Progression Of Periodontitis Research Articles

Impact of Photobiomodulation and Melatonin on Periodontal Healing of Periodontitis in Immunosuppressed Rats.

Introduction: Periodontitis is an inflammatory disease due to bacterial origin; it has a chronic course and progresses by immunosuppressive therapy. However, adjuvant therapies such as photobiomodulation (PBM) and melatonin can reduce the severity of the inflammation and inhibit the progression of periodontitis. Therefore, the present study evaluated the effects of PBM (PBM) and melatonin, as adjuvant therapies, on periodontal healing in immunosuppressed rats with periodontitis. Methods: Random allocation was performed on 36 albino Wistar rats, divided into the following groups: control, periodontitis, immunosuppressant only, immunosuppressant+PBM, immunosuppressant+melatonin, and immunosuppressant+melatonin+PBM. Periodontitis caused by ligature in all groups, except for the control group. Subcutaneous administration of dexamethasone was performed in the immunosuppressant groups for immunosuppression. All the groups except the control group received scaling and root planning (SRP). Each group was subdivided into three equal subgroups according to the evaluation period: (A), one week, (B) two weeks (C), 4 weeks. Histological examination was done with haematoxylin & eosin and Masson's Trichrome for inflammation and periodontal healing. Statistical Analysis of the data was done by using the chi-square test. The significance level was set at P≤0.05. Results: Regarding the inflammatory response and periodontal healing, histological examination revealed statistically significant difference in all treated groups in comparison with the control untreated immunosuppressed group (P<0.001). The combined application of melatonin and PBM resulted in a best histological response presented by lower inflammatory response and better periodontal healing, when compared with all other treated groups (P<0.001). Conclusion: After considering the circumstances of this research, the combination of melatonin and PBM by a 650 nm diode laser with output power of 100 mw for one minute for three sessions appeared to be a beneficial adjunct in periodontal healing in immunosuppressed rats with periodontitis.

ETIOPATHOGENETIC ASPECTS OF SYNTROPY AND MUTUAL BURDEN IN THE PATHOLOGY OF THE GASTROINTESTINAL TRACT AND THE DISEASES OF THE ORAL CAVITY

The purpose of the work is to study the main etiopathogenetic mechanisms of development and peculiarities of the clinical course in the comorbidity of diseases of the oral cavity and pathology of the gastrointestinal tract by analyzing the results of scientific research published in modern scientific publications.Material and methods. Search, systematization, elaboration and analysis of scientific works of domestic and foreign authors, which present the modern results of research on etiopathogenesis and peculiarities of the clinical course in comorbidity of diseases of the oral cavity and gastrointestinal tract, with the involvement of search engines Google Scholar, PubMed and other electronic resources. The bibliosematic and analytical methods are used in the research.Results. The problem of syntropies, the basis of which is the association of etiological and pathogenetic factors of certain diseases, is an actual problem in modern medicine. The analysis of data from modern scientific literary sources proves that the development and progression of periodontal and oral mucosa diseases depends not only on the influence of local factors but also is a reaction to the influence of pathogenic factors that arise as a result of diseases of the gastrointestinal tract.Steady persistence of microflora in certain areas of the digestive tract can complicate the course of dental and gastrointestinal diseases. A gradual change in the properties of representatives of the conditionally pathogenic group of microorganisms, their association with specific diseases of the oral cavity and gastrointestinal tract indicates their role in the pathogenesis of many diseases. Mechanisms of free radical damage to cellular structures and changes in humoral and cellular immunity are important common links in the pathogenesis of periodontal and gastrointestinal tract diseases. The development of an imbalance of the endocrine system and psycho-emotional stress has a significant impact on the process of mutual burden of diseases of the gastrointestinal tract and oral cavity.Conclusion. Тoday considerable factual material has been accumulated regarding the understanding of common mechanisms of etiopathogenesis and syntropy of diseases of the oral cavity and pathology of the gastrointestinal tract. This knowledge makes it possible to develop effective comprehensive measures for the diagnosis, prevention and treatment of both diseases of the oral cavity and diseases of the gastrointestinal tract, taking into account the mutual burden of these pathologies.

Salivary and serum inflammatory biomarkers during periodontitis progression and after treatment.

