Porphyromonas gulae has emerged as a notable pathogen in canine periodontal disease, akin to Porphyromonas gingivalis in human periodontitis. This review examines the initial isolation, phylogenetic analysis, habitat, host range, relationships with host health status and age, and key pathogenic determinants, including fimbriae, proteases, citrullinating enzyme, and lipopolysaccharide. Control strategies discussed include polyphosphate to disrupt haeme/iron utilization, clindamycin with interferon alpha to reduce bacterial load and enhance the immune response, and a protease inhibitor. Further research is needed to understand strain-level diversity of virulence factors and interactions between P. gulae and other oral bacteria, particularly Fusobacterium nucleatum, a common pathogen in both dogs and humans. The potential for interspecies transmission between dogs and humans warrants further research into these interactions. Extensive in vivo studies across various breeds are crucial to validate the effectiveness of proposed treatment strategies. This review emphasizes P. gulae's role in periodontal health and disease, setting the stage for future research and improved management of canine periodontal disease.

Periodontitis is a common chronic inflammatory disease primarily caused by pathogenic microorganisms in the oral cavity. Without appropriate treatments, it may lead to the gradual destruction of the supporting tissues of the teeth. While current treatments can alleviate symptoms, they still have limitations, particularly in eliminating pathogenic bacteria, promoting periodontal tissue regeneration, and avoiding antibiotic resistance. In recent years, functional nanomaterials have shown great potential in the treatment of periodontitis due to their unique physicochemical and biological properties. This review summarizes various functionalization strategies of nanomaterials and explores their potential applications in periodontitis treatment, including metal-based nanoparticles, carbon nanomaterials, polymeric nanoparticles, and exosomes. The mechanisms and advances in antibacterial effects, immune regulation, reactive oxygen species (ROS) scavenging, and bone tissue regeneration are discussed in detail. In addition, the challenges and future directions of applying nanomaterials in periodontitis therapy are also discussed.

The osteogenic differentiation of periodontal ligament stem cells (PDLSCs) plays a fundamental role in endogenous bone regeneration during periodontitis treatment, yet achieving consistent differentiation under inflammatory conditions remains clinically challenging. Kaempferol, a phytochemical flavonol, has demonstrated osteoprotective efficacy in osteoporosis and bone repair models. However, whether kaempferol exerts pro-osteogenic effects on PDLSCs within the pathologically complex microenvironment of periodontitis, and through what molecular mechanisms, remains unexplored.

This study aimed to systematically characterize the therapeutic efficacy of kaempferol in restoring osteogenic differentiation of human PDLSCs under inflammatory stress, and promoting bone regeneration in a mice periodontitis model, and elucidate novel molecular targets and downstream mechanisms mediating these regenerative actions.

An in vitro inflammatory microenvironment was established using lipopolysaccharide (LPS)-stimulated human PDLSCs to mimic periodontitis-induced osteogenic impairment. Osteogenic recovery was assessed through alkaline phosphatase (ALP), alizarin red S staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis of osteogenesis-related markers (ALP, RUNX2, OSX, OPN). The bioinformatics, network pharmacology and siRNA transfection were performed to identify EphrinB2 as kaempferol's putative cellular target. Downstream PI3K/Akt and p38 MAPK pathway activation was evaluated through phosphoprotein analysis. In vivo validation employed micro-CT quantification of alveolar bone loss and immunohistochemical profiling of pathways key proteins in a mice periodontitis model.

Kaempferol dose-dependently rescued LPS-impaired osteogenic differentiation in human PDLSCs, especially at 10 μM, where kaempferol significantly reversed suppressed ALP activity, mineralized nodule formation, and transcriptional and protein expression of osteogenic markers (ALP, RUNX2, OSX, OPN). Mechanistically, kaempferol upregulated the key target EphrinB2 under inflammatory stress, thereby reactivating the downstream PI3K/Akt and p38 pathways. In periodontitis mice, kaempferol administration (10 mg/kg) significantly promoted the periodontal expression of OPN and EphrinB2, restored the phosphorylation of PI3K, AKT, and P38, attenuating alveolar bone loss by 63.8 % (BV/TV: 72.4 % ± 2.07 vs. 44.2 % ± 3.19 in CON).

Kaempferol could rescue PDLSCs' osteogenic differentiation and mitigates bone loss in periodontitis microenvironments by targeting EphrinB2 to activate PI3K/Akt and P38 pathways. This work underscores kaempferol's potential as a natural therapeutic for reversing pathological bone resorption and promoting periodontal regeneration.

A real-time and rapid detection of salivary pH for periodontal diagnosis is an emerging point-of-care (POC) technology trend. The precise and non-invasive sensitive POC devices, which could be used as chair-side tools to improve clinical dental inspections, are essential for an excellent periodontal diagnosis. In this paper, we report on developing a POC technology based on optical fiber sensors as a promising marker, to the best of our knowledge, to detect the role of salivary pH in periodontitis diagnosis and support dentists' inspection. The optical fiber sensor based on a drop-like structure was fabricated by bending single-mode fiber (SMF) into a section of a thin capillary tube. In this work, firstly, the performance of the proposed sensor towards different pH levels ranging from 1 to 7 was experimentally investigated. Experimentations showed that the pH sensor responded to various pH levels with a calibration curve sensitivity of -2.075 nm/pH and a high linearity of 0.985. Then, 66 patients were enrolled in this study and divided into two groups according to clinical outcomes: Group A with clinically healthy periodontium and Group B with chronic periodontitis. The real saliva from each patient was collected, and the salivary pH was evaluated immediately using the aforementioned proposed sensor. The experimental results show that Group A and Group B salivary pH mapping ranged from 6.5 to 7.3 and 5.5 to 6.4, respectively. The proposed sensor offers substantial practical benefits, providing a rapid response time of less than 2 s, instantaneous, noninvasive, and easily monitored tool for the early detection and diagnosis of periodontal health status.

Emerging evidence suggests a potential association between periodontitis and adverse outcomes in COVID-19. Both conditions share risk factors and exhibit similar immune dysregulation, including elevated pro-inflammatory cytokines, altered myeloid compartments, and T-cell dysfunction. SARS-CoV-2 uses angiotensin-converting enzyme type 2 and transmembrane protease serine 2 membrane proteins, highly expressed in the oral cavity, for cellular entry. Periodontitis may exacerbate COVID-19 through mechanisms such as oral microbe aspiration, increased viral receptor expression, and systemic inflammation. The shared immunopathogenesis, characterized by cytokine storms and perturbed immune profiles, suggests periodontitis can predispose patients to more severe COVID-19 outcomes. This article aims to review the associations between periodontitis and the severity of COVID-19 and the possible immune mechanisms involved.

