Search Results (435)

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

From a psychoneuroimmunology standpoint, stress and cigarette smoking are plausible modulators of periodontal inflammation through neuroendocrine–immune pathways and cytokine networks. Interleukin-18 (IL-1 family), interleukin-21 (common γ-chain cytokine), and interleukin-15 (tissue-resident lymphocyte activation/homeostasis) are mechanistically relevant candidates to characterize in relation to these exposures. We aimed to quantify serum IL-15, IL-18, and IL-21 and examine their associations with stress, smoking, and periodontal status in Mexican adults. Methods: Cross-sectional study (n = 65; 18–60 years; 70.8% female). Smoking status (23.1% smokers) and periodontal status were recorded; due to low periodontitis frequency (n = 3), periodontal status was analyzed as healthy (23.1%) versus periodontal disease (76.9%; gingivitis + periodontitis). Stress was assessed using the 18-item Symptomatic Stress Questionnaire and dichotomized as no/low stress (0–10; 52.3%) versus pathological stress (11–54; 47.7%). Systolic and diastolic blood pressure were recorded. IL-15, IL-18, and IL-21 were measured in serum by immunoassay. Analyses used medians (IQR), Mann–Whitney U tests with rank-biserial effect sizes, and exploratory Benjamini–Hochberg false discovery rate (FDR) adjustment across the nine primary cytokine-by-contrast tests; correlations with age and diastolic blood pressure were exploratory. Results: Cytokine distributions were right-skewed, particularly for IL-21. Across smoking, stress, and periodontal-status contrasts, no comparison met q < 0.05 after FDR adjustment. Effect-size patterns were heterogeneous rather than uniformly monotonic across exposures (e.g., IL-18 showed higher central tendency in healthy vs. periodontal disease; IL-21 showed higher central tendency in no/low stress vs. pathological stress), indicating substantial inter-individual variability in circulating cytokines within this cohort. Conclusions: In this exploratory cross-sectional sample, serum IL-15, IL-18, and IL-21 did not show robust, multiplicity-resistant differences by smoking, stress, or periodontal status. The findings provide a transparent description of distributional properties and hypothesis-generating patterns that motivate larger, longitudinal studies with repeated cytokine sampling, standardized periodontal assessment, and improved control of key confounders to clarify the relevance of these cytokines to periodontal inflammation under behavioral exposures. Full article

Background: The growing body of evidence linking dietary factors to oral and periodontal health is characterized by substantial heterogeneity in study design, dietary assessment methods, and reported outcomes, warranting a comprehensive narrative synthesis. Diet is a key determinant of oral and periodontal health, influencing inflammation, oxidative stress, salivary composition, and the oral microbiome. Objectives: This narrative review aims to synthesize current clinical, epidemiological, and mechanistic evidence on how dietary patterns and specific nutrients affect oral and periodontal health, focusing on inflammatory pathways, microbiome modulation, nutrient-dependent tissue mechanisms, and clinical outcomes. Methods: A structured narrative search was conducted in PubMed, Scopus, Web of Science, and Google Scholar (2000–2025). Studies examining diet, nutrients, the oral microbiome, caries, gingival inflammation, or periodontal disease were screened through a multistep process, resulting in 98 included articles. Results: High-sugar and ultra-processed diets trigger inflammation and oral dysbiosis, increasing caries and periodontal susceptibility. In contrast, nutrient-rich and anti-inflammatory diets improve immune regulation, support microbial balance, and are associated with better periodontal parameters. Conclusions: Dietary habits significantly shape oral and periodontal outcomes through interconnected metabolic, microbial, and immunological pathways. Integrating targeted nutritional counseling into dental care may strengthen prevention strategies and improve long-term oral health. Full article

Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus. Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, and autophagy. Dysregulation of autophagy contributes to pathogenesis and treatment resistance of several oral diseases, including oral squamous cell carcinoma (OSCC), periodontitis, and gingival inflammation. This review delineates the molecular crosstalk between cannabinoid receptor type I (CB1) and type II (CB2) activation and autophagic pathways across oral tissues. Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), modulate key regulators like mTOR, AMPK, and Beclin-1, thereby influencing autophagic flux, inflammation, and apoptosis. Experimental studies indicate that cannabinoids inhibit the PI3K/AKT/mTOR pathway, promote reactive oxygen species (ROS)-induced autophagy, and modulate cytokine secretion, mechanisms that underline their dual anti-inflammatory and anti-cancer capabilities. In addition, cannabinoid-induced autophagy has been shown to enhance stem cell survival and differentiation, offering promise for dental pulp regeneration. Despite these promising prospects, several challenges remain, including receptor selectivity, dose-dependent variability, limited oral bioavailability, and ongoing regulatory constraints. A deeper understanding of the context-dependent regulation of autophagy by cannabinoid signaling could pave the way for innovative therapeutic interventions in dentistry. Tailored cannabinoid-based formulations, engineered for receptor specificity, tissue selectivity, and optimized delivery, hold significant potential to revolutionize oral healthcare by modulating autophagy-related molecular pathways involved in disease resolution and tissue regeneration. Full article