To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment. Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1-2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log-transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models. P2 presented higher levels (p < .05) of salivary IFNγ, IL-6, VEGF, IL-1β, MMP-8, IL-10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL-6, IL-8, IL-1β, MMP-8, IL-10, OPG and MMP-9 in saliva and of CRP, MMP-8, MMP-9 and MPO in serum. Periodontitis progression results from a sustained pro-inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes.

Potential Roles of Long Non-coding RNAs in the Pathogenesis of Periodontitis: Inflammation Response, Immune Infiltration, Collagen Fibers Synthesis, and Bone Remodeling.

It is evident that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of periodontitis. However, the detailed functional mechanisms remain unknown. This study aimed to elucidate the pathogenic mechanisms of lncRNAs in periodontitis by investigating their regulation of protein-coding gene expression. Human Gingival Fibroblasts-1 (HGF-1) were stimulated with 5 μg/mL of Lipopolysaccharide (LPS) for 24 hours to construct the periodontitis cell model. qRTPCR and western blot analyses were carried out to determine mRNA and protein levels of genes induced by LPS or involved in the inflammatory response. Cytokine levels and inflammatory proteins were assayed using ELISA. Transcriptome sequencing and analysis were conducted to reveal the expression signatures of lncRNAs. DESeq2 (v1.4.5) was used to analyze differentially expressed genes. Gene function enrichment was carried out using Phyper. AnimalTFDB v3.0 was used to analyze transcription factors involved in the pathogenesis of periodontitis. Prot\ein domains and families of the target proteins were identified based on the Pfam protein family database. In LPS-treated HGF-1 cells, we detected the secretion of TNF-α and IL-1β, along with the production of MDA and ROS, indicating that LPS significantly triggered inflammatory responses and oxidative stress in HGF-1 cells. A total of 15,295 lncRNAs were detected in both the control (ConT) and LPS-treated groups. We selected 10 significantly differentially co-expressed lncRNA-coding genes (MIR222HG, SNHG15, SNHG12, URS00005F6AA3, URS00009C153E, URS0000D57D7F, URS00019A4688, URS00019AF240, URS00019C6526, and URS0001A00B79) as potential biomarkers for diagnosing the progression of periodontitis. An interaction network consisting of 2 lncRNA- encoding genes (MIR222HG and SNHG15) and protein-encoding genes (CBX5, NUPR1, CHAC1, and MAB21L3) may be involved in the pathogenesis of periodontitis. The ceRNA network analysis revealed the differentially expressed lncRNAs to be involved in inflammatory response, immune infiltration, collagen fiber synthesis, and bone remodeling in LPS-induced periodontitis. This study has identified pivotal molecules implicated in the pathogenesis of periodontitis, including those involved in inflammation regulation, collagen fiber synthesis, and bone remodeling. Our findings may contribute to explaining how lncRNAs participate in the pathological process of periodontitis.

Periodontal microbiology from undergraduate perspective: a questionnaire study

Background: Periodontal diseases are inflammatory conditions affecting the supporting structure of the teeth, leading to potential consequences such as gingivitis and periodontitis. The intricate interaction between host’s immune system and oral microbiome promotes this disease. The human oral cavity harbors a vast and diverse microbial community, collectively known as the oral microbiome comprising of bacteria, viruses, fungi, this ecosystem is influenced by factors such as genetics, host immunity, oral hygiene practices, diet and environmental variables. Among these microorganisms, bacteria take center stage in the initiation and progression of periodontal diseases. The objective was to assess the knowledge and awareness about the periodontal microbiology (periopathogens) among dental students. Methods: A self-designed questionnaire in English language containing 26 items was circulated using Google forms and was distributed among third, final year students and interns of PMNM dental college and Hospital, Bagalkot, India. The framework covered 3 domains: The first domain containing microorganism’s interaction in host causing periodontal disease, second domain about colonizers in dental plaque and certain aspects covered inflammatory response in host and the third domain containing therapeutic planning and future perspectives. Results: When looked into 1st domain student had a good knowledge on microorganism interaction in host, student had fair knowledge about the 2nd domain, they lack knowledge about the 3rd domain that is about therapeutic planning. Conclusions: Student have a fair knowledge about the periodontal pathogen and they lack knowledge about the therapeutic planning. It is indicative of students’ commitment to understanding the complex dynamics of oral microbiology.

