Periodontal inflammation is a chronic condition affecting the tissues surrounding teeth. Initiated by dental plaque, it triggers an immune response leading to tissue destruction. The AIM-2 inflammasome regulates this response, and understanding its peptide sequences could aid in developing targeted therapeutics. This study explores using transformers and graph attention networks (GAT) to treat periodontal inflammation. UniProt was used to download AIM-2 inflammasome proteins and FASTA sequences with 100%, 90%, and 50% similarity. DeepBio, a web service for developing deep-learning architectures, analyzed these sequences. Peptide sequence prediction methods were evaluated using a transformer, RNN-CNN, and GAT models. The transformer model achieved 84% accuracy, the GAT model 86%, and the RNN-CNN 64%. Both transformer and GAT models predicted peptide sequences more effectively than the RNN-CNN model, with the Transformer showing the highest class accuracy at 85%, followed by the GAT model at 80%. Models exhibited varying sensitivity and specificity, with the Transformer demonstrating superior performance in overall and class-specific peptide sequence prediction. AI-based peptide sequence prediction using transformers, GAT, and RNN-CNN shows promise for accurately predicting AIM-2 peptide sequences, with transformers and GAT outperforming RNN-CNN in accuracy and class accuracy.

 This investigation aims to investigate the association between HIF-1α genetic polymorphism and periodontitis and examine and contrast the levels of HIF-1α present in the saliva of subjects afflicted with periodontitis and in the control group. Additionally, this study aims to establish diagnostic proficiency of this biomarker in distinguishing between periodontal health and disease.

 This study entailed the collection of venous blood samples and unstimulated saliva samples from a total of 160 participants, encompassing 80 individuals diagnosed with periodontitis and 80 periodontitis-free individuals. The periodontal parameters were evaluated, involving the measurement of clinical attachment loss, the probing pocket depth, and the bleeding on probing percentage. Subsequently, genetic analysis of HIF-1α using polymerase chain reaction (PCR) technique, DNA sequencing, and enzyme-linked immunosorbent assays was conducted.

 The genetic analysis of 352 bp of the HIF-1α gene revealed the presence of 66 single-nucleotide polymorphisms (SNPs) in control samples, whereas 78 SNPs were found in periodontitis sample. The nucleotide A was replaced with a C nucleotide at position 207 of the amplified PCR fragments. The homozygous AA pattern was predominant in the control group, with significant differences between the two groups. In contrast, the homozygous CC pattern was more dominant in the periodontitis group, with significant differences between the two groups. The analysis of Hardy-Weinberg equilibrium for the comparison between the observed and the expected genotypes showed significant differences between the observed and the expected values in the control and periodontitis groups, as well as the total sample. The highest mean values of the measured periodontal parameters were found in the periodontitis group (clinical attachment loss = 4.759, probing pocket depth = 4.050, and bleeding on probing = 30.950) with statistically significant differences between the groups. The periodontitis group showed significantly higher salivary HIF-1α levels compared to control group (p < 0.001). Besides, HIF-1α is a good biomarker in distinguishing between periodontal health and periodontitis.

 rs1951795 SNP of HIF-1α has no significant impact on the progression of periodontitis and the salivary level HIF-1α. Periodontitis results in a notable elevation in HIF-1α salivary levels, with an outstanding diagnostic ability to distinguish between periodontitis and periodontal health.

The aim of the study is to compare the clinical efficacy of the application of "Armenicum" paste as an adjunct to SRP for the non-surgical treatment of patients with periodontitis.

The current RCT prospective study was conducted on 157 patients with chronic periodontitis. The patients were blind randomly assigned into two groups: Group A (SRP + Armenicum" paste) 81 patients (42 males and 39 females, 37 to 68 years) and Group B (SRP) 76 patients (39 males and 37 females, 37 to 68 years). Periodontal indices BOP, PPD, and DPI within each treatment group were measured before periodontal therapy, 3 and 6 months after the treatment. Group A underwent a periodontal treatment which included: supragingival and subgingival scaling, and additional use of local "Armenicum" paste. The Group B group only received supragingival and subgingival scaling.

In our study, the mean BOP, DPI, and PPD showed a statistically significant difference from baseline to 3 months and 6 months (p ≤ 0.05) in both Group A and Group B. But, mean BOP and mean PPD reduction gain was found to be greater in Group-A than Group B at 3 months and 6 months. No statistical differences in clinical indices were recorded depending on gender and age.

These results indicate that topical "Armenicum" paste provides an effective adjunctive treatment of chronic periodontitis.

The results of the current study showed that the adjunctive use of "Armenicum" reduced signs of inflammation compared to standard SRP treatment alone. Periodontal therapy using Armenicum paste application can be considered as a promising method in the treatment of periodontitis.

Peri-implantitis remains a substantial challenge. This study investigated the effect of titanium particles on human oral epithelial cells, focusing on the nucleotide-binding domain and leucine-rich repeat protein (NLRP) 3 inflammasome.

The Ca9-22 human gingival epithelial cell line was subjected to incubation with titanium particles. To evaluate cell viability, the MTT assay was employed. Total RNA was extracted, and messenger RNA (mRNA) expressions of COX2, TGF-β1, NLRP1, NLPR3, CASP1, and AIM2 were analyzed. The concentration of interleukin (IL)1β in cell supernatants was quantified through enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) were visualized using an ROS assay Kit.

Ca9-22 cells treated with titanium particles showed >75% cell viability across all concentrations tested, with consistent results. mRNA expressions of inflammation-related genes (COX2 and TGF-β1) significantly increased in a dose-dependent manner. The mRNA expression of NLRP3 and CASP1, as well as the secretion of IL1β, increased after 6-h incubation with titanium particles. Moreover, the ROS assay results showed increased production of ROS after treatment with titanium particles, whereas NLRP3 expression and IL1β secretion reduced after treatment with N-acetyl-l-cysteine (ROS scavenger).

Our findings indicate that titanium particles possess a distinct ability to trigger the NLRP3 inflammasome, partly by producing ROS.

