deep layers of the biofilm, facilitating prolonged residence time in the buccal cavity, and reducing the emergence of drug-resistant phenotypes. These formulations have a strong potential to give new life to therapeutic agents that have limited physicochemical characteristics.     

Oral commensal bacterial flora is responsible for peripheral differentiation of neutrophils in the oral mucosa in the steady state

ObjectivesCommensal bacteria in the host body play a fundamental role in the differentiation and maintenance of the immune system. Studies on intestinal immunity have revealed that, under steady-state conditions, microflora have an important role in the maintenance of health. However, the role of oral commensal bacteria on the oral immune system is still unclear. Here, we clarify the interactions between commensal bacteria and the oral mucosal immune system under steady-state conditions.MethodsWe used germ-free mice that had never been exposed to bacteria and conventional mice grown with normal bacterial flora. Oral cells were isolated from the oral mucosa, stained with specific antibodies, and analyzed by flow cytometry. For the detection of myeloperoxidase and intracellular cytokines, oral cells were stimulated with N-formyl-methionine-leucyl-phenylalanine and phorbol 12-myristate 13-acetate/ionomycin, respectively.ResultsWe found that the oral mucosa harbored more neutrophils in germ-free mice than in conventional mice. However, the majority of neutrophils in the germ-free oral mucosa exhibited an immature phenotype. Other immune cells, including macrophages, T cells, and B cells, in the oral mucosa of germ-free mice showed similar differentiation to those in conventional mice. These results indicate that in the steady-state oral mucosa, the normal commensal flora promote the peripheral differentiation of neutrophils.ConclusionsThe presence of commensal flora is critical for the development of adequate immune system in the oral mucosa.     

Dental restorative materials containing quaternary ammonium compounds have sustained antibacterial action

BackgroundThis narrative review addresses dental restorative materials with sustained antibacterial action, especially those containing quaternary ammonium compounds. Secondary caries occurs around restorations, causing further loss of mineral and breakdown of the restoration. Lesions adjacent to restorations account for more than 40% of needed restorations. Restorative materials with antibacterial properties will potentially solve this problem.Types of Studies ReviewedSeveral groups are researching composite restorative materials that incorporate antibacterial agents. These agents are mostly exhausted over time. Newer studies involve materials that incorporate antibacterial microparticles that remain active and do not leach out.ResultsOne such antibacterial agent, quaternary ammonium coupled with inorganic silica into minute particles (QASi), has been studied in the laboratory and in humans. QASi particles incorporated into dental materials retain their antibacterial action over time without leaching or loss of activity. A clinical in situ study in humans using dental composite containing QASi resulted in highly significantly less demineralization in the adjacent enamel than the control composite material.Conclusions and Practical ImplicationsDental restorative materials that contain QASi have sustained antibacterial properties, have mechanical properties comparable to those of presently marketed materials, and have been cleared by the US Food and Drug Administration. Clinical studies have shown that composites incorporating QASi have the potential to markedly reduce the occurrence of caries around restorations. Because caries around restorations is a major problem, restorative materials with sustained antibacterial properties will have an important effect in reducing secondary caries around restorations.     

Fabrication of calcium phosphate composite polymer/SLS-stabilized emulsion-based bioactive gels and their application for dentine tubule occlusion

ObjectivesCalcium phosphate/SLS/P123 composite bioactive gels were prepared to achieve dentine tubule occlusion.MethodsGels containing calcium phosphate particles were prepared in a water-in-oil microemulsion system with a mixture of triblock copolymer pluronic (P123) as a co-surfactant and sodium lauryl sulfate (SLS) as a surfactant in cyclohexane. Subsequently, calcium chloride dihydrate and sodium hydrogen phosphate aqueous solutions were added in a water phase. Finally, slow evaporation of the oil phase at room temperature was performed to produce a hybrid gel. The obtained gels were investigated for their toxicity by the sulforhodamine B (SRB) assay and applied on human dentine specimens to examine their ability to occlude dentine tubules.ResultsThe size and morphology of the calcium phosphate particles embedded in the gel depended on the concentration of P123 and SLS, which were used as a template for mineral precipitation. The prepared calcium phosphate particles (200–500 nm in diameter) with the maximum polymer and surfactant content exhibited spherical shapes. Further, on reducing their content twice and tenfold yields micro-particles with flower-like shapes. These bioactive gels were able to occlude into dentine tubules after 3 days of application with a plugging rate of 79.22% when using the smallest particles. In addition, calcium phosphate nanorods were transformed into dentine tubules with a maximum depth of 6 μm on increasing the amount of gel.ConclusionsThe bioactive gels were effectively used as bioactive fillers to occlude exposed human dentine tubules.     