Impact of Malocclusions on Periodontopathogenic Bacterial Load and Progression of Periodontal Disease: A Quantitative Analysis.

(1) Periodontal disease (PD) is a globally prevalent chronic inflammatory condition, exacerbated by the dysbiosis of the oral microbiota. This study aims to evaluate the bacterial load of specific periodontopathogenic bacteria in patients with malocclusions (MAL) compared to those without. (2) Methods: Conducted at the "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania, this pilot study involved two groups: patients with MAL and PD, and patients with PD but without MAL. We included 20 patients: 10 with MAL (9 with crowding and 1 with an open bite) and 10 without MAL. Gingival crevicular fluid was collected for bacterial DNA extraction and quantified bacterial load using real-time PCR, focusing on 12 periodontopathogenic bacteria across different complexity classes. (3) Results: The study identified significantly higher concentrations of Treponema denticola (p = 0.023, median = 4.32, IQR = 2.76-5.53 vs. median = 1.93, IQR = 0-3.19), Tannerella forsythia (p = 0.020, mean = 6.04 ± 0.72 vs. mean = 4.4 ± 1.89) and Porphyromonas gingivalis (p = 0.002, median = 5.64, IQR = 4.94-5.98 vs. median = 2.48, IQR = 0-4.05) in patients with MAL compared to those without. This suggests that MAL contributes to an environment conducive to the proliferation of specific pathogens, potentially accelerating PD progression. Additionally, Eikenella corrodens (p = 0.040, mean = 4.55 ± 1.02 vs. mean = 3.23 ± 1.56), Campylobacter rectus (p < 0.001, mean = 4.2 ± 0.56 vs. mean = 1.8 ± 1.51), Prevotella intermedia (p = 0.043, median = 5.04, IQR = 0-5.49 vs. median = 0, IQR = 0-3.39), Capnocytophaga sputigena (p = 0.011, median = 5.91, IQR = 5.47-6.17 vs. median = 4.63, IQR = 3.83-5.64), and Capnocytophaga gingivalis (p = 0.007, median = 5.87, IQR = 5.34-6.03 vs. median = 4.4, IQR = 3.5-5.71) also showed elevated concentrations, indicating the broad impacts of MAL on oral microbial profiles. (4) Conclusions: The findings demonstrate a significant relationship between MAL and increased bacterial loads, underscoring the need for its integration in managing PD. Future research should expand demographic diversity and employ longitudinal designs to better understand the causative mechanisms at play.

Residual vertical defects: risk of disease progression, retreatment rates, and cost: a retrospective analysis.

This study aimed to explore the relationship between Radiographic Residual Vertical Defects (RVDs) and the progression of periodontitis in patients undergoing periodontal maintenance therapy (PMT). Teeth with RVDs were compared to the same contralateral teeth in the same patient. The study investigated the effect of smoking, diabetes, compliance, disease Stage, and Grade, baseline probing depth (PD), periodontal risk score (PRS), baseline pocket closure (PC) (≤ 4mm), and tooth mobility on disease progression. We calculated the need for retreatment during PMT and its associated cost. Generalized estimation equations and linear and multilevel logistic regression analyses were employed for data analysis. Each group had 139 teeth, accounting for 80 patients. Although the group with RVDs had similar PD reduction compared to the control teeth, the prevalence of PC at the last follow-up was reduced to half in the RVDs group (odds ratio OR = 0.5; p-value = 0.028), regardless of PC status at the baseline. RVDs were also significant predictors of tooth loss due to periodontitis (TLP), with an OR of 2.28 (p = 0.043). Patients with diabetes, Stage IV, higher mobility, and higher PRS scores had a higher risk of tooth loss due to periodontitis (OR = 4.71, 3.84, 3.64, and 5.97, respectively (P < 0.01). Incidences of sites requiring retreatment were similar in both groups, but the cost of treatment was 30% higher for teeth with RVDs. Grade C had the most significant influence on receiving retreatments (OR = 18.8, p = 0.005). Teeth with RVDs represent a risk indicator for tooth loss compared to identical contralateral teeth with similar PD in the same patient. Teeth with RVD had more risk of pocket opening during follow-up. While teeth with RVDs can be maintained long-term, they have twice the risk of pocket opening and tooth loss due to periodontitis during follow-up. Patients with systemic and local risk factors need to be monitored closely as they are at the highest risk of losing teeth with RVDs. The increased cost of retreatment for teeth with RVDs also has implications in terms of retention versus extraction and replacement.