Periodontitis is a chronic inflammatory disease involving plaque biofilm as a pathogenic factor. Potassium ion plays an important role in cellular homeostasis; a large outflow of potassium may lead to local inflammation progression. In this work, the multifunctional short peptide molecule BmKTX-33 was designed by modifying the BmKTX, a Kv1.3 potassium channel inhibitor. This was to explore its antibacterial properties, capability of maintaining cell ion homeostasis, and bone-forming capacity. The results showed that BmKTX-33 had inhibitory effects on S. gordonii, F. nucleatum, and P. gingivalis. Moreover, BmKTX-33 also inhibited excessive potassium outflow in inflammatory environments. Finally, BmKTX-33 promoted MC3T3-E1 early osteogenesis while suppressing the NLRP3 inflammasome's production. In conclusion, BmKTX-33 not only has antibacterial properties, but also can inhibit the expression of NLRP3 inflammasome and play an anti-inflammatory role.

Tissue-invasive bacteria have been proposed to be a crucial factor in the etiopathogenesis of periodontitis, with the probable interaction of tissue-invasive bacteria with the innate immune response through inflammasomes, perpetuating periodontal attachment loss. This study aims to reveal the correlation between such tissue-invasive bacteria in upregulating inflammasomes and pro-inflammatory cytokines.

This study recruited a total of 10 patients with stage III/IV and grade C periodontitis based on the bone loss to age ratio. Patient sites were grouped into group I: healthy sites with no clinical attachment loss (CAL); group II (mild-to-moderate): 1-4 mm of CAL; group III: severe (≥ 5 mm of CAL). Tissue samples were collected in these sites during periodontal flap surgery and assessed for both the bacterial genomic DNA and assessed for the upregulation of pro-inflammatory markers NOD-like receptor - Pyrin domain containing protein 3 (NLRP3), Human AIM2, Human Pro-TNFα, Human Pro-IL-1β, Human Pro-IL 6 and Human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes.

The levels of NLRP3, AIM2, and pro-inflammatory cytokine levels were all higher in the severe sites when compared with the other two sites. The tissue invasive bacterial phylotypes in these sites were thereafter compared with the levels of the pro-inflammatory markers in the various groups. The fold changes in the pro-inflammatory markers evaluated in this study all hovered around 1, indicating not much difference in the upregulation of these markers of inflammation. Statistically, significant correlation between bacterial phenotypes in the healthy sites group and the pro-interleukin-6 (IL-6) cytokine expression was observed (r = 0.68; p < 0.04).

This study has highlighted the presence of tissue-invasive bacteria in sites with or without CAL. The fact that these healthy sites, after non-surgical therapy, have comparable levels of pro-inflammatory markers in the tissues may be explained by immune priming, by tissue- invasive periodontal pathogens.

Tissue-invasive bacteria are present in periodontally healthy sites too, and non-surgical periodontal therapy is inadequate to eliminate them. Greater importance should be given to the soft tissue walls of the periodontal pocket in clinical management of periodontitis. How to cite this article: Victor DJ, Anandan NS, Appukuttan D, et al. Tissue-invasive Pathogens in Periodontitis Patients and Their Correlation with Pro-inflammatory Markers: An Analytical Case-control Study. J Contemp Dent Pract 2024;25(10):992-996.

Periodontitis is an inflammatory oral disease that occurs as a result of the damaging effects of the immune response against the subgingival microflora. Among the mechanisms involved, the nucleotide-binding oligomerization domain, leucine-rich repeat-containing proteins family member NLRP3 (NLR family pyrin domain-containing 3), proposed as the key regulator of macrophage-induced inflammation, is strongly associated with periodontal disease due to the bacterial activators. This paper aimed to present key general concepts of NLRP3 inflammasome activation and regulation in periodontal disease.

A narrative review was conducted in order to depict the current knowledge on the relationship between NLRP3 inflammasome activity and periodontal disease. In vitro and in situ studies were retrieved and commented based on their relevance in the field.

The NLRP3 inflammasome activity stimulated by periodontal microbiota drive periodontal disease pathogenesis and progression. This occurs through the release of proinflammatory cytokines IL-1β, IL-18, and DAMPs (damage-associated molecular pattern molecules) following inflammasome activation. Moreover, the tissue expression of NLRP3 is dysregulated by oral microbiota, further exacerbating periodontal inflammation.

The review provides new insights into the relationship between the NLRP3 inflammasome activity and periodontal disease pathogenesis, highlighting the roles and regulatory mechanism of inflammatory molecules involved in the disease process.

The bidirectional relationship between periodontitis and type 2 diabetes mellitus has been well-established. However, the underlying molecular mechanisms remain unclear. Diabetic retinopathy (DR) is an important complication of diabetes, but there are few studies on the relationship between DR and periodontitis, especially on the intrinsic inflammatory pathway mechanism. This article reviews the latest clinical data on how diabetes promotes susceptibility to periodontitis from the epidemiological and molecular perspectives, with a special focus on the key roles of systemic inflammation and endothelial dysfunction in the interplay between DR and periodontitis. Comprehension of the intertwined pathogenesis of DR and periodontitis can better guide the development of comprehensive management strategies for glycemic control and periodontal health, with the aim of mitigating the progression of DR and enhancing overall well-being.

Chronic inflammatory processes in the oral mucosa and periodontitis are common disorders caused by microflora and microbial biofilms. These factors activate both the innate and adaptive immune systems, leading to the production of pro-inflammatory cytokines. Cytokines are known to play a crucial role in the pathogenesis of gingivitis and periodontitis and have been proposed as biomarkers for diagnosis and follow-up of these diseases. They can activate immune and stromal cells, leading to local inflammation and tissue damage. This damage can include destruction of the periodontal ligaments, gingiva, and alveolar bone. Studies have reported increased local levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumor necrosis factor (TNF), IL-6, IL-17, and IL-23, in patients with periodontitis. In experimental models of periodontitis, TNF and the IL-23/IL-17 axis play a pivotal role in disease pathogenesis. Inactivation of these pro-inflammatory pathways through neutralizing antibodies, genetic engineering or IL-10 function has been demonstrated to reduce disease activity. This review discusses the role of cytokines in gingivitis and periodontitis, with particular emphasis on their role in mediating inflammation and tissue destruction. It also explores new therapeutic interventions that offer potential for research and clinical therapy in these chronic inflammatory diseases.

