Salivary levels of azurocidin and soluble azurophilic granules in periodontal disease.

Periodontitis is an infection-driven inflammatory condition of the periodontium. Neutrophils are one of the most important first-line immune cells that protect against pathogen microorganisms in the saliva, but they may also mediate tissue death in inflammatory disorders. The aim of our study was to estimate salivary levels of azurocidin and extracellular azurophilic granules cluster of differentiation (CD63) as biomarkers of neutrophil activation in patients with periodontal diseases and to study the correlation between the levels of these two biomarkers and clinical periodontal parameters. The study included 60 patients with periodontal disease (30 patients with periodontitis and 30 with gingivitis) and 25 healthy controls. The assessed parameters were bleeding on probing, the plaque index, clinical attachment loss, and probing pocket depth. Saliva samples were taken from each study participant, and azurocidin and CD63 levels were measured using ELISA. Azurocidin and CD63 levels were significantly higher in patients with periodontitis and patients with gingivitis than in controls (P < 0.05), and significantly higher in patients with periodontitis than in patients with gingivitis (P < 0.05). Moreover, we found a significant positive correlation between the two biomarkers with clinical attachment loss in the periodontitis group. This study has shown that increased salivary azurocidin and extracellular CD63 levels are associated with enhanced innate response in periodontal disease and can be considered biomarkers of neutrophil activation.

Periodontitis is associated with altered brain structure and function in normal cognition middle-aged and elderly individuals.

BACKGROUND: Numerous studies have proposed that periodontitis is a potential risk factor for Alzheimer's disease. However, the association between periodontitis and brain normal cognition in aged and elderly individuals (NCs) is unclear. Such a link could provide clues to Alzheimer's disease development and strategies for early prevention. OBJECTIVE: To explore the associations between periodontal condition and metrics of both brain structure and function among NCs with the help of multimodal magnetic resonance imaging (MRI). METHODS: High-resolution T1-weighted structural data, resting-state functional-MRI data, and measures of periodontal condition were collected from 40 NCs. Cortical volume, thickness, and area as well as regional homogeneity were calculated with the aid of DPABISurf software. Correlation analyses were then conducted between each imaging metric and periodontal index. RESULTS: Consistent negative correlations were observed between severity of periodontitis (mild, moderate, severe) and cortical volume, area, and thickness, not only in brain regions that took charge of primary function but also in brain regions associated with advanced cognition behavior. Among participants with mild attachment loss (AL) and a shallow periodontal pocket depth (PPD), periodontal index was positively correlated with most measures of brain structure and function, while among participants with severe AL and deep PPD, periodontal index was negatively correlated with measures of brain structure and function (all p < .005 for each hemisphere). CONCLUSIONS: Our results demonstrate that periodontitis is associated with widespread changes in brain structure and function among middle-aged and elderly adults without signs of cognitive decline, which might be a potential risk factor for brain damage.

Co-occurrence of periodontal lesions and dental wear in incisor and masticatory teeth in two sheep flocks in Brazil.

BACKGROUND: Periodontitis and tooth wear are multifactorial diseases with distinct etiopathogenesis that affect the health, feed efficiency and welfare of sheep. METHODS: This study evaluated the co-occurrence of tooth wear and periodontal lesions in 129 ewes from two Brazilian flocks, clinically classified the lesions and presence of dental calculus, and identified potential pathogens in the dental biofilm of 63 ewes by polymerase chain reaction. RESULTS: Of the 129 ewes included in the study, 75 presented periodontal lesions, while all animals presented tooth wear and dental calculus. Of the animals with periodontal lesions, 16.2% had lesions in incisor teeth and 52.7% in masticatory teeth. Regarding excessive tooth wear, 38.6% had severe wear on the incisor teeth and 89.1% on the masticatory teeth. Ewes older than 36 months had a higher frequency of periodontal lesions in incisor teeth (p < 0.001) and a greater amount of dental calculus (p < 0.001), but there was no association between tooth wear and animal age. Fusobacterium nucleatum, Tannerella forsythia and Fusobacterium necrophorum predominated in periodontal lesions. LIMITATION: This study is limited by the small sample size and lack of diagnostic imaging to assess periodontal disease. CONCLUSION: The co-occurrence of periodontal lesions and excessive dental wear involving both the incisor and masticatory teeth suggests that although the two diseases have different aetiologies, they likely have common risk factors.

