Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

OBJECTIVES: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. MATERIALS AND METHODS: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. CONCLUSIONS: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. CLINICAL RELEVANCE: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

Small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells inhibit cell apoptosis and alveolar bone loss in periodontitis.

OBJECTIVE: This study aimed to explore the effects of small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells (L-D-sEV) on periodontal ligament cells from periodontitis affected teeth (p-PDLCs) in vitro and experimental periodontitis in mice. DESIGN: In vitro, the biological function of p-PDLCs and the underlying molecular mechanism were investigated by flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR) analysis. Eighteen-eight-week-old male C57BL/6 mice were randomly divided into three groups: control (Con), periodontitis (Peri), and L-D-sEV groups. Mice periodontitis model was induced by placing the 5-0 silk thread (around the maxillary second molar) and P.gingivalis (1 ×107 CFUs per mouse). In vivo, the alveolar bone loss, osteoclast activity, and macrophage polarization were measured by micro-computed tomography and histological analysis. RESULTS: In vitro, the RANKL/OPG ratio and phosphorylation of JNK and P38 protein levels of p-PDLCs were significantly decreased after L-D-sEV administration. Besides, flow cytometry and qRT-PCR analysis showed that L-D-sEV reduced apoptosis of p-PDLCs, down-regulated apoptosis-related genes Caspase-3 and BCL-2-Associated X expression, and up-regulated B-cell lymphoma-2 gene levels. In vivo, L-D-sEV administration significantly reduced alveolar bone loss, inhibited osteoclast activity, and induced M2 polarization. The histological analysis showed that iNOS/CD206, RANKL/OPG, p-JNK/JNK, and p-P38/P38 ratios were significantly lower in the L-D-sEV group than in the Peri group. CONCLUSIONS: L-D-sEV administration alleviated alveolar bone loss by mediating RANKL/OPG-related osteoclast activity and M2 macrophage polarization, alleviating p-PDLCs apoptosis and proliferation via the JNK and P38 pathways.

Association between carotenoid intake and periodontitis in diabetic patients.

This study aimed to evaluate the association between dietary carotenoid intake and periodontitis in diabetic patients. Data on diabetic patients were collected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 for this cross-sectional study. Dietary intake of carotenoids was assessed through the first 24-hour dietary recall interview. Full-mouth periodontal examinations were conducted by trained dental examiners. Subgroup analysis was conducted in terms of age, gender, the number of missing teeth, cardiovascular disease, smoking, and anti-diabetic drugs. Totally 1914 diabetic patients were included, with 1281 (66.93%) in the periodontitis group. After adjusting for age, gender, race, education, smoking, dental implants, hepatitis, and the number of missing teeth, α-carotene intake ≥55.82 mcg was associated with lower odds of periodontitis than α-carotene intake <55.82 mcg [OR = 0.70, 95% CI: 0.53-0.91, P = 0.010]; lutein and zeaxanthin intake ≥795.95 mcg was associated with decreased odds of periodontitis than lutein and zeaxanthin intake <795.95 mcg (OR = 0.75, 95%CI: 0.57-0.98, P = 0.039). The association between carotenoid intake and periodontitis varied across different subpopulations. In diabetes, dietary intake of α-carotene and lutein and zeaxanthin was inversely associated with the odds of periodontitis, which may facilitate clinical periodontitis management.

Co-Culture of P. gingivalis and F. nucleatum Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes.