Periodontitis and peri-implantitis are inflammatory diseases of infectious etiology that lead to the destruction of the supporting tissues located around teeth or implants. Although both pathologies share several characteristics, it is also known that they show important differences which could be due to the release of particles and metal ions from the implant surface. The activation of the inflammasome pathway is one of the main triggers of the inflammatory process. The inflammatory process in patients who suffer periodontitis or peri-implantitis has been mainly studied on cells of the immune system; however, it is also important to consider other cell types with high relevance in the regulation of the inflammatory response. In that context, mesenchymal stromal cells (MSCs) play an essential role in the regulation of inflammation due to their ability to modulate the immune response. This study shows that the induction of NLRP3 and absent in melanoma 2 (AIM2) inflammasome pathways mediated by bacterial components increases the secretion of active IL-1β and the pyroptotic process on human alveolar bone-derived mesenchymal stromal cells (hABSCs). Interestingly, when bacterial components are combined with titanium ions, NLRP3 expression is further increased while AIM2 expression is reduced. Furthermore, decrease of NLRP3 or AIM2 expression in hABSCs partially reverses the negative effect observed on the progression of the inflammatory process as well as on cell survival. In summary, our data suggest that the progression of the inflammatory process in peri-implantitis could be more acute due to the combined action of organic and inorganic components.

Clinical studies have shown that Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans. This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A. actinomycetemcomitans.

The global increase in the prevalence of type 2 diabetes mellitus (T2DM) and its complications presents significant challenges to public health. Recently, per-iodontal disease (PD) was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative stress. In this editorial, we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024, which investigated the correlation between PD and diabetic retinopathy (DR) in T2DM patients, with emphasis on the association between periodontal swollen surface area, glycated hemoglobin (HbA1c), interleukin-6 (IL-6), and lipoprotein (a). The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM patients. This correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR, a complication of diabetes. The integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients . A few studies have established an interconnection between PD and diabetic complication, specifically DR, in T2DM patients, which we aim to highlight in this editorial. Emphasis was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM, where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular mechanisms. This article highlights the importance of collaboration amongst diabetes specialists, ophthalmologists, periodontists, and public health professionals to advance the prevention, early detection, and treatment of PD and DR. This will improve the health and quality of life of T2DM patients. Moreover, the editorial highlights the need for further research on the specific molecular and immunological mechanisms that underlie the link between periodontitis and DR, with identification of common inflammatory biomarkers and signaling pathways. This is expected to facilitate effective direction of therapeutic objectives, thereby improving the management of diabetes and its complications through integrated care that incorporates oral health.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Periodontal disease is an inflammatory condition characterized by an aberrant immune response against a dysbiotic dental biofilm, with oxidative stress performing an essential role in its pathogenesis. This paper presents a patent mining, performed in the Orbit Intelligence patent database, related to antioxidant phytochemicals in the technological developments that are working to prevent and treat periodontal disease. To access the documents, the descriptors "PERIODONTAL" and "ANTIOXIDANT" were typed in the title, abstract, and claim search fields. A total of 322 patents demonstrate the growing interest in researching natural antioxidants for scientific and technological purposes. The top ten countries regarding the number of family patents produced were the United States, the European Office, Japan, South Korea, China, India, Mexico, Denmark, Canada, and Great Britain. The most cited compounds were vitamin C, green tea, quercetin, melatonin, lycopene, resveratrol, and curcumin. These compounds have been used for the technological development of gels, membranes, dentifrices, chewing gum, orally disintegrating film, mouthwash, mouth spray, and mouth massage cream and exhibit the ability to neutralize free radicals and reduce oxidative stress, a critical factor in the development and progression of periodontal diseases. The patent documents have shown that using antioxidant compounds in conjunction with traditional periodontal treatments is a promising area of interest in periodontal therapy.

Specific bacterial plaque and environmental factors cannot be considered the only cause of periodontitis. Still, several genetic factors affect the host response to the bacteria, like gene polymorphisms in anti-inflammatory cytokines. Several studies have reported that clones of T-helper 2 lymphocytes (TH2) are generated in response to dental plaque in periodontitis patients, while in healthy individuals, they are regulated by T-helper 1 (TH1) lymphocytes. Accordingly, such patients consistently produce more IL-4 (TH2) in response to bacterial stimulation, whereas healthy controls with intact periodontal tissues produce a significantly higher level of TH1.

The effectiveness of Oil Pulling Therapy (OPT) with coconut (CO) and sesame oil (SO) on gingivitis patients is of interest. Forty patients were randomly distributed into group A and B for CO and SO respectively. Participants of group A were explained in detail about the OPT with CO and group B with SO along with their routine oral hygiene practice for 30 days. The mean plaque index of CO and SO reduced from 1.5 to 1.32 and 1.65 to 1.36 (p<0.05) respectively after 30 days. The mean gingival index of CO and SO declined from 1.12 to 0.9 and 1.1 to 0.81 respectively after 30 days (p<0.05) compared to initial scores. The mean no. of colonies in the case of CO and SO declined from 35.8 x 103 to 32.4 x 103 and 6.8 x 103 to 34.6 x 103 after 30 days (p<0.05). OPT reduced plaque and gingivitis, according to the results of one month. Hence, we must increase awareness about oil pulling, as this home therapy can prevent gingival diseases in countries with limited resources like ours.

The two-way relationship between periodontitis and type 2 diabetes mellitus (T2DM) is well established. Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis, accentuating diabetic complications. An inflammatory link exists between diabetic retinopathy (DR) and periodontitis, but the studies regarding this association and the role of lipoprotein(a) [Lp(a)] and interleukin-6 (IL-6) in these conditions are scarce in the literature.

To determine the correlation of periodontal inflamed surface area (PISA) with glycated Hb (HbA1c), serum IL-6 and Lp(a) in T2DM subjects with retinopathy.

This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR. All subjects were assessed for periodontal parameters [bleeding on probing (BOP), probing pocket depth, clinical attachment loss (CAL), oral hygiene index-simplified, plaque index (PI) and PISA], and systemic parameters [HbA1c, fasting plasma glucose and postprandial plasma glucose, fasting lipid profile, serum IL-6 and serum Lp(a)].