Periodontal Tissue Homoeostasis, Immunity, the Red Complex Pathogens, and Dysbiosis: Unraveling the microRNA Effect.

microRNAs are a family of small, non-coding RNA molecules that can regulate the translation of messenger RNAs (mRNAs). Numerous miRNAs have been proposed as potential indicators for periodontal disease, and their regulation might serve as a potent means of restricting the disease process. MiRNAs act as important immune system regulators that promote the production of many cytokines, including interferon (IFN), tumour necrosis factor (TNF), and IL-1as well as RANK. Investigations pertaining to the use of specific miRNAs as therapeutic agents are underway. They can influence a variety of regulatory organs and target several genes. Additionally, distinct components of the same expression pathway can be controlled by combining miRNAs and their antagonists. In recent years, many miRNA delivery methods have been created for therapeutic applications. Studies pertaining to the role of miRNAs in periodontal disease pathogenesis may pave the way for the use of miRNAs as biomarkers of periodontal disease. A complete understanding of the role of miRNA in periodontal disease and its mechanism of action can pave the way towards therapeutic strategies that can reduce or even prevent the progression of periodontal diseases.

The Protective Role Antioxidant of Vitamin C in the Prevention of oral Disease: A Scoping Review of Current Literature.

This review meticulously examined the connection between vitamin C and periodontal disease, as well as the potential of vitamin C to prevent this condition. To gather relevant data, comprehensive electronic searches were conducted across various databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, focusing on studies that explored the relationship between vitamin C and periodontal disease in individuals aged between 18 and above. From an initial pool of 421 articles, 14 were ultimately chosen for detailed analysis. This selection encompassed seven cross-sectional studies, two case-control studies, two cohort studies, and three randomized controlled trials. The analysis of these studies revealed a consistent negative association between vitamin C intake, as well as its levels in the blood, and the incidence of periodontal disease across all seven cross-sectional studies. This indicates that higher vitamin C intake and blood levels are linked to a decreased risk of developing periodontal disease. In the two case-control studies, individuals suffering from periodontitis were found to have both a lower intake of vitamin C and reduced levels of vitamin C in their blood compared to those without the disease, further underscoring the potential protective role of vitamin C against periodontal disease. The progression of periodontal disease was observed to be more rapid in patients with lower dietary intake or blood levels of vitamin C compared to controls. Regarding the effects of vitamin C administration as an intervention, there was an improvement noted in gingival bleeding among patients with gingivitis; however, no significant benefits were observed in cases of periodontitis, specifically concerning alveolar bone absorption. Through the meticulous examination of available studies, this systematic review underscores the notion that adequate vitamin C intake and maintaining sufficient levels of vitamin C in the blood can contribute significantly to reducing the risk of periodontal disease.

Methylome-wide analysis in systemic microbial-induced experimental periodontal disease in mice with different susceptibility.

The study delved into the epigenetic factors associated with periodontal disease in two lineages of mice, namely C57bl/6 and Balb/c. Its primary objective was to elucidate alterations in the methylome of mice with distinct genetic backgrounds following systemic microbial challenge, employing high-throughput DNA methylation analysis as the investigative tool. Porphyromonas gingivalis (Pg)was orally administered to induce periodontitis in both Balb/c and C57bl/6 lineage. After euthanasia, genomic DNA from both maxilla and blood were subjected to bisulfite conversion, PCR amplification and genome-wide DNA methylation analysis using the Ovation RRBS Methyl-Seq System coupled with the Illumina Infinium Mouse Methylation BeadChip. Of particular significance was the distinct methylation profile observed within the Pg-induced group of the Balb/c lineage, contrasting with both the control and Pg-induced groups of the C57bl/6 lineage. Utilizing rigorous filtering criteria, we successfully identified a substantial number of differentially methylated regions (DMRs) across various tissues and comparison groups, shedding light on the prevailing hypermethylation in non-induced cohorts and hypomethylation in induced groups. The comparison between blood and maxilla samples underscored the unique methylation patterns specific to the jaw tissue. Our comprehensive methylome analysis further unveiled statistically significant disparities, particularly within promoter regions, in several comparison groups. The differential DNA methylation patterns observed between C57bl/6 and Balb/c mouse lines suggest that epigenetic factors contribute to the variations in disease susceptibility. The identified differentially methylated regions associated with immune regulation and inflammatory response provide potential targets for further investigation. These findings emphasize the importance of considering epigenetic mechanisms in the development and progression of periodontitis.