Comparison of immunoexpression of dendritic cells, mast cells and blood vessels in periodontal disease between adults and elderly.

OBJECTIVE: The aim of this study was to compare, in adults and elderly individuals, the immunoexpression of immature and mature dendritic cells (DCs), mast cells, and blood vessels in healthy and diseased gingival tissues. MATERIALS AND METHODS: The expressions of immunohistochemical markers, including CD1a (immature dendritic cells), CD83 (mature dendritic cells), tryptase (mast cells) and CD34 (blood vessels), were analyzed in gingival biopsies from elderly (n = 27) and adult (n = 127) patients presenting health, gingivitis and periodontitis. Positive cells for each specimen and marker were counted. RESULTS: There were no differences in the immunostaining of DCs, mast cells and the amount of blood vessels among gingival biopsies with health, gingivitis and periodontitis in adult and elderly subjects (p > 0.05). Immature DCs were more frequent in tissues with gingivitis and periodontitis in elderly patients, when compared to adults (p < 0.05). Furthermore, degranulated mast cell counts were higher, whereas the number of microvessels was lower in gingivitis in the elderly, when compared to adults (p < 0.05). CONCLUSIONS: Diseased periodontal sites in the elderly present an overall significant overexpression of immature DCs and degranulated mast cells, in relation to those of adults. Furthermore, gingivitis in elderly is associated with decreased microvessel growth. These immunoinflammatory differences between elderly and adults may have implications in periodontal tissue breakdown in the late adulthood. Further studies should be performed to elucidate this hypothesis. CLINICAL RELEVANCE: Understading the relationship between aging and changes in immune cells during periodontal inflammation may lead to therapeutic targets for the future management of periodontal diseases.

Dental health in Roman dogs: A pilot study using standardized examination methods.

OBJECTIVE: To utilize standardized clinical veterinary methods to analyze dental health in a series of Roman dog maxillae and mandibles and to compare results to modern clinical data. MATERIALS: 28 skulls of juvenile and adult dogs from three archaeological sites in Switzerland and Germany dating to the Roman period. METHODS: Standardized examination was carried out, which included metric radiographic assessment to diagnose oral pathology and estimate age at death. In one case, CT analysis was undertaken. RESULTS: The estimated average age at death was between three and four years old. Tooth fracture, periodontal disease, the presence of non-vital teeth, and brachycephalic skull form were found in the sample. Tooth resorption was unexpectedly noted. CONCLUSION: The study provides valuable insights into the dental health of dogs in the Roman era. Compared to modern dogs, Roman dogs examined in this study appear to have a shorter lifespan but display a high rate of pathological dental disease, while disease patterns were very similar to those of modern dogs. Dogs with pronounced brachycephalic features were found. SIGNIFICANCE: This pilot study is the first to use standardized clinical examination and recording techniques to assess dental health in dogs from archaeological contexts. It provides insight into the dental health of Roman era dogs and offers data upon which cross-populational studies can be initiated. LIMITATIONS: The sample size and geographic location of the archaeological sites were limited. SUGGESTIONS FOR FURTHER RESEARCH: Subsequent standardized studies, preferably in as many different Roman Empire regions as possible, are recommended.

Imbalance of helper T cell subtypes and adipokine secretion in perivascular adipose tissue as a trigger of atherosclerosis in chronic Porphyromonas gingivalis W83 infection.

Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.

An optical fiber-based point-of-care test for periodontal MMP-8 detection: A proof of concept.