Background: Smoking alters oral ecological balance, yet its influence on posterior teeth restored with lithium disilicate endocrowns is insufficiently documented. This study assessed the clinical and microbiological impact of smoking on the peri-coronal environment of endocrown-restored teeth, using an age-stratified approach to evaluate cumulative effects. Methods: A cross-sectional study was conducted on 100 adults, equally divided into smokers and non-smokers. Salivary pH, papillary bleeding index, and plaque index were clinically recorded. Subgingival samples collected from endocrown-restored posterior teeth were analyzed using a polymerase chain reaction (PCR) assay targeting major periodontal pathogens. Age-related variation in clinical and microbiological parameters was examined using one-way analysis of variance (ANOVA), followed by Tukey’s HSD post hoc test. Results: Smokers showed consistently lower salivary pH and higher plaque accumulation across all age groups. Gingival bleeding was reduced in younger smokers but increased in older individuals. Microbiological analysis identified markedly elevated levels of orange-complex organisms in smokers, including Prevotella intermedia and Fusobacterium nucleatum. Clinically, endocrowns in smokers presented more frequent marginal degradation, localized inflammation, and early signs of recurrent caries. These effects intensified with age. Conclusions: Smoking adversely modifies the peri-coronal biological environment of lithium disilicate endocrowns by increasing acidity, promoting plaque maturation, and supporting dysbiotic microbial communities. Age further amplifies these changes. Considering smoking status and patient age during treatment planning may improve long-term restorative outcomes. Full article

Introduction: Non-invasive methods to modulate orthodontic tooth movement have gained interest, particularly those targeting inflammatory mediators such as IL-1β and TNF-α, which regulate osteoclast and osteoblast activity. High-frequency vibrations (HFV), including those delivered by sonic toothbrushes, have been proposed to influence these biological responses. The aim of the study is to assess whether sonic vibrations affect IL-1β and TNF levels in patients undergoing clear aligner therapy. Materials and Methods: Twenty Invisalign^® patients were evaluated. For each patient, one tooth received HFV via a 285 Hz sonic toothbrush (experimental), while the contralateral served as a control. Gingival crevicular fluid was sampled at baseline (T0), after one week without HFV (T1), and after one week with HFV (T2). Cytokines were measured by ELISA. Because data were non-normally distributed, non-parametric tests were applied. Results: No significant differences across T0–T2 were found within the HFV group. At T2, IL-1β levels were significantly lower in the HFV group (mean: 23.04; SD: ± 20.18) than in controls (mean: 44.44; SD: ± 47.14), which showed an IL-1β increase with orthodontic force alone. TNF-α levels remained near the ELISA detection limit. Conclusions: Sonic vibrations combined with clear aligners appear to reduce IL-1β secretion and local inflammation without adverse effects. Sonic toothbrushes provide a simple HFV delivery method, though larger studies are needed to confirm these findings. Full article

