The impact of salivary lactoperoxidase and histatin-5 on early childhood caries severity in relation to nutritional status

IntroductionEarly childhood caries is a multifactorial disease. Saliva plays an important role in initiation and protection against caries, and its composition is greatly affected by nutritional status. This study was conducted to determine the impact of salivary lactoperoxidase and histatin-5 on the severity of ECC in relation to nutritional status.Materials and methodsThe sample consisted of 120 children aged 5 years, classified into eight groups: mild ECC in underweight children, mild ECC in normalweight children, moderate ECC in underweight children, moderate in ECC normal weight children, severe ECC in underweight children, severe ECC in normalweight, caries-free (control) underweight children and caries-free normalweight children. Each group consisted of 15 children. Stimulated saliva was collected. Salivary lactoperoxidase was analysed using Human LPO/ Lactoperoxidase ELISA Kit (CLIA)-LS-F29892, and salivary histatin-5 was analysed using Human Histatin-5 ELISA Kit MBS705083_48T.ResultsLactoperoxidase and histatin-5 concentrations were significantly higher in caries-free children than in children with ECC, and they were higher in children with mild ECC than in children with moderate ECC or in children with severe ECC. They were significantly higher among children with normal weight than among those who were underweight (p < 0.01). ECC and nutritional status recorded non-significant interactions with both LPO and HST-5 (p > 0.01), but there was significant interaction between these two variables and LPO and HST-5 together (p < 0.01). The Pearson's correlation coefficient test recorded significant negative correlations between ECC severity and both salivary lactoperoxidase and histatin-5 among the eight study groups, whereas significant positive correlations were recorded between BMI values and both salivary lactoperoxidase and histatin-5 among the eight study groups.ConclusionSalivary lactoperoxidase and histatin-5 may be affected by nutritional status, and these two parameters may play an important role in caries prevention at high concentrations. There is interaction between these two parameters and ECC severity and nutrition.     

Assessment of the possible ameliorative effect of curcumin nanoformulation on the submandibular salivary gland of alloxan-induced diabetes in a rat model (Light microscopic and ultrastructural study)

BackgroundNowadays, attention is directed to herbal treatments in an attempt to lessen the adverse effects of diabetes. Nanoformulation of curcumin (NC) was shown to enhance stability and water solubility compared to native curcumin.ObjectiveTo examine the effect of different NC concentrations on the histopathological structure of the submandibular salivary gland of diabetic rats.Methods28 rats were divided equally into 4 groups. Group I: Control group, Group II (diabetic), III (diabetic + nanocurcumin low dose), and IV (diabetic + nanocurcumin high dose): Rats of groups II, III and IV were injected with a single dose of alloxan (140 mg/kg) to induce diabetes. After 7 days, groups III and IV were treated for 6 weeks with NC (100 mg/kg/day) for group III, and (200 mg/kg/day) for group IV. Submandibular salivary glands were assessed histologically, immunohistochemically using α smooth muscle actin (α SMA) and ultrastructurally.ResultsDiabetic samples showed destruction of parenchymal elements of the gland, with thick fiber bundles encircling the excretory ducts and minimal reaction for α SMA. Amelioration of the gland's architecture was detected in groups III and IV with reduction of collagen deposition and elevation of positive immunoreactivity to α SMA.ConclusionNC profoundly repaired the induced diabetic histopathological and ultrastructural alterations of the gland in a dose dependent manner.     

Peri-implantitis and systemic inflammation: A critical update

Peri-implantitis is an inflammatory condition induced by bacterial biofilm that affects the soft and hard tissues surrounding dental implants, compromising the success of implant therapy. Recent studies have highlighted the potential links between peri-implant health and systemic inflammation, including uncontrolled diabetes mellitus, psychological stress, cardiovascular disease, obesity, and infectious diseases such as COVID-19. As an inflammatory disease, peri-implantitis may trigger systemic inflammation by elevating circulating levels of pro-inflammatory cytokines, which could have unknown impacts on overall health. While the relationship between periodontal health and systemic conditions is better understood, the association between peri-implant disease and systemic inflammation remains unclear. Therefore, this comprehensive review aims to summarize the most recent evidence on the relationship between peri-implantitis and systemic inflammation, focusing on biological complications, microbiology, and biomarkers. This review aims to enhance our understanding of the links between peri-implantitis and systemic inflammation and promote further research in this field by discussing the latest insights and clinical implications.     

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.     

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.     