Amixicile depletes the ex vivo periodontal microbiome of anaerobic bacteria

ObjectivesAlthough periodontal diseases result from overgrowth of anaerobic bacteria, the effect of a specific knockdown of anaerobes on the disease outcome has yet to be examined. We have reported that amixicile, a non-toxic, readily bioavailable, and novel antimicrobial, specifically targets selected oral anaerobes through inhibition of the activity of pyruvate ferredoxin oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate.MethodsHere, we generated an ex vivo microbiome derived from gingival pockets of human subjects with chronic periodontal disease and evaluated the efficacy of amixicile in generating a specific knockdown of anaerobic bacteria present in the microbiome.ResultsOur bioinformatics analysis identified PFOR-like coding capacity in over 100 genomes available from the HOMD database. Many of those bacteria were present in our ex vivo microbiome. Significantly, the anaerobic pathogens relying on PFOR for energy generation were specifically reduced in abundance following treatment with amixicile while non-PFOR bacteria were spared. Specifically, Prevotella, Veillonella, Slackia, Porphyromonas, Treponema, Megasphera, and Atobium were reduced in abundance. Such treatment resulted in the conversion of a microbiome resembling a microbiome derived from sites with periodontal disease to one resembling a microbiome present at healthy sites. We also compared the inhibitory spectrum of amixicile to that of metronidazole and showed that the antibiotics have a similar inhibitory spectrum.ConclusionsThis work further demonstrates that amixicile has the potential to reverse and prevent the outgrowth of anaerobic pathogens observed in subjects with periodontal disease.     

Pathophysiological association between periodontal disease and Alzheimer's disease: Importance of periodontal health in the elderly

BackgroundAs the global aging population is rapidly advancing, recognizing the full potential of periodontal disease (PD) in the onset or progression of Alzheimer's disease (AD) is important for reducing geriatric morbidity. This review explores the possible role of PD in the pathogenesis of AD, as the pathological mechanisms underlying AD are the most well-studied among all types of dementia. The investigation was conducted using the electronic academic databases PubMed and ScienceDirect, employing a combination of keywords “periodontal disease,” “periodontitis,” “Alzheimer's disease,” “dementia,” and “Porphyromonas gingivalis.” After applying the selection and eligibility criteria and removing overlaps, from an initial search finding of 5933 studies, 11 were finally included for qualitative analysis.HighlightThe inflammatory reaction induced by oral pathogenic bacteria related to PD, through complex pathways, may exacerbate inflammation in the central nervous system, thereby contributing to the progression of AD.ConclusionMaintenance of adequate oral hygiene in patients diagnosed with AD is significant because they suffer from a gradual loss of manual dexterity as the disease advances. Additionally, the evidence presents the potential of systemic inflammation from PD-induced pathogenic bacteria, illustrating the grave cyclical progression of AD.     

Screening testing in health care: Getting it right

BackgroundThere is a movement to engage oral health care professionals in administering tests to identify people at risk of developing contagious diseases and other medical conditions. The purpose of this overview was to provide clinicians with fundamental concepts to understand how to evaluate a screening test’s capability to give a correct result and its implications for practice (health outcomes).Types of Studies ReviewedThe authors reviewed epidemiologic and statistical articles addressing the purpose of performing screening tests for medical conditions with a special emphasis on understanding and interpreting test results on the basis of specific test characteristics.ResultsTests with different sensitivities and specificities will provide different probabilities of correctly classifying people with or without a disease of interest. By understanding how to interpret tests results and how to communicate the consequences (that is, impact on health outcomes) of positive and negative test results, oral health care professionals will be able to generate appropriate medical referrals and determine the need for further testing, as well as provide a public service.Conclusions and Practical ImplicationsAn understanding by oral health care professionals of how to interpret screening test results will benefit their patients substantially and, in the case of contagious diseases, the public at large.     

