Search Results (916)

Background: Dental caries remains one of the most prevalent oral diseases worldwide, largely driven by the virulence of Streptococcus mutans. Although plant phenolics from green tea and pomegranate are known for their antimicrobial properties, their molecular mechanisms of action against key S. mutans virulence targets remain insufficiently characterized. Aim: This study investigated the antibacterial and anti-virulence properties of Viroelixir, a phenolic-rich formulation derived from green tea (Camellia sinensis) and pomegranate (Punica granatum), against S. mutans, with particular emphasis on predictive molecular docking interactions with critical virulence-associated proteins. Methods: Viroelixir phytochemical composition was characterized by LC–MS using a C18 reverse-phase column and negative electrospray ionization mode. Antibacterial activity was evaluated using growth kinetics, agar plating, and crystal violet assays. Acidogenicity, hemolytic activity, and biofilm formation were assessed using pH modulation, hemolysis assays, SEM, and biofilm biomass quantification. Virulence gene expression was analyzed by RT-qPCR. In silico molecular docking was performed to explore potential interactions between major LC–MS-supported phenolic constituents and S. mutans virulence proteins, including glucosyltransferase B (GtfB), LuxS, and SpaP. Biocompatibility was evaluated in human gingival epithelial cells. Results: The LC-MS analysis revealed a complex mixture of phenolic compounds consistent with catechins and ellagitannins. Compound identification was considered tentative and based on mass spectral range and chromatographic behavior. Viroelixir significantly inhibited S. mutans growth, acid production, hemolytic activity, and biofilm formation in a concentration-dependent manner. Key virulence genes were markedly downregulated. Docking analyses suggested stable binding of selected phenolics—particularly punicalagin, catechin, and epigallocatechin—within the active sites of GtfB, LuxS, and SpaP. Importantly, Viroelixir showed no cytotoxic effects on gingival epithelial cells. Conclusions: Viroelixir exerts potent antibacterial and anti-virulence effects against S. mutans through a multi-target mechanism combining transcriptional suppression and predictive molecular inhibition of virulence proteins, supporting its potential as a safe, natural therapeutic for caries prevention. Full article

Background: Oral biofilms are a major etiological factor in dental caries, periodontal disease, peri-implantitis, and endodontic infections. Increasing antimicrobial resistance and the limitations of conventional therapies have intensified interest in antimicrobial photodynamic therapy (aPDT). Hypericin, a natural photosensitizer derived from Hypericum perforatum, demonstrates potent reactive oxygen species generation and broad antimicrobial activity; however, its dental applications remain insufficiently synthesized. Objective: To systematically evaluate the antimicrobial efficacy, treatment parameters, safety, and clinical potential of hypericin-mediated aPDT against oral biofilms and infections in dentistry. Methods: This systematic review was conducted according to PRISMA 2020 and registered in PROSPERO CRD42024617727. Electronic searches of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library (January 2010 to December 2025) were performed. Studies assessing hypericin-mediated aPDT in oral or dental contexts were included. Methodological quality was evaluated using a predefined nine-domain risk-of-bias tool. Results: Eleven studies met the inclusion criteria. Hypericin-mediated aPDT demonstrated strong antimicrobial effects, achieving up to 99% planktonic inactivation and significant biofilm reduction across bacterial and fungal species. Activity was particularly pronounced against Gram-positive organisms, including Staphylococcus aureus and Enterococcus faecalis. However, efficacy against mature biofilms was variable and often dependent on formulation and irradiation parameters. Most studies showed moderate methodological quality, with frequent deficiencies in reporting light calibration and dosimetry. Advanced delivery systems, including liposomal and nanoparticle formulations, improved photodynamic performance. Conclusions: Hypericin-mediated aPDT shows promising antimicrobial activity against oral pathogens and biofilms, with favorable selectivity and safety profiles. Nevertheless, the evidence remains predominantly preclinical and heterogeneous. Standardized protocols and well-designed clinical trials are required before routine dental implementation can be recommended. Full article