Background/Objectives: End-stage chronic kidney disease (ESKD) represents a complex condition that also impacts oral health. This pilot study evaluates and compares some approaches to oral health assessment and aims to define the specific oral features common in adolescents with ESKD. Methods: A total of 50 children aged 12 to 17 years were examined, including 30 adolescents with ESKD (Group 1) and 20 adolescents without urinary pathology (Group 2). The decayed, missing, filled teeth (DMFT) index, oral hygiene index-simplified, papillary marginal attached index, and periodontal index were used for dental and periodontal assessment. The Milwaukee PH56 device was used to determine salivary pH. Oral microbiota was analyzed by chromatography–mass spectrometry and polymerase chain reaction detection of periodontopathogenic bacteria. Salivary and gingival crevicular fluid (GCF) biomarkers (IL-1β, TNF-α, IL-8, VEGF, sIgA) and total antioxidant capacity (TAC) were determined using an enzyme-linked immunosorbent assay. Results: DMFT did not differ between the groups. Periodontal indices in Group 1 were increased compared to Group 2 (p < 0.0001). Salivary pH in Group 1 was slightly alkaline; in Group 2, it was slightly acidic (p < 0.0001). Oral dysbiosis and periodontopathogenic bacteria were found in ESKD adolescents. Salivary IL-1β, TNF-α, VEGF, and IL-1β in GCF were elevated in Group 1 compared to Group 2 (p < 0.05). TNF-α, IL-8, and VEGF in GCF and TAC in both fluids were lower in Group 1 compared to Group 2 (p < 0.0001). Salivary IL-8 and sIgA in both saliva and GCF did not differ between the groups. Conclusions: ESKD adolescents had poor oral hygiene and significant oral dysbiosis including periodontopathogenic bacteria. Evaluation of biomarkers in saliva and GCF allowed us to vindicate inflammation, dysbiosis severity, and periodontal diseases. Full article

Background/Objectives: Amlodipine, a widely prescribed calcium channel blocker, has been associated with gingival enlargement, yet the mechanisms underlying this adverse effect remain unclear. The present study aimed to explore molecular and histopathological factors potentially contributing to gingival changes in patients receiving amlodipine therapy, with a particular focus on molecules implicated in extracellular matrix turnover and tissue remodeling. Methods: The study included three groups of participants: patients with amlodipine-induced gingival enlargement, patients with gingival enlargement of inflammatory origin, and amlodipine-treated patients without gingival overgrowth. Gingival tissue samples were analyzed using hematoxylin-eosin staining to assess inflammatory changes and general tissue architecture, and Picrosirius Red staining to visualize collagen fibers. Relative gene expression of alpha-smooth muscle actin (α-SMA), IL-13, MMP-1, and procollagen was determined by real-time PCR, while collagen content was quantified using ImageJ software. Results: Histopathological evaluation revealed a less pronounced inflammatory response in amlodipine-related gingival enlargement compared to those who did not use amlodipine. The highest expression of α-SMA was detected in patients who did not receive amlodipine, whereas IL-13 and procollagen expression were markedly elevated in the amlodipine-induced group compared to others. MMP-1 expression was significantly lower in amlodipine-treated patients relative to those who did not use amlodipine, suggesting impaired collagen degradation. These findings, together with our previous results indicating enhanced expression of profibrotic mediators, suggest that altered extracellular matrix metabolism is potentially dominant in this condition. Conclusions: Amlodipine-induced gingival enlargement appears to involve a multifactorial process characterized by a prominent fibrotic component, reduced matrix degradation, and secondary inflammation. Full article

Background/Objectives: This study aimed to investigate the effects of a new alcohol-free marine mouthwash containing an algae extract, a coastal plant extract, and seawater on plaque reduction, gingivitis, and oral microbiota balance. Methods: In a single-center, prospective, randomized comparative study, 50 subjects with gingivitis were assigned to either a marine mouthwash group (Test, n = 26) or a marketed mouthwash group (Comparator, n = 24). Clinical assessments included plaque, gingivitis, halitosis, and volunteer self-evaluation at baseline (T0) and after 7 days (T7). Gingival microbiota was sampled using swabs at baseline (T0) and after 7 days (T7). Conclusions: Both groups demonstrated reductions in dental plaque, gingivitis, and halitosis at T7 compared to baseline. Improvements in halitosis were observed in both groups but did not reach statistical significance. Microbiota analysis revealed that the Test group experienced the enrichment of health-associated bacterial taxa and a reduction in disease-associated species, notably Porphyromonas endodontalis, while the Comparator group showed an increase in pathogenic taxa. The marine mouthwash was well tolerated and positively rated by participants. Combining an algae extract, a coastal plant extract, and seawater, it effectively reduces plaque and gingivitis and may contribute to oral microbiota balance. It represents a promising alternative to conventional chemical oral care products. Full article