The proportion of periodontitis in T2DM with and without DR was 47.5% and 27.5% respectively. Severity of periodontitis, CAL, PISA, IL-6 and Lp(a) were higher in T2DM with DR group compared to T2DM without DR group. Sig-nificant difference was observed in the mean percentage of sites with BOP between T2DM with DR (69%) and T2DM without DR (41%), but there was no significant difference in PI (P > 0.05). HbA1c was positively correlated with CAL (r = 0.351, P = 0.001), and PISA (r = 0.393, P ≤ 0.001) in study subjects. A positive correlation was found between PISA and IL-6 (r = 0.651, P < 0.0001); PISA and Lp(a) (r = 0.59, P < 0.001); CAL and IL-6 (r = 0.527, P < 0.0001) and CAL and Lp(a) (r = 0.631, P < 0.001) among study subjects.

Despite both groups having poor glycemic control and comparable plaque scores, the periodontal parameters were higher in DR as compared to T2DM without DR. Since a bidirectional link exists between periodontitis and DM, the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Inflammatory illnesses, such as periodontitis and atherosclerotic coronary heart disease (ASCHD), trigger the production of pro-inflammatory mediators. The aim of this study was to assess the accuracy of using salivary interleukin-1β (IL-1β), interleukin-18 (IL-18), and gasdermin D (GSDMD) in discerning patients with periodontitis with and without ASCHD from healthy individuals, and to assess their correlation with clinical periodontal parameters and low-density lipoprotein (LDL) levels. The study involved 120 participants: 30 were healthy subjects (control group, C), 30 had generalized periodontitis (group P), 30 had ASCHD and clinically healthy periodontium (group AS-C), and 30 had ASCHD and generalized periodontitis (group AS-P). Saliva and blood samples were collected, and periodontal characteristics such as plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss were examined. IL-1β, IL-18, and GSDMD levels from saliva were determined using ELISA. LDL levels were determined from the blood samples. Groups P, AS-C, and AS-P had higher levels of salivary IL-1β, IL-18, and GSDMD than group C. The receiver operating characteristic (ROC) curves of all biomarkers showed high diagnostic accuracy, with a significant positive correlation with the clinical parameters and LDL levels. The observed correlations between the studied pro-inflammatory mediators and disease severity suggest that these biomarkers could serve as indicators of disease progression in conditions such as periodontitis and ASCHD.

To investigate the proportional variation of macrophage and T-lymphocytes subpopulations in acute coronary syndrome (ACS) patients, its association with periodontitis (P), and to compare with control individuals.

Three groups of subjects participated: one group consisted of 17 ACS patients with P (ACS + P), another group consisted of 22 no ACS + P patients, and a control group consisted of 23 participants with gingivitis (no ACS + G). Macrophage, CD4 + , and CD8 + T-lymphocytes and CD4 + /CD8 + ratio values in gingival tissue were determined histometrically.

Significant differences were found among three groups regarding the mean number of macrophage (no ACS + P > ACS + P > no ACS + G; p < 0.05) and CD8 + T-lymphocytes (no ACS + P > ACS + P > no ACS + G; p < 0.05). Significant variations were observed between the groups both CD4 + T-lymphocytes densities (ACS + P > no ACS + P and ACS + P > no ACS + G; p < 0.05) and CD4 + / CD8 + ratio (no ACS + P < no ACS + G and ACS + P < no ACS + G; p < 0.05).

The increased number of CD8 + T-lymphocytes in both group ACS + P and group no ACS + P resulted in a reduction of the CD4 + /CD8 + ratio in gingival tissue when compared with no ACS + G group.

The decrease of CD4 + /CD8 + ratio in gingival tissue reflects periodontitis and may be associated with severe adverse outcomes in people with ACS.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Chlorhexidine gluconate (CHX) has been still regarded as the most efficient mouthwash. Due to its recognized negative effects, it can only be used for a short duration. Octenidine dihydrochloride (OCT), an antiseptic substance found by Sterling Winthrop in the 1980s, has proven helpful in preventing the co-aggregation of dental plaque microbial invaders without disrupting the typical, healthy oral flora. However, there is very little research on octenidine's effectiveness as a mouthwash for preventing plaque. Therefore, this study is being conducted to examine the effectiveness of mouthwashes containing 0.1% Octenidine and 0.2% chlorhexidine.

In this clinical trial, subjects were divided into two groups, 60 patients each with gingivitis and periodontitis. Then, from each group, 30 patients were advised to use octenidine mouthwash, and 30 patients were prescribed chlorhexidine mouthwash as an adjunct to scaling and root planning. Clinical parameters like O'Leary plaque index, Bleeding index, Probing pocket depth, and clinical attachment loss were evaluated at baseline and after 3 months.

In both the gingivitis and periodontitis groups, the octenidine group significantly outperformed the chlorhexidine group in all clinical metrics.

Octenidine showed better results in comparison to chlorhexidine with respect to all the above-mentioned clinical parameters. Hence, it can be considered a promising mouthwash for future therapeutic and research studies.

This review aimed at searching literature for data regarding the inflammasomes' involvement in the pathogenesis of oral diseases (mainly periodontitis) and general pathologies, including approaches to control inflammasome-related pathogenic mechanisms. The inflammasomes are part of the innate immune response that activates inflammatory caspases by canonical and noncanonical pathways, to control the activity of Gasdermin D. Once an inflammasome is activated, pro-inflammatory cytokines, such as interleukins, are released. Thus, inflammasomes are involved in inflammatory, autoimmune and autoinflammatory diseases. The review also investigated novel therapies based on the use of phytochemicals and pharmaceutical substances for inhibiting inflammasome activity. Pharmaceutical substances can control the inflammasomes by three mechanisms: inhibiting the intracellular signaling pathways (Allopurinol and SS-31), blocking inflammasome components (VX-765, Emricasan and VX-740), and inhibiting cytokines mediated by the inflammasomes (Canakinumab, Anakinra and Rilonacept). Moreover, phytochemicals inhibit the inflammasomes by neutralizing reactive oxygen species. Biomaterials functionalized by the adsorption of therapeutic agents onto different nanomaterials could represent future research directions to facilitate multimodal and sequential treatment in oral pathologies.