Effects of salivary pH on coating durability of two different aesthetic archwire coatings under a simulated intraoral environment

ObjectivesThis study compared the effects of normal salivary pH, and acidic pH found in patients with poor oral hygiene, on the durability of aesthetic archwire coated with epoxy resin and polytetrafluoroethylene (PTFE).MethodsThe posterior parts of the archwires were sectioned into 20 mm segments (N = 102) and divided among six groups. Four groups were treated with different pH levels and two served as controls. The specimens were immersed in individual test tubes containing 10 ml of artificial saliva adjusted to a pH of 6.75 or 3.5. The tubes were sealed and stored in a 37 °C water bath for 28 days. After 28 days, the specimens were ligated to brackets embedded in an acrylic block and subjected to mechanical stress using an electronic toothbrush for 210 s. The specimens were photographed, and images were measured for coating loss using AutoCAD® software. Surface morphology was observed using a scanning electron microscope (SEM).ResultsSignificant coating loss (p < 0.001) was found in the epoxy resin groups, regardless of pH value, but not in the PTFE groups. The acidic pH caused epoxy resin layer coating loss by twice as much as normal pH. SEM revealed existing manufacturing defects on the as-received epoxy resin coating, whereas the retrieved epoxy resin demonstrated rupture, roughness, and coating loss in multiple locations.SignificanceEpoxy resin coatings demonstrate poor durability in acidic environments. This condition is worsened by the existing manufacturing defects found on as-received archwires. Hence, archwires coated with epoxy resin are not recommended in patients with poor oral hygiene.     

Adipose-derived mesenchymal stem cells promote salivary duct regeneration via a paracrine effect

ObjectivesThe self-regeneration of exocrine tissues, including salivary glands, is limited and their regeneration mechanism has not yet been fully elucidated. Here we identify the role of adipose-derived mesenchymal stem cells (AMSCs) in salivary gland regeneration.MethodsAMSCs expressing mesenchymal stem cell markers were applied to a submandibular gland injury model and the mechanism of salivary gland repair and regeneration was analyzed.ResultsTransplanted green fluorescent protein (GFP)-labeled AMSCs grew tightly together and promoted ductal regeneration in the regenerative nodule, with slight infiltration of nonspecific immune cells. A comprehensive gene analysis through RNA-sequencing revealed increased expression of bone morphogenetic protein (BMP), transforming growth factor (TGF), and Wnt in AMSC-transplanted regenerative nodules. The factors released from AMSCs scavenge hydrogen peroxidase-induced reactive oxygen species (ROS) through Wnt promoter activity in vitro. Furthermore, AMSC-conditioned medium recovered the growth of the hydrogen peroxidase-damaged primordium of the submandibular gland culture ex vivo.ConclusionsThese results suggest that AMSC-released factors scavenge ROS and maintain salivary gland repair and regeneration via paracrine effects. Thus, AMSCs could be a practical and applicable tool for use in salivary gland regeneration.     

Localization of phospholipid-related signal molecules in salivary glands of rodents: A review

BackgroundIn the 1950s, Hokin conducted initial studies on phosphoinositide turnover/cycle in salivary glandular cells. From these studies, the idea emerged that receptor-mediated changes in intramembranous levels of phosphoinositides represent an early step in the stimulus-response pathway. Based on this idea and the general view that knowledge of the exact localization of a given endogenous molecule in cells in situ is important for understanding its functional significance, we have reviewed available information about the localization of several representative phosphoinositide-signaling molecules in the salivary glands in situ in mice.HighlightWe focused on phosphatidylinositol 4-kinase, phosphatidylinositol 4 phosphate 5-kinase α, β, γ, phospholipase Cβ, muscarinic cholinoceptors 1 and 3, diacylglycerol kinase ζ, phospholipase D1 and 2, ADP-ribosylation factor 6 and its exchange factors for Arf6, and cannabinoid receptors. These molecules individually exhibit differential localization in a spatiotemporal manner in the exocrine glands, making it possible to deduce their functional significance, such as their involvement in secretion and cell differentiation.ConclusionAlthough phosphoinositide-signaling molecules whose in situ localization in glandular cells has been clarified are still limited, the obtained information on their localization suggests that their functional significance is more valuable in glandular ducts than in acini. It thus suggests the necessity of greater attention to the ducts in their physio-pharmacological analyses. The purpose of this review is to encourage more in situ localization studies of phosphoinositide-signaling molecules with an aim to further understand their possible involvement in the pathogenesis of salivary gland diseases.     