Periodontitis, characterized by persistent inflammation in the periodontium, is intricately connected to systemic diseases, including oral cancer. Bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, play a pivotal role in periodontitis development because they contribute to dysbiosis and tissue destruction. Thus, comprehending the interplay between these bacteria and their impacts on inflammation holds significant relevance in clinical understanding and treatment advancement. In the present work, we explored, for the first time, their impacts on the expressions of pro-inflammatory mediators after infecting oral keratinocytes (OKs) with a co-culture of pre-incubated P. gingivalis and F. nucleatum. Our results show that the co-culture increases IL-1ß, IL-8, and TNF-α expressions, synergistically augments IL-6, and translocates NF-kB to the cell nucleus. These changes in pro-inflammatory mediators-associated with chronic inflammation and cancer-correlate with an increase in cell migration following infection with the co-cultured bacteria or P. gingivalis alone. This effect depends on TLR4 because TLR4 knockdown notably impacts IL-6 expression and cell migration. Our study unveils, for the first time, crucial insights into the outcomes of their co-culture on virulence, unraveling the role of bacterial interactions in polymicrobial diseases and potential links to oral cancer.

Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study.

BACKGROUND: To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. METHODS: Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1ß, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. RESULTS: Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively). CONCLUSION: Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.

NHANES-based analysis of the correlation between leisure-time physical activity, serum cotinine levels and periodontitis risk.

OBJECTIVE: To investigate the association of leisure-time physical activity and serum cotinine levels with the risk of periodontitis in the general population and to further analyze the interaction between leisure-time physical activity and serum cotinine levels on the risk of periodontitis. METHODS: This was a cross-sectional study, extracting data from 9605 (56.19%) participants in the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2014, and analyzing the relationship and interaction effects of serum cotinine level, leisure time physical activity, and risk of periodontitis by weighted univariate logistic modeling; Effect sizes were determined using ratio of ratios (OR), 95% confidence intervals (95% CI). RESULTS: 5,397 (56.19%) of 9,605 participants had periodontitis; an increased risk of periodontitis was found in those in the leisure time physical activity intensity < 750 MET × min/week group (OR = 1.44, 95% CI: 1.17-1.78). Serum cotinine levels ≥ 0.05 ng/ml were associated with an increased risk of periodontitis (OR = 1.99, 95% CI: 1.69-2.33). The group with low leisure physical activity and serum cotinine levels ≥ 0.05 ng/ml had an increased risk of periodontitis compared to the group with high leisure physical activity and serum cotinine levels < 0.05 ng/ml (OR = 2.48, 95% CI: 1.88-3.27). Interaction metrics RERI = 0.90 (95% CI: 0.44-1.36) and API = 0.36 (95% CI: 0.18-0.55); CI for SI = 2.55 (95% CI: 1.03-6.28). for API 0.36. CONCLUSION: Leisure time physical activity intensity interacted with smoking exposure on periodontitis risk and may provide the general population with the opportunity to Increasing leisure-time physical activity and smoking cessation may provide recommendations for the general population.

[Review of clinical effects of disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation in 10 years].

PURPOSE: To analyze the bone remodeling around the implant 10 years after disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation and to investigate the influence of different factors on implant retention. METHODS: The clinical and imaging data of patients undergoing DSR-based sinus floor elevation with simultaneous implantation were collected from the Department of Dental Implantology, Affiliated Hospital of Qingdao University from January 2008 to December 2011. Panoramic film and CBCT were used to measure the changes of bone mass around implant in different periods. Kaplan-Meier and Log-rank tests were used to analyze the effects of different factors on implant retention with SPSS 26.0 software package. RESULTS: The study included 98 patients with a total of 128 implants. During the follow-up of 0-168 months, 7 implants failed, and the remaining formed good osseointegration and functioned, with a 10-year cumulative retention rate of 94.53%. The height of bone formation was (0.29±0.15) mm at the top and (2.74±0.66) mm in the sinus of 75 implant sites with complete imaging data obtained ten years after surgery. Kaplan-Meier and Log-rank tests showed that 8 factors including initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis had significant effects on implant retention. CONCLUSIONS: The DSR-based internal sinus floor elevation with implantation is a reliable and stable bone augmentation operation for vertical bone defect in maxillary posterior region, with a 10-year cumulative retention rate of no less than 94%. Initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis are the important factors affecting the long-term retention rate of implants.

Systemic benefits of periodontal therapy in patients with obesity and periodontitis: a systematic review.