The activation of inflammasomes is thought to induce the inflammatory process around dental implants. No information is available on the correlation between microbiota and inflammasomes in clinical samples from patients suffering peri-implantitis. For this cross-sectional study, 30 biofilm samples were obtained from 19 patients undergoing surgical treatment for peri-implantitis because of the presence of bleeding on probing, probing depth higher than 6 mm, and radiographic bone loss higher than 3 mm. Then, soft tissue samples from around the implant were also collected. The relative abundance of bacteria and alpha-diversity indexes were calculated after analyzing the 16S rRNA gene using next-generation sequencing. The soft-tissue samples were processed for evaluation of the inflammasomes NLRP3 and AIM2 as well as caspase-1 and IL-1β. The relative abundance (mean (SD)) of specific species indicated that the most abundant species were Porphyromonas gingivalis (10.95 (14.17)%), Fusobacterium vincentii (10.93 (13.18)%), Porphyromonas endodontalis (5.89 (7.23)%), Prevotella oris (3.88 (4.94)%), Treponema denticola (2.91 (3.19)%), and Tannerella forsythia (2.84 (4.15)%). Several correlations were found between the species and the immunohistochemical detection of the inflammasomes NLRP3 and AIM2 as well as caspase-1 and IL-1β, both in the epithelium and the lamina propria. A network analysis found an important cluster of variables formed by NLRP3 in the lamina propria and AIM2, caspase-1, and IL-1β in the lamina propria and the epithelium with Prevotella dentalis, Prevotella tannerae, Tannerella forsythia, or Selenomonas timonae. Thus, it could be concluded that inflammasomes NLRP3 and AIM2 and their downstream effectors caspase-1 and interleukin-1β can be significantly associated with specific bacteria.

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.

To investigate the effects of long intergenic noncoding RNA-erythroid prosurvival (lincRNA-EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA-EPS-/- ) and WT (lincRNA-EPS+/+ ) mice to compare the periodontal bone loss and inflammation by using micro-computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate-specific proteinase-11 (caspase-11) and NOD-like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor-kappa B (NF-κB) activation in mouse gingival fibroblasts (MGFs), were measured by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA-EPS. RNA pull-down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA-EPS. LincRNA-EPS-expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA-EPS increased bone loss and expression of myeloperoxidase, interleukin-1α (IL-1α) and IL-1β in the inflammatory periodontium. LincRNA-EPS KO MGFs exhibited increased expression and activation of caspase-11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA-EPS overexpressed MGFs. Mechanistically, lincRNA-EPS directly bound to transactive response DNA-binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF-κB activation and the inflammasomes as lincRNA-EPS overexpression. Locally injecting lincRNA-EPS-expressing lentivirus weakened the periodontal damage. LincRNA-EPS inhibits the LPS-induced production and activation of caspase-11 and NLRP3 inflammasomes by suppressing the activation of the NF-κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis.

Inflammasome components NLRP3 and AIM2 contribute to inflammation development by the activation of caspase-1 and IL-1β. They have not been yet evaluated in samples from patients with active peri-implantitis. Thus, the aim of the present study is to analyze the expression of inflammasomes NLRP3 and AIM2 and subsequent caspase 1 and IL-1β assessing the microenvironment of leukocyte subsets in samples from patients with active peri-implantitis.

Biopsies were collected from 33 implants in 21 patients being treated for peri-implantitis. Biopsies from gingival tissues from 15 patients with healthy periodontium were also collected for control. These tissues were evaluated through conventional histological stainings. Then, immunohistochemical detection was performed to analyze NLRP3, AIM2, caspase-1, and IL-1β and markers of different leukocyte subsets. PCR for inflammasomes and related genes was also done.

This manuscript reveals a high immunohistochemical and mRNA expression of NLRP3 and AIM2 inflammasomes, caspase-1, and IL-1β in biopsies collected from human peri-implantitis. The expression of the tested markers was significantly correlated with the increase in inflammatory infiltrate, probing depth, presence of biofilm, and bleeding on probing. In these peri-implantitis lesions, the area of biopsy tissue occupied by inflammatory infiltrate was intense while the area occupied by collagen was significantly lower. In comparison with periodontal healthy tissues, the inflammatory infiltrate was statistically significantly higher in the peri-implantitis biopsies and was mainly composed of plasma cells, followed by T and B lymphocytes.

In human peri-implantitis, chronic inflammation can be explained in part by the action of IL-1β/caspase 1 induced through NLRP3 and AIM2 inflammasome activation.

Numerous genetic variations in inflammasome components are linked to prevalent disorders in the general population, including periodontitis and cardiovascular illness. Polymorphisms in the genes play a critical in the initiation and development of inflammatory diseases. The limited study on AIM2 gene variation associated with inflammatory disease and no study of PYCARD gene variation associated with inflammatory disease.

This case-control study was to examine the association between the single nucleotide polymorphism of AIM2 and Pycard genes with susceptibility to periodontitis with and without coronary heart disease, to determine interleuken-18 and gasdermin D levels in the saliva of periodontitis with and without coronary heart disease patients, as well as their correlation with salivary interleuken-18 and gasdermin D levels and clinical periodontal parameters.

The present study recruited 120 participants: 30 were healthy subjects (control, C), 30 had generalized periodontitis (P), 30 had atherosclerosis coronary heart disease with clinically healthy periodontium (AS-C), and 30 had atherosclerosis coronary heart disease with generalized periodontitis (AS-P). All individuals' demographic data recorded, saliva and blood samples collected, then periodontal characteristics were detailed. These parameters include plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss. AIM2 and Pycard gene polymorphisms were analyzed by polymerase chain reaction assay, electrophoresis and sequencing. An enzyme-linked immunosorbent assay (ELISA) was conducted to determine the level of interleuken-18 and gasdermin D in their saliva.

The study result of high frequency (T) in single-nucleotide polymorphisms. The high genotypes distribution of GT and TT genotypes in the AIM2 gene and the CT and TT genotypes in the Pycard gene were detected in the periodontitis, atherosclerosis coronary heart disease with healthy periodontium and atherosclerosis coronary heart disease with generalized periodontitis groups as compared to control group. Elevation of salivary interleuken-18 and gasdermin D levels in three patients' groups compared to healthy controls. Both these single-nucleotide polymorphisms also significantly correlated with higher salivary interleuken-18 and gasdermin D levels and worse clinical indices of periodontitis.