Polyols are widely used as non-cariogenic sweeteners in foods and oral care products, yet their comparative activity against diverse oral microbes and their potential relevance to the oral–systemic axis remain incompletely defined. Here, we performed an in vitro, optical density (OD)-based screening of four polyols—allulose, D-mannose, erythritol, and xylitol—against Streptococcus mutans, Streptococcus anginosus, Candida albicans, and Fusobacterium nucleatum. Cultures were grown with polyols at 1–20% (w/v), and OD600 was recorded at organism-specific endpoints (~24 h). Allulose, erythritol, and xylitol produced strong, concentration-dependent suppression of streptococcal growth at ≥5–10%, whereas C. albicans showed minimal changes across the tested range. F. nucleatum was highly sensitive to allulose, D-mannose, and xylitol at ≥5% (reducing OD to ≤13% of the untreated control), while low concentrations of D-mannose and erythritol increased OD beyond that of the control, suggesting species-specific utilization or stress responses. One-way ANOVA with Tukey’s HSD post hoc testing supported significant between-polyol differences for most concentrations in Streptococcus spp. and F. nucleatum. Collectively, these results identify polyol- and taxon-specific growth phenotypes that can inform the formulation of swallow-safe oral hygiene products and motivate follow-up work in polymicrobial biofilm models and clinical studies targeting oral inflammation and downstream systemic risk. Full article

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies. Full article

Oral biofilms are complex polymicrobial communities involved in the development of dental caries and periodontal diseases. Chemical antiseptics are commonly used as adjuncts to mechanical plaque control; however, their antimicrobial efficacy varies depending on composition and mechanism of action. The aim of this study was to comparatively evaluate the antimicrobial and antibiofilm activities of four commercially available dental products (Corsodyl, Ozosan, HybenX, and Elugel) against a broad spectrum of oral microorganisms. This in vitro study included Gram-positive and Gram-negative bacterial strains, comprising both reference strains and clinical isolates, as well as Candida albicans. Antimicrobial activity was assessed using the disc diffusion assay, while antibiofilm activity was evaluated using a crystal violet microplate assay. All experiments were performed in triplicate. Statistical analysis was conducted using two-way ANOVA followed by Tukey’s post hoc test (p < 0.05). All tested products exhibited antimicrobial activity. Inhibition zones ranged from 9 to 56 mm for Gram-positive bacteria, 12 to 38 mm for Gram-negative bacteria, and 13 to 43 mm for Candida albicans. Two-way ANOVA revealed a significant effect of the dental product (p < 0.001), while incubation time was not significant (p > 0.05). HybenX showed the highest antimicrobial efficacy, while chlorhexidine-based products demonstrated consistent activity. Antibiofilm inhibition exceeded 80% for several strains. Dental antiseptics exhibit significantly different antimicrobial and antibiofilm profiles, highlighting the importance of appropriate product selection in oral biofilm control. Full article

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Beyond genetic and proteostatic mechanisms, infection- and dysbiosis-based models of AD have gained renewed attention, including the antimicrobial protection hypothesis, in which Aβ may participate in innate immune defense. Here, we reanalyzed ribosomal depleted (Ribo-Zero) RNA-seq data from dorsolateral prefrontal cortex (DLPFC) samples from the Mount Sinai Brain Bank cohort (GSE53697) to screen for non-human transcripts. Reads underwent quality control and adapter trimming, taxonomic classification with Kraken2, abundance re-estimation with Bracken, and differential abundance testing with edgeR. Across 17 samples (9 advanced AD and 8 controls), we detected low-biomass microbial signals, with Acinetobacter radioresistens showing enrichment in the AD group (FDR = 0.018). Several additional taxa showed suggestive group differences but did not remain significant after multiple testing correction, including Lactobacillus iners (FDR = 0.051). We also performed an exploratory in silico analysis of an A. radioresistens biofilm-associated protein homolog, identifying predicted amyloidogenic motifs and surface-exposed regions that may be relevant to cross-seeding hypotheses, although no mechanistic inference can be drawn without experimental validation. Given the technical challenges of inferring microbial signals from post-mortem brain RNA-seq data, including contamination risk, low microbial biomass, and overwhelming host background, these findings should be interpreted as hypothesis-generating and warrant orthogonal validation in larger, microbiome-aware cohorts. Full article