Background/Objectives: The correlation between cardiovascular diseases, particularly infective endocarditis, and oral disorders such as periodontitis and dental caries has been widely discussed in the scientific literature. In this mapping review, we aim to examine the available evidence on the link between these conditions, focusing on the pathogenetic mechanisms that underlie the development of endocarditis in patients with oral diseases. Methods: A systematic search was conducted across three major databases-PubMed, Scopus, and ScienceDirect-as well as grey literature in Google Scholar. Relevant articles were selected based on inclusion and exclusion criteria, focusing primarily on systematic reviews. The data extracted included study characteristics, main outcomes, and risk-of-bias evaluations. Results: A total of 13 systematic reviews were included in this mapping review. The findings suggest there is a significant connection between periodontal disease, dental caries, and the incidence of infective endocarditis. The evidence highlights that oral bacteria, particularly Streptococcus species, can enter the bloodstream during daily activities and invasive dental procedures, contributing to the development of endocarditis in susceptible individuals. However, the role of antibiotic prophylaxis in preventing endocarditis following dental procedures remains controversial. Conclusions: This review reinforces the importance of oral health in preventing cardiovascular complications, especially infective endocarditis. Although antibiotic prophylaxis may reduce the risk in high-risk individuals, further research is needed to clarify its effectiveness. Enhanced awareness of and education on the shared risks between oral and cardiovascular health could improve prevention strategies and patient outcomes.

This study investigated the association between periodontal disease and systemic health indicators in Korean adults, based on the hypothesis that shared inflammatory pathways may underlie the link between oral and systemic health. Although numerous studies have investigated the association between periodontal disease and systemic health, few have utilized nationally representative data from Korean adults. This study used data from the Korea National Health and Nutrition Examination Survey, including 1324 participants aged ≥40 years. Systemic health indicators were obtained through physical measurements and biochemical tests. Periodontal disease was evaluated using the Community Periodontal Index, and associations were examined using logistic regression analysis. The weighted prevalence of periodontal disease was 48.3% in men and 38.1% in women. Among men, fasting blood glucose (OR = 1.20; 95% CI = 1.101-1.444) and glycated hemoglobin (OR = 1.32; 95% CI = 1.150-1.514) were significantly associated with periodontal disease. In women, fasting blood glucose (OR = 1.15; 95% CI = 1.064-1.199) and glycated hemoglobin (OR = 1.21; 95% CI = 1.055-1.312) also showed significant associations. Glucose-related indicators demonstrated the most consistent associations across sexes. These findings highlight the association between glycemic control and periodontal disease, and suggest that sex-specific patterns may exist, which could be explored in future research.

Background/Objectives: Periodontal disease involves chronic immunoinflammatory processes and microbial dysbiosis, making phytochemicals with anti-inflammatory properties potential therapeutic agents. This study aimed to assess the modulatory effects of yellow passion fruit bagasse extract (PFBE) on periodontal cells under microbial condition. Methods: A human periodontal ligament (PDL) cell line was exposed to F. nucleatum ATCC 25586 to simulate a microbial environment in vitro in the presence and absence of PFBE containing three different concentrations (0.25, 0.50, and 1.00 µg/mL) of piceatannol. Pro-inflammatory markers (TNF-α, IL-8, CCL2), the antioxidant enzyme SOD2, and the protease marker MMP-1 were analyzed by real-time PCR. Protein levels were assessed via ELISA and NF-κB nuclear translocation by immunofluorescence. Cell viability was investigated using live/dead and alamarBlue assays, and in vitro wound healing was evaluated by an automated scratch assay. Results: PDL cells exposed to F. nucleatum significantly increased the gene and protein expression of all inflammatory markers. The stimulatory effects of F. nucleatum were significantly reduced when PDL cells were simultaneously exposed to PFBE. F. nucleatum triggered the NF-κB nuclear translocation while PFBE abrogated the F. nucleatum-stimulated NF-κB nuclear translocation at 60 min. Viability assays demonstrated that neither PFBE nor F. nucleatum were toxic or significantly affected PDL cell viability. In vitro wound closure was improved by the addition of PFBE to F. nucleatum. Conclusions: PFBE exhibited anti-inflammatory and anti-proteolytic effects while improving in vitro wound healing, suggesting a potential modulatory role of PFBE in periodontal disease prevention and treatment.

Evidence suggest an inflammatory link between respiratory health and periodontitis. This study aims to evaluate the impact of periodontal therapy on lung function.

Sixty-two never-smoking patients with mild periodontitis and without other medical conditions participated in this single-blind, prospective trial. Patients underwent periodontal therapy following an infection control approach. Lung function was measured using forced oscillation technique, assessing airway resistance and reactance, and spirometry evaluating FEV1, FVC, and FEV1/FVC. Lung function and fractional exhaled nitric oxide were assessed at baseline, three and six weeks, and every three months for a year. Periodontal parameters were recorded at baseline, six weeks, six and 12 months. Data were analysed using mixed-effects regression models.

Patients (mean age 36 years, 58% female) showed significant improvements in periodontal parameters (p < 0.001). Oscillometry revealed a significant decrease in airway resistance at 11 Hz and 19 Hz after six weeks, with further significant decreases throughout the study. Resistance at 5 Hz (R5) consistently declined, reaching significance at three months (p = 0.001). By one year, R5, R11, R19, and R5 - 20 showed significant reductions (all p < 0.05). Airway reactance at 5 Hz became less negative at three months (p = 0.002), while the reactance area (AX) decreased significantly at six months (p = 0.008). No significant changes were observed in spirometry or fractional exhaled nitric oxide.

A decrease in airway resistance was observed after periodontal therapy, underscoring its positive impact on small airway function. These findings suggest that oral infection control is valuable for respiratory health in young adults before chronic conditions establish.

The trial was registered at ClinicalTrials.gov (NCT04781153) on February 19, 2021, prior to participant enrolment.

Periodontitis can induce systemic inflammation, and it may affect the testicles and male reproductive performance. This study investigated the effects of periodontitis on the testicles, reproductive performance, and offspring development in male rats.

Male Wistar rats were induced with periodontitis by ligating their first molars. After 14 days of inducing periodontal lesions, the animals were observed for an additional 54 days, corresponding to a complete cycle of spermatogenesis. Rats from the periodontitis group (GP, n = 12) and the control group (GC, n = 12) were paired with healthy females (n = 48) for 10 days, equivalent to 2 estrous cycles. Post-mating, the males underwent microtomographic, histological, and reproductive parameter assessments.

Microtomographic analysis revealed higher porosity around the first molar in GP (26 ± 6%) and greater distance between the amelocemental junction and the alveolar bone (1.37 [1.12-1.90] mm), indicative of bone resorption. GP also exhibited significant decreases in final body weight, reduced Sertoli and Leydig cell counts, and lowered testosterone levels compared to GC. Significant morphological alterations in sperm tails were observed in GP compared to GC.

Periodontitis adversely affected reproductive performance, evoking, and offspring development in male rats. These findings highlight the systemic impacts of periodontal disease on male reproductive health in an animal model.

Our study investigated how periodontitis can affect male reproductive health in rats and offspring development. We induced periodontitis in male rats and, after a full cycle of sperm production, these rats were mated with healthy females. We observed that the rats with periodontitis had worse reproductive performance compared to the control group without periodontitis. Additionally, the offspring of the rats with periodontitis showed signs of compromised intrauterine development and a higher incidence of congenital malformations. These results highlight that the inflammation caused by periodontitis can have adverse effects beyond the mouth, significantly impacting male reproductive health and offspring development. These findings suggest the need for further research into the clinical implications of periodontitis on reproductive health.