Background: Chronic inflammation is a hallmark of many oral and systemic diseases and has long been recognised as a risk factor for cancer development. Central to inflammatory responses are inflammasomes—multiprotein complexes that, upon activation, trigger caspase-1–mediated release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Their emerging contribution to chronic oral inflammatory conditions has generated interest in understanding whether persistent inflammasome activity may also influence pathways involved in oral carcinogenesis. This review summarises current evidence on the role of inflammasomes in oral inflammatory diseases and explores their potential involvement in the transition from chronic inflammation to malignant transformation. Methods: A narrative review of the literature was conducted by searching major scientific databases for studies investigating inflammasome activation in oral tissues, inflammatory oral diseases, and mechanisms linking chronic inflammation to oral cancer. Eligible articles included experimental studies, animal models, observational clinical research, and review papers that provided mechanistic or associative insights. Due to heterogeneity in study designs, a qualitative synthesis was performed. Results: Available evidence indicates that inflammasomes, particularly NLRP3 and AIM2, contribute to the pathophysiology of pulpitis, periodontitis, and several systemic conditions that affect oral health. Preclinical and observational findings also suggest potential involvement of inflammasome-related pathways in early tumorigenic processes, although these associations require further clarification. Preliminary biomarker-based studies demonstrate that inflammasome components measurable in saliva, pulpal blood, or gingival crevicular fluid may offer minimally invasive indicators of inflammatory burden and oral health status. Conclusions: Inflammasomes appear to play a meaningful role in oral inflammatory diseases, and growing evidence links their persistent activation to mechanisms relevant to oral carcinogenesis. However, current findings are largely associative and derived primarily from experimental and early clinical research. Additional work is needed to define precisely how inflammasomes contribute to the progression from chronic oral inflammation toward malignant change and to evaluate whether targeting inflammasome pathways offers viable therapeutic or diagnostic potential. Full article

Background: Chlorhexidine (CHX) is an effective antiseptic rinse for managing gingival inflammation; however, side effects such as staining and altered taste limit its long-term use. StellaLife^® (SL), an herbal-based mouth rinse and a gel, has shown promising in vitro effects, including enhanced biocompatibility and wound healing. This study aimed to compare the clinical efficacy of SL and 0.12% CHX in an experimental gingivitis model. Methods: In this randomized, controlled, cross-over clinical trial, 34 dental students received both treatment regimens in alternating two-week phases following prophylaxis. Group 1 used SL (mouth rinse and the gel) and then crossed over to CHX with placebo gel. Group 2 followed the reverse sequence. Participants refrained from oral hygiene during treatment phases. Clinical parameters and gingival crevicular fluid (GCF) were assessed at baseline and post-treatment. Paired t-tests and Bonferroni corrections were applied (p < 0.05). Bacterial count was determined by an external laboratory using a PCR test. Mean values for bacteria after SL and CHX use measured in genome copies/mL for Aggregatibacter actinomycetemcomitans, P. gingivalis, T. denticola, T. forsythia and F. nucleatum. Results: No statistically significant differences were observed between the SL and CHX groups for PI (p = 0.057), GI (p = 0.960), PD (p = 0.112), BOP (p = 0.895), GR (p = 0.768), CAL (p = 0.112), or GCF (p = 0.951). Both regimens improved periodontal parameters similarly. No significant differences were found between CHX and SL use in respect to periodontal pathogenic bacteria in the oral cavity. Conclusions: SL demonstrated clinical efficacy comparable to CHX in managing experimental gingivitis. Given its favorable safety profile, SL may serve as a promising alternative to CHX, though larger and longer-term studies are warranted. Full article

Background/Objectives: Oral health in children remains a key public health concern, particularly in regions with limited access to preventive programs. Despite improvements in dental care availability, the prevalence of plaque accumulation, gingival inflammation, and carious lesions remains high. This study provides updated regional data for Western Romania—a population previously underrepresented in oral health surveillance—and aims to evaluate oral hygiene behaviors, dietary habits, and clinical oral health indicators among Romanian schoolchildren, identifying potential areas for preventive action. Methods: An observational cross-sectional study was conducted in October 2025 on 202 schoolchildren aged 5–14 years from Western Romania. Data were collected through a structured questionnaire assessing socio-demographic characteristics, oral hygiene practices, and dietary behaviors, followed by a standardized intraoral examination. Plaque Index (PI) and Gingival Index (GI) were recorded, and statistical analysis was performed using chi-square tests (p < 0.05). Results: Most participants (83.7%) reported brushing their teeth at least twice daily, whereas only 24.8% used dental floss and 13.4% used interdental aids. The prevalence of carious lesions or restorations was 66.8%, visible plaque was 69.8%, and gingival inflammation was 50.0%. A significant positive correlation was observed between PI and GI (r = 0.58, p < 0.001). Children aged 5–7 years exhibited the highest rate of active carious lesions (71.2%, p = 0.014). Conclusions: Although brushing frequency among Romanian schoolchildren was generally satisfactory, inadequate interdental hygiene and suboptimal plaque control were common. School-based preventive programs emphasizing proper brushing technique, dietary counseling, and early education may contribute to improved oral health outcomes in this population. Full article