The pediatric dental workforce in 2016 and beyond

BackgroundChildhood caries is a major oral and general health problem, particularly in certain populations. In this study, the authors aimed to evaluate the adequacy of the supply of pediatric dentists.MethodsThe authors collected baseline practice information from 2,546 pediatric dentists through an online survey (39.1% response rate) in 2017. The authors used a workforce simulation model by using data from the survey and other sources to produce estimates under several scenarios to anticipate future supply and demand for pediatric dentists.ResultsIf production of new pediatric dentists and use and delivery of oral health care continue at current rates, the pediatric dentist supply will increase by 4,030 full-time equivalent (FTE) dentists by 2030, whereas demand will increase by 140 FTE dentists by 2030. Supply growth was higher under hypothetical scenarios with an increased number of graduates (4,690 FTEs) and delayed retirement (4,320 FTEs). If children who are underserved experience greater access to care or if pediatric dentists provide a larger portion of services for children, demand could grow by 2,100 FTE dentists or by 10,470 FTE dentists, respectively.ConclusionsThe study results suggest that the supply of pediatric dentists is growing more rapidly than is the demand. Growth in demand could increase if pediatric dentists captured a larger share of pediatric dental services or if children who are underserved had oral health care use patterns similar to those of the population with fewer access barriers.Practical ImplicationsIt is important to encourage policy changes to reduce barriers to accessing oral health care, to continue pediatric dentists’ participation with Medicaid programs, and to urge early dental services for children.     

Impact of antibiotic prophylaxis on the incidence,nature, magnitude,and duration of bacteremia associated with dental procedures: A systematic review

BackgroundAntibiotic prophylaxis (AP) is used routinely in high-risk groups of patients to reduce bacteremia and the risk of developing infective endocarditis (IE). In this systematic review, the authors evaluated the efficacy of AP on the incidence, nature, magnitude, and duration of post-dental procedure bacteremia.MethodsThe authors conducted a systematic search of the literature using MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to and including May 2019. They included randomized clinical trials in which researchers compared antibiotics with a placebo or no treatment (as the control). They undertook random-effects meta-analyses to evaluate the incidence of bacteremia after dental procedures.ResultsThe authors included 12 studies in the review. The studies evaluated the incidence of bacteremia after AP with American Heart Association (AHA) protocol antibiotics (amoxicillin, clindamycin, cephalosporin, and azithromycin) or non-AHA protocol antibiotics (moxifloxacin and intravenous [IV] amoxicillin-clavulanic acid). The pooled analysis revealed that antibiotics significantly reduced the bacteremia incidence, but their effectiveness was moderate (risk ratio, 0.50; 95% confidence interval, 0.38 to 0.67). IV amoxicillin-clavulanic acid promoted a considerable reduction in bacteremia. However, in patients with penicillin allergies, antibiotics (that is, clindamycin and cephalosporin) had lower efficacy.Practical ImplicationsOral amoxicillin is still the antibiotic of choice to reduce bacteremia. IV amoxicillin-clavulanic acid could be used for patients at high risk of developing IE who require invasive dental procedures, have high levels of dental infection, and are to be treated under general anesthesia. In patients with penicillin allergies, oral azithromycin showed a higher efficacy for the reduction of bacteremia and the use of clindamycin should be reviewed. Antibiotic premedication should be limited to patients at high risk of developing IE, according to the indications of the AHA guide.     

Effect of vitamin E on periodontitis: Evidence and proposed mechanisms of action

BackgroundPeriodontitis is a noncommunicable inflammatory disease of the soft tissue and bone surrounding the teeth in the jaw, which affects susceptible individuals with poor oral hygiene. A growing interest has been seen in the use of dietary supplements and natural products for the treatment and prevention of periodontitis. Vitamin E consists of two major groups, namely tocopherols and tocotrienols, which are botanical lipophilic compounds with excellent anti-inflammatory and antioxidant properties.HighlightThis review aimed to summarize the preclinical and clinical findings on the effects of vitamin E on periodontitis. The current literature suggests that vitamin E could improve the periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing, thus highlighting the potential of vitamin E in the management of periodontitis.ConclusionDirect evidence for the use of vitamin E supplementation or treatment of periodontitis in humans is still limited. More well-designed and controlled studies are required to ascertain its effectiveness.     

