Search Results (1,226)

Background: This article describes the biocompatibility of denture adhesives, focusing on their cytotoxicity towards oral fibroblasts, their influence on biofilm formation and microbial infections, and their potential to induce inflammatory responses in oral tissues. By examining these factors, we aim to shed light on the effectiveness and safety of denture adhesives, providing clinicians with helpful advice and highlighting important topics for further research. Methods: A systematic literature review was conducted using the Medline (PubMed) and SCOPUS databases. The search strategy included the following MeSH terms: denture adhesives, complete dentures, cytotoxicity, inflammation, and biofilm formation. Only peer-reviewed articles were included. Results: Studies have shown that denture adhesives may have cytotoxic effects on oral mucosal fibroblasts, as well as on biofilm formation and adhesion. Moreover, there is still little research on the effect of denture adhesives on inflammation of the denture-bearing area and cytokine production. Conclusions: The obtained results highlight the need for long-term patient investigations, and thorough clinical trials are absolutely essential to evaluate the actual safety of denture adhesives. Since this aspect is still under investigation, particular focus should be placed on understanding the inflammatory reactions these compounds induce. Improving the safety profile of denture adhesives will require cooperation among manufacturers, dental practitioners, and researchers to ensure that patients are adequately informed and that product formulations are improved for biocompatibility. Full article

Essential oils (EOs) are complex plant-derived products known for their broad-spectrum antibacterial activity. This study aims to evaluate the chemical composition of eight essential oils-EOs (Caryophylli aetheroleum, Menthae aetheroleum, Origani aetheroleum, Rosmarini aetheroleum, Salviae aetheroleum, Melaleucae aetheroleum, Limonis aetheroleum, and Curcumae aetheroleum) and to evaluate their antibacterial and antibiofilm activity against five opportunistic pathogens with biofilm-forming potential (methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae). GC-MS was used to determine the chemical composition of the EOs, and antibacterial activity was evaluated using broth microdilution to determine the minimum inhibitory concentration and minimum bactericidal concentration. Biofilm inhibition was assessed by a crystal violet assay. Oxygenated monoterpenes and phenolic compounds were dominant in Origani, Menthae, Rosmarinus, Melaleucae, and Caryophylli aetheroleum. Potent inhibitory effects against the tested bacterial strains were observed for clove, tea tree, oregano, and rosemary EOs. The antimicrobial efficacy of EOs is closely linked to their chemical composition. Tea tree and oregano EOs exhibited the broadest spectrum of antimicrobial activity, while peppermint and curcuma oils were the least potent. Cytotoxicity thresholds from the literature suggest that some effective EO concentrations exceed safe mucosal limits, particularly in continuous high-dose applications, but short-contact delivery systems or adjunctive use with different agents may mitigate safety concerns. These findings support further investigation into their therapeutic applications in oral health products. Full article

Background: Oral mucositis (OM) is a frequent complication of anticancer therapy which arises from cytotoxic injury, having significant clinical implications. Nutritional and supplement-based interventions have been proposed as adjunctive strategies to improve outcomes. Objectives: This systematic review aimed to identify and synthesize evidence from randomized controlled trials (RCTs) evaluating nutritional or natural supplement interventions for prevention or management of OM in pediatric oncology. Methods: We conducted a systematic search (17 August 2025) of Scopus, PubMed/MEDLINE, and Google Scholar (1 January 2000–1 June 2025) following PRISMA guidelines and registered in PROSPERO (CRD420251134454). The review included randomized controlled trials in pediatric cancer patients (≤18 years; up to 25 years for follow-up) receiving chemo-/radiotherapy, assessing nutritional, dietary, or natural product interventions for oral mucositis prevention or treatment. Non-randomized, adult, non-English, non-peer-reviewed, or inaccessible studies were excluded. Outcomes included incidence, severity, duration of OM, and mucositis-associated pain. Risk of bias was assessed using the NIH Study Quality Assessment Tools and the Cochrane RoB 2 tool. Results were qualitatively summarized. Results: Of 5870 records identified, 20 RCTs met inclusion criteria resulting in 1430 total included patients. Interventions tested included systemic supplements (e.g., glutamine, zinc, and bovine colostrum), topically applied agents (e.g., honey, vitamin E, Aloe vera, and olive oil), and nutrient-containing rinses (e.g., chamomile, Caphosol, and Traumeel S). Honey-based interventions showed promising outcomes. Discussion: Study designs and sample sizes varied considerably, and outcome measures were heterogeneous. Challenges with blinding, variable compliance, and inconsistent reporting reduce confidence and precision in the findings. Conclusions: Evidence from pediatric RCTs remains limited but highlights nutritional and natural products as promising supportive care options for OM. Findings suggest potential for practical, low-cost adjuncts to established oral care protocols, warranting further high-quality multicenter trials. Full article