Candida species can shift from commensal organisms to opportunistic pathogens. Both Candida albicans and non-albicans Candida (NAC) species colonize oral biofilms and periodontal pockets, where they may contribute to inflammation and the progression of periodontal disease. This study aimed to determine the prevalence and antifungal susceptibility profiles of Candida species in individuals with different stages of periodontal disease. A cross-sectional study was conducted in 100 participants whose periodontal status was clinically evaluated. Saliva samples were cultured on chromogenic agar for yeast isolation, species identification was confirmed by MALDI-TOF MS, and antifungal susceptibility to fluconazole, clotrimazole, nystatin, and amphotericin B was assessed. Candida spp. was detected in 35% of participants, where C. albicans was the most prevalent species, followed by Nakaseomyces glabratus (formerly Candida glabrata), Candida parapsilosis, Candida dubliniensis, and Candida tropicalis. Species distribution varied according to periodontal status, with N. glabratus predominating in early periodontitis and C. albicans appeared more frequently in higher severe stages of periodontitis. Susceptibility testing showed resistance of C. albicans to clotrimazole (63.6%) and nystatin (22.7%), whereas amphotericin B and fluconazole remained effective. NAC species, particularly N. glabratus, exhibited resistance to nystatin and variable resistance to clotrimazole but remained susceptible to amphotericin B. These findings underscore the importance of early detection and personalized antifungal strategies for managing periodontal disease complicated by Candida colonization. Full article

Background: Helicobacter pylori is a well-established risk factor for gastric carcinogenesis. Increasing evidence suggests that the oral cavity may serve as an extragastric reservoir for the bacterium, potentially contributing to persistent infection and reinfection. Orthodontic appliances can modify oral biofilm ecology and may facilitate bacterial colonization. This study aimed to investigate the association between oral H. pylori colonization and gastric cancer, while exploring the potential modifying role of fixed orthodontic appliances. Materials and Methods: In this cross-sectional observational study, 212 participants were recruited from gastroenterology and dental clinics between January 2023 and March 2025. Oral samples were collected and analyzed for H. pylori DNA using polymerase chain reaction (PCR). Gastric diagnoses were established through endoscopic examination and histopathological evaluation, classifying participants into gastric cancer, precancerous gastric lesions, non-atrophic gastritis, and control groups. Demographic, clinical, and oral health variables were recorded. Multivariable logistic regression models were used to evaluate the association between oral H. pylori detection and gastric cancer while adjusting for potential confounders, including age, sex, smoking status, oral hygiene indicators, and socioeconomic factors. Results: Oral Helicobacter pylori DNA was detected in 35/54 (64.8%) patients with gastric cancer, 30/56 (53.6%) with precancerous lesions, 21/52 (40.4%) with non-atrophic gastritis, and 15/50 (30.0%) controls. Gastric H. pylori infection was identified in 41/54 (75.9%) gastric cancer cases compared with 18/50 (36.0%) controls. Oral H. pylori positivity was more frequent among patients undergoing active orthodontic treatment (22/36, 61.1%) than among those without orthodontic appliances (79/188, 42.0%). In multivariable analysis, oral H. pylori positivity remained independently associated with gastric cancer (adjusted OR 3.02, 95% CI 1.51–6.03, p = 0.002). Conclusions: Our findings support an association between oral–gastric microbial interactions and H. pylori–associated disease, and suggest that the oral cavity may serve as a potential reservoir for gastric infection dynamics. The presence of orthodontic appliances may be associated with altered oral microbial ecology and could be linked to sustained H. pylori colonization. Full article

Biofilm formation on denture base materials may contribute to oral diseases such as denture stomatitis and therefore represents an important factor in prosthodontic treatment. This in vitro study investigated biofilm formation on dental prosthetic materials manufactured by additive, subtractive, and conventional techniques. Disc-shaped specimens were fabricated from 3D-printed Denture Base Resin (Formlabs), milled Lucitone Digital Fit (Dentsply Sirona), and conventionally processed cold-polymerized PALAPress (Kulzer). Biofilm formation by Streptococcus mutans and Streptococcus sanguinis was assessed separately over a 21-day incubation period using crystal violet staining and photometric determination of optical density at eight predefined time points. Surface characteristics before and after microbial colonization were qualitatively evaluated by scanning electron microscopy. For S. mutans, significant material-dependent differences were observed only at selected time points, while overall biofilm accumulation remained low. In contrast, S. sanguinis exhibited pronounced and repeated differences, with milled PMMA generally showing lower biofilm accumulation compared with additively manufactured and conventionally processed materials. Overall, S. sanguinis formed significantly more biofilm than S. mutans across all materials and time points. These findings indicate that both manufacturing technique and bacterial species influence biofilm formation on denture base materials. Full article

