Oral Inflammatory Disease Research Articles

ATF3 triggers M2 macrophage polarization to protect against pulp inflammation through WNT4 regulation.

Pulpitis is a common inflammatory oral disease that can lead to pulp necrosis. The aim of this study is to investigate the expression and regulatory mechanisms of ATF3, a potential therapeutic marker, in pulpitis. A mouse pulpitis model with different degrees of inflammation is established, and the expression of ATF3 in pulpitis is explored. The histological features of healthy pulp and pulpitis are analyzed by HE staining, and classical inflammatory factors are detected by immunohistochemistry (IHC). In an in vitro study, we investigate the role of ATF3 in the regulation of WNT4 transcription and explore the effects of the ATF3/WNT4 axis on the polarization of RAW264.7 macrophages, the inflammatory response and the osteogenic differentiation of human dental pulp stem/stromal cells (hDPSCs). Our results show that ATF3 is expressed at low levels in inflamed pulp tissues; overexpression of ATF3 reduces the area of pulp necrosis, decreases the level of pro-inflammatory factors, and promotes macrophage polarization toward the M2 type. Furthermore, we reveal that ATF3 binds to the WNT4 promoter region and positively regulates the expression of WNT4 and that ATF3 downregulates M1 markers and increases the expression of M2 markers by regulating WNT4 expression. In addition, ATF3 promotes the osteogenic differentiation of dental pulp stem cells. In summary, this study reveals that ATF3 promotes M2 macrophage polarization by regulating WNT4, which in turn inhibits pulpal inflammatory responses and promotes the osteogenic differentiation of dental pulp stem cells. These findings suggest that ATF3 may be a potential target for pulpitis treatment.

Mitochondrial dysfunction in the pathogenesis and treatment of oral inflammatory diseases

Oral inflammatory diseases (OIDs) include various prevalent conditions, such as periodontal disease and pulpitis. The most common causes of OIDs are microorganisms, injuries, occlusion factors, autoimmune diseases, and radiation therapy. If not treated properly, these diseases not only affect the oral health, but may also compromise the overall well-being. Thus, early detection of OIDs and new treatment strategies are key challenges of oral therapy research. Mitochondria are essential organelles for numerous cellular processes. Mitochondrial dysfunction not only affects cell metabolism, but also has an indirect impact on health and life expectancy. Several common polygenic diseases, such as cardiovascular and neurodegenerative disorders, are associated with mitochondrial dysfunction. Recent evidence suggests that mitochondrial dysfunction plays a significant role in the development and progression of OIDs and associated systemic diseases. This review provides critical insights into mitochondrial dysfunction and its role in inflammatory reactions in OIDs.

Correlation between inflammatory biomarkers in biological fluids in patients with ovarian endometriosis

BACKGROUND: To date, there are no available screening techniques allowing to distinguish groups of women with the risk of endometriosis. Therefore, many researchers are searching for meaningful biomarkers for non-invasive diagnosis. The peritoneal fluid is subject to multidirectional changes in patients with external genital endometriosis, although its sampling requires invasive procedure. Testing of the inflammatory markers in saliva is a simple and safe method of particular interest, given that its sampling is non-invasive. AIM: To assess the correlations between the level of inflammatory biomarkers in the peritoneal fluid and saliva in patients with ovarian endometriosis. MATERIAL AND METHODS: A prospective cohort comparative study of 46 women with ovarian endometriosis was carried out. Inclusion criteria: confirmed diagnosis of ovarian endometriosis; age between 18 and 40 years; written informed consent for surgical intervention and for participation in the study; no prior hormonal treatment. Non-inclusion criteria: patient's refusal to participate in the study; age below 18 and above 40 years; contraindications for surgical treatment; oral inflammatory diseases. Patients were excluded if the diagnosis could not be visually confirmed during surgery or if there were histological discrepancies. All patients underwent laparoscopic cystectomy. Peritoneal fluid samples were collected during surgery. Mixed unstimulated saliva was collected before surgery in the morning, on an empty stomach. The levels of interleukins and of vascular endothelial growth factor were assessed in biological fluids. RESULTS: The mean age of the study subjects was 32,4±6,1 years. Correlation analysis showed a direct statistically significant moderate relationship between the levels of IL-6 (r=0.548; p=0.001) and IL-8 (r=0.360; p=0.026) in the peritoneal fluid and saliva, respectively. CONCLUSION: These data suggest that the onset and progression of endometriosis are associated with the increase of inflammatory cytokine levels both in the peritoneal fluid and in saliva. This may serve a potential tool for diagnosis and assessment of the severity of endometriosis. Evaluation of IL-6 and IL-8 levels in saliva may be useful in clinical practice in patients with external genital endometriosis.