Single-nucleotide polymorphisms in the AIM2 and Pycard genes are associated with an increased risk of developing periodontitis with and/or without coronary heart disease. Elevation of salivary interleuken-18 and gasdermin D levels associated and impacted on periodontitis with and/or without coronary heart disease. These single-nucleotide polymorphisms may provide evidence for a genetic role in the pathogenesis of periodontitis with and without atherosclerosis coronary heart disease.

Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.

 The nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome regulates the maturation and release of the cytokines as well as the activation of caspase in response to danger signals derived from pathogenic infection, tissue damage, andmetabolic changes that have a role in the pathogenesis of different diseases as periodontitis. Yet, the susceptibility to this illness could be determined by population-based genetic differences. The aim of this study was to determine whether periodontitis in Arab populations from Iraq is correlated with NLRP3 gene polymorphisms and measure clinical periodontal parameters and investigate their association with genetic polymorphisms of the NLRP3.

 The study sample consisted of 94 participants ranging from 30 to 55 years old, both males and females who fulfilled the study's criteria. The selected participants were divided into two groups: the periodontitis group (62 subjects) and the healthy control group (32 subjects). The examination of clinical periodontal parameters of all participants was carried out, followed by a collection of venous blood for NLRP3 genetic analysis using the polymerase chain reaction-sequencing technique.

 The genetic analysis of NLRP3 genotypes at four single nucleotide polymorphisms (SNPs) (rs10925024, rs4612666, rs34777555, and rs10754557), by Hardy-Weinberg equilibrium, identified nonsignificant differences in studied groups. The C-T genotype among periodontitis was significantly different from controls, while the C-C genotype among control was significantly different from periodontitis at NLRP3 rs10925024. Overall, there were 35 SNPs in the periodontitis group and 10 SNPs in the control group for rs10925024 with significant differences versus nonsignificant differences of the other SNPs between the studied groups. Clinical attachment loss and NLRP3 rs10925024 additionally demonstrated a significant positive correlation in the periodontitis subjects.

 The findings suggested that polymorphisms of the NLRP3 gene may have a role and increasing the genetic susceptibility to periodontal disease in Arabs Iraqi patients.

The active form of vitamin D is the hormonally active 1,25(OH)2D3 (Vit D) vitamin, which plays an important role in bone biology and host immunity. The vitamin D receptor (VDR) is a nuclear ligand-dependent transcription factor expressed by many cells. Ligation of VDR by VitD regulates a wide plethora of genes and physiologic functions through the formation of the complex Vit D-VDR signaling cascade. The influence of Vit D-VDR signaling in host immune response to microbial infection has been of interest to many researchers. This is particularly important in oral health and diseases, as oral mucosa is exposed to a complex microbiota, with certain species capable of causing disruption to immune homeostasis. In this review, we focus on the immune modulatory roles of Vit D in the bone degenerative oral disease, periodontitis.

Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) has myriads of virulence factors among which leukotoxin provides A. actinomycetemcomitans with the advantage to thrive in the surrounding hostile environment and evade host immune defences. The NLRP3 inflammasome has been associated with periodontal disease development. However, our understanding of the involvement of caspase-1, caspase-4, and NLRP3 in the release of IL-1β and other inflammatory mediators from gingival epithelial cells during a A. actinomycetemcomitans infection is limited. The aim of this study was to investigate how the inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 regulate the immune response of gingival epithelial cells during a A. actinomycetemcomitans infection. Human gingival epithelial cells (Ca9-22) deficient in NLRP3, caspase-1 or caspase-4 were created using CRISPR/Cas9. Gingival epithelial cells were stimulated with the A. actinomycetemcomitans low-leukotoxic strain NCTC9710 or the highly leukotoxic JP2 strain HK 165 for 6, 12 and 24 h. The results showed that the JP2 strain HK1651 induced higher IL-1β and IL-1RA release and mediated more epithelial cell death compared to the NCTC9710 strain. These findings were found to be capsase-1, caspase-4 and NLRP3-dependant. A targeted protein analysis of inflammation-related proteins showed that the expression of 37 proteins were identified as being significantly altered after HK1651 infection compared to unstimulated Cas9 and NLRP3-deficient cells. Of the 37 proteins, 23 of these inflammation-related proteins released by NLRP3-deficient cells differed significantly compared to Cas9 cells after infection. This suggests that NLRP3 has a broad effect on the inflammatory response in gingival epithelial cells.

To study whether damaged epithelial cells and gingival fibroblast could affect the expression of inflammatory cytokines in healthy cells.

Cell suspensions were submitted to different treatments to obtain the lysates: no treatment (supernatant control), sonication, and freeze/thawing. All treatments were centrifuged, and the supernatants of the lysates were used for experimentation. Cell viability assays, RT-qPCR of IL1, IL6 and IL8, IL6 immunoassay, and immunofluorescence of NF-kB p65 were applied to verify the inflammatory crosstalk of damaged cells over healthy plated cells. Furthermore, titanium discs and collagen membranes were treated with lysates and checked for IL8 expression by RT-qPCR.

Lysates obtained upon sonication or freeze/thawing of oral squamous carcinoma cell lines provoked a robust increase in the expression of IL1, IL6, and IL8 by gingival fibroblasts, which was confirmed by IL6 immunoassays. Lysates obtained from the gingival fibroblasts failed to increase the expression of inflammatory cytokines in oral squamous carcinoma cells. Additionally, oral squamous carcinoma cell lysates caused the activation of the NF-kB signalling cascade in gingival fibroblasts as indicated by the phosphorylation and nuclear translocation of p65. Finally, oral squamous carcinoma cell lysates adhered to the titanium and collagen membrane surfaces and increased IL8 expression by gingival fibroblasts growing in these materials.

Injured oral epithelial cells can release factors that incite gingival fibroblasts to become pro-inflammatory.

Injuries affecting the oral mucosa generate epithelial fragments that may reach the underlying connective tissue and provoke inflammation. These injuries are routinely caused by mastication, sonication for teeth cleaning, teeth preparation, prostheses maladaptation, and implant drilling.