Multiscale interface engineering has influenced the engineering of orthopedic and dental implants through the integration of macroscale architecture, micro-textured surfaces and nanoscale bio-cues. These characteristics help to increase mechanical stability and support early biological responses, as well as increase resistance to microbial colonization. Multiscale interface engineering also helps to explore fabrication schemes that facilitate load-sharing lattices and micro-roughened attachment zones, as well as immune-interactive nano-chemistry. In this study, the biological responses of protein adsorption, osteogenic differentiation, connective-tissue sealing, and macrophage polarization are investigated, together with functional barriers in stress transfer, fatigue resistance and biofilm control. New clinical data with regard to arthroplasty and dental implantology are reviewed to put these factors into perspective. Even though engineered surfaces are reliable in promoting early fixation and initial osseointegration, in the long term, their performance depends on the host’s biological variability, the mechanical forces of loading, coating integrity and peri-implant microbial pressure. Altogether, multiscale interface engineering is an evolving approach to enhancing the lifespan of implants and facilitating biologically sound skeletal and oral reconstruction. A structured literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify studies published between 2000 and 2025. Approximately 320 articles were initially identified, of which about 140 relevant publications were selected for detailed review. Full article

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies. Full article

The methodical work describes all the necessary steps for establishing a stable oral ex vivo biofilm using saliva and crevicular plaque samples from periodontal healthy donors. First, cover slips were preconditioned with saliva supernatants and subsequently inoculated with crevicular plaque suspensions. Ex vivo biofilm formation was characterized by confocal laser scanning microscopy (cLSM) after 1, 4, 24, 48 and 72 h of anaerobic cultivation. Exemplarily, the inhibitory characteristics of blackcurrant fruit extracts [all-fruit juice (AFJ); alcoholic fraction from berry skins (AFBS)] were observed on 1, 4 and 24 h-aged ex vivo biofilms. Chlorhexidine (CHX, 0.2%) served as positive control. After direct contact (3 min), biofilms were dispersed, plated onto agar and anaerobically cultivated for 24 h. Early ex vivo biofilms (1 h-biofilm) showed scattered microbial colonies. After 4 h of cultivation, a multilayered biofilm was formed. Biofilm mass gradually increased, displaying a complex polymicrobial structure after 24 h. At 72 h, the biofilms had a dense three-dimensional appearance. Treatment with AFJ and CHX was more efficient in inhibiting biofilm growth compared to AFBS. Early biofilms (1 h, 4 h) were more susceptible to AFJ and CHX compared to 24 h-biofilms. The introduced model can be recommended for testing the efficiency of plaque-controlling agents. Full article

Oral fungal infections resulting from non-albicans Candida species and new opportunistic yeasts are increasingly linked to antifungal resistance, especially in individuals with periodontal disease. Bioactive compounds may serve as potential alternatives; nevertheless, there is a paucity of research that has comprehensively assessed their antifungal and antibiofilm efficacy against clinically defined oral yeast isolates. This study aimed to (i) describe the variety and antifungal resistance profiles of oral yeasts isolated from women with various periodontal diseases; (ii) assess four ethanolic extracts of Aseer medicinal plants (Foeniculum vulgare, Solanum incanum, Forsskaolea tenacissima, and Abutilon pannosum) for their antifungal and antibiofilm properties; and (iii) correlate phytochemical composition determined by GC–MS with biological activity. Oral samples (saliva and subgingival plaque) were collected from 50 female participants with documented periodontal parameters. Fungal isolates were identified using morphological, biochemical (VITEK 2), and molecular (ITS rDNA sequencing) methods. Testing for antifungal susceptibility was performed according to CLSI guidelines. Plant extracts were evaluated for antifungal activity (disk diffusion, MIC, MFC), antibiofilm activity (crystal violet assay and light microscopy), and phytochemical profiling (GC–MS). Fungal growth was detected in 37 of 50 samples (74%), yielding six yeast species: Nakaseomyces glabratus (40.5%), Candida tropicalis (18.9%), C. parapsilosis (13.5%), Pichia kudriavzevii (10.8%), Rhodotorula mucilaginosa (8.1%), and Aureobasidium melanogenum (8.1%). N. glabratus demonstrated reduced susceptibility to fluconazole. A. pannosum and F. vulgare exhibited the strongest in vitro antifungal activity (inhibition zones up to 19.2 mm; MIC 0.19–0.78 mg/mL; MFC 0.39–1.56 mg/mL), significantly greater than F. tenacissima (p < 0.0001). Sub-MIC concentrations of A. pannosum reduced C. tropicalis biofilm biomass by 59.6%. GC–MS analysis identified methyl salicylate (20.3–40.2%) and cyclohexanol derivatives (8.0–23.2%) as major constituents. Antifungal activity showed a trend in relation to methyl salicylate content (R² = 0.78). However, because only four plant extracts were included, this relationship should be interpreted as a descriptive observation rather than a statistically testable association. Ethanolic extracts of Abutilon pannosum and Foeniculum vulgare demonstrated significant in vitro antifungal and antibiofilm activity against clinically relevant oral yeasts, including azole-tolerant Nakaseomyces glabratus. The observed trends between phytochemical composition and biological activity warrant further investigation into their potential as adjunct therapeutic agents for oral fungal infections. Further studies are required to confirm these results and see if they can be used in therapeutic settings. Full article

