Search Results (166)

Background/Objectives: Early childhood caries (ECC) remains a major public health concern, with Streptococcus mutans as a primary etiological agent. Current treatments rely on broad-spectrum antimicrobials, which can disrupt the oral microbiome and promote resistance. This study applied a structure-based in silico pipeline to identify molecule modulators of Toll-like receptor 2 (TLR2), a key host receptor implicated in ECC, and to explore their binding potential against major S. mutans proteins. Methods: ECC-related genes were collected from public databases and analyzed by functional enrichment and protein–protein interaction (PPI) network analysis. Hub genes were ranked using centrality algorithms. Virtual screening on TLR2 (DrugCLIP) was followed by molecular docking of selected compounds against the TLR1/TLR2 heterodimer and 50 S. mutans proteins, complemented by in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Results: Fifty-four ECC-related genes and nine hub genes were identified, with TLR2 and cathelicidin antimicrobial peptide (CAMP) as central nodes. Virtual screening yielded five lead compounds fulfilling drug-likeness and toxicity criteria. Docking to TLR1/TLR2 showed favorable binding energies, with Z7684613096 showing the most consistent binding. V026-2549 displayed the highest number of strong interactions with S. mutans targets, including dTDP-glucose 4,6-dehydratase (rmlB), NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (gapN), glucosyltransferase C (gtfC), and 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase (metE). Conclusions: Five candidate compounds with promising dual activity against TLR1/TLR2 and S. mutans proteins were prioritized for experimental validation, including TLR2 functional assays and in vitro anti-biofilm studies. Full article

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

Advances in dental material science over recent decades have significantly improved the mechanical, physical, esthetic, and adhesive properties of restorative systems. As clinical performance and durability have reached high standards, research has progressively shifted from purely mechanical replacement toward the development of bioactive materials capable of interacting beneficially with biological tissues. Rather than functioning solely as passive restoratives, contemporary materials are increasingly designed to contribute to disease prevention and tissue repair. Bioactive functionality encompasses both bioprotective and biopromotive effects, including antimicrobial activity, reinforcement of the dental substrate, promotion of remineralization, modulation of inflammatory responses, and stimulation of regenerative pathways. In this context, the surface pre-reacted glass ionomer (S-PRG) particle has emerged as a multifunctional bioactive technology. Its unique three-layer structure enables sustained release of multiple ions, fluoride, strontium, boron, sodium, silicate, and aluminum, associated with mineralization, biofilm inhibition, inflammatory regulation, and activation of cellular signaling pathways. An integrative review was conducted through a literature search in PubMed, SciELO and Scopus using the descriptors “Surface-reaction-type prereacted glass ionomer” and “S-PRG.” Experimental studies evaluating antimicrobial, anti-inflammatory, remineralizing, cellular, or regenerative effects of S-PRG-containing materials were considered eligible. A total of 49 studies met the inclusion criteria and were analyzed through descriptive synthesis. The available evidence indicates that the biological activity of S-PRG-containing materials extends beyond caries prevention, including modulation of inflammatory responses, enhancement of mineralization processes, and stimulation of cellular pathways related to tissue repair. These findings highlight the potential of S-PRG technology as a promising strategy for the development of restorative materials with regenerative and preventive properties. 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

Background: Dental caries, primarily caused by Streptococcus mutans (S. mutans), is a prevalent condition with significant global impact. Trans-cinnamaldehyde (TC), a phytochemical derived from the cinnamon plant, has shown promising antibacterial and antibiofilm activity against S. mutans. This study aimed to evaluate the anti-cariogenic effects of TC on S. mutans using an innovative mouse jaw explant model. Methods: TC was diluted in an organic solvent across various concentrations. Initially, cytotoxicity assays were performed at all tested TC concentrations. Sub-minimum bactericidal concentrations were then used to examine the distribution and morphology of S. mutans biofilms. Hemi-mandibles were dissected from euthanized, healthy, seven-week-old female mice to study the impact of TC on the cariogenic activity of S. mutans using stereoscopic analysis. Finally, pH changes during exposure to cariogenic conditions and post-treatment bacterial viability were measured. Results: In vitro data demonstrate that TC doses of ≤625 µg/mL were non-cytotoxic. Treatment groups exposed to TC exhibited altered bacterial morphology, including abnormal and incomplete cell division. In the mouse jaw explant model, TC doses of ≥625 µg/mL showed anti-cariogenic effects, evidenced by the absence of visible carious lesions. Additionally, pH changes and post-treatment viable bacterial counts corresponded with the observed anti-cariogenic activity. TC doses ≤625 µg/mL led to a pH drop over time and the presence of bacterial colonies. Conclusions: TC exhibits significant anti-cariogenic activity against S. mutans in the mouse model. Our findings suggest that 625 µg/mL is the lowest non-toxic concentration of TC that effectively inhibits cariogenic activity. Full article