This study aimed to investigate the regulatory mechanism of miR-205-3p in Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced atherosclerosis.

In an in vitro setting, human umbilical vein endothelial cells (HUVECs) were exposed to P.g-LPS to simulate the vascular endothelial damage induced by periodontitis. Subsequently, ELISA and flow cytometry were employed to assess the inflammatory response and apoptotic status of these cells.To quantify the expression levels of protein arginine methyltransferase 5 (PRMT5), BCL2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), P65 and miR-205-3p within the HUVECs, Western Blot and qPCR were respectively utilized. Moreover, small interfering RNA (siRNA) targeting PRMT5 and miR-205-3p were applied to monitor the changes in PRMT5 expression. Bioinformatics analysis was carried out to predict the potential binding sites between miR-205-3p and PRMT5. Finally, the interaction between miR-205-3p and PRMT5 was validated through the dual-luciferase reporter assay.

The results indicate that P.g-LPS intervention exacerbates damage to HUVECs and increases the expression of PRMT5. Silencing PRMT5 reduces cell inflammation and apoptosis. After stimulation with P.g-LPS, the level of miR-205-3p decreases, and its overexpression alleviates inflammation and apoptosis in the cells. Bioinformatics analysis and dual luciferase reporter assays confirm that PRMT5 is a target of miR-205-3p, and the overexpression of PRMT5 can reverse the protective effects of miR-205-3p.

miR-205-3p can mitigate vascular endothelial injury by decreasing PRMT5 expression, providing new insights for potential treatments.

This study aimed to investigate the presence of asprosin hormone in the biological fluids of patients with periodontal inflammation and compare it to those with periodontal healthy.

Seventy-five individuals between the ages of 18 to 45, 25 periodontal healthy, 25 with gingivitis, and 25 with periodontitis, were included in the study. Gingival crevicular fluid (GCF), blood serum and saliva were obtained from individuals in each group. Tumour necrosis factor-alpha (TNF-α) and asprosin levels in these fluids were determined using the ELISA. Clinical periodontal measurements were recorded and body mass index was calculated. One-way ANOVA and Bonferroni tests were performed for statistical analysis. Spearman test was used to evaluate correlations. The significance level was determined as p < 0.05.

Body mass index values were not different between the groups (p = 0.446). Clinical periodontal measurements were significantly higher in the periodontitis group. Concentrations of TNF-α in GCF, serum and saliva increased significantly in patients with gingivitis and periodontitis (p < 0.001). The higher TNF-α levels were obtained in patients with periodontitis than in individuals with gingivitis (p = 0.001). While asprosin levels were found to be significantly higher in patients with gingivitis and periodontitis (p < 0.001), no significant difference was observed between both groups (p > 0.05). GCF-asprosin levels were positively correlated with the concentrations in serum and saliva in all individuals included in the study (p < 0.05).

The periodontal inflammation caused an increase in asprosin hormone in gingival crevicular fluid independently of the type of periodontal disease.

This study is registered with number of "NCT06627972" in ClinicalTrials.gov website from the date of October 3, 2024.

This systematic review evaluates the clinical effectiveness of hyaluronic acid (HA) in periodontal therapy, oral surgery, and temporomandibular joint (TMJ) disorders. Background. HA, a biocompatible glycosaminoglycan with anti-inflammatory and regenerative properties, is increasingly used in dentistry to enhance healing, reduce pain, and support periodontal regeneration. However, its efficacy compared to conventional treatments remains debated. Materials and Methods. A systematic search was conducted following PRISMA guidelines across PubMed, Scopus, and Web of Science databases (2015-2025). Twenty-one clinical studies, including randomized controlled trials (RCTs) and case-control studies, were analyzed for outcomes related to pain reduction, tissue regeneration, and functional recovery. HA improved clinical attachment levels, reduced probing depth, and enhanced wound healing in periodontal therapy and oral surgery. It accelerated healing after extractions and frenectomies. However, TMJ disorder studies showed mixed results, with some reporting pain relief and functional improvement, while others found no significant advantage over platelet-rich plasma (PRP) or corticosteroids. Variability in HA formulations and protocols influenced outcomes. HA is a promising adjunct for periodontal therapy and wound healing. However, its role in TMJ treatment remains uncertain. Further RCTs with standardized protocols are needed to determine its optimal clinical application.

Neutrophil percentage-to-albumin ratio (NPAR) is a novel biomarker of systemic inflammation. The aim of this study was to explore the relationship between NPAR and periodontitis.

Data from the National Health and Nutritional Examination Survey (NHANES) between 2009 and 2014 (N = 10,128) were utilized in this cross-sectional study. Periodontitis categories were defined according to the Centres for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. The NPAR was calculated by dividing the neutrophil percentage by serum albumin. Covariates included age, sex, race, education level, annual household income, marital status, smoking status, BMI, recreational activity, work activity, diabetes mellitus, hypertension, and cardiovascular disease. Weighted logistic regression analysis was conducted to investigate the linkage between NPAR and moderate/severe periodontitis, and weighted linear regression analysis was performed to explore the relationship of NPAR with mean attachment loss (AL) and mean probing pocket depth (PPD).

Our analysis revealed a positive linear relationship between NPAR and periodontitis. Specifically, we found that the risk of moderate/severe periodontitis increased by 12% for each standard deviation increase in NPAR. Individuals in the highest tertile of NPAR were 28% more likely to have periodontitis compared to those in the lowest tertile (ORtertile3vs1 = 1.28, 95% CI: 1.10-1.49). These findings were consistent across different subgroups analysed. Furthermore, our study demonstrated that NPAR was also positively correlated with mean AL and PPD, which are key indicators of periodontal health.

Our results suggest that NPAR is significantly linked to poor periodontal health. However, owing to the cross-section design of this study, additional longitudinal studies are necessary to further enhance our comprehension of the impact of NPAR on periodontal status.

Elevated neutrophil counts and low albumin levels correlate with moderate/severe periodontitis. Monitoring these markers may aid in assessing periodontitis risk.

Cognitive decline is thought to be more prevalent in elderly persons with periodontitis. Greater adherence to Healthy Eating Index (HEI)-2015 has been reported to improve cognitive function in the elderly population. However, whether the benefits of HEI-2015 on cognitive function apply to elderly patients with periodontitis remains unknown.

This is a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data were extracted from database 2011-2014. Cognitive function was measured through the Consortium to Establish a Registry for Alzheimer's Disease battery for immediate recall (CERAD-WL) and delayed recall (CERAD-DR), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The data of HEI-2015 were acquired from 24-hour dietary recalls. Weighted linear regression models were performed to investigate the association between HEI-2015 and cognitive function in elderly patients with periodontitis. The associations were further investigated in subgroups of sex, cardiovascular disease status, and depression status.