Background: Patients with diabetes mellitus exhibit increased susceptibility to peri-implant inflammation and implant failure due to systemic metabolic dysfunction, impaired immunity, and delayed tissue healing. The oral microbiome is increasingly recognized as a key intermediary in these pathogenic processes. Aims: This review aims to systematically evaluate the available literature examining the relationships among the oral microbiome, biomaterial biocompatibility, and inflammatory changes in peri-prosthetic tissues in insulin-dependent diabetic patients. Methods: A systematic search of PubMed and Scopus databases identified studies published between January 2000 and July 2025. Eligible studies (25 in total) included clinical, histological, microbiological, or immunohistochemical investigations involving diabetic patients rehabilitated with dental implants or prostheses. Study selection and reporting followed PRISMA 2020 guidelines. Results: Diabetic cohorts showed consistent microbial alterations, including a higher relative abundance of periopathogenic species (P. gingivalis, T. forsythia, and F. nucleatum), lower microbial diversity, and greater biofilm-forming potential. Histological analyses frequently described increased inflammatory infiltrates, higher cytokine expression, and reduced soft-tissue integration. Biomaterial surface characteristics were also associated with differences in microbial adhesion, while hyperglycemia was linked to microbial and host-response patterns suggestive of greater pathogenicity and inflammation. Collectively, these findings suggest that diabetes-associated dysbiosis may be associated with increased peri-implant inflammatory changes and altered peri-implant homeostasis. Conclusions: The oral microbiome may be involved in inflammatory activity and biocompatibility at the tissue–implant interface in diabetic patients. A better understanding of host–microbe–material interactions may support risk assessment and help inform future personalized management strategies, such as targeted antimicrobial approaches, probiotic modulation, and biomaterial surface optimization, although these implications should be interpreted cautiously given the predominantly observational and heterogeneous nature of the available evidence. Full article

Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; however, their effects on S. sanguinis have not been thoroughly studied. Here, we investigated the antimicrobial and antibiofilm efficacy of ZnO NPs against this bacterial species. ZnO NPs exhibited a minimal inhibitory concentration (MIC) of 100 µg/mL and caused rapid, dose-dependent suppression of intracellular ATP levels and overall metabolic activity within 2–4 h of exposure. ZnO NPs induced reactive oxygen species (ROS) production in a dose-dependent manner. The free radical scavenger α-tocopherol partly prevented the antibacterial effect of ZnO NPs, suggesting that lipid peroxidation contributes to ZnO NP-mediated toxicity, although it is not the sole mechanism involved. Short-term exposure (2 h) to ZnO NPs did not significantly affect membrane integrity or cellular morphology, whereas prolonged treatment (24 h) resulted in pronounced membrane permeabilization, membrane hyperpolarization, and cellular swelling. Computational morphometric analyses of high-resolution scanning electron microscopy (HR-SEM) images of planktonic growing bacteria after a 24 h treatment confirmed a significant, dose-dependent increase in cell surface area and surface roughness. Importantly, ZnO NPs also reduced the metabolic activity and compromised the structural integrity of mature, preformed biofilms. Collectively, these findings demonstrate that ZnO NPs exert antimicrobial and antibiofilm effects against S. sanguinis through early metabolic inhibition associated with oxidative stress followed by progressive membrane dysfunction. Full article