This systematic review aimed to answer the focused question: "What are the benefits of subgingival periodontal therapy on blood hematological and biochemical index, biomarkers of inflammation and oxidative stress, quality of life, and periodontal pathogen counts in patients with obesity and periodontitis?". A systematic literature search was performed in six databases: PubMed, Embase, LILACS, Web of Science, Cochrane and SCOPUS and other sources, and a manual search was conducted as well. Inclusion criteria were randomized and non-randomized clinical trials, and before-and-after studies on patients with obesity subjected to periodontal therapy. The results were synthesized qualitatively. Risk of bias within studies was assessed using RoB 2 and ROBINS-I tools. The certainty of evidence was evaluated following the GRADE approach. Three randomized controlled trials and 15 before-and-after studies were included. Randomized controlled trials were considered to have a low risk of bias, as compared to before-and-after studies assessed as having low, serious, and critical risks of bias. Non-surgical periodontal therapy plus azithromycin, chlorhexidine, and cetylpyridinium chloride reduced blood pressure and decreased serum levels of HbA1c, hsCRP, IL-1ß, and TNF-α. Salivary resistin level also decreased in patients with obesity and periodontitis after therapy and chlorhexidine mouth rinse. Before-and-after data suggest an improvement in total cholesterol, LDL, triglycerides, insulin resistance, C3, GCF levels of TNF-α, chemerin, vaspin, omentin-1, visfatin, 8-OHdG, and periodontal pathogen counts after therapy.

Gums make IL-23, no professionals needed.

IL-23 activates pathogenic Th17 cells to drive inflammatory disease at barrier surfaces. Kim et al. now identify oral epithelial cells as the critical producers of IL-23 in human and mouse periodontitis, linking microbial dysbiosis to non-hematopoietic regulation of IL-17-associated inflammation.

[The relationship between the expression of PGE2 and COX-2 and the osteogenic activity and oxygen level of alveolar bone].

PURPOSE: To study the relationship between the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) and the osteogenic activity and oxygen level of alveolar bone. METHODS: The alveolar bones of 56 patients with chronic periodontitis who received dental treatment from March 2021 to March 2023 were collected as the experimental (periodontitis) group, and the healthy alveolar bones of 53 patients who received dental treatment during the same period were selected as the control group. The osteoblasts were cultured by tissue block culture, and modified Kaplow's alkaline phosphatase (ALP) staining was used to identify the cells. COX-2, PGE2 and osteoclastogenesis inhibitory factor (OPG) receptor activator of nuclear factor-κb ligand (RANKL) and other indicators were determined by ELISA. PGE2, COX-2, OPG, internal oxygen level, ALP, RANKL and their correlation were compared between the two groups. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: PGE2, COX-2 and RANKL in periodontitis group were significantly higher than those in the control group, but OPG, internal oxygen level and ALP were significantly lower than those in the control group (P＜0.05). PGE2 and COX2 were highly positively correlated with OPG, internal oxygen level and ALP, but were highly positively correlated with RANKL(P＜0.05). CONCLUSIONS: The expression of PGE2 and COX-2 is highly negatively correlated with ALP and oxygen levels. Clinical treatment may consider increasing oxygen levels, increasing oxygen partial pressure, and regulating ALP levels by drugs, so as to change the inflammatory condition of periodontitis or other dental diseases.

The potential crosstalk genes and molecular mechanisms between glioblastoma and periodontitis.

Despite clinical and epidemiological evidence suggestive of a link between glioblastoma (GBM) and periodontitis (PD), the shared mechanisms of gene regulation remain elusive. In this study, we identify differentially expressed genes (DEGs) that overlap between the GEO datasets GSE4290 [GBM] and GSE10334 [PD]. Functional enrichment analysis was conducted, and key modules were identified using protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). The expression levels of CXCR4, LY96, and C3 were found to be significantly elevated in both the test dataset and external validation dataset, making them key crosstalk genes. Additionally, immune cell landscape analysis revealed elevated expression levels of multiple immune cells in GBM and PD compared to controls, with the key crosstalk genes negatively associated with Macrophages M2. FLI1 was identified as a potential key transcription factor (TF) regulating the three key crosstalk genes, with increased expression in the full dataset. These findings contribute to our understanding of the immune and inflammatory aspects of the comorbidity mechanism between GBM and PD.