Streptococcus mutans is a primary contributor to dental caries due to its ability to form biofilms rich in extracellular polysaccharides (EPS). While erythritol has been recognized for its anti-cariogenic effects, the molecular pathways involved have remained unclear. In this study, we combined phenotypic and transcriptomic approaches to uncover the mechanism by which erythritol inhibits EPS synthesis. We found that erythritol treatment significantly reduces EPS production and biofilm density, and that these changes are accompanied by marked downregulation of the phosphotransferase system (PTS), particularly the celB gene. Functional validation through gene deletion demonstrated that loss of celB mimics the effects of erythritol, resulting in reduced bacterial growth, impaired biofilm formation and decreased EPS production. Our results establish celB as a key mediator of erythritol-induced biofilm inhibition and suggest that targeting carbohydrate transport systems could offer a novel approach to caries prevention. Full article

Dental caries, one of the most prevalent diseases worldwide, poses a significant threat to oral health. Streptococcus mutans is one of the key pathogenic bacteria associated with dental caries. Numerous Chinese botanical products (CBPs) have been shown to possess antibacterial effects against S. mutans. However, given the wide variety of CBPs that have been investigated, a systematic summary of their effects is needed. To address this need, in the present review, CBPs are categorized into five groups based on their major bioactive components: organic acid-based CBPs, alkaloid-based CBPs, phenol-based CBPs, anthraquinone-based CBPs, and other types. In addition to their chemical composition, the conventional use, pharmacological effects, and toxicity of these CBPs are also discussed, followed by an exploration of their anti-S. mutans mechanisms, including the synthesis of biofilm scaffolds and water-insoluble glucans, energy metabolism and soluble glucan production, acid generation and tolerance, bacterial cell integrity, remineralization processes, and intercellular communication via quorum sensing (QS). In summary, it is suggested that CBPs have considerable benefits in caries prevention and could be promisingly applied in clinical treatments. Full article

Silver diamine fluoride/potassium iodide (SDF/KI) Riva Star (SDI) is a tooth desensitizing and anti-caries agent that may be indicated for arresting caries before restoring the tooth in selective caries approach. The aim was to determine the effect of SDF/KI pretreatment on the bonding of SDR Plus Bulk-Fill Flowable (Dentsply) with Clearfil SE Bond 2 (Kuraray) and G-Premio Bond (GC) in self-etch mode on sound dentin. A total of 240 dentin samples were prepared and assigned to 12 groups based on SDF/KI pretreatment (with or without), adhesive type, and testing time (1, 3, and 6 months). The shear bond strength (SBS) was measured using an UltraTester. SBS data were analyzed using three-way factorial model (Adhesive × Pretreatment × Time) and Wald (F) tests, with α = 0.05. Fracture modes were analyzed using χ² and Fisher’s exact test, with α = 0.05. Clearfil performed significantly better than G-Premio at all time points (p < 0.001). Riva Star pretreatment significantly reduced SBS for both adhesives at all time points (p < 0.001). SBS reduction was significantly higher for Clearfil (p < 0.001). The effect of storage was not significant (p = 0.388). Fracture mode distribution differed significantly between adhesives (p < 0.001). Pretreatment × fracture interaction was significant for Clearfil (p = 0.0052). Mixed fractures in G-premio were rare. Full article