A total of 1862 participants were included, and 1223 of them had periodontitis. Periodontitis was negatively associated with cognitive function (β = -0.45; 95% confidence interval [CI], -0.87 to -0.03). No statistically significant relationship was observed between HEI-2015 and cognitive function (β = 0.33; 95% CI, -0.02 to 0.69). Low HEI-2015 score was associated with high odds of cognitive decline in patients with periodontitis (β = -0.73; 95% CI, -1.25 to -0.21; P for trend = .01). Higher HEI-2015 was related to the lower incidence of cognitive function decline in patients with periodontitis who were female (β = -0.53; 95% CI, -1.03 to -0.03), had a socioeconomic status from 0 to 3 (β = -0.55; 95% CI, -1.00 to -0.09), did not have cardiovascular disease (β = -0.60; 95% CI, -1.14 to -0.05), and did not have depression (β = -0.57; 95% CI, -1.11 to -0.03).

Greater HEI-2015 adherence may improve cognitive function amongst elderly patients with periodontitis. Further studies are needed to investigate this putative association in elderly persons with periodontitis.

To examine the immune responses in patients diagnosed as grade C periodontitis during orthodontic treatment.

Our study included seven orthodontic patients with grade C periodontitis and measured their levels of inflammatory cytokines in gingival crevicular fluid and plasma before orthodontic treatment, during the alignment and levelling phase, and during the detailing and finishing phase. The key signal pathways in the orthodontic process of patients with periodontitis were detected by KEGG analysis.

Studies have shown that orthodontic treatment brings great improvement to patients with grade C periodontitis, and most of the local/systemic inflammatory cytokines can be reduced after orthodontic treatment. Simultaneously, orthodontic treatment can reduce the percentage of IFN-γ+ Th1 cells in patients with grade C periodontitis. Through KEGG analysis, the IL-17 signalling pathway and TNF signalling pathway are closely interrelated in the orthodontic treatment of patients diagnosed with grade C periodontitis (p-value < 0.001).

Orthodontic treatment can effectively control the local and system levels of inflammation in patients with grade C periodontitis, with IL-17A and TNF-α as potential distinctive inflammatory markers for orthodontic-periodontal combined treatment in individuals with periodontitis.

The study aimed to provide evidence for a relationship between a high dietary intake of advanced glycation end products, and periodontitis.

A total of 2334 adults from the National Health and Nutrition Examination Survey (NHANES) during 2003-2004 were included in this study. Binary regression analysis was conducted to measure the association between periodontitis and dietary advanced glycation end products (AGEs), and two adjusted models were constructed to further explore the relationship.

Participants with AGEs intake above 21.41 U/kcal had a higher prevalence of periodontitis compared to those with lower AGEs intake. After fully adjusting for associated factors, the odds ratios for periodontitis in relation to higher AGEs intake were 1.229 (95% confidence interval 1.015-1.488, p = .034), 1.349 (95% confidence interval 1.157-1.642, p = .003), and 1.331 (95% confidence interval 1.088-1.630 p = .006), respectively.

Our cross-sectional study reveals a strong association between periodontitis and AGEs.

An association between advanced glycation end products in the diet and periodontitis implies the importance of the quality of food intake for good oral health.

The consumption of dietary advanced glycation end products is associated with an increased susceptibility to periodontitis development.

These findings contribute to recognizing the harm of advanced glycation end products in various foods to periodontitis, and guiding clinical oral education.

Periodontitis is a widespread disease, associated with challenges both in its diagnosis and in selecting from various therapeutic approaches, which do not always yield the expected success. This literature review was conducted to explore diverse therapeutic approaches, especially those focused on nanotechnologies, and their potential contribution to the successful modulation of the host's response. The effects of the existing microbial diversity and the imbalance of key microbial species in contributing to the progression and worsening of the host's response in periodontitis are well known. It is essential to understand the role of a well-structured treatment plan for periodontitis, providing opportunities for new research and innovative treatment strategies aimed at reducing the impact of periodontitis on oral and overall systemic health. This will be beneficial for dental professionals, enabling them to effectively prevent and treat periodontitis, ultimately improving the overall health and well-being of patients.

Theobromine intake usually comes from coffee, tea, and cocoa foods. Related studies have shown that theobromine is a bioactive molecule with anti-inflammatory, antithrombotic, anti-fat, and other effects. Periodontitis is a kind of oral inflammatory disease with high incidence, which is characterized by alveolar bone resorption leading to tooth loosening and loss. Therefore, this study aims to investigate whether theobromine intake correlates with periodontitis and whether it is a risk or protective factor for periodontitis. It hopes to provide a basis for theobromine-related diet or drugs to prevent and treat periodontitis.

The study employed a cross-sectional design and utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2009 and 2014. The exposure factor was theobromine intake, derived from two-day, 24-hour total nutrient intake data from dietary data. Periodontitis-related indicators as outcome factors were derived from the oral health component of the examination data. We used weighted multiple logistic regression, fractional Response Model, subgroup analysis, and the effect moderation test to explore the relationship between theobromine dietary intake and periodontitis severity based on weighting and adjusting for confounding factors.

After adjusting for relevant confounding factors, weighted logistic regression showed that theobromine intake was negatively correlated with periodontitis-related indicators (mean periodontal pocket depth, mean clinical attachment loss, and the percentage of sites with PD ≥ 4 mm). And theobromine intake was positively correlated with the number of teeth.

This study demonstrated theobromine intake may serve as a protective factor against the development of periodontitis.

Unstable atherosclerotic plaques are a major cause of acute cardiovascular events and ischemic stroke. Clinical studies have suggested a link between periodontitis and atherosclerotic plaque progression, but the underlying mechanisms remain unclear. To investigate this, transcriptomic datasets related to periodontitis and atherosclerosis were downloaded from Gene Expression Omnibus. A weighted gene co-expression network analysis was used to identify gene modules associated with periodontitis, and the Limma R package identified differentially expressed genes (DEGs) between unstable and stable plaques. Overlapping genes were defined as periodontitis-related DEGs, followed by functional enrichment analysis and protein-protein interaction network construction. Machine learning methods were used to identify biomarkers for unstable plaques related to periodontitis, which were validated using external datasets. Immune infiltration and single-cell analyses were performed to explore the relationship between biomarkers and immune cells. A total of 161 periodontitis-related DEGs were identified, with the pathway analysis showing associations with immune regulation and collagen matrix degradation. HCK, NCKAP1L, and WAS were identified as biomarkers for unstable plaques, demonstrating a high diagnostic value (AUC: 0.9884, 95% CI: 0.9641-1). Immune infiltration analysis revealed an increase in macrophages within unstable plaques. Single-cell analysis showed HCK expression in macrophages and dendritic cells, while NCKAP1L and WAS were expressed in macrophages, dendritic cells, NK cells, and T cells. Consensus clustering identified three expression patterns within unstable plaques. Our findings were validated in atherosclerotic mouse models with periodontitis. This study provides insights into how periodontitis contributes to plaque instability, supporting diagnosis and intervention in patients with periodontitis.

Periodontitis is the leading cause of tooth loss in adults due to progressive bone destruction, which is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). Existing evidence suggests that mitochondrial disorders are associated with periodontitis. However, whether mitochondrial dysregulation contributes to the osteogenic impairment of BMSCs and the underlying mechanisms remain unclear. Macrophages have been shown to communicate extensively with BMSCs in periodontitis. Recent studies have reported a novel manner of cellular communication in which mitochondria-rich extracellular vesicles（MEVs） transfer mitochondria from parent cells to recipient cells, playing a role in both physiological and pathological conditions. Therefore, we aimed to investigate the role of MEVs in orchestrating the crosstalk between macrophages and BMSCs in periodontitis to formulate management strategies for bone loss.