The role of Fusobacterium nucleatum in cancer and its implications for clinical applications.

Fusobacterium nucleatum, a gram-negative anaerobic bacterium abundantly found in the human oral cavity, is widely recognized as a key pathobiont responsible for the initiation and progression of periodontal diseases due to its remarkable aggregative capabilities. Numerous clinical studies have linked F. nucleatum with unfavorable prognostic outcomes in various malignancies. In further research, scholars have partially elucidated the mechanisms underlying F. nucleatum's impact on various types of cancer, thus gaining a certain comprehension of the role played by F. nucleatum in cancer. In this comprehensive review, we present an in-depth synthesis of the interplay between F. nucleatum and different cancers, focusing on aspects such as tumor initiation, metastasis, chemoresistance, and modulation of the tumor immune microenvironment and immunotherapy. The implications for cancer diagnosis and treatment are also summarized. The objective of this review is to enhance our comprehension of the intricate relationship between F. nucleatum and oncogenic pathogenesis, while emphasizing potential therapeutic strategies.

Dipotassium glycyrrhizate prevents oral dysbiosis caused by Porphyromonas gingivalis in an in vitro saliva-derived polymicrobial biofilm model

ObjectivesOral microbiome dysbiosis prevention is important to avoid the onset and progression of periodontal disease. Dipotassium glycyrrhizate (GK2) is a licorice root extract with anti-inflammatory effects, and its associated mechanisms have been well-reported. However, their effects on the oral microbiome have not been investigated. This study aimed to elucidate the effects of GK2 on the oral microbiome using an in vitro polymicrobial biofilm model. MethodsAn in vitro saliva-derived polymicrobial biofilm model was used to evaluate the effects of GK2 on the oral microbiome. One-week anaerobic culture was performed, in which GK2 was added to the medium. Subsequently, microbiome analysis was performed based on the V1–V2 region of the 16 S rRNA gene, and pathogenicity indices were assessed. We investigated the effects of GK2 on various bacterial monocultures by evaluating its inhibitory effects on cell growth, based on culture turbidity. ResultsGK2 treatment altered the microbiome structure and decreased the relative abundance of periodontal pathogenic bacteria, including Porphyromonas. Moreover, GK2 treatment reduced the DPP4 activity —a pathogenicity index of periodontal disease. Specifically, GK2 exhibited selective antibacterial activity against periodontal pathogenic bacteria. ConclusionsThese findings suggest that GK2 has a selective antibacterial effect against periodontal pathogenic bacteria; thus, preventing oral microbiome dysbiosis. Therefore, GK2 is expected to contribute to periodontal disease prevention by modulating the oral microbiome toward a state with low inflammatory potential, thereby utilizing its anti-inflammatory properties on the host.

The Role of Different Types of Cannabinoids in Periodontal Disease: An Integrative Review.