The lactoperoxidase system (LpoS) is an enzymatic antimicrobial mechanism of saliva that oxidizes (pseudo)halide substrates to reactive compounds capable of limiting microbial growth. This study evaluated how different LpoS variants—utilizing iodide (LpoS-I⁻), thiocyanate (LpoS-SCN⁻), selenocyanate (LpoS-SeCN⁻), and a thiocyanate–iodide mixture (LpoS-SCN⁻ + I⁻)—affect virulence, metabolism, and biofilm structure in Streptococcus mutans. Using qRT-PCR, pyruvate assays, MTT reduction, and confocal microscopy, we found that LpoS-I⁻ most effectively reduced atpD and ldh expression, impaired acid tolerance, and decreased lactate and pyruvate production. LpoS-SCN⁻ and LpoS-SeCN⁻ also downregulated atpD and gtfB, although LpoS-SeCN⁻ upregulated ldh. Despite minimal structural biofilm disruption, LpoS-I⁻ markedly inhibited intracellular and extracellular pyruvate accumulation, suggesting altered glycolytic flux. These findings indicate that iodide-based LPO systems modulate key metabolic and regulatory pathways in S. mutans and may hold potential for inclusion in anticaries oral formulations. 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

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5′-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell–cell and cell–matrix interactions, reducing the regenerative and reparative potential of the dentin–pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp. Full article

Nicotinamide adenine dinucleotide (NAD⁺) serves as a critical cofactor in redox reactions and metabolic transformations catalyzed by NAD-dependent enzymes and is essential for bacterial survival and virulence. The biosynthesis of NAD⁺ in the cariogenic pathogen Streptococcus Sobrinus (S. sobrinus), a pivotal participant in oral cavities of children and adolescents with a history of caries, has yet to be explored. Bioinformatics, genetics, and biochemical techniques were used to identify NAD⁺ biosynthesis pathways and corresponding regulator in S. Sobrinus. S. sobrinus lacks de novo NAD⁺ synthesis pathway but comprises NA and Nam salvage pathway I (PncA-PncB-NadD-NadE) and PnuC-NadR salvage pathway III. NiaY and PnuC were involved in the salvage pathways. N-terminal domain of SsNrtR regulator was identified as DNA-binding domain binding to the pnuC and pncB probe, and addition of ADP-ribose reversed the binding of SsNrtR to the target promoters to regulate NAD⁺ salvage pathways. C-terminal domain of SsNrtR was non-catalytic, consistent with loss of Nudix motif conservation. Furthermore, the abrogation of niaR compromised multiple pathogenic traits, including cellular proliferation, acidogenesis, and the architecture/mechanical integrity of biofilms. Consequently, this mutant exhibited attenuated virulence in a rat caries model. Our findings conclusively demonstrate that SsNrtR-mediated regulation of NAD⁺ homeostasis is a critical determinant of the cariogenic potential of S. sobrinus. This study identifies SsNrtR as a previously uncharacterized NAD⁺-responsive regulator that integrates metabolic homeostasis with the control of virulence in Streptococcus sobrinus. These findings elucidate a novel metabolic–virulence regulatory axis in this species and position SsNrtR as a promising target for the development of anti-caries interventions. Full article

Background/Objectives: Phytotherapy, the use of plant-derived bioactive compounds for therapeutic purposes, has gained increasing attention in dentistry as a natural, well-tolerated, and culturally acceptable adjunct to conventional treatments. In pediatric dentistry, its potential relevance lies in its antimicrobial, anti-inflammatory, and antioxidant properties, which may support oral health, caries prevention, pulp vitality, and gingival health. This narrative review aimed to summarize the current clinical evidence regarding the application of phytotherapeutic agents in pediatric oral care. Methods: A narrative review was conducted according to SANRA guidelines, including clinical studies on plant-based products used for preventive or therapeutic purposes in children and adolescents. Results: Forty-three clinical studies met the inclusion criteria. The most commonly investigated agents included licorice, green tea, cocoa husk, cranberry, pomegranate, Aloe vera, and miswak. These agents demonstrated antimicrobial activity against cariogenic bacteria, reduction in plaque and gingival indices, and favorable healing in pulp therapies. In endodontics, Aloe vera-derived acemannan and Ankaferd Blood Stopper^® showed outcomes comparable to conventional materials, while pomegranate and apple cider vinegar exhibited partial antibacterial effects as irrigants. Conclusions: Phytotherapy shows promise as a complementary approach in pediatric dentistry, contributing to caries prevention, gingivitis control, and pulp healing. However, current evidence remains limited by small sample sizes, short-term follow-ups, and heterogeneity in formulations. Further trials are required to confirm efficacy, ensure safety, and standardize phytotherapeutic applications in pediatric oral care. Full article