Our results revealed that macrophages underwent significant mitochondrial dysfunction and inflammation in periodontitis and that MEVs derived from these macrophages played a role in alveolar bone destruction. Furthermore, cell imaging showed that inflammatory macrophages packaged numerous damaged mitochondria into MEVs, and the entry of these impaired mitochondria into BMSCs disrupted mitochondrial dynamics and hindered donut-shaped mitochondria formation, leading to osteogenic dysfunction. Proteomic analysis revealed that the proteins enriched in macrophage-derived MEVs were largely related to mitochondria and the formation and transport of vesicles. Additionally, we found that MEVs from macrophages significantly increased lipocalin 2 (LCN2) in BMSCs in periodontitis and that LCN2 perturbed mitochondrial morphological changes in BMSCs by inducing the degradation of OMA1 and accumulation of OPA1, resulting in osteogenesis impairment in BMSCs. Inhibition of LCN2 rescued the osteogenic dysfunction of BMSCs and alveolar bone loss in periodontitis.

The transfer of mitochondria to BMSCs via MEVs exacerbates alveolar bone resorption through LCN2/OMA1/OPA1 signaling in periodontitis. Inhibition of LCN2 alleviates inflammatory bone loss, suggesting a promising therapeutic strategy for periodontitis.

Periodontitis and heart failure (HF) impact millions of individuals globally with heavy social and economic burden. Prior research has indicated a connection between them. However, the conclusions have been somewhat inconsistent. Our objective is to confirm, through meta-analysis and Mendelian randomisation studies, whether patients with periodontitis have an increased risk of HF. Therefore, we conducted a comprehensive analysis to explore the causal association between periodontitis and the risk of HF.

In this meta-analysis, we searched online to identify studies involving periodontitis on the risk of HF. The main endpoint assessed in this study was the risk of HF. We used R language to calculate the pooled results and create plots. A random-effects model was employed in the analyses. In the Mendelian randomisation (MR) analyses, we obtained data from public databases. MR analyses were conducted using genome-wide association data for acute and chronic periodontitis. Independent genetic variants associated significantly with each exposure (P 5*10-6) were considered as instruments. The primary analysis employed the inverse variance weighted (IVW) method, which was subsequently supplemented by a series of sensitivity analyses to ensure the robustness and reliability of the findings.

Our meta-analysis included three publications, with a total of 21,997 participants. The pooled result demonstrated that periodontitis increased the risk of HF (OR = 1.62, 95% CI 1.29-2.03). Periodontitis increased the risk of heart failure with reduced ejection fraction (HFrEF) with a low level of heterogeneity (OR = 1.99, 95% CI 1.22-3.23) and heart failure with preserved ejection fraction (HFpEF) with little heterogeneity (OR = 1.36, 95% CI 1.00-1.86). In the MR study, acute or chronic periodontitis did not increase the risk of HF. Sensitivity analyses revealed that the causal association estimations were robust.

In summary, the meta-analysis results indicate that individuals with periodontitis are at a higher risk of HF. The findings from the MR study fail to establish a causal link between the two variables under investigation. To validate this assertion and elucidate the fundamental mechanism, additional research is imperative.

Based on the current evidence, it cannot be concluded that there is a causal relationship between acute or chronic periodontitis and HF.

This study aimed to identify crosstalk genes shared between periodontitis (PD) and atherosclerosis (AS) and to investigate their potential connections with pyroptosis-related genes. The goal was to uncover common regulatory mechanisms underlying these two inflammatory conditions.

Gene expression datasets for PD (GSE10334) and AS (GSE43292) were retrieved from public databases. Following batch effect correction and normalization, differential expression analysis was conducted using the limma package in R. Functional enrichment analysis was performed with the clusterProfiler package to identify key pathways, while heatmaps and pathway networks were constructed to visualize the relationships among pyroptosis genes and crosstalk genes. Weighted gene co-expression network analysis (WGCNA) was applied to identify critical modules, and the diagnostic potential of core genes was evaluated via receiver operating characteristic (ROC) analysis. Protein-protein interaction (PPI) networks were also constructed to explore molecular interactions.

A total of 28 downregulated and 105 upregulated genes were identified in the PD dataset, while the AS dataset revealed 55 downregulated and 56 upregulated genes. Thirteen crosstalk genes were identified between the two datasets. Enrichment analyses of these crosstalk genes highlighted their involvement in inflammation- and immune-related pathways. The observed association of pyrototic phenotypes with PD and AS indicated significant overexpression of pyroptosis-related genes such as CASP1, NLRP3, and GSDMD, suggesting the participation of pyroptosis in the progression of disease. The WGCNA suggested that pyroptosis genes are closely relevant to immune responses and cell death processes. Data up to October 2023 were used to perform receiver operating characteristics (ROC) curves to confirm the diagnostic value of the enriched core genes, and all of them presented AUC values >0.8, which meant that they were key genes with effective diagnostic power.

We report a novel study that identifies differentially expressed genes and pyroptosis-related pathways in PD and AS with shared inflammatory mechanisms. These results underscore the crucial role of pyroptosis in disease progression, suggesting its potential as a focus of diagnostic and therapeutic strategies. These findings provide insights for dissecting the molecular basis of inflammatory diseases.

Chronic infectious bone destruction diseases, such as periodontitis, pose a significant global health challenge. Repairing the bone loss caused by these chronic infections remains challenging. In addition to pathogen removal, regulating host immunity is imperative. The retention of neutrophil extracellular traps (NETs) in chronic infectious niches is found to be a barrier to inflammation resolution. However, whether ruining the existing NETs within the local infectious bone lesions can contribute to inflammation resolve and bone repair remains understudied. Herein, a nanocapsuled delivery system that scavenges NETs dual-responsively to near-infrared light as a switch and to NETs themselves as a microenvironment sensor is designed. Besides, the photothermal and photodynamic effects endow the nanocapsules with antibacterial properties. Together with the ability to clear NETs, these features facilitate the restoration of the normal host response. The immunocorrective properties and inherent pro-osteogenic effects finally promote local bone repair. Together, the NET scavenging nanocapsules address the challenge of impaired bone repair in chronic infections due to biased host response caused by excessive NETs. This study provides new concepts and strategies for repairing bone destruction attributable to chronic infections via correcting biased host responses in chronic infectious diseases.

Periodontal disease, a chronic inflammatory condition affecting the supporting structures of teeth, is driven by an imbalanced interaction between the periodontal microbiota and the host inflammatory response. Beyond its local impact, periodontal disease is associated with systemic conditions such as diabetes mellitus, cardiovascular disease, and inflammatory bowel disease, emphasizing the importance of understanding its mechanisms. Traditional pre-clinical models, such as monolayer cultures and animal studies, have provided foundational insights but are limited by their physiological relevance and ethical concerns. Recent advancements in tissue engineering and microfluidic technologies have led to the development of three-dimensional (3D) organotypic culture models and organ-on-chip systems that more closely mimic native tissue microenvironments. This review provides an overview of the evolution of methods to study periodontal host-microbe interactions, from simple 2D monolayer cultures to complex 3D organotypic and microfluidic organ-on-chip (OoC) models. We discuss various fabrication strategies, host-microbe co-culture techniques, and methods for evaluating outcomes in these advanced models. Additionally, we highlight insights gained from gut-on-chip platforms and their potential applications in periodontal research and understanding oral-systemic links of periodontal disease. Through a comprehensive overview of current advancements and future directions, this review provides insights on the transformative potential of OoC technology in periodontal research, offering new avenues for studying disease mechanisms and developing therapeutic strategies.