This integrative review addresses the potential of the Endocannabinoid System (ES) and cannabinoids in the pathogenesis and treatment of periodontal disease (PD). Cannabinoid receptors are expressed in healthy and inflamed periodontal tissues, indicating a potential regulatory role for SEC in oral homeostasis. Healthy periodontal cells express more CB1 receptors, while inflamed sites show increased CB2 receptors. This suggests a dynamic involvement of the SEC in the inflammatory response associated with PD. Cannabinoids such as cannabidiol (CBD) and cannabinoid receptor agonists such as HU-308, anandamide (AEA), and methanamide (Meta-AEA) have demonstrated promising therapeutic potential in studies. CBD has been associated with the control of bone resorption, antibacterial activity, and increased production of gingival fibroblasts, indicating effects in mitigating the progression of PD. HU-308 demonstrated preventive effects against alveolar bone loss, and anti-inflammatory, osteoprotective, and pro-homeostatic properties in animal models of periodontitis. AEA and Meta-AEA have anti-inflammatory effects by reducing pro-inflammatory mediators such as IL-1, IL-6, and TNF-α. The activation of cannabinoid receptors attenuates inflammatory processes, inhibits alveolar bone loss, exerts antibacterial effects, and promotes tissue repair. However, clinical trials are especially needed to validate these results and explore the therapeutic potential of cannabinoids in the treatment of PD in humans.

Treatment of Unfavorable Intrabony Defects with Autogenous Bone Graft in Combination with Leukocyte- and Platelet-Rich Fibrin or Collagen Membranes: A Non-Inferiority Study.

Background and Objectives: Unfavorable intrabony defects (IBDs) are associated with the progression of periodontal disease and tooth loss. Growing scientific evidence has demonstrated the effectiveness of platelet concentrations in periodontal treatment. The aim of our study was to demonstrate the non-inferiority of an autogenous bone graft (ABG) associated with leukocyte- and platelet-rich fibrin (L-PRF) compared to ABG + Collagen Membrane in the treatment of IBDs. Material and Methods: Sixty-four patients with at least one IBD were randomly assigned to two groups: ABG+L-PRF and CM+ABG. Clinical and radiographic evaluations were performed at baseline and 12-month follow-up. Clinical attachment level (CAL), gingival recession (GR), probing pocket depth (PPD), and radiograph defect bone level (DBL) were compared between the two treatments. To evaluate the effectiveness of ABG+L-PRF, a non-inferiority margin of =1 mm (-1 mm for GR) was chosen; a second non-inferiority margin of =0.5 mm (-0.5 mm for GR) was set for clinical relevance. Results: At 12-month follow up, both treatments showed clinical and radiographic improvements. The 90% confidence intervals of the CM+ABG-L-PRF+ABG mean difference for CAL gain (-0.0564 mm [-0.316 to 0.203]), DBL gain (-0.433 mm [-0.721 to -0.145]), and PPD reduction (0.232 mm [0.015 to 0.449]) were below the 0.5 mm non-inferiority margin; the GR increase (0.255 mm [0.0645 to 0.445]) stayed above the -0.5 mm. Conclusions: the L-PRF+ABG treatment of unfavorable IBDs is non-inferior with respect to the CM+ABG therapy for CAL gain, but with a lower GR, a slightly higher PPD, and DBL gain.

Expression of Regulatory T Cell and Related Interleukins in Gingivitis Versus Stage 3, Grade B Generalized Periodontitis: Synergy or Cacophony—A Cross-Sectional Study

Abstract Aim: To raise “personalized periodontal diagnosis and prognosis” knowledge, Tregs, pro/anti-inflammatory interleukins (ILs) beside vitamin D-binding protein (VDBP) in serum and gingival cervical exudate of periodontally healthy individuals, plaque-induced gingivitis, and stage 3, grade B periodontitis patients were evaluated. Materials and Methods: An observational trial of different periodontal statuses according to 2018 periodontal classification was established from 60 subjects segregated into three equivalent groups (control periodontally healthy, gingivitis, and stage 3, grade B periodontitis). Peripheral blood and gingival crevicular fluid (GCF) were collected, to get GCF samples, inserted paper point in the pocket of the patient's teeth then the samples were placed with phosphate-buffered saline in Eppendorf. The peripheral blood was collected in ethylenediaminetetraacetic acid-coated vacutainer tubes. Frequency of CD4+ CD25+High Tregs was detected using flow cytometry. Cytokines were measured using an enzyme-linked immunosorbent assay. Mann–Whitney U test analysis was manipulated to distinguish the statistical discrepancies. Pearson’s correlation coefficient test was utilized to tie in the studied parameters. Result: Frequency of CD4+ CD25+High T cells were significantly ascendant in periodontitis than gingivitis and healthy (P ≤ 0.01; P = 0.04) and significantly superior in gingivitis than healthy (P = 0.01). There was no interdependence between systemic IL-21, IL-33, IL-22, IL-35, and the periodontal conditions except systemic VDBP, which significantly increased with the progression of the periodontal tissue inflammation. GCF compartments of IL-21, IL-33, and VDBP significantly increased with progression inflammation and GCF compartments of IL-22 and IL-35 significantly decreased with periodontal breakdown. Conclusion: Local increase of Treg is positively associated with increased local pro-inflammatory cytokines. This increment is more aggravated in periodontitis. Therefore, Tregs may have synergistic effects with periodontal disease progression.