Mediating role of immune cells in association between volatile organic compounds and periodontitis: NHANES 2011-2014.

The relationship between humans and volatile organic compounds (VOCs) is a persistent concern due to their widespread sources and high evaporation rates. However, there is currently limited direct evidence linking VOC exposure to the development of periodontitis. This cross-sectional study analyzed 1525 participants and 21 urinary VOCs in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, aiming to investigate the relationship between periodontitis risk, assessed by attachment loss (AL) and probing depth (PD) and individual VOCs using logistic regression, quantile regression, and subgroup analysis. Weighted quantile sum analysis (WQS) and subgroup analysis were utilized to evaluate whether VOC mixtures were associated with periodontitis risk. Multiple linear regression models were used to examine the association between VOC co-exposure and peripheral immune cell counts. A mediation analysis was performed to evaluate whether peripheral immune cells are involved in the effect of VOC co-exposure on periodontitis prevalence. Urinary levels of 2-aminothiazoline-4-carboxylic acid, mandelic acid, and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine were positively associated with the risk of periodontitis after adjusting for all covariates. The WQS models demonstrated a positive correlation between the mixture of VOCs and the risk of periodontitis, wherein 2-aminothiazoline-4-carboxylic acid emerged as the most important contributor. The mediation analysis suggested that monocytes may play a role in the observed association between VOC co-exposure and the prevalence of periodontitis. Exposure to VOCs is associated with a greater prevalence of periodontitis. Monocytes' mediating role plays a crucial function in the association between the risk of periodontitis and co-exposure to VOCs. Volatile organic compounds (VOCs) are chemicals that evaporate quickly and are found all around us-from paints to cleaning products. Understanding how these compounds affect our health is crucial, especially regarding conditions like periodontitis, a common oral chronic inflammatory disease. In our study, we looked at urine samples from 1525 people who participated in a national health survey between 2011 and 2014 to find out if there is an association between VOC exposure and the risk of developing periodontitis. We found that certain chemicals in the urine, which show VOC exposure, were indeed associated with a greater risk of the disease. We further investigated the collective impact of these VOCs on the risk of periodontitis, revealing that certain chemicals exert a more significant influence than their counterparts. Additionally, our research hints at a potential role for monocytes in the interplay between VOCs and the risk of periodontitis. Our data suggest that exposure to VOCs could be associated with a greater likelihood of periodontitis, with monocytes potentially playing a role in this relationship. This study helps us better understand the potential health impacts of daily chemical exposure and underscores the importance of investigating further how our environment affects our health.

Detection of Amyloid-β Peptides in Gingival Crevicular Fluid and Its Effect on Oral Pathogens.

Periodontitis is the most common oral inflammatory disease, contributing to the onset and progression of Alzheimer's disease. However, a full investigation has not been performed on the expression level of amyloid-β (Aβ) peptides in gingival crevicular fluid (GCF) and its effects on oral pathogens. This study aimed to analyze the expression level of Aβ peptides in GCF of patients with periodontitis and the effects of Aβ peptides against common oral pathogens. GCF samples were collected from patients with periodontitis (n=15) and periodontally healthy people (n=10). The antimicrobial effects of Aβ peptides were evaluated on four common oral pathogenic strains using an MTT assay, crystal violet staining, fluorescence microscope, and transmission electron microscope. The protein levels of Aβ40 and Aβ42 were upregulated in the GCF of periodontitis group compared with the healthy group. Both Aβ40 and Aβ42 exhibited antimicrobial effects on Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Lactobacillus acidophilus in both planktonic and biofilm conditions. Further, only Aβ40 showed an antimicrobial effect on the Fusobacterium nucleatum. The results of this study demonstrate that Aβ peptides in GCF may be a relevant indicator of periodontitis status. Besides, the antimicrobial peptides derived from Aβ peptides have great potential in periodontal therapy.