OBJECTIVES: The evaluation of salivary biomarkers has been proposed as a simple and non-invasive aid to the conventional periodontal diagnosis based on clinical-radiographic parameters. Matrix metalloproteinase-8 (MMP-8), especially in its active form, is considered one of the most reliable biomarkers of periodontitis, and point-of-care tests (POCTs) have been proposed for its clinical monitoring. In this proof-of-concept study, a novel highly sensitive POCT based on a plastic optical fiber (POF) biosensor exploiting surface plasmon resonance (SPR) to detect salivary MMP-8 is described. METHODS: A SPR-POF biosensor was functionalized with a specific antibody to develop a surface-assembled monolayer (SAM) for the detection of total MMP-8. A white light source and a spectrometer connected to the biosensor were used to quantify MMP-8 level in both buffer and real matrix (saliva) by analysing the shift of the resonance wavelength determined by the specific antigen-antibody binding upon the SAM. RESULTS: Dose-response curves by serial dilutions of human recombinant MMP-8 were realized, obtaining a limit of detection (LOD) of 40 pM (1.76 ng/ml) in buffer and 225 pM (9.9 ng/ml) in saliva and high selectivity compared to interferent analytes (MMP-2 and IL-6). CONCLUSIONS: The proposed optical fiber-based POCT was able to detect and measure total MMP-8 with high selectivity and very low LOD in both buffer and saliva. CLINICAL SIGNIFICANCE: The SPR-POF technology may be employed to create highly sensitive biosensors to monitor salivary MMP-8 levels. The possibility of specifically detecting its active, rather than total, form need to be further investigated. If confirmed and clinically validated, such a device may represent a promising tool to make an immediate, highly sensitive and reliable diagnosis of periodontitis, and to carry out a timely and targeted therapy, possibly helping to prevent the onset of local and systemic periodontitis-related complications.

Insights into the aetiologies of hypercementosis: A systematic review and a scoring system.

OBJECTIVES: This paper aims to better define hypercementosis, investigate its described potential aetiologies, and determine whether there are different patterns of cementum apposition and if they are a function of their supposed aetiology. DESIGN: A literature review was undertaken using the Medline, DOSS, Scopus and Cochrane Library electronic databases. Two co-authors selected the published works independently, extracted the data in accordance with the PRISMA statement. RESULTS: Among 546 articles, 75 articles were finally selected. Eight different supposed aetiologies were identified: (1) intensive masticatory effort, (2) systemic disease, (3) carious lesion and apical periodontitis, (4) impaction, (5) periodontal disease, (6) concrescence, (7) super-eruption, and (8) drugs. Some of these aetiologies can be combined in the same tooth. Hypercementosis manifestations are various in nature and extent with different patterns that may be aetiology-specific. To improve the description and associated consistency in the characterisation of hypercementosis, in this review but also in future studies, we propose a new qualitative scoring system to quickly characterise hypercementosis and determine its most relevant aetiology. CONCLUSIONS: This systematic review demonstrates that hypercementosis is a complex and not yet well-defined condition. Some forms of apposition are specific to a given aetiology. The hypercementosis characterisation may contribute to document the oral condition and/or the individuals masticatory activity.

The Effects of Orthodontic Tooth Movement on Clinical Attachment Level Changes in Treated Periodontitis Adult Patients with Malocclusion: A Systematic Review and Meta-analysis

ABSTRACT Objective: To investigate the effects of orthodontic tooth movement on clinical attachment level (CAL) changes in treated periodontitis in adult patients with malocclusion. Material and Methods: Present study is based on PRISMA guidelines; all articles published in international databases such as PubMed, Scopus, Science Direct, and Embase between 2012 to May 2022 are included. 95% confidence interval (CI) for mean difference with fixed effect modal and inverse-variance were calculated. Data analysis was performed using STATA.V16 software. Results: In the initial review, duplicate studies were eliminated, abstracts of 175 studies were reviewed, two authors reviewed the full text of 21 studies, and finally, eleven studies were selected. The mean of CAL gain was 2.29 mm (MD, 95% CI -2.47 mm, -2.12 mm; p=0.00) (I2=91.81%; p=0.00; high heterogeneity). The mean difference of PPD changes was -1.93 mm (MD, 95% CI -2.07 mm, -1.80 mm; p=0.00) (I2=98.52%; p=0.00; high heterogeneity). Conclusion: Due to the limitations of the study and based on the meta-analysis, it is observed that orthodontic treatment is performed with higher success after reconstructive surgery with periodontal improvement.