Analyzing the Relationship Between Chronic Periodontitis and Psychological Stress in Elderly Patients: A Study Protocol.

Although stress is the body's physiological response to challenging life events, chronic exposure to a stressor may not cause stress. In such cases, stress negatively impacts some physiological functions, which can lead to psychosomatic diseases. According to research, inadequate coping mechanisms and long-term stress are factors that moderate the risk and progression of periodontitis. As a result, theories explaining how stress affects the periodontium have been put forth. The clinical examination comprised measurements of the probing pocket depth (PPD), clinical attachment level, number of teeth present, and plaque index. The current study uses a questionnaire to examine how psychosocial stress affects periodontium. A written consent form will be obtained after each patient has received an extensive description of the study's objectives. The instrument for diagnosis and natural illumination will be used during the patient's examination. PPD and clinical attachment loss will be compared with a questionnaire. Patients who are under stress should receive additional periodontal care to prevent periodontal disease from emerging or, if the issue already exists, from progressing to a more critical stage. Stress here deserves special attention because it is a natural part of people's life experiences with various intensities.Prejudice suggests that psychological stress and anxiety have a role in the advancement of periodontitis, which is consistent with the findings.

Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity

IntroductionExaggerated neutrophil recruitment and activation are the major features of pathological alterations in periodontitis, in which neutrophil extracellular traps (NETs) are considered to be responsible for inflammatory periodontal lesions. Despite the critical role of NETs in the development and progression of periodontitis, their specific functions and mechanisms remain unclear. ObjectivesTo demonstrate the important functions and specific mechanisms of NETs involved in periodontal immunopathology. MethodsWe performed single-cell RNA sequencing on gingival tissues from both healthy individuals and patients diagnosed with periodontitis. High-dimensional weighted gene co-expression network analysis and pseudotime analysis were then applied to characterize the heterogeneity of neutrophils. Animal models of periodontitis were treated with NETs inhibitors to investigate the effects of NETs in severe periodontitis. Additionally, we established a periodontitis prediction model based on NETs-related genes using six types of machine learning methods. Cell-cell communication analysis was used to identify ligand-receptor pairs among the major cell groups within the immune microenvironment. ResultsWe constructed a single-cell atlas of the periodontal microenvironment and obtained nine major cell populations. We further identified a NETs-related subgroup (NrNeu) in neutrophils. An in vivo inhibition experiment confirmed the involvement of NETs in gingival inflammatory infiltration and alveolar bone absorption in severe periodontitis. We further screened three key NETs-related genes (PTGS2, MME and SLC2A3) and verified that they have the potential to predict periodontitis. Moreover, our findings revealed that gingival fibroblasts had the most interactions with NrNeu and that they might facilitate the production of NETs through the MIF-CD74/CXCR4 axis in periodontitis. ConclusionThis study highlights the pathogenic role of NETs in periodontal immunity and elucidates the specific regulatory relationship by which gingival fibroblasts activate NETs, which provides new insights into the clinical diagnosis and treatment of periodontitis.