Crosstalk between periodontitis and cardiovascular risk.

Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota. Clinically, both NCDs are highly associated; however, shared risk factors such as smoking, obesity, type II diabetes mellitus and chronic stress represent only an insufficient explanation for the multifaceted interactions of both disease entities. Specifically, the crosstalk between both diseases is not yet fully understood. This review summarizes current knowledge on the clinical association of periodontitis and CVD, and elaborates on how periodontitis-induced pathophysiological mechanisms in patients may contribute to increased cardiovascular risk with focus on atherosclerosis. Clinical implications as well as current and future therapy considerations are discussed. Overall, this review supports novel scientific endeavors aiming at improving the quality of life with a comprehensive and integrated approach to improve well-being of the aging populations worldwide.

FC13 Comparative analysis of the oral microbiota in patients with psoriasis, their cohabiting partners, and healthy controls

Abstract Accumulating evidence supports an association between altered oral microbiota and inflammatory diseases. However, the existing literature on the role of the oral microbiota in patients with psoriasis is limited. Previous studies demonstrated conflicting results and have never been based on shotgun metagenomic sequencing. Several differences have been found in taxa abundance between patients and controls, and culture-based studies all found increased levels of Candida species in patients with psoriasis. The objective was to investigate the differences in the composition and the functional potential of the oral microbiota in patients with psoriasis compared with their partners and healthy controls. A case–control study was conducted with 123 participants divided into three groups; patients with psoriasis not receiving systemic anti-psoriatic treatment (n = 52), cohabiting partners of the patients (n = 21), and age-, sex- and body mass index-matched healthy controls (n = 50). One saliva sample was collected from each participant and analysed by shotgun metagenomic sequencing. Statistical analyses included a comparison of α- and β-diversity, as well as an abundance of the different taxa and Kyoto Encyclopedia of Genes and Genomes (KEGG) modules. A total of 115 samples were included in the statistical analysis, divided into patients with psoriasis (n = 47), partners (n = 21) and healthy controls (n = 47). No significant differences in baseline characteristics were found between patients with psoriasis and their partners. Smoking status (P < 0.0001) and physical activity levels (P = 0.0071) differed between the psoriasis and control groups. We observed a significant difference in α-diversity in the oral microbiome between patients with psoriasis and controls (P = 0.014), showing lower diversity in patients with psoriasis. β-Diversity analysis showed shifts in composition due to smoking (P = 0.014), but no other investigated variable had a significant association with the β-diversity, although the psoriasis group tended to cluster together apart from the two control groups. Abundance analysis was performed using both Mann–Whitney U-test and linear regression, with the former method showing one species (Leptotrichia sp018128225, FDR = 0.079) and one family (Leptotrichiaceae, FDR = 0.059) significantly different between patients and controls, whereas the latter method identified two taxa significantly different between psoriasis and control groups, as well as 21 taxa and 1 KEGG module significantly different between the psoriasis group and their partners at an FDR-adjusted P-value cut-off of 0.1. No differences were found in the abundances of Candida species. A comparison of the microbiomes of individuals with psoriasis and controls indicates that psoriasis is associated with changes in oral microbiota diversity, composition and function.

Rationale for the Use of Topical Calcineurin Inhibitors in the Management of Oral Lichen Planus and Mucosal Inflammatory Diseases.