Interleukin 17 (IL-17) is a crucial mediator at the interface of periodontal dysbiosis and host immunity. This review synthesizes current evidence on IL-17 in periodontitis (PD), its systemic connections, and the role of IL-17 gene variants. Clinical and experimental studies show that IL-17 rises in periodontal disease and is associated with the severity of PD via action on epithelial, stromal and osteoblastic cells to promote chemokine release, neutrophil recruitment, cyclooxygenase 2 and prostaglandin E2 synthesis, RANKL expression, osteoclastogenesis, and matrix metalloproteinase activity. Periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans pre-activate the local inflammation-maintaining Th17 response. There is converging evidence linking IL-17-centered signaling with rheumatoid arthritis, diabetes mellitus, and psoriasis in favor of a shared inflammatory network in barrier tissues and synovium. Despite these associations, IL-17 biology is contextually determined with mucosal defense and bone homeostatic roles that caution against unidimensional explanations. Evidence on IL-17A and IL-17F polymorphisms is still heterogeneous across populations with modest and variable risk associations with PD. Clinically, IL-17 in gingival crevicular fluid, saliva, or serum is a potential monitoring biomarker when utilized along with conventional indices. Therapeutically, periodontal therapy that reduces microbial burden may inhibit IL-17 function, and IL-17-targeted therapy has to balance potential benefit to inflammation and bone resorption against safety in oral tissues. The following research must utilize harmonized case definitions, standardized sampling, and multiethnic cohorts, and it must include multiomics to be able to differentiate between causal and compensatory IL-17 signals. Full article

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

Background: Commercial oral care products commonly incorporate synthetic antimicrobials such as cetylpyridinium chloride (Cetyl Cl.), L-Arginine (L-arg.), and stannous fluoride (SnF₂). Although effective against oral pathogens, these agents are often associated with adverse effects including mucosal irritation, taste alteration, and disruption of the oral microbiome. These limitations have spurred growing interest in safer, plant-based alternatives. In this study, we present a two-pronged in vitro oral care testing model that integrates cell assays with machine-guided quantitative microscopy analyses to assess both antibacterial efficacy and host biocompatibility of botanical extracts. Methods: Using Miswak (Salvadora persica) and Neem (Azadirachta indica) as representative natural products, we conducted antibacterial and antibiofilm testing including the evaluation of the minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC), alongside biocompatibility assessments via MTT cell viability assays on probiotic bacteria and mammalian oral cells. To evaluate biofilm structure and disruption, we employed scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), augmented with machine-guided Weka segmentation and automated image analysis. Results: Our findings show that Miswak and Neem extracts exhibited 75–100% antibacterial and antibiofilm efficacy against all tested bacteria, as demonstrated by cell assays and microscopy analyses, comparable to synthetic oral care agents. They also maintained ~100% viability toward commensal microbes and mammalian oral cells, whereas Cetyl Cl. and SnF₂ showed dose-dependent cytotoxicity. Conclusions: This dual-assessment oral care testing model provides a comprehensive and biologically relevant framework for the discovery and screening of safe and effective natural herbal extracts in oral care applications. Full article