Vitamin C and eggshell membrane facilitate orthodontic tooth movement and induce histological changes in the periodontal tissue

ObjectivesCollagen remodeling of the periodontal tissue is an important mechanism that involves several biologically active substances to accelerate orthodontic tooth movement. It is known that Vitamin C (VC) enhances collagen production and induces tooth movement. Moreover, the eggshell membrane (ESM) is an integral component of various formulations used to promote wound healing. The purpose of our study was to determine the effects of combined treatment with VC and ESM on periodontal tissues during tooth movement.MethodsNine-week-old male osteogenic disorder Shionogi rats were randomized into four groups: control, VC, ESM, and VC + ESM. The control group was given tap water, and the VC, ESM, and VC + ESM groups were orally administered 0.1% VC solution, 1 wt% ESM solution, and a combination of 0.1 wt% VC and 1 wt% ESM solutions, respectively. A force of 25 or 75 g was applied for 10 days to produce orthodontic tooth movement. Distances of tooth movement were measured on days 3, 7, and 10 of treatment. Histological examination of the periodontal ligament was performed to determine the increase in type I and III collagen levels in response to treatment.ResultsDistances of tooth movement were significantly greater in the VC + ESM group than in the control group. The compression area of the alveolar bone showed increased osteoclastic activity and higher levels of bone resorption in the VC + ESM group. Expression levels of type I and III collagen in the tension area of the alveolar bone were higher in the VC + ESM group than in the control group.ConclusionsThis study revealed that the combined administration of VC and ESM accelerated tooth movement by protecting the periodontal tissue during orthodontic treatment. The combined clinical application of VC and ESM could potentially shorten orthodontic treatment time.     

Efficacy of artificial intelligence in the detection of periodontal bone loss and classification of periodontal diseases: A systematic review

BackgroundArtificial intelligence (AI) can aid in the diagnosis and treatment planning of periodontal disease by means of reducing subjectivity. This systematic review aimed to evaluate the efficacy of AI models in detecting radiographic periodontal bone loss (PBL) and accuracy in classifying lesions.Types of Studies ReviewedThe authors conducted an electronic search of PubMed, Scopus, and Web of Science for articles published through August 2022. Articles evaluating the efficacy of AI in determining PBL were included. The authors assessed the articles using the Quality Assessment for Studies of Diagnostic Accuracy tool. They used the Grading of Recommendations Assessment, Development and Evaluation criteria to evaluate the certainty of evidence.ResultsOf the 13 articles identified through electronic search, 6 studies met the inclusion criteria, using a variety of AI algorithms and different modalities, including panoramic and intraoral radiographs. Sensitivity, specificity, accuracy, and pixel accuracy were the outcomes measured. Although some studies found no substantial difference between AI and dental clinicians’ performance, others showed AI’s superiority in detecting PBL. Evidence suggests that AI has the potential to aid in the detection of PBL and classification of periodontal diseases. However, further research is needed to standardize AI algorithms and validate their clinical usefulness.Practical ImplicationsAlthough the use of AI may offer some benefits in the detection and classification of periodontal diseases, the low level of evidence and the inconsistent performance of AI algorithms suggest that caution should be exercised when considering the use of AI models in diagnosing PBL. This review was registered at PROSPERO (CRD42022364600).     

Sclerostin and its role as a bone modifying agent in periodontal disease

BackgroundPeriodontitis is a highly prevalent inflammatory disease affecting the periodontium that results from an imbalance between periodontopathogens and host mechanisms. Continuous progression of the disease may lead to tissue and bone destruction, eventually resulting in tooth loss. The extent of bone loss depends on the dysregulated host immune response. Various host-elicited molecules play a major role in disease progression. The discovery of the glycoprotein sclerostin and its role as a regulator of bone mass has led to a better understanding of bone metabolism.HighlightSclerostin, which is primarily expressed by osteocytes, is a negative regulator of bone formation. It is a potent antagonist of the canonical Wingless-related integration site (Wnt) pathway, which is actively involved in bone homeostasis. Sclerostin is known to stimulate bone resorption by altering the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa- β ligand (RANKL) balance. Additionally, in periodontitis, activation of the inflammatory cascade also increases the synthesis of sclerostin.ConclusionThe recently discovered sclerostin antibody has emerged as a positive therapeutic tool for the treatment of metabolic bone diseases. It has been reported to improve bone strength, bone formation, osseointegration around implants and lower the risk of bone fractures in various animal and human models. This review describes the properties and action of sclerostin, its role in periodontal diseases, and the advent and efficacy of sclerostin antibodies.     

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.     