[Clinical and morphological picture of chronic tonsillitis and its pathogenetic relationship with periodontal diseases: literature review]. / Kliniko-morfologicheskaya kartina khronicheskogo tonzillita i ego patogeneticheskaya svyaz' s parodontopatiyami: obzor literatury.

The article is devoted to the study of chronic tonsillitis from the point of view of the clinical and morphological picture of the disease, histological changes in the palatine tonsils in various forms of CT. The authors raise the question of studying the assessment of the effect of conservative therapy on the morpho-functional state of the palatine tonsils. The article focuses on the study and influence of extratonsillary oropharyngeal loci of focal infection, such as periodontopathies, on the course of chronic inflammation of the palatine tonsils. The association of periodontitis with CT and various somatic diseases has been demonstrated. The necessity of further study of the cause-and-effect relationships of CT and periodontal diseases, as well as a more in-depth study of the morphological picture in CT using immunohistochemical methods of research, which will allow us to develop new principles for the diagnosis and treatment of this disease, is justified.

[Salivary Metabolic Profiling in Patients with Periodontitis].

Objective: To analyze the salivary metabolic profile of patients with periodontitis through metabolomic techniques and to explore the metabolic patterns associated with periodontal diseases. Methods: Liquid chromatography/mass spectrometry (LC/MS) technique in conjunction with principal component analysis (PCA) analysis and orthogonal partial least squares identification (OPLS-DA) method was used to study the metabolomics of saliva samples from gingivitis patients, periodontitis patients, and healthy controls, with 10 samples for each group. We examined the correlation between migration in metabolic profile and the progression of periodontal diseases. Results: Saliva metabolite profiles of gingivitis and periodontitis patients was significantly different from those of the healthy controls. Significant differences were identified between the different groups for eight salivary metabolites, including arachidonic acid, tyramine, L-arginine, thymine, N-acetylgalactosamine sulfate, prostaglandin E2, L-phenylalanine, and 5-aminoimidazole-4-carboxamide-riboside (AICAR). In comparison with those of the health controls, the concentration of AICAR in patients with gingivitis and periodontitis was lower and the metabolic trend was down-regulated, while the other metabolites were up-regulated. Conclusion: Salivary metabolic profile changes along with the progression of periodontal diseases. Abnormal metabolism of the periodontal tissue and of pathogenic microorganisms related to periodontal diseases is one of the mechanisms involved in the pathogenesis, development and prognosis of periodontal diseases.

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction.

Argpyrimidine (APMD), a methylglyoxal-arginine-derived product, is one of the main products of diabetes mellitus. We aimed to systematically investigate the role of APMD in regulating autophagy activity, with a specific focus on the finding of APDM binding molecule, matching amino acid residues, autophagy flux and proteins, cell cycle arrest, cell skeleton and migration, PI3K/AKT/mTOR pathways, inflammatory signals, alveolar bone destruction, and inhibition verification. In this study, binding to 59/94/121 amino acid residues of advanced glycosylation end product receptor (RAGE), APMD suppressed PI3K/AKT/mTOR pathway to attenuate cell survival of periodontal ligament cells (PDLCs). Simultaneously, autophagy proteins ATG5, Beclin1, and LC3-II/I expression ratio were upregulated while P62/SQSTM was downregulated. Cell cycle arrested at G0/G1 with enhancing Cyclin D1/CDK4 and decreasing Cyclin A/CDK2 expression. Inhibition of autophagy abrogated APMD-induced cell cycle arrest. Furthermore, the inflammation regulation network of matrix metalloproteinase (MMP)-2, MMP-9, MAPKs and NF-κB pathways were activated by APMD. Rat periodontal models confirmed that APMD induced alveolar bone resorption, increased inflammatory infiltrates, and degraded collagen fibers through RAGE and PI3K. APMD-induced autophagy, G0/G1 arrest, pro-inflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.

A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease.

The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonas gingivalis infection is a risk factor for systemic diseases. We investigated the association of P. gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P. gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P. gingivalis positivity (P. gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p < 0.0001). A P. gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P. gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had > 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.