Imbalanced EphB4/EphrinB2 Signaling Modulates Bone Resorption in Periodontitis Induced by Porphyromonas gingivalis.

Periodontitis, a chronic infectious disease in periodontal tissues, is characterized by an imbalance of alveolar bone resorption and remodeling, which eventually results in tooth loosening and even tooth loss. The etiology of periodontitis is polymicrobial synergy and dysbiosis, in which Porphyromonas gingivalis (P. gingivalis) is one of the primary pathogens responsible for periodontitis progression. The interplay of EphrinB2/EphB4 is crucial for osteoblast-osteoclast communication during bone remodeling and healing. This study investigates the mechanism of EphB4/EphrinB2 transduction modulating osteogenesis inhibition and bone resorption in periodontitis induced by P. gingivalis. An in vivo model of chronic periodontitis provoked by P. gingivalis was constructed, the inflammation and bone resorption were evaluated. The expression of EphB4 and EphrinB2 proteins in periodontal tissues was detected, which was also evaluated, respectively, in osteoblasts and osteoclasts infected with P. gingivalis in vitro. Then, a simulated coculture model of osteoblasts and osteoclasts was established to activate the forward and reverse pathways of EphB4/EphrinB2 with P. gingivalis infection. This study showed that P. gingivalis infection promoted alveolar bone resorption in rats and enhanced EphB4 and EphrinB2 expression in periodontal tissues. EphB4 and molecules associated with osteogenesis in osteoblasts infected with P. gingivalis were inhibited, while EphrinB2 and osteoclast differentiation-related markers in osteoclasts were activated. In conclusion, this study suggested that EphB4/EphrinB2 proteins were involved in alveolar bone remodeling in the process of periodontitis induced by P. gingivalis infection. Moreover, attenuated EphB4/EphrinB2 with P. gingivalis infection weakened osteoblast activity and enhanced osteoclast activity.

Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.

[Periodontitis - an often neglected risk factor for several other diseases]. / Parodontit ­ en ofta förbisedd riskfaktor för en rad sjukdomar.

Periodontitis is a chronic inflammatory disease that degrades dental supporting tissues, including the alveolar bone. The global prevalence is 19%, in Sweden it is 11%. Left untreated, periodontitis can cause loss of teeth. The initial clinical manifestations of periodontitis usually start between 35 and 45 years of age. The underlying pathological mechanism is an aberrant inflammatory response to the bacteria colonizing the gingival crevice. Periodontitis has been associated with several other diseases, most prominently diabetes. The relation between periodontitis and diabetes is bidirectional in the sense that diabetes increases the risk for periodontitis and vice versa. Periodontitis also increases the risk for cardiovascular disease and cancer.

Laser Therapy Effects on Periodontal Status: A Randomized Study Using Gaussian Network Analysis and Structural Equation Modeling Approach.

Background and Objectives: This paper aims to assess the role of laser therapy in periodontitis through an innovative approach involving computational prediction and advanced modeling performed through network analysis (Gaussian graphical models-GGMs) and structural equations (SEM). Materials and Methods: Forty patients, exhibiting periodontal pockets with a minimum depth of 5 mm, were randomly divided into two groups: a control group and a laser group. Four specific indicators were measured for each tooth, namely periodontal pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI), and the mean of six measured values was recorded at five time markers (baseline, 6 months, 1 year, 2 years, and 4 years). The assessment algorithm included enrollment, measurements, and differential non-surgical periodontal treatment, according to the group allocation. Scaling, root planing, and chlorhexidine 1% were conducted for the control group, and scaling, root planing and erbium, chromium:yttrium-scandium-gallium-garnet (Er,CR:YSGG) laser therapy were conducted for the laser group. Results: The main results highlight that the addition of laser treatment to scaling and root planing led to notable clinical improvements, decreasing the PPD values, reducing the BOP scores, and increasing the CAL. Conclusions: Notable relationships between the specific indicators considered were highlighted by both the GGMs and by SEM, thus confirming their suitability as proxies for the success of periodontal treatment.