Background: Functional imbalance within the stomatognathic system can develop long before clinical symptoms become evident. Subtle biological changes, such as low-grade inflammation or metabolic disturbance, may precede gingival inflammation, temporomandibular discomfort, or masticatory muscle sensitivity. This study introduces the BioRisk-S (Biological Risk–Stomatognathic System) algorithm, a predictive model designed to identify early systemic alterations associated with the subclinical stage of stomatognathic dysfunction. Methods: A total of 260 clinically healthy adults without apparent stomatognathic disorders were enrolled and evaluated at baseline (T0) and re-examined after six months (T1). Routine laboratory tests were performed to determine high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and 25-hydroxyvitamin D levels. These biomarkers were integrated into the BioRisk-S algorithm to estimate systemic biological imbalance. Follow-up examinations focused on detecting early functional changes, including gingival inflammation, signs of temporomandibular joint (TMJ) dysfunction, and masticatory muscle tenderness. Results: Participants with higher baseline BioRisk-S scores showed significantly higher hs-CRP and NLR values, as well as lower vitamin D levels, indicating a mild but persistent inflammatory profile. After six months, these individuals exhibited early gingival inflammation, muscle tenderness, or mild TMJ discomfort more frequently than those with low BioRisk-S values (p < 0.01). The predictive model demonstrated good accuracy for detecting early biological imbalance preceding clinical dysfunction, with an area under the curve (AUC) of 0.84 (95% CI: 0.78–0.89). Conclusions: The BioRisk-S algorithm represents a feasible, low-cost tool for early systemic screening of functional imbalance within the stomatognathic system. By integrating routine laboratory parameters, this method may help identify individuals at risk before the onset of visible symptoms, supporting preventive and personalized approaches in oral and systemic health management. Full article

Periodontal disease is a progressive inflammatory condition frequently diagnosed in dogs, particularly in small breeds such as Yorkshire Terriers, Toy Terriers, Spitz, Toy Poodles and other breeds predisposed to rapid plaque and tartar accumulation. As the field of regenerative medicine becomes more popular, more and more attention is being paid to substances that promote tissue regeneration, one of which is platelet-rich plasma (PRP). PRP is an autologous blood-derived product rich in growth factors that stimulate tissue regeneration and modulate inflammation. This study aimed to evaluate the clinical effectiveness of PRP injections without additional activating agents in the management of stage 2–3 periodontitis in small-breed dogs. Forty-two adult dogs (Yorkshire Terriers, Toy Terriers, Pomeranians, Toy Poodles, and Havanese) were enrolled and divided into two groups: PRP (n = 30) and control (n = 12). Following standard dental prophylaxis, the PRP group received gingival, submucosal, and periodontal pocket injections of PRP (0.1 mL per site). Periodontitis stage, gingival index, periodontal pocket depth, and horizontal bone loss were evaluated at baseline and 30 days post-treatment. PRP therapy significantly improved all evaluated parameters (p < 0.05). The gingival index decreased threefold, periodontal pocket depth was reduced twofold, and horizontal bone loss decreased by more than twofold compared with baseline and controls. No adverse reactions, discomfort, or postoperative complications were observed. The administration of non-activated PRP as an adjunct to dental cleaning significantly enhances soft and hard tissue regeneration in small-breed dogs with stage 2–3 periodontitis. PRP therapy represents a safe, minimally invasive, and effective regenerative approach for improving periodontal health in routine veterinary dentistry. Full article

Gingival crevicular fluid (GCF) reflects both local periodontal inflammation and systemic conditions. This review highlights the role of oxidative stress, oxidised low-density lipoprotein (oxLDL), and apolipoprotein B (apoB) as molecular links between periodontitis and metabolic disorders. Elevated GCF levels of oxLDL and apoB indicate enhanced vascular permeability and local oxidative modification, particularly in diabetes. Furthermore, oxLDL promotes the formation of neutrophil extracellular trap (NET) via connecting oxidative stress with immune-mediated tissue injury. These insights establish GCF as a valuable, non-invasive biomarker for understanding the interplay between periodontal and systemic diseases. Full article