Efeito antioxidante e anti-inflamatório do probiótico Lactobacillus rhamnosus EM1107 adjunto a terapia periodontal não cirúrgica em modelo experimental de periodontite / Antioxidant and anti-inflammatory effect of the probiotic Lactobacillus rhamnosus EM1107 adject to non-surgical periodontal therapy in experimental model of periodontitis

A doença periodontal (DP) é caracterizada por uma resposta imuno-inflamatória mediada pelohospedeiro associada a patógenos, que compromete os tecidos de proteção e sustentação do periodonto. É tratada, comumente, através da terapia periodontal não cirúrgica incluindo a raspagem e alisamento da superfície radicular (RAR). Entretanto, em algumas situações, como no controle de bolsas periodontais profundas, de difícil acesso e com destruição e progressão da doença ao longo do tempo, pode ser indicada a prática de terapias adjuvantes. Nesse sentido, o objetivo desse estudo é avaliar os efeitos antioxidante e anti-inflamatório da administração do probiótico Lactobacillus rhamnosus EM1107 (LR) como adjuvante ao tratamento periodontal não cirúrgico da periodontite induzida por ligadura em camundongos e na inflamação intestinal. Para o estudo, foi utilizado o modelo de indução da doença periodontal por colocação de ligadura com fio de seda 4.0 ao redor do segundo molar superior esquerdo de 40 camundongos. Os animais foram divididos em quatro grupos: Grupo I: sem intervenção; Grupo II: indução da DP; Grupo III: indução da DP + RAR; Grupo IV: indução da DP + administração do probiótico + RAR. Foram realizadas análises bioquímicas das funções hepáticas e renais, contagem de leucócitos, concentração tecidual intestinal de glutationa (GSH), malondialdeído (MDA) e superóxido dismutase (SOD) e expressão sérica e nos tecidos periodontais das citocinas IL-1ß e IL-6. Não foram encontradas diferenças estatisticamente significativas entre os grupos para os níveis teciduais de GSH e SOD. Para o MDA, foi observado um maior nível em relação ao grupo DP + RACR, cuja diferença foi estatisticamente significativa em relação ao grupo controle da DP e sem intervenção (p<0,05). Não foi verificada diferença estatisticamente significativa na concentração sérica das citocinas inflamatórias IL-1ß e IL-6, apesar de ser observada uma menor concentração tecidual de IL-1ß em relação ao grupo que recebeu o probiótico e seus respectivos controles. Houve também menor expressão da citocina pró-inflamatória IL- 6 no grupo DP + RACR em relação aos demais grupos. A expressão de IL-1ß nos tecidos periodontais apresentou média mais elevada no grupo controle da DP (436.0 ± 0.0). Já na IL-6 gengival, a maior média foi observada no grupo DP + RACR (453.9 ± 230.93). A utilização do Lactobacillus rhamnosus EM1107 no tratamento adjuvante da periodontite experimental induzida por ligadura em camundongos foi capaz de modular o estresse oxidativo gerado a partir da redução do nível demalondialdeído (MDA) e embora não tenha sido observada diferença estatística significante, foi capaz de reduzir o marcador inflamatório IL-1ß (AU).