NOD-like receptor family pyrin domain containing 6 (NLRP6) is a new pattern recognition receptor in the mammalian innate immune system. Both the liver and the gut exhibit substantial levels of cytoplasmic expression. It can speed up cell response to endogenous danger signals or exogenous pathogen infection. NLRP6 can function in various ways as an inflammasome or a noninflammasome. The understanding of NLRP6 is steadily increasing thanks to ongoing investigations, but due to discrepancies in how those studies have described their link with tumors, the significance of NLRP6 in the emergence of cancer is still debatable as of this writing. This article will use the structure and function of NLRP6 as the pivotal point and thoroughly explain the present interactions between NLRP6 and tumors and any possible clinical benefits.

Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue. However, the mechanisms underlying the effects of G-CSF on abnormal bone remodeling have not yet been fully elucidated. Human periodontal ligament stem cells (hPDLSCs) are major modulators of osteogenic differentiation in periodontal tissues. Thus, the aim of this study was to investigated whether G-CSF acts effects on hPDLSC proliferation and osteogenic differentiation, as well as periodontal tissue repair.

hPDLSCs were cultured and identified by short tandem repeat analysis. The expression patterns and locations of G-CSF receptor (G-CSFR) on hPDLSCs were detected by immunofluorescence analysis. The effects of G-CSF on hPDLSCs in a lipopolysaccharide (LPS)-induced inflammatory microenvironment were investigated. Specifically, Cell-Counting Kit 8 (CCK8) and Alizarin red staining were used to examine hPDLSC proliferation and osteogenic differentiation; reverse transcription-polymerase chain reaction was performed to detect the expression patterns of osteogenesis-related genes (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], and osteocalcin [OCN]) in hPDLSCs; and Western blotting was used to detect the expression patterns of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) of PI3K/Akt signaling pathway.

hPDLSCs exhibited a typical spindle-shaped morphology and good clonogenic ability. G-CSFR was mostly localized on the cell surface membrane. Analyses showed that G-CSF inhibited hPDLSC proliferation. Also, in the LPS-induced inflammatory microenvironment, G-CSF inhibited hPDLSC osteogenic differentiation and reduced the expression levels of osteogenesis-related genes. G-CSF increased the protein expression levels of hPDLSC pathway components p-PI3K and p-Akt.

We found that G-CSFR was expressed on hPDLSCs. Furthermore, G-CSF inhibited hPDLSC osteogenic differentiation in vitro in the LPS-induced inflammatory microenvironment.

Periodontitis is an inflammatory disease, mainly caused by the formation of a subgingival plaque biofilm. In recent years, growing attention has been paid to immunotherapy in the treatment of periodontitis, and the importance of communal intervention associated with macrophage polarization was emphasized. Herein, resveratrol (RES) and 20(S)-protopanaxadiol (PPD) were successfully self-assembled into RES@PPD nanoparticles (NPs) by the phenolic resin reaction. RES@PPD NPs have good stability and biocompatibility. The combined application of PPD and RES enhances the anti-inflammatory and antioxidant properties of nanocomposites, remarkably reduces the level of reactive oxygen species, and finally realizes the coordinated regulation of host immunity in periodontitis. The detailed mechanism is as follows: RES@PPD NPs inhibit M1 polarization of macrophages, promote M2 polarization by scavenging ROS, and then inhibit the NF-κB signalling pathway to regulate host immunity. In the animal model of periodontitis, RES@PPD NPs can remarkably decrease the level of pro-inflammatory cytokines, up-regulate the anti-inflammatory cytokines, and exhibit a profound therapeutic effect on local inflammation. Therefore, RES@PPD NPs are effective in antioxidation and anti-inflammation, thus providing a promising candidate drug for the treatment of periodontitis.

To evaluate the expression and function of the nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in caries induced pulpitis.

NLRP3 expression was determined with immunohistochemistry in the dental pulp and qPCR in dental pulp cells (DPCs). THP-1 macrophages expressing the apoptosis-related speck-like protein (ASC) and green fluorescent protein (GFP) fusion protein were used to assess NLRP3 inflammasome activation by live cell imaging, following treatment with lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Caspase I inhibitor was used to confirm inflammasome activation. An ex-vivo pulpitis model in which the DPCs were co-cultured with THP-1 macrophages was used to study the effect of the NLRP3 inflammasome inhibitor (MCC950), and cytokines were measured using ELISA and multiplex array. Data were analysed using the t-test or anova followed by a Bonferroni post hoc test with the level of significance set at p ≤ .05.

NLRP3 inflammasome was differentially expressed in dental pulp of sound and carious teeth. Treatment of DPCs with LTA significantly upregulates NLRP3 and IL-1 β-expression (p < .05) and in induces more ASC specks formation compared to LPS. IL-β release in response to LTA treatment is significantly reduced with Caspase I inhibitor suggesting inflammasome dependent mechanism (p < .01). NLRP3-specific inhibitor, MCC950, significantly reduced IL-1β and IL-6 in an ex-vivo pulpitis model (p < .01) but had no effect on IL-8 or matrix metalloproteinase-9 (MMP-9).

Expression and upregulation of NLRP3 inflammasome with caries and LTA treatment suggest a role in caries-induced pulpitis. NLRP3 inhibitor attenuated the release of selective inflammatory cytokines and could be a potential treatment target that merit further investigation.

Periodontitis is defined as a chronic inflammatory disease in which the continuous activation of oxidative stress surpasses the reactive oxygen species (ROS) scavenging capacity of the endogenous antioxidative defense system. Studies have demonstrated that ROS-scavenging biomaterials should be promising candidates for periodontitis therapy. To benefit the understanding and design of scavenging biomaterials for periodontitis, this review details the relationship between ROS and periodontitis, including direct and indirect damage, the application of ROS-scavenging biomaterials in periodontitis, including organic and inorganic ROS-scavenging biomaterials, and the various dosage forms of fabricated materials currently used for periodontal therapy. Finally, the current situation and further prospects of ROS-scavenging biomaterials in periodontal applications are summarized. Expecting that improved ROS-scavenging biomaterials could be better designed and developed for periodontal and even clinical application.