Dental caries is a major global health concern, with Streptococcus mutans playing a key role in biofilm formation and acid production, which lead to enamel demineralization. Natural products, particularly plant-derived extracts, offer promising alternatives to conventional antibacterial agents. This study aimed to analyze the chemical composition of Ferula varia 70% ethanol extract (FVE) and evaluate its potential to inhibit biofilm formation by S. mutans. The aerial parts of F. varia were extracted with 70% ethanol and analyzed using LC-UV-ESI-MS/MS to determine the chemical profile. The anti-biofilm activity of FVE was evaluated using a crystal violet assay against S. mutans. Phytochemical analysis identified 14 compounds, including major phenolic acids (e.g., chlorogenic acid, gallic acid) and flavonoids (e.g., isoquercitrin, isorhamnetin-3-O-glucoside). FVE exhibited significant, dose-dependent inhibition of S. mutans biofilm formation. Importantly, the FVE concentration of 5 mg/mL inhibited S. mutans biofilm development by 100%. The potent antibiofilm activity of FVE against S. mutans is likely due to the synergistic action of its rich content of phenolic acids and flavonoids, which possess known anti-virulence properties. These findings support the potential use of FVE as a natural ingredient in oral hygiene products to prevent dental plaque and caries. Full article

Background: Early childhood caries (ECC) is a common chronic disease in young children, influenced by multiple factors, including the activity of bacteria and other microorganisms, diet, and immune response. Pro-inflammatory cytokines like interleukin-8 (IL-8) and anti-inflammatory cytokines like interleukin-10 (IL-10) play crucial roles in the inflammatory process of caries. However, their relationship with ECC severity remains unclear. This study aimed to compare salivary IL-8 and IL-10 levels in children with and without ECC and analyze their association with caries severity using the International Caries Detection and Assessment System (ICDAS). Children with and without central obesity were included to evaluate the potential influence of nutritional status on cytokine expression. Methods: A cross-sectional study was conducted from March 2022 to December 2023 in San Luis Potosí, México, including 76 children aged 3 to 5 years (40 with ECC and 36 caries-free). Anthropometric measurements were taken to classify children as centrally obese or non-centrally obese. Unstimulated saliva samples were collected, and IL-8 and IL-10 levels were measured using ELISA. Statistical analysis included the Mann–Whitney U test, Spearman’s rank correlation coefficient, and binary logistic regression analysis, considering p < 0.05 as statistically significant. Results: IL-8 levels were higher in the ECC group (85 ± 119 pg/mL) than in the control group (45 ± 74 pg/mL), but this difference was not significant (p = 0.3613). IL-10 levels were lower in the ECC group (3 ± 2 pg/mL) than in the control group (11 ± 44 pg/mL; p = 0.6481). The difference between IL-8 and IL-10 levels was greater in the ECC group (27 ± 41 pg/mL) than in the control group (17 ± 33 pg/mL; p = 0.1709). No significant correlation was found between cytokine levels and ICDAS scores (p > 0.05), and binary logistic regression did not show an association between IL-8, IL-10, WHtR, and cavitated caries lesions. Conclusions: Although IL-8 tended to be elevated and IL-10 reduced in children with ECC, the differences were not statistically significant. The observed trend suggests a possible local immunological imbalance in children with caries, which may contribute to disease progression independently of bacterial activity or behavioral influences. Full article