This systematic review investigates the effectiveness of natural extracts with anti-inflammatory properties for improving oral health, particularly in managing gingivitis and periodontal disease (PD). With PD being a major global health issue, exacerbated by microbial dysbiosis and oxidative stress, the integration of phytochemicals and herbal formulations into periodontal therapy offers a promising avenue for adjunctive treatments.

A systematic review was conducted following PRISMA guidelines and registered under the International Prospective Register of Systematic Reviews (ID: 641944). Databases, including PubMed, Scopus, and Web of Science, were searched between 18-24 December 2024, using Boolean keywords combining terms such as "herbal medicine", "plant extracts", "anti-inflammatory", and "periodontal therapy". Studies involving animal models, in vitro data, or non-peer-reviewed articles were excluded.

Seventeen studies met inclusion criteria. Polyherbal formulations and single-component extracts (e.g., Camellia sinensis, Punica granatum, Zingiber officinale, and Rosmarinus officinalis) demonstrated comparable efficacy to conventional agents like chlorhexidine (CHX). Polyherbal rinses, camellia sinensis gels, and extracts like Punica granatum reduced inflammation, improved gingival health, and showed antimicrobial properties, offering effective natural alternatives.

Natural products, including single extracts and polyherbal formulations, provide effective and safe alternatives for managing gingivitis and PD. Their anti-inflammatory, antimicrobial, and antioxidant properties support their adjunctive role alongside with scaling and root planning therapy (SRP) in periodontal therapy. However, further large-scale, long-term studies are needed to standardize formulations and establish optimal protocols.

Psychological stress is linked to elevated salivary cortisol levels, potentially worsening periodontitis by exacerbating inflammation. This study examines the impact of stress on cortisol levels in periodontitis patients, aiming to explore salivary cortisol as a biomarker for disease severity and its role in improving management strategies.

This case-control study, conducted at Dow University of Health Sciences in Karachi from January to December 2022, involved 120 dental clinic patients aged 30-60. Participants were selected based on the presence (cases) or absence (controls) of periodontitis, excluding those with systemic diseases, taking hydrocortisone, immunosuppressives, antidepressants, systemic antibiotics, having oral ulcers and pregnancy or lactation. Periodontal parameters, stress levels (using the Perceived Stress Scale), and morning salivary cortisol (measured via ELISA) were assessed. Statistical analyses were performed using SPSS version 23, including descriptive statistics, independent t-tests, ANOVA, and odds ratio calculations with a 95% confidence interval at 0.05.

The study cohort comprised 120 subjects, equally divided between periodontitis patients and healthy controls. Predominantly male (63%) with a mean age of 41.75 years, participants were subjected to comprehensive evaluations. Oral health indices (Gingival index, Plaque index, Clinical attachment loss, Periodontal probing depth, Tooth mobility) and stress markers (Perceived Stress Score, Salivary cortisol levels [SCLs]) were significantly higher in cases compared to controls (p < 0.001). Majority of cases (58.3%) had stage II periodontitis. Notably, cases exhibited significantly higher stress levels (2.05 ± 0.59 vs. 1.38 ± 0.52; p < 0.001) and elevated salivary cortisol levels (6.67 ± 1.64 vs. 2.54 ± 0.88; p < 0.001) compared to controls. The odds ratio (OR) of 3.73 (95% CI [1.75, 7.93], p = 0.0006) indicated that periodontitis patients were over 3.5 times more likely to have elevated SCLs. Stress prevalence was 42.5% in periodontitis patients compared to 18.33% in controls.

This study highlights a potential link between stress, cortisol levels, and periodontitis, suggesting that salivary cortisol could be a valuable biomarker. Incorporating cortisol measurements into routine dental evaluations may enable personalized treatment plans, addressing both biological and psychological contributors to periodontitis. Further research is needed to explore the long-term effects of stress on cortisol levels and periodontal disease progression, as well as the role of stress management in managing periodontitis.

Periodontitis is a prevalent oral disease that significantly impacts human quality of life. This study aimed at the influence of microRNA-299-5p (miR-299-5p) on regulating lipopolysaccharide (LPS)-induced osteogenic differentiation of periodontal ligament stem cells (PDLSCs).

The 105 periodontitis patients and 102 healthy periodontal volunteers (HC) were recruited with their clinical baseline data. miR-299-5p expression in saliva was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). To identify the target relationship between miR-299-5p and pumilio RNA-binding family member 2 (PUM2), the dual luciferase reporter gene was explored. PDLSCs were treated with LPS and subjected to osteogenic differentiation induction. The secretion of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) was determined by enzyme-linked immunosorbent assay. mRNA expression of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OCN) was detected by qRT-PCR.

miR-299-5p expression was markedly reduced in periodontitis patients' saliva and negatively correlated with patients' attachment loss, bleeding index, plaque index, probing pocket depth, and TNF-α, IL-6, and IL-1β levels. miR-299-5p could be well distinguished between periodontitis and HC. LPS induction dramatically stimulated the secretion of inflammatory factors and inhibited the differentiation of PDLSCs, which was counteracted by miR-299-5p overexpression. miR-299-5p was detected to target PUM2, which could exacerbate the inflammatory condition of PDLSCs and lead to differentiation defects.

miR-299-5p has emerged as a promising diagnostic marker for periodontitis and may attenuate inflammation and contribute to osteogenic differentiation in PDLSCs cells by targeting PUM2.

Background/Objectives: Dental caries and periodontal diseases are the most common illnesses in the oral cavity and represent a public health concern globally. In recent decades, diverse studies showed that Kefir, a traditional beverage that can be milk- or water-based, contains a complex microbial community and has health benefits. The goal of this review was to update the current knowledge of kefir consumption and its impact on oral health. Methods: The search of a combination of keywords-kefir; dental caries; probiotics; microbiota; periodontal diseases; biofilm; and oral health-was conducted using PubMed, Google Scholar, and Web of Science databases for studies in human subjects. Discussion: The research suggests that kefir consumption may aid in decreasing counts of microorganisms typically associated with oral illness. Conclusions: Kefir has the potential to inhibit certain oral pathogens and reduce biofilm formation by promoting diversity within the oral microbiota, suggesting that kefir could be a promising adjuvant treatment for dental caries and periodontal diseases by improving oral health.

To evaluate the effects of Xianling Gubao Capsules (XGC) on alveolar bone and inflammatory mediators in the gingival crevicular fluid in patients with periodontitis.