Role of interleukin-1 and inflammasomes in oral disease

BackgroundInflammation promotes immune cell infiltration into tissues and induces production of pro-inflammatory cytokines that mediate innate immune responses. Acute or temporary inflammation results in the required repair of the inflamed tissues. However, chronic inflammation leads to pathogenesis of inflammatory conditions such as periodontal disease. In periodontal tissues, pro-inflammatory cytokines mediate inflammatory responses and accelerate the bone-resorbing activity of osteoclasts, resulting in destruction of alveolar bone. Levels of interleukin-1 (IL-1), a major pro-inflammatory cytokine that strongly promotes osteoclastic activity, are elevated in oral tissues of patients with periodontitis. Therefore, elucidation of the mechanisms underlying IL-1 production will enhance our understanding of the pathogenesis of periodontal disease.HighlightIL-1 has two isoforms: IL-1α and IL-1β. Both isoforms bind to the same IL-1 receptor and have identical biological activity. Unlike that of IL-1α, the IL-1β precursor is not bioactive. To induce its bioactivity, the IL-1β precursor is cleaved by caspase-1, whose activation is mediated by multiprotein complexes termed inflammasomes. Thus, IL-1β maturation and activity are strictly regulated by inflammasomes. This review highlights the current understanding of the molecular mechanisms underlying IL-1 production and the related inflammasome activity.ConclusionInhibition of IL-1 production or the inflammasomes via their regulatory mechanisms may facilitate prevention or treatment of periodontal disease and other inflammatory diseases.     

Tooth loss in patients with and without diabetes: A large-scale,cross-sectional study of Mexican adults

BackgroundThe objective of this study was to compare the experience and distribution of tooth loss in people with and without diabetes.MethodsThe authors conducted a comparative cross-sectional study of patients at a public university. Analysis included medical records of those treated from 2013 through 2017. The dependent and main independent variables were the number of missing teeth and a diagnosis of diabetes, respectively. As covariables, the authors analyzed the sociodemographic and socioeconomic characteristics, as well as the general and oral health status of patients. A multivariate model based on negative binomial regression was constructed.ResultsOf the 3,406 medical records analyzed, 64.2% (n = 2,185) pertained to women, the mean age was 42.45 years, 87.9% did not have diabetes, and 12.1% had received a diagnosis of diabetes. The mean (standard deviation) number of missing teeth was 7.46 (7.89), 7.09 (7.60) in patients without diabetes, and 10.12 (9.32) in patients with diabetes. According to our final multivariate model, the expected mean number of missing teeth was 11.4% higher in patients with diabetes than in those without (P = .006). For every 1-year increase in age, the expected mean number of missing teeth increased by 3.9% (P < .001). Other variables related to tooth loss included occupation, marital status, and type of insurance.ConclusionsThe results of the study indicate that the mean number of missing teeth is higher in people with diabetes and suggest that certain socioeconomic inequalities exist in the area of oral health.Practical ImplicationsThe population needs to be apprised of the impact of diabetes on oral health.     

Adipokines in dental pulp: Physiological,pathological, and potential therapeutic roles

BackgroundHundreds of adipokines have been identified, and their extensive range of endocrine functions—regulating distant organs such as oral tissues—and local autocrine/paracrine roles have been studied. In dentistry, however, adipokines are poorly known proteins in the dental pulp; few of them have been studied despite their large number. This study reviews recent advances in the investigation of dental-pulp adipokines, with an emphasis on their roles in inflammatory processes and their potential therapeutic applications.HighlightsThe most recently identified adipokines in dental pulp include leptin, adiponectin, resistin, ghrelin, oncostatin, chemerin, and visfatin. They have numerous physiological and pathological functions in the pulp tissue: they are closely related to pulp inflammatory mechanisms and actively participate in cell differentiation, mineralization, angiogenesis, and immune-system modulation.ConclusionAdipokines have potential clinical applications in regenerative endodontics and as biomarkers or targets for the pharmacological management of inflammatory and degenerative processes in dental pulp. A promising direction for the development of new therapies may be the use of agonists/antagonists to modulate the expression of the most studied adipokines.