A Ser252Trp substitution in mouse FGFR2 results in hyperplasia of embryonic salivary gland parenchyma

ObjectivesMutations in the fibroblast growth factor receptor 2 (FGFR2) gene are responsible for several severe forms of craniosynostotic disorders, such as Apert and Crouzon syndromes. Patients with craniosynostotic disorders caused by a mutation in Fgfr2 present with several clinical symptoms, including hypersalivation. Here we used a transgenic mouse model of Apert syndrome (Fgfr2^+/S252W mice) to evaluate the morphology of the submandibular glands at embryonic day 15.5 (E15.5), the time point reported to mark the start of lumen formation.MethodsFgfr2^+/S252W mice were generated by crossing ACTB-Cre^+/+ and Fgfr2^+/Neo-S252W mice. After measuring body weight, the submandibular glands were collected at E15.5. H&E staining, immunostaining, and RT-qPCR were performed to investigate the development of the submandibular gland.ResultsThe number of ducts and acini in Fgfr2^+/S252W mice was significantly higher than in control littermates; however, lumen formation was not affected. The mRNA expression of Fgf1, Fgfr1, Mmp2, Bmp4, Bmp7, Dusp6, and Etv5 in Fgfr2^+/S252W mice was significantly higher compared to control littermates. Immunoreactivity for FGF3, FGF1, BMP4, and F4/80 was detected in the parenchyma of Fgfr2^+/S252W mice. The area of apoptotic cells stained with TUNEL in Fgfr2^+/S252W mice was significantly larger than that of the control littermates.ConclusionsThese results suggested that increased FGFR1 signaling and apoptosis in the submandibular glands of Fgfr2^+/S252W mice occurred at E15.5, leading to parenchymal hyperplasia. This study demonstrated that a Ser252Trp substitution in mouse FGFR2 resulted in hyperplasia of the submandibular gland parenchyma during development.     

Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice

ObjectivesSjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.MethodsSubmandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.ResultsMyd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)-regulated genes.ConclusionsMyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation.     

Effect of being overweight and obese on periodontal treatment costs

BackgroundObesity can increase a person’s risk of developing periodontal disease, and patients with obesity have greater health care costs. However, the effect of obesity on periodontal treatment costs has not been examined.MethodsThis retrospective cohort study used data from the electronic dental records of adult patients examined from July 1, 2010, through July 31, 2019 at a US dental school. Primary exposure was body mass index, which was categorized as obese, overweight, or normal. Periodontal disease was categorized using clinical probing measures. Fee schedules and procedure codes were used to compute the primary outcome, which was total periodontal treatment costs. A generalized linear model with gamma distribution was used to examine the relationship between body mass index and periodontal costs after controlling for initial periodontal disease severity and other confounding variables. Parameter coefficients and mean ratios with 95% CIs were estimated.ResultsThe study sample included 3,443 adults, of whom 39% were normal weight, 37% were overweight, and 24% were obese. Mean (SD) total periodontal treatment costs for patients who were obese were considerably higher ($420 [$719]) than those for patients who were overweight ($402 [$761]) and patients who were normal weight ($268 [$601]). After controlling for covariates and disease severity, patients who were obese had 27% higher periodontal treatment costs than patients who were normal weight. The additional periodontal treatment costs attributable to obesity were greater than those attributable to either diabetes or smoking.ConclusionsThe study results suggest that among patients at a dental school, those who were obese incurred substantially higher periodontal treatment costs than patients who were normal weight, independent of initial periodontal disease severity.Practical ImplicationsThe study findings have important implications for clinical guidelines and dental benefit design and coverage policies.     

Risk of postoperative bleeding following dental extractions in patients on antithrombotic treatment

IntroductionThe risk of bleeding after dental extractions in patients taking antithrombotic medication is not well known. This study aims to investigate the incidence of postoperative bleeding following dental extractions in adult patients taking antithrombotic medication in Saudi Arabia.MethodsThis retrospective study included 539 patients aged 18–93 years who attended 840 appointments for dental extractions from January 2012 to June 2016 at a tertiary care hospital in Saudi Arabia. Patients who returned with a complaint of bleeding were treated with local hemostatic measures as outpatients.Results and Conclusion: Only 1.7% of extraction appointments were associated with postoperative bleeding. The highest risk of bleeding was noted in patients receiving warfarin (3.88%), whereas those on clopidogrel had no significant risk of bleeding. Women were found to have the highest rate of bleeding, particularly those on newer oral anticoagulant medications.Dental extractions can be safely done in adults receiving antithrombotic treatment, provided established guidelines are followed; therefore, dental professionals must exercise caution when planning invasive dental treatment for patients on continued antithrombotic therapy.