A retrospective analysis was conducted on 90 periodontitis patients who received medication treatment at Daqing Longnan Hospital from September 2022 to June 2023. Patients were categorized into three groups: a control group (n=30, receiving basic periodontal treatment), a Caltrate group (n=30, receiving basic treatment plus Caltrate), and an XGC group (n=30, receiving basic treatment plus Xianling Gubao Capsules). Changes in alveolar bone defect height, alveolar bone density, plaque index (PI), probing depth (PD), gingival index (GI), gingival crevicular fluid volume, and inflammatory mediator levels were compared before and after treatment.

After 3 and 6 months of treatment, the XGC group exhibited significantly reduced alveolar bone defect height in incisors, canines, premolars, and molars and significantly increased alveolar bone density compared with the other two groups (all P<0.05). The XGC group also exhibited lower tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and higher interleukin-17 (IL-17) levels than the Caltrate and control groups (all P<0.05). Additionally, PI, PD, GI, and gingival crevicular fluid volume were significantly lower in the XGC group at both time points (all P<0.05). The incidence of adverse reactions did not differ significantly among the three groups (P>0.05).

Xianling Gubao Capsules, when combined with conventional periodontal treatment, may enhance alveolar bone density, reduce alveolar bone defects, alleviate periodontal inflammation, and modulate inflammatory mediator levels in the gingival crevicular fluid. These findings suggest clinical benefits for periodontitis management.

This study aimed to investigate the relationship between the pan-immune-inflammation value (PIV) and periodontitis based on a large national survey.

In the present cross-sectional study, data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, which included a total of 10,300 participants. The categorization of periodontitis was based on the 2017 classification scheme. The PIV was determined using the formula: (neutrophils count × monocyte count × platelet count)/lymphocytes count. Restricted cubic spline and weighted multivariable logistic regression analyses were employed to evaluate the associations between the PIV with periodontitis.

The associations between PIV and stage III/IV periodontitis followed a U-shaped pattern (Pnon-linearity < 0.001). The risk of developing stage III/IV periodontitis showed an increasing trend among participants in the first quartile (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.01-1.46), third quartile (OR = 1.34; 95% CI: 1.11-1.61), and fourth quartile (OR = 1.47; 95% CI: 1.25-1.73) compared to those in the second quartile. Subgroup analysis indicated stronger associations of PIV with periodontitis in males (ORQ4vs2 = 1.72, 95% CI: 1.36-2.18) and individuals with hypertension (ORQ4vs2 = 1.78, 95% CI: 1.38-2.28) with significant interactions (Pinteraction < 0.05).

There is a U-shaped association between PIV and stage III/IV periodontitis, which suggests a potential adjunctive treatment strategy for periodontitis. Higher PIV values were found to have a stronger correlation with stage III/IV periodontitis in males and individuals with hypertension. Further prospective trials are needed to confirm the validity of our results.

A U-shaped association exists between the pan-immune inflammation value and periodontitis in US adults, suggesting that maintaining a moderate immune inflammation response is crucial for periodontal health.

Melatonin, the "sleep hormone," shows significant promise in dentistry owing to its antioxidant, anti-inflammatory, and immunomodulatory properties. It is beneficial for treating periodontal disorders and aiding osseointegration of dental implants. Additionally, melatonin helps to manage dental anxiety, offering an alternative to traditional sedatives. Periodontal disease is orchestrated by bacterial plaques along with an exaggerated immune-inflammatory host response. Treatment of periodontitis not only involves the removal of plaque, but also aims to minimize the cytokine load and control the reactive oxygen species burden in the tissues, which would re-establish a healthy periodontium and a balanced bone metabolism. Melatonin is known to exert beneficial effects, such as regulation of circadian rhythm, bone remodeling, and antimicrobial effects. Recent studies have demonstrated the successful use of melatonin as an adjunct to mechanical debridement for the treatment of periodontal disease. Its various uses include systemic administration of melatonin after one-stage full-mouth Non-Surgical Periodontal Therapy in healthy subjects as well as patients. This article provides a summary of the various clinical applications of melatonin, describing its mechanism of action, uses, and potential avenues for future research in dentistry.

Periodontitis is a prevalent inflammatory disease affecting the supporting structures of the teeth, leading to gum recession, tooth loss, and systemic health complications. Traditional diagnostic methods and treatments, such as clinical evaluation and scaling, often fall short in early detection and targeted therapy, particularly in complex or advanced cases. Recent advancements in nanomedicine offer promising solutions for improving both the diagnosis and treatment of periodontitis. Nanoparticles, such as liposomes, quantum dots, and nanorods, have demonstrated potential in enhancing diagnostic accuracy by enabling more precise detection of periodontal pathogens and biomarkers at the molecular level. Furthermore, nanotechnology-based therapies, including drug delivery systems and antimicrobial agents, offer localized and controlled release of therapeutic agents, enhancing efficacy and reducing side effects compared to conventional treatments. This study reviews the current applications of nanomedicine in the diagnosis and treatment of periodontitis, highlighting its potential to revolutionize periodontal care by improving early detection, reducing treatment times, and enhancing therapeutic outcomes.

Periodontal disease (PD) is a chronic inflammatory condition affecting oral and systemic health. Luteolin (LUT), a natural flavonoid, has shown anti-inflammatory effects, but its therapeutic potential and mechanisms in PD remain unclear.

This study aimed to investigate the effects of LUT on PD, focusing on its impact on mitochondrial dynamics, macrophage polarization, and the JAK2/STAT3 signaling pathway.

A combination of network pharmacology analysis and in vivo and in vitro experiments was employed. The efficacy of LUT was evaluated using a ligature-induced rat PD model and LPS-stimulated THP-1-derived macrophages. Key assessments included micro-CT for bone loss, flow cytometry for macrophage polarization, and Western blot for pathway analysis.

LUT significantly reduced alveolar bone loss and enhanced M2 macrophage polarization, as indicated by increased CD206 and Arg1 expression. Additionally, it improved mitochondrial function by reducing ROS and restoring membrane potential, decreasing mitochondrial fission, and promoting mitochondrial fusion. Mechanistically, LUT inhibited JAK2/STAT3 phosphorylation, promoting anti-inflammatory effects.

These findings suggest that LUT ameliorates periodontal inflammation and bone loss by modulating mitochondrial dynamics, promoting M2 macrophage polarization, and suppressing the JAK2/STAT3 signaling pathway. This highlights LUT as a promising multitarget candidate for PD treatment.

Advances in tissue engineering and microfluidic technologies have enabled the development of sophisticated in vitro models known as organ-on-a-chip (OoC) or microphysiological systems. These systems enable to potential to simulate the dynamic interactions between host tissues and their microenvironment including microbes, biomaterials, mechanical forces, pharmaceutical, and consumer-care products. These fluidic technologies are increasingly being utilized to investigate host-microbe and host-material interactions in oral health and disease. Of interest is their application in understanding periodontal disease, a chronic inflammatory condition marked by the progressive destruction of periodontal tissues, including gingiva, periodontal ligament, and alveolar bone. The pathogenesis of periodontal disease involves a complex interplay between microbial dysbiosis and host immune responses, which can lead to a loss of dental support structures and contribute to systemic conditions such as cardiovascular disease, diabetes, and inflammatory bowel disease. This provides a comprehensive overview of the latest developments in millifluidic and microfluidic systems designed to emulate periodontal host-microbe and host-material interactions. We discuss the critical engineering and biological considerations in designing these platforms, their applications in studying oral biofilms, periodontal tissue responses, and their potential to unravel disease mechanisms and therapeutic targets in periodontal disease.