Periodontal disease (PD) is characterized by a host-mediated immune-inflammatory response associated with pathogens, which compromises the protective and supporting tissues of the periodontium. It is commonly treated with non-surgical periodontal therapy including scaling and root surface planing (SRP). However, in some situations, such as in the control of deep periodontal pockets, which are difficult to access and with destruction and progression of the disease over time, the practice of adjuvant therapies may be indicated. In this sense, the objective of this study is to evaluate the antioxidant and anti-inflammatory effects of the administration of the probiotic Lactobacillus rhamnosus EM1107 (LR) as an adjunct to the non-surgical periodontal treatment of ligature-induced periodontitis in mice and in intestinal inflammation. For the study, the periodontal disease induction model was used by placing a 4.0 silk thread ligature around the upper left second molar of 40 mice. The animals were divided into four groups: Group I: without intervention; Group II: PD induction; Group III: induction of PD + SRP; Group IV: PD induction + probiotic administration + SRP. Biochemical analyzes of liver and kidney functions, leukocyte count, intestinal tissue concentration of glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) and serum and periodontal tissue expression of cytokines IL-1ß and IL-6 were performed. No statistically significant differences were found between groups for tissue levels of GSH and SOD. For MDA, an increase in levels was observed in relation to the PD + RACR group, whose difference was statistically significant in relation to the PD control group and without intervention (p<0.05). There was no statistically significant difference in the serum concentration of the inflammatory cytokines IL-1ß and IL-6, despite a reduction in the tissue concentrations of IL-1ß in relation to the group that received the probiotic and their respective controls. There was also lower expression of the pro-inflammatory cytokine IL-6 in the DP + RACR group compared to the other groups. The expression of IL-1ß in periodontal tissues showed a higher mean in the PD control group (436.0 ± 0.0). As for gingival IL-6, the highest mean was observed in the PD + RACR group (453.9 ± 230.93). The use of Lactobacillus rhamnosus EM1107 in the adjuvant treatment of experimental ligature-induced periodontitis in mice was able to modulate the oxidative stress generated from the reduction in the level of malondialdehyde (MDA) and although there was no statistically significant difference, it was able to reduce the inflammatory marker IL-1ß (AU).

Understanding the role of endotoxin tolerance in chronic inflammatory conditions and periodontal disease.

OBJECTIVE: This review aims to present the current understanding of endotoxin tolerance (ET) in chronic inflammatory diseases and explores the potential connection with periodontitis. SUMMARY: Subsequent exposure to lipopolysaccharides (LPS) triggers ET, a phenomenon regulated by different mechanisms and pathways, including toll-like receptors (TLRs), nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB), apoptosis of immune cells, epigenetics, and microRNAs (miRNAs). These mechanisms interconnect ET with chronic inflammatory diseases including periodontitis. While the direct correlation between ET and periodontal destruction has not been fully elucidated, emerging reports point towards the potential tolerization of human periodontal ligament cells (hPDLCs) and gingival tissues with a significant reduction of TLR levels. CONCLUSIONS: There is a potential link between ET and periodontal diseases. Future studies should explore the crucial role of ET in the pathogenesis of periodontal diseases, as evidence of a tolerized oral mucosa may represent an intrinsic mechanism capable of regulating the oral immune response. A clear understanding of this host immune regulatory mechanism might lead to effective and more predictable therapeutic strategies to treat chronic inflammatory diseases and periodontitis.

Wnt signalling in oral and maxillofacial diseases.

Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and noncanonical pathways, which play an important role in tooth development, alveolar bone regeneration, and related diseases. In recent years, with the in-depth study of Wnt signalling in oral and maxillofacial-related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarise the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases.

Evaluation of Antimicrobial Photodynamic Therapy as an Adjuvant in Periodontal Treatment in Individual with Down Syndrome

Abstract Objective: To evaluate the effectiveness of Antimicrobial Photodynamic Therapy (aPDT), associated with scaling and root planing in the non-surgical periodontal treatment of individuals with Down Syndrome. Material and Methods: A controlled, randomized, split-mouth study was conducted. A total of 8 participants diagnosed with Down Syndrome aged 17-38 years of both sexes with clinical periodontitis were included in the study. Participants were treated at least three times: at the baseline, Plaque Index (PI), Bleeding on Probing (BOP), and Probing Pocket Depth (PPD) were obtained. After one week, conventional scaling and root planing were performed, and two quadrants were randomly selected for aPDT application. The reassessment was obtained one month after the aPDT application. The significance level was set at 5%. Analyses were performed considering a 95% confidence interval. Results: In the intergroup evaluation, no statistically significant differences were observed (p>0.05). In the intragroup evaluation, no statistically significant variations were observed in relation to the PI (p>0.05) and PPD (p>0.05); however, a statistically significant reduction in the BOP was observed between the test group (p=0.013) and control group (p=0.015). Conclusion: The use of aPDT as adjuvant therapy did not promote additional benefits in decreasing PI and PPD after 1 month of treatment. However, a significant reduction in the BOP was observed in the intragroup evaluation.

Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis.

Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.

Role of the Filifactor alocis Hypothetical Protein FA519 in Oxidative Stress Resistance.

In the periodontal pocket, there is a direct correlation between environmental conditions, the dynamic oral microbial flora, and disease. The relative abundance of several newly recognized microbial species in the oral microenvironment has raised questions on their impact on disease development. One such organism, Filifactor alocis, is significant to the pathogenic biofilm structure. Moreover, its pathogenic characteristics are highlighted by its ability to survive in the oxidative-stress microenvironment of the periodontal pocket and alter the microbial community dynamics. There is a gap in our understanding of its mechanism(s) of oxidative stress resistance and impact on pathogenicity. Several proteins, including HMPRFF0389-00519 (FA519), were observed in high abundance in F. alocis during coinfection of epithelial cells with Porphyromonas gingivalis W83. Bioinformatics analysis shows that FA519 contains a "Cys-X-X-Cys zinc ribbon domain" which could be involved in DNA binding and oxidative stress resistance. We have characterized FA519 to elucidate its roles in the oxidative stress resistance and virulence of F. alocis. Compared to the wild-type strain, the F. alocis isogenic gene deletion mutant, FLL1013 (ΔFA519::ermF), showed significantly reduced sensitivity to hydrogen peroxide and nitric oxide-induced stress. The ability to form biofilm and adhere to and invade gingival epithelial cells was also reduced in the isogenic mutant. The recombinant FA519 protein was shown to protect DNA from Fenton-mediated damage with an intrinsic ability to reduce hydrogen peroxide and disulfide bonds. Collectively, these results suggest that FA519 is involved in oxidative stress resistance and can modulate important virulence attributes in F. alocis. IMPORTANCE Filifactor alocis is an emerging member of the periodontal community and is now proposed to be a diagnostic indicator of periodontal disease. However, due to the lack of genetic tools available to study this organism, not much is known about its virulence attributes. The mechanism(s) of oxidative stress resistance in F. alocis is unknown. Therefore, identifying the adaptive mechanisms utilized by F. alocis to survive in the oxidative stress environment of the periodontal pocket would lead to understanding its virulence regulation, which could help develop novel therapeutic treatments to combat the effects of periodontal disease. This study is focused on the characterization of FA519, a hypothetical protein in F. alocis, as a multifunctional protein that plays an important role in the reactive oxygen species-detoxification pathway. Collectively, our results suggest that FA519 is involved in oxidative stress resistance and can modulate important virulence attributes in F. alocis.

Periodontal diseases and potential risk factors in Egyptian adult population-Results from a national cross-sectional study.

BACKGROUND: Despite the interdependence of general and periodontal health, there is paucity of national representative data on the prevalence of periodontal diseases and their associated risk factors in Egyptian population. This cross-sectional study, thus, aimed to assess the prevalence of periodontitis and tooth loss among Egyptian adults and investigate the association between potential risk factors and periodontal diseases. METHODS: A total of 5,954 adults aged ≥ 20 years were included in this study as a subsample from Egypt's national oral health survey. Periodontitis was diagnosed with Community Periodontal Index 'CPI' scores ≥3 and tooth loss not due to caries was included in the analysis. Socio-demographic data and information on behavioral factors and history of diabetes were gathered in a face-to-face interview. Logistic regression was done to interpret the impact of potential predictors on the incidence of the two selected outcome variables. RESULTS: The overall prevalence of periodontitis was 26% and regression analysis revealed that higher odds of periodontitis existed among illiterate participants (OR = 1.74; 95% CI: 1.40-2.17), smokers (OR = 1.93; 95% CI: 1.69-2.20) and rural residents (OR = 1.16; 95% CI: 1.03-1.30). On the other hand, old age, frequency of dental attendance and history of diabetes were the main predictive factors for tooth loss. CONCLUSIONS: Among Egyptian adults, periodontal diseases were strongly associated with a multitude of modifiable and non-modifiable risk factors and inequalities in distribution of periodontal treatment needs were determined mainly by age, gender, level of education and residency location.