Pyroptosis could be responsible for the bone loss from bone metabolic diseases, leading to the negative impact on people's health and life. It has been shown that osteoclasts, osteoblasts, macrophages, chondrocytes, periodontal and gingival cells may be involved in bone loss linked with pyroptosis. So far, the involved mechanisms have not been fully elucidated. In this review, we introduced the related cells involved in the pyroptosis associated with bone loss and summarized the role of these cells in the bone metabolism during the process of pyroptosis. We also discuss the clinical potential of targeting mechanisms in the osteoclasts, osteoblasts, macrophages, chondrocytes, periodontal and gingival cells touched upon pyroptosis to treat bone loss from bone metabolic diseases as well as the challenges of avoiding potential side effects and producing efficient treatment methods.

Circulating levels of interleukin-17 (IL-17) are associated with the presence and severity of periodontitis. However, whether IL-17 is causal for disease development is unknown. We investigated the effect of genetically proxied IL-17 on periodontitis using instrumental variable analysis.

We identified 12 genetic variants from genome-wide association study (GWAS) of 7760 European descent individuals, used these variants as instrumental variables for IL-17, and linked them to a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Generalized weighted least squares analysis accounted for linkage disequilibrium of variants.

We found an inverse association of genetically proxied IL-17 and periodontitis (odds ratio, 0.84; 95% confidence interval: 0.75-0.94; p = 0.003), which was corroborated after sensitivity analysis for horizontal pleiotropy.

The findings suggest that IL-17 protects against initial periodontitis.

Whether there is an association between TFAs and periodontitis is unclear. The purpose of this study was to investigate the relationship between moderate/severe periodontitis and plasma level of elaidic acid, a major trans-fatty acid component, in American adults.

The National Health and Nutrition Examination Survey (NHANES) years 2009-2010 were used to screen a total of 1,610 people. The independent variable of interest is plasma elaidic acid level, the dependent variable is periodontitis, and the covariates include socio-demographic variables, lifestyle variables, systemic diseases, etc. The distribution of variables in the covariate differences between the different independent groups according to tertile was investigated using a multiple linear regression model. To examine the association between plasma elaidic acid levels and moderate/severe periodontitis, three models were used.

Multiple logistic regression analysis showed a significant association between plasma elaidic acid level and moderate/severe periodontitis after adjustment for potential confounders (OR = 1.021, 95%CI: 1.004-1.039, P = 0.01394). Subjects with the highest tertile of plasma elaidic acid levels were 51.9% more likely to have periodontitis compared with subjects with the lowest tertile of plasma elaidic acid levels (OR = 1.519, 95% CI: 1.136-2.030, P = 0.00477). No possible sources of heterogeneity were identified in the subgroup analyses.

Plasma elaidic acid levels are associated with periodontal disease in American adults.

Inflammatory bone diseases include osteoarthritis (OA) and rheumatoid arthritis (RA), which can cause severe bone damage in a chronic inflammation state, putting tremendous pressure on the patients' families and government agencies regarding medical costs. In addition, the complexity of osteoimmunology makes research on these diseases difficult. Hence, it is urgent to determine the potential mechanisms and find effective drugs to target inflammatory bone diseases to reduce the negative effects of these diseases. Recently, pyroptosis, a gasdermin-induced necrotic cell death featuring secretion of pro-inflammatory cytokines and lysis, has become widely known. Based on the effect of pyroptosis on immunity, this process has gradually emerged as a vital component in the etiopathogenesis of inflammatory bone diseases. Herein, we review the characteristics and mechanisms of pyroptosis and then focus on its clinical significance in inflammatory bone diseases. In addition, we summarize the current research progress of drugs targeting pyroptosis to enhance the therapeutic efficacy of inflammatory bone diseases and provide new insights for future directions.

The aim of this study was to evaluate the IFI16 and IFN-α/β receptors expression during the genesis and development of experimental apical periodontitis (AP) in mice teeth.

Apical periodontitis was induced in the lower first molars of 40 C57BL/6 mice. They were divided according to the experimental periods 2, 7, 14, 21 and 42 days (n = 8 per group). Five animals were used as a control group (without AP). Specimens were submitted to histological processing for description of the inflammatory process, immunostaining for the presence/absence and localization of IFI16 and IFN-α/β receptors (qualitative and semi-quantitative analysis) and tartrate-resistant acid phosphatase (TRAP) histoenzimology.

The results showed a gradual development of AP over the experimental times. The expression of IFI16 was noticeably more exacerbated in the experimental early period (day 2) whilst the lowest expression was observed in the control group (p = .02). For IFN-α/β receptors, a higher intensity staining was observed 42 days after AP induction, that was statistically different from the control group (p = .02). In addition, the number of TRAP-positive cells was higher on the later periods (days 21 and 42; p < .001).

IFI16 protein expression was highest during the early periods after AP induction in mice teeth, whilst IFN-α/β receptor expression was highest after AP became established.

Pyroptosis has both a caspase-1-dependent canonical pathway and a caspase-4/-5/-11-dependent noncanonical pathway. They play an important role in inflammatory damage and related diseases. Canonical pyroptosis was reported to be involved in periodontitis. However, knowledge of caspase-4/-5/-11-dependent noncanonical pathway involvement remains limited. The aim of this study was to investigate the outcomes of pyroptosis inhibition on periodontitis as well as the possible mechanism, in order to provide a potential target for alleviating periodontitis.

Human and rat periodontitis tissues were collected for immunohistochemistry (IHC). Micro-computed tomography was used to assess alveolar bone loss in experimental periodontitis model. Pyroptosis-related proteins were tested by western blot. propidium iodide staining and lactate dehydrogenase release were used to verify pyroptosis activation. RNA sequencing was applied to investigate the preliminary mechanism of the reduced periodontal inflammation induced by YVAD-CHO.

Both canonical- and noncanonical-related proteins were detected in human and rat periodontitis tissue. The pyroptosis-inhibited group demonstrated less inflammatory response and bone absorption. In vitro, pyroptosis was activated by lipopolysaccharide and inhibited by YVAD-CHO. RNA sequencing demonstrated that the expression of A20 and IκB-ζ was increased and verified by western blot in vitro and IHC in vivo.

These results suggest that inhibition of pyroptosis-reduced inflammation and alveolar bone resorption in periodontitis.