Oral lichen planus (OLP) is a chronic inflammatory condition that affects the mucous membranes of the oral cavity and is characterized by a T-cell-mediated autoimmune response. It presents a therapeutic challenge due to its relapsing nature, causing significantly decreased quality of life and, in some cases, increasing the risk of malignant transformation. While topical corticosteroids have long been the first-line therapy for OLP, their long-term use is associated with adverse effects, such as mucosal atrophy and candidiasis. This has driven interest in alternative therapies, particularly topical calcineurin inhibitors (TCIs), such as tacrolimus, which offer a steroid-sparing approach. This review explores the pathophysiological basis of OLP, examines the role of TCIs in its treatment, and evaluates emerging therapies, with a specific focus on the use of a topical liposomal formulation of tacrolimus. These formulations aim to achieve high local drug concentrations while minimizing systemic absorption.OLP is a complex and multifactorial disease that requires a multifaceted approach to management. While current therapies provide symptomatic relief, there is a need for more effective and safer treatment options. Emerging therapies, including advanced drug delivery systems, biologics, and alternative therapies, hold promise for improving the management of OLP. Future research should focus on identifying novel therapeutic targets and developing strategies that can achieve sustained remission with minimal side effects.

The unrevealed links: periodontal health, human milk composition, and infant gut microbiome dynamics.

This review aims to identify the mechanistic relationships related to periodontal diseases and its possible association with changes in human milk composition and the composition and function of infants' gut microbiome. Maternal health conditions, especially inflammatory, are associated with altered human milk composition. It is not known whether maternal oral inflammatory diseases, including periodontal diseases, deleteriously affect human milk composition. A narrative review was conducted according to SANRA, the Scale for the Assessment of Narrative Review Articles, guidelines. PubMed, Google Scholar, and Cochrane database of systematic reviews were searched from September 2019 up to December 2023 using keywords such as breast/human milk, maternal health/infections, and periodontal diseases. Reference lists of relevant articles were also screened. Our primary outcome of interest was human milk composition (i.e., any changes in macronutrients, immunological components, etc.). Secondary outcomes included changes in human milk microbiome and subsequent changes in the infant gut microbiome. Outcomes were synthesized using a narrative approach where the existing evidence and current literature were summarized. No risk of bias assessment of the studies was performed in this review. The search yielded no studies investigating the relationship between periodontal diseases in nursing mothers and changes in human milk composition. However, a dose-response relationship exists between the severity of periodontal diseases and the risk of adverse pregnancy outcomes such as preterm birth. Mastitis and diabetes affected milk lipids. Immunoglobulin A (sIgA) was increased in mastitis, whereas reduced concentrations were reported in diabetes. Potential biological pathways through which periodontal diseases can negatively affect human milk composition include the systemic dissemination of inflammatory cytokines like IL-6, PGE2, and tumor necrosis factor (TNF)-β that can be up-regulated by bacterial by-products. This biological plausibility needs to be investigated, given the potentially negative impact on the quality of human milk that could be caused by periodontal inflammation.

Advances of Oxidative Stress Impact in Periodontitis: Biomarkers and Effective Targeting Options.

Periodontitis is the most common inflammatory oral disease that affects around 15% of adults and contributes to severe periodontal tissue destruction with subsequent tooth loosening and loss. Among the main pathogenic mechanisms underlying periodontitis, excessive reactive oxygen species production and oxidative stress play a predominant role in inducing both local and systemic damage. Current therapeutic approaches have expanded the conventional methods combined with herbal antioxidant compounds to free radical-scavenging nanomaterials and infrared laser therapy, offering promising pre-clinical evidence in periodontitis management. Herein, we review the pathogenic mechanisms of reactive oxygen species tissue damage, along with recent advances in oxidative stress biomarkers and novel targeting options.

Alterations of oral microbiome and metabolic signatures and their interaction in oral lichen planus

ABSTRACT Background Oral lichen planus (OLP) is a chronic oral mucosal inflammatory disease with a risk of becoming malignant. Emerging evidence suggests that microbial imbalance plays an important role in the development of OLP. However, the association between the oral microbiota and the metabolic features in OLP is still unclear. Methods We conducted 16S rRNA sequencing and metabolomics profiling on 95 OLP patients and 105 healthy controls (HC).To study oral microbes and metabolic changes in OLP, we applied differential analysis, Spearman correlation analysis and four machine learning algoeithms Results The alpha and beta diversity both differed between OLP and HC. After adjustment for gender and age, we found an increase in the relative abundance of Pseudomonas, Aggregatibacter, Campylobacter, and Lautropia in OLP, while 18 genera decreased in OLP. A total of 153 saliva metabolites distinguishing OLP from HC were identified. Notably, correlations were found between Oribacterium, specific lipid and amino acid metabolites, and OLP’s clinical phenotype. Additionally, the combination of Pseudomonas, Rhodococcus and (±)10-HDoHE effectively distinguished OLP from HC. Conclusions Based on multi-omics data, this study provides comprehensive evidence of a novel interplay between oral microbiome and metabolome in OLP pathogenesis using the oral microbiota and metabolites of OLP patients.