Background: Lichen planus (LP) is a chronic immune-mediated inflammatory disorder affecting skin, mucosae, nails, and appendages, often with significant impact on quality of life. While associations between oral LP (OLP) and other localizations have been described, comprehensive analyses of patients presenting with multiple LP localizations remain limited. The aim of the study was describing the association of multisite LP among our patients in order to contribute to knowledge about this rare, but possible, clinical situation and its clinical implications in terms of follow-up. Methods: We conducted a retrospective observational study including 44 adult patients with histologically confirmed OLP and at least two additional LP subtypes. Data were collected at the joint dermatology–oral pathology clinic of Policlinico Sant’Orsola Malpighi, Bologna, between January 2022 and December 2024. Demographic characteristics, clinical manifestations, comorbidities, and therapeutic approaches were analyzed. Results: The cohort comprised 31 women and 13 men (mean age at first LP diagnosis: 56 years). All patients presented OLP, predominantly erosive (73%). During a follow-up, 39 patients developed three LP subtypes, and 5 patients developed four LP subtypes. Cutaneous LP was universal, while mucosal involvement included genital LP (n = 23), esophageal/pharyngeal/laryngeal LP (n = 8), and vulvar lichen sclerosus (n = 6). Nail LP was diagnosed in seven cases and frontal fibrosing alopecia in ten cases. Autoimmune comorbidities were frequent, including thyroiditis, psoriasis, systemic sclerosis, lupus, and Sjögren’s syndrome. First-line therapy consisted of topical and systemic corticosteroids, with adjuvant retinoids, cyclosporine, or immunosuppressants in refractory cases. No malignant transformation or dysplasia was detected during the observation period, and the mean follow-up period was 24 months (range: 12–36 months). Conclusions: Multisite LP is a complex, underrecognized condition requiring multidisciplinary management. OLP frequently represents the initial manifestation, followed by progressive involvement of cutaneous and mucosal sites. Regular full-body, oral, and genital examinations, together with tailored systemic treatments, are essential to prevent scarring sequelae and improve quality of life. Our findings highlight the need for heightened clinical vigilance and integrated care pathways for patients with multi-site LP. Full article

Background: Oral lichen planus (OLP) is a chronic mucosal disease associated with a risk of malignant transformation. Although topical corticosteroids are the standard therapy, prolonged administration may result in local and systemic complications. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been proposed as a less invasive and safer alternative. Methods: In this prospective study, 44 patients with histologically verified OLP underwent a protocol consisting of ten consecutive weekly PDT sessions, each comprising a single irradiation. A 5% ALA formulation was topically applied, followed by illumination with a 630 nm red light device. Clinical outcomes were evaluated at baseline, immediately after therapy, and at 12- and 48-month follow-ups. Changes in lesion surface, REU index, and pain intensity on a visual analog scale (VAS) were analyzed. Results: Significant improvements were noted, with progressive and sustained decreases in lesion extent, REU scores, and VAS values throughout the 4-year observation period. The therapeutic response was consistent across different mucosal sites (keratinized and non-keratinized). No treatment-related adverse reactions were recorded. Conclusions: Long-term follow-up indicates that ALA-mediated PDT is a safe and effective management option for both reticular and erosive variants of OLP. Its durable clinical benefits and favorable safety profile support its role as an alternative to corticosteroid therapy. Full article

Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple mechanical wear. This Perspective introduces the Nallan–Nickel Effect, a theoretical model proposing that a host- and environment-dependent threshold of bioavailable nickel ions (Ni²⁺), once exceeded, may trigger a neuro-immune cascade culminating in a burning phenotype. Within this framework, slow corrosion at exposed PFM interfaces releases Ni²⁺ into saliva and crevicular fluid, facilitating epithelial uptake and activation of innate immune sensors such as TLR4 and NLRP3. The resulting cytokine milieu (IL-1β, IL-6, TNF-α) drives NF-κB, mediated inflammation and T-cell activation, while neurogenic mediators—including nerve growth factor (NGF), substance P, and CGRP—sensitize TRPV1/TRPA1 nociceptors, establishing feedback loops of persistent burning and neurogenic inflammation. Modifying factors such as low salivary flow, acidic oral pH, mixed-metal galvanic coupling, and parafunctional stress can lower this threshold, whereas replacement with high-noble or all-ceramic materials may restore tolerance. The model generates testable predictions: elevated local free Ni²⁺ levels and increased expression of TLR4 and TRPV1 in symptomatic mucosa, along with clinical improvement following substitution of nickel-containing restorations. Conceptually, the Nallan–Nickel Effect reframes PFM-associated burning and lichenoid lesions as threshold-governed, neuro-immune phenomena rather than nonspecific irritations. By integrating corrosion chemistry, mucosal immunology, and sensory neurobiology, this hypothesis offers a coherent, testable framework for future translational research and patient-centered management of PFM-related complications. Full article