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway.

BACKGROUND: Periodontitis is a chronic inflammatory disease resulting from bacterial plaque infection. While the involvement of activating transcription factor 1 (ATF1) has been extensively explored in various human diseases, its specific role in periodontitis remains unclear. This study aims to elucidate the expression and biological function of ATF1 in the context of periodontitis. METHODS: Primary human periodontal ligament cells (hPDLCs) were procured from clinical samples and subsequently characterized. Following treatment with P. gingivalis lipopolysaccharide (LPS, 10 µg/mL), hPDLCs underwent transfection with either ATF1 vector or siRNA. The expression levels of ATF1 in LPS-treated hPDLCs or transfected cells were evaluated through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß), were quantified using Enzyme-linked Immunosorbent Assay (ELISA). The assessment of osteogenic proteins, such as runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG), as well as noncanonical nuclear factor-kappaB (NF-κB) pathway-related proteins (p65, p-p65, IkBα, p-IkBα), was conducted using western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry assays were employed to detect cell viability. RESULTS: LPS induced an inflammatory response and hindered the osteogenic differentiation of hPDLCs (p < 0.05, p < 0.01). Furthermore, ATF1 silencing enhanced cell proliferation and suppressed apoptosis in LPS-stimulated hPDLCs (p < 0.05, p < 0.01). ATF1 silencing not only restrained the inflammatory response but also promoted the osteogenic differentiation of LPS-stimulated hPDLCs (p < 0.05, p < 0.01). Importantly, ATF1 silencing effectively blocked the LPS-induced activation of the NF-κB signaling pathway (p < 0.05, p < 0.01, p < 0.001). CONCLUSIONS: ATF1 emerges as a promising treatment option, inhibiting the osteogenic differentiation of hPDLCs and mitigating the inflammatory response by preventing the phosphorylation of the NF-κB signaling pathway.

Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

[Periodontal tissue regeneration: current therapeutic strategies and future directions in further research].

Chronic and progressive destruction/damage of the periodontal tissues resulted from periodontitis is the leading cause of tooth loss in adults. Traditional periodontal therapies such as scaling and root planning or flap surgery have demonstrated effective in controlling local inflammation and in suppressing/arresting the disease progression of periodontitis. However, those infection control measures cannot help to regenerate lost periodontal tissues to a statistically or clinically significant degree. Although some successes regarding the reduction of the intrabony defect and maintenance of the periodontal homeostasis have been achieved in periodontal regenerative procedures, comprising but not limited to guided tissue regeneration (GTR) or bone grafting technique, the restorative effectiveness of the architecture and function of the lost or injured tissues is far from our clinical expectation. The use of the concept, technique, and method of tissue engineering for periodontal regeneration is a hotspot and animal studies have shown interesting outcomes in terms of functional regeneration of lost/damaged support tissues in the periodontium, including alveolar bone, periodontal ligament, and cementum. However, numerous issues need to be addressed before those regenerative approaches can be responsibly transformed to novel clinical therapies. Recently, paradigm that induces homing of host stem cells to site of the periodontium and encourage the body's innate capability to repair is a new research field termed endogenous regeneration. Given that endogenous regenerative technique avoids ex-vivo cell culture and transplantation, it should be relatively easier to be used in the treatment of clinical patients. Due to the limited oral microenvironment and harsh periodontal local condition for tissue regeneration, as well as poor understanding of periodontal regenerative biology, there is still a long way ahead to explore new effective, practical, and economical therapies to save and protect natural tooth and for combating highly prevalent periodontal disease.