The Role of Pericyte Migration and Osteogenesis in Periodontitis

A ligature-induced periodontitis model was established in wild-type and CD146CreERT2; RosatdTomato mice to explore the function of pericytes in alveolar bone formation. We found that during periodontitis progression and periodontal wound healing, CD146+/NG2+ pericytes were enriched in the periodontal tissue areas, which could migrate to the alveolar bone surface and colocalize with ALP+/OCN+ osteoblasts. Chemokine C-X-C motif receptor 4 (CXCR4) inhibition using AMD3100 blocked CD146-Cre+ pericyte migration and osteogenesis, as well as further exacerbated periodontitis-associated bone loss. Next, primary pericytes were sorted out by magnetic-activated cell sorting and demonstrated that C-X-C motif chemokine ligand 12 (CXCL12) promotes pericyte migration and osteogenesis via CXCL12-CXCR4-Rac1 signaling. Finally, the local administration of an adeno-associated virus for Rac1 overexpression in NG2+ pericytes promotes osteoblast differentiation of pericytes and increases alveolar bone volume in periodontitis. Thus, our results provided the evidence that pericytes may migrate and osteogenesis via the CXCL12-CXCR4-Rac1 axis during the pathological process of periodontitis.

Periodontal ageing and its management via pharmacological glucose modulation

Periodontal disease (PD), a widespread non-communicable disease, affects over 90% of the global population with no known cure. Current management strategies focus on stabilization of disease progression, which is successfully achieved to a limited extent. Yet the never-ending battle of bacteria and the gingiva involves a complex interplay between genetic, microbial and environmental factors, demanding innovative approaches to improve prevention and stabilisation of this disease. Glucose is the body's source of energy and research has shown that dysregulation of the glucose metabolism impacts PD establishment and progression, as well as impact development of systemic non communicable diseases. Metformin, a drug known for its efficacy in diabetes treatment via controlling glucose metabolism, also demonstrated cardioprotective effects, increased longevity, and anti-inflammatory properties. Metformin has been used in gel format in clinical trials for PD non-surgical treatment, however, its systemic use in normoglycemic individuals with PD is less explored. A recent study presented compelling evidence of Metformin's preventive potential, impacting PD and markers of systemic health involved in metabolic health liked to improvement of lifespan. Therefore, this review discusses the aspects of ageing as a concept in the periodontium and the potential benefits of modulating glucose metabolism through Metformin to prevent PD, indirectly preventing systemic conditions involved in multi-morbidity, addressing a critical gap in current management. It also examines the choice between implementation of behaviour change and/or medication as strategy to add to current oral hygiene strategies. Finally, it discusses the ethical implications of prescribing systemic medication in dentistry.

Role of Nonalcoholic Fatty Liver Disease in Periodontitis: A Bidirectional Relationship.

Nonalcoholic fatty liver disease (NAFLD) and periodontitis share common risk factors such as obesity, insulin resistance (IR), and dyslipidemia, which contribute to systemic inflammation. It has been suggested that a bidirectional relationship exists between NAFLD and periodontitis, indicating that one condition may exacerbate the other. NAFLD is characterized by excessive fat deposition in the liver and is associated with low-grade chronic inflammation. There are several risk factors for the development of NAFLD, including gender, geriatric community, race, ethnicity, poor sleep quality and sleep deprivation, physical activity, nutritional status, dysbiosis gut microbiota, increased oxidative stress, overweight, obesity, higher body mass index (BMI), IR, type 2 diabetes mellitus(T2DM), metabolic syndrome (MetS), dyslipidemia (hypercholesterolemia), and sarcopenia (decreased skeletal muscle mass). This systemic inflammation can contribute to the progression of periodontitis by impairing immune responses and exacerbating the inflammatory processes in the periodontal tissues. Furthermore, individuals with NAFLD often exhibit altered lipid metabolism, which may affect oral microbiota composition, leading to dysbiosis and increased susceptibility to periodontal disease. Conversely, periodontitis has been linked to the progression of NAFLD through mechanisms involving systemic inflammation and oxidative stress. Chronic periodontal inflammation can release pro-inflammatory cytokines and bacterial toxins into the bloodstream, contributing to liver inflammation and exacerbating hepatic steatosis. Moreover, periodontitis-induced oxidative stress may promote hepatic lipid accumulation and IR, further aggravating NAFLD. The interplay between NAFLD and periodontitis underscores the importance of comprehensive management strategies targeting both conditions. Lifestyle modifications such as regular exercise, a healthy diet, and proper oral hygiene practices are crucial for preventing and managing these interconnected diseases. Additionally, interdisciplinary collaboration between hepatologists and periodontists is essential for optimizing patient care and improving outcomes in individuals with NAFLD and periodontitis.