Periodontitis is one of the most common oral diseases. It is generally treated by non-surgical and/or surgical therapy with adjunctive approaches for prevention and control. The current understanding of the pathogenesis of periodontitis has unraveled the importance of the inflammatory and immune reactions to combat periodontitis whose etiology is an overlap of microbial, genetic, and environmental factors in a susceptible host. Based on this premise, many therapeutic modalities have been investigated or attempted to resolve this inflammatory disease. Amongst these, nanomedicine has been shown to have therapeutic applications in periodontitis, especially focused on immunomodulation because periodontitis is characterized by over-reactive immune response. This mini-review explores the potential of nanosystems in treating periodontitis by providing an overview of the research efforts in this field of therapeutics. The unique physicochemical and targeting properties of nanosystems seem to be potentially effective platforms for treating periodontitis.

Periodontitis is increasingly recognized for its role in overall health and its associations with systemic conditions. Shared etiological factors, including microbiological, immunological, genetic, and environmental influences, have prompted interest in the potential impact of periodontal therapy on broader health outcomes. The oral microbiome plays a key role in the pathogenesis of periodontitis, with microbial imbalances (dysbiosis) contributing to inflammation and systemic disease progression. Additionally, immune responses to periodontal infection, such as chronic inflammation and dysregulated immune activity, are central to linking periodontitis with conditions like diabetes, cardiovascular disease, and autoimmune disorders. This chapter explores the connections between periodontal treatment and systemic diseases, such as diabetes, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, Alzheimer's disease, digestive disorders, and respiratory disease. It also reviews the current research on the mechanisms, including microbial and immune factors, that underlie these associations. By emphasizing the role of periodontal health, the oral microbiome, and immune regulation in disease prevention and management, this chapter underscores the importance of integrated healthcare approaches to improve patient outcomes.

The aim of this study was to evaluate the effect of periodontal Porphyromonas gingivalis (P. gingivalis) infection on lung homeostasis and to explore the underlying mechanism.

In in vivo experiments, twelve mice were divided into two groups. The P. gingivalis infection group received P. gingivalis around the maxillary second molar, and the control group was left untreated. After 12 weeks, the histopathological changes of the lung tissue and the autophagy and apoptosis in the lung tissue cells were detected. In in vitro experiments, alveolar epithelial cell A549 was co cultured with P. gingivalis and treated with autophagy inhibitor chloroquine (CQ). Western blot was then used to detect autophagic markers LC3 and P62, and mRFP-GFP-LC3 was used to observe autophagic flux. Cell viability and apoptosis were also detected.

For the in vivo experiments, pathological changes were observed in the lung tissue of the P. gingivalis infection group at 12 weeks, along with higher levels of autophagy and apoptosis in the lung tissue cells. For the in vitro experiments, infection of alveolar epithelial cells with P. gingivalis inhibited cell viability and promoted cell autophagy and apoptosis. Interestingly, we found that inhibiting P. gingivalis-activated autophagy significantly improved cell apoptosis and viability damage induced by P. gingivalis.

Periodontal P. gingivalis infection can cause pathological changes and abnormal homeostasis in lung tissue, and the up-regulation of autophagy induced by P. gingivalis may play a synergistic role in this process.

Periodontitis is associated with systemic health. One of the underlying mechanisms is the translocation of periodontal pathogens, among which Porphyromonas gingivalis (Pg) is the most common. Here, we aimed to illustrate the biodistribution and dynamics of Pg from gingiva to multiple organs through blood circulation.

Pg tagged by Cyanine 7 (Cy7-Pg) was injected into the gingiva of healthy and periodontitis mice. In vivo imaging system (IVIS) was applied to monitor the distribution of Cy7-Pg in multiple organs which were isolated at serial timepoints. Polymerase chain reaction (PCR) was conducted to determine the Pg DNA copies in the gingiva, blood and organs. Cy7-Pg in the gingiva and organs was also confirmed by frozen section staining. Furthermore, to figure out whether the bacteremia derived from oral-gut axis, mice received gavage of Cy7-Pg. Then the blood and organ samples were detected in the similar way as above.

Intra-gingival injection induced larger amounts of Cy7-Pg accumulating in the gingiva of periodontitis mice (P < 0.05) as confirmed by above three methods. Twenty minutes after injection, Pg DNA copies in the blood of periodontitis group were 36.3-fold higher than healthy group (P < 0.05). IVIS results, combined with PCR and frozen sections, demonstrated periodontitis induced longer retention with higher amounts of Cy7-Pg in the periodontitis group. Pg was enriched more significantly in the liver for the longer duration than the kidney and pancreas.

Our study showed Pg, which accumulated in the gingiva, could translocate through blood circulation to multiple organs with varied duration and amounts.

Periodontitis, characterized by inflammatory loss of tooth-supporting tissues associated with biofilm, is among the most prevalent chronic diseases globally, affecting approximately 50% of the adult population to a moderate extent and cases of severe periodontitis surpassing the one billion mark. Proteomics analyses of blood, serum, and oral fluids have provided valuable insights into the complex processes occurring in the inflamed periodontium. However, until now, proteome analyses have been primarily limited to small groups of diseased versus healthy individuals. The emergence of population-scale analysis of proteomic data offers opportunities to uncover disease-associated pathways, identify potential drug targets, and discover biomarkers. In this review, we will explore the applications of proteomics in population-based studies and discuss the advancements it brings to our understanding of periodontal inflammation. Additionally, we highlight the challenges posed by currently available data and offer perspectives for future applications in periodontal research. This review aims to explain the ongoing efforts in leveraging proteomics for elucidating the complexities of periodontal diseases and paving the way for clinical strategies.

To investigate the association between periodontitis and inflammatory biomarkers, including systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio.

Our study comprised a cross-sectional analysis (an indirect evidence group and a periodontal health control group from January to October 2023) and a retrospective study (a direct evidence group and a non-maintenance group from January 2014 to March 2022). We analyzed demographic data, imaging measurements, and peripheral blood counts.

The study included 131 participants in the indirect evidence group, 132 in the healthy control group, 123 in the direct evidence group, and 76 in the non-maintenance group. The indirect evidence group exhibited significantly altered inflammatory biomarker levels compared to the healthy controls. Receiver operating characteristic curve analysis indicated that SII was the most effective biomarker for diagnosing periodontitis, with an area under the curve 0.758 and a Youden index 0.409. The optimal cut-off value was 437.07 × 10⁹/L, achieving a sensitivity 46.2% and a specificity 94.7%. Correlation analyses revealed significant associations between the biomarker levels and periodontitis grades, with SII showing the highest correlation coefficient (0.942). In the direct evidence group, supportive periodontal therapy significantly mitigated changes in these biomarkers.

An SII level exceeding 437.07 × 109/L could facilitate the periodontitis diagnosis and disease grade determination. SII can be utilized to assess and monitor periodontitis severity and treatment response.