Changes in heavy metal levels in the oral fluid of young patients with and without plaque-induced gingivitis undergoing treatment with braces

Relevance. Research into the effects of nickel-titanium alloys and heavy metal ions on the development of inflammatory oral diseases is becoming increasingly significant in orthodontics. The relationship between toxic elements and inflammatory responses remains under-researched and controversial. Data on the connection between heavy metals and inflammatory reactions could influence the choice of orthodontic appliance materials and guide the subsequent management and monitoring of patients with braces. The question of the safe use of nickel-titanium alloy braces continues to be a relevant concern.Purpose. To assess the levels of heavy metals in the oral fluid of young patients with braces, both in those who developed plaque-induced gingivitis and those who did not.Materials and Methods. The study involved 50 clinically healthy patients (Groups I and II health categories) with intact teeth, including patients with compensated dental caries (isolated carious lesions – Grade I) and no periodontal diseases (PMA index <20), presenting with dental crowding and malocclusion (K07.2, K07.3). The average age of the patients was 22.1 ± 2.7 years, all of whom were undergoing treatment with metal braces. Oral fluid samples were analyzed for 12 heavy metal elements using inductively coupled plasma mass spectrometry (ICP-MS) in a laboratory setting. Additionally, lysozyme activity and oral fluid pH were measured before appliance placement and six months into orthodontic treatment.Results. Adaptation to braces in young patients is frequently complicated by the development of gingivitis and periodontitis due to impaired oral hygiene and the mechanical pressure exerted on teeth and gums, leading to elemental imbalances. Patients with gingivitis during orthodontic treatment are particularly at risk of developing such imbalances and therefore require timely correction of their mineral metabolism.

Neutrophils suppress osteogenic differentiation of Gli1+ stem cells via neutrophil extracellular traps and contribute to bone loss in periodontitis

Periodontitis is a severe and chronic oral inflammatory disease that leads to the progressive and irreversible destruction of periodontal tissues, ultimately resulting in tooth loss. Among the immune cell subtypes involved, neutrophils play a crucial role in the initiation and progression of periodontitis. Mesenchymal stem cells (MSCs) are essential components of periodontal tissue, contributing to tissue development, homeostasis, and regeneration. Recent studies have demonstrated that neutrophils significantly affect the function of MSCs by changing the inflammatory environment. However, the specific effects of neutrophils on periodontal MSCs during periodontitis remain unclear, highlighting a gap in our understanding of the disease mechanisms. In this study, we utilized the Gli1-CreERT2;mT/mG transgenic mouse model to specifically mark Gli1+ cells, a critical and representative subset of MSCs in the periodontal tissues responsible for maintaining tissue homeostasis. We reveal that neutrophils inhibit the osteogenic differentiation of Gli1+ cells and exacerbate alveolar bone destruction by secreting neutrophil extracellular traps (NETs), which induce endoplasmic reticulum stress in Gli1+ cells. These findings highlight the pivotal impact of neutrophils on distinct subpopulations of periodontal MSCs in the pathogenesis of periodontitis, offering valuable insights into the underlying mechanisms of the disease and suggesting potential future therapeutic strategies aimed at modulating the interactions between neutrophils and MSCs.

Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C0.08 loaded with dexamethasone (Dx-CMS-C0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

A Tissue-Engineered Model of T-Cell–Mediated Oral Mucosal Inflammatory Disease

T-cell-mediated oral mucocutaneous inflammatory conditions, including oral lichen planus, are common, but development of new treatments aimed at relieving symptoms and controlling oral lichen planus progression is hampered by the lack of experimental models. In this study, we developed a tissue-engineered oral mucosal equivalent containing polarized T-cells to replicate oral lichen planus pathogenesis. Peripheral blood CD4+ and CD8+ T-cells were isolated, activated, and polarized into T helper 1 and cytotoxic T cells. Oral mucosal equivalents were constructed by culturing oral keratinocytes on an oral fibroblast-populated hydrogel to produce a stratified squamous epithelium. Oral mucosal equivalent stimulated with IFN-γ and TNF-α or medium from T helper 1 cells caused increased secretion of inflammatory cytokines and chemokines. A model of T-cell-mediated inflammatory disease was developed by combining oral mucosal equivalent on top of a Thelper 1 and cytotoxic T-cell-containing hydrogel, followed by epithelial stimulation with IFN-γ and TNF-α. T-cell recruitment toward the epithelium was associated with increased secretion of T-cell chemoattractants CCL5, CXCL9, and CXCL10. Histological assessment showed tissue damage associated with cleaved caspase-3 and altered laminin-5 expression. Treatment with inhibitors directed against Jak, KCa3.1 channels, or clobetasol in solution and through a mucoadhesive patch prevented cytokine and chemokine release and tissue damage. This disease model has potential to probe for mechanisms of pathogenesis or as a test platform for novel therapeutics or treatment modalities.

Recent Advances in the Therapeutic Potential of Fucoidan: A Comprehensive Review

Fucoidan, a polysaccharide primarily comprised of l-fucose and sulfate groups possesses a unique chemical structure that underpins its notable therapeutic potential. Its remarkable biological functions such as antioxidant, anticarcinogenic, antiviral, anticoagulant, antithrombotic, immunoregulatory, and anti-inflammatory properties have gained substantial recognition in the global food and pharmaceutical industries. This review highlights recent advancements in understanding fucoidan’s potential biological activities that could innovate treatments for oral infections and inflammatory diseases. A systematic search for relevant articles published between January 2000 and July 2024 was conducted across multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Manual searches of references listed in the identified publications were conducted to ensure thorough coverage of the subject. The inclusion criteria focused on peer-reviewed articles in English-language, encompassing meta-analysis, randomized clinical trials, cohort studies, case-control studies and in vitro studies. Exclusion criteria comprised abstracts, opinion pieces, review articles not providing original analysis, and studies not directly addressing the therapeutic effects of fucoidan. This rigorous selection process aims to encapsulate the most significant and recent scientific evidence regarding the therapeutic applications of fucoidan. Fucoidans, with their diverse pharmacological properties, hold promising therapeutic potential which could emerge as a novel therapeutic option for treating wide range of diseases. Fucoidans have demonstrated anti-inflammatory properties, which may be beneficial in reducing inflammation related to periodontal diseases and other oral conditions. We anticipate that this review will serve as a foundational guide and inspire continued product development centered on fucoidan. Clinical relevance to interdisciplinary dentistry:  Fucoidan, a polysaccharide rich in fucose holds wide pharmacological effects  Enhancement of oral health outcomes through anti- inflammatory properties  Antimicrobial activity against oral pathogens  Wound healing property may aid in periodontal diseases.

IRISIN AS A NOVEL DIAGNOSTIC BIOMARKER FOR INFLAMMATORY DISEASES: A REVIEW.

Inflammatory biomarkers are molecules that can offer vital information on the intricate chain of happenings and molecular processes underpinning the pathophysiology of any inflammatory disease. They can be measured in various biological samples such as blood, urine, or saliva, and are used as indicators of the presence and severity of inflammation. Measuring salivary inflammatory biomarkers is a non-invasive and relatively easy way to monitor inflammation, and it has been shown to be a useful tool in the diagnosis and management of various oral and systemic inflammatory diseases. Irisin is a novel anti-inflammatory protein and its implication and diagnostic role in inflammation have been widely studied; however, not much have been studied in oral inflammation per se. Irisin is predominantly downregulated in several inflammatory conditions, including obesity, type 2 diabetes, periodontitis, and cardiovascular diseases. This suggests that irisin may be involved in the inflammatory process, but more research is needed, especially of salivary irisin to understand its precise role. Overall, the role of irisin as an inflammatory biomarker is still an area of active research, and more studies are needed to determine its diagnostic and therapeutic potential. This review highlights the diagnostic and therapeutic potential of irisin in various systemic and oral inflammatory conditions.

GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice.

G protein-coupled receptor (GPR)40 and GPR120 are receptors for medium- and long-chain free fatty acids. It has been well documented that GPR40 and GPR120 activation improves metabolic syndrome (MetS) and exerts anti-inflammatory effects. Since chronic periodontitis is a common oral inflammatory disease initiated by periodontal pathogens and exacerbated by MetS, we determined if GPR40 and GPR120 activation with agonists improves MetS-associated periodontitis in animal models in this study. We induced MetS and periodontitis by high-fat diet feeding and periodontal injection of lipopolysaccharide, respectively, and treated mice with GW9508, a synthetic GPR40 and GPR120 dual agonist. We determined alveolar bone loss, osteoclast formation, and periodontal inflammation using micro-computed tomography, osteoclast staining, and histology. To understand the underlying mechanisms, we further performed studies to determine the effects of GW9508 on osteoclastogenesis and proinflammatory gene expression in vitro. Results showed that GW9508 improved metabolic parameters, including glucose, lipids, and insulin resistance. Results also showed that GW9508 improves periodontitis by reducing alveolar bone loss, osteoclastogenesis, and periodontal inflammation. Finally, in vitro studies showed that GW9508 inhibited osteoclast formation and proinflammatory gene secretion from macrophages. In conclusion, this study demonstrated for the first time that GPR40/GPR120 agonist GW9508 reduced alveolar bone loss and alleviated periodontal inflammation in mice with MetS-exacerbated periodontitis, suggesting that activating GPR40/GPR120 with agonist GW9508 is a potential anti-inflammatory approach for the treatment of MetS-associated periodontitis.

TFEB alleviates periodontitis by activating autophagy and inhibiting inflammation

Periodontitis is a chronic inflammatory oral disease that impaired the tooth-supporting apparatus, including gingival tissue destruction and alveolar bone resorption. The initiation of periodontitis is linked to the presence of oral bacteria, particularly P. gingivalis within pathogenic biofilms. Here, we demonstrated the central role of the autophagy regulator Transcription Factor EB (TFEB) in orchestrating autophagy activation and modulating the host immune response against P. gingivalis in periodontitis. Upregulation of TFEB expression at the protein level and heightened nuclear localization occurred during the progressive stages of periodontitis. Functionally, TFEB overexpression emerges as a potent alleviator of periodontitis-associated phenotypes, operating through the activation of autophagy and the inhibition of the NF-κB pathway in both in vivo and in vitro models. In addition, TFEB knockdown exacerbates the inflammatory response by upregulating pro-inflammatory cytokines. The dual regulatory role of TFEB in governing both autophagy and inflammatory responses unveils novel insights into periodontitis pathogenesis, positioning TFEB as a promising therapeutic target for periodontitis intervention.

Twenty-first century knowledge mapping on oral diseases and physical activity/exercise, trends, gaps, and future perspectives: a bibliometric review.

Maintenance and improvement of an individual's overall well-being require a multidisciplinary approach that encompasses everything from oral health care to regular physical exercise. The notion that poor oral health can influence general health and athletic performance has sparked an interest in this relationship. This study offers an overview of relevant research and a knowledge map,and discusses publication metrics and key topics concerning the relationship between physical activity or exercise and oral diseases. We searched the Web of Science database for articles published in the 21st century that addressed the relationship between physical activity and oral diseases. Under the stipulated inclusion criteria, a rigorous selection process yielded 276 from 3,883 retrieved articles. The articles were classified by what was assessed as follows: occurrence of oral diseases in athletes or sports enthusiasts (n = 174); impact of physical activity or exercise on the oral cavity (n = 59); effects of oral changes on sports performance and physical fitness (n = 31); and the connection between oral health status, physical activity or exercise, and systemic conditions (n = 12). Orofacial trauma has received the most attention among all investigated oral diseases. However, there is a need for greater attention of dysfunctional habits that can contribute to premature tooth wear, as well as oral inflammatory diseases that can have systemic implications. This mapping can encourage the development of new primary research.