Bovine colostrum stands out as a natural supplement with rich bioactive components that attract attention for its therapeutic potential in the maintenance and improvement of gastrointestinal (GI) health. The major bioactive components of bovine colostrum include immunoglobulin (Ig) (especially immunoglobulin G), lactoferrin (LF), growth Factors (IGF-I, TGF-β, EGF), oligosaccharides (OS), and bioactive peptides. These components play a role in epithelial repair, suppression of inflammation, balancing the microbiota, and enhancing the mucosal barrier. Various animal models and recent human studies show that bovine colostrum has various positive effects against gastrointestinal tract diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), non-steroidal anti-Inflammatory drug (NSAID)-induced enteropathy, and necrotizing enterocolitis (NEC). These effects include preservation of epithelial integrity, reduction of inflammatory markers, and improvement of intestinal permeability. Studies on the tolerability and efficacy profiles of various bovine colostrum formulations for oral, oropharyngeal, and enteral administration are increasing. In this review, the multifaceted effects of bovine colostrum on the gastrointestinal tract are explained at a mechanistic level, and potential areas of study for clinical translation are presented. Bovine Colostrum stands out as a promising natural biotherapeutic agent for both preventive and therapeutic approaches. Full article

Oral mucosal wound healing is a rapid, precisely regulated process distinct from cutaneous repair due to the specialized anatomical, microbial, and physiological features of the oral cavity. This review outlines the sequential healing phases—hemostasis, inflammation, proliferation, and remodeling—and examines the coordinated roles of keratinocytes, fibroblasts, endothelial cells, and immune cell subsets in tissue restoration. Central molecular pathways, including PI3K/Akt, JAK/STAT, Ras/MAPK, TGF-β/SMAD, and Wnt/β-catenin, along with growth factors such as TGF-β, FGF, EGF, and VEGF, are discussed in relation to their regulatory influence on cell behavior and extracellular matrix dynamics. Unique intraoral factors—namely saliva-derived histatins and a distinct resident microbiota—promote accelerated re-epithelialization and attenuated fibrosis. Systemic conditions such as diabetes, aging, and tobacco exposure are identified as key modulators that compromise repair efficiency. Emerging therapeutic strategies, including stem-cell-based interventions, microbiota modulation, bioengineered scaffolds, and photobiomodulation, offer translational potential to enhance clinical outcomes in oral tissue regeneration. Full article

Background: Low birth weight (LBW) is correlated with gut microbiota dysbiosis and intestinal barrier function disruption, increasing susceptibility to enteric diseases. These alterations underscore the critical need to identify key regulators of gut homeostasis, among which bile acids are increasingly recognized as pivotal for barrier integrity, microbial ecology, and host metabolism. Methods: Eight pairs of LBW (the initial BW was 0.850 ± 0.053 kg) and normal-birth-weight (NBW; 1.488 ± 0.083 kg) piglets were compared to evaluate cecal morphology and bile acid profiles. Subsequently, sixteen LBW piglets and eight NBW piglets were allocated into three groups: NBW (1.563 ± 0.052 kg), LBW control (LBW-CON; 0.950 ± 0.120 kg), and LBW with bile acid supplementation (LBW-bile powder; 0.925 ± 0.116 kg). Piglets in the LBW-bile powder group received 25 mg/kg BW of bile powder (hyodeoxycholic acid-enriched) by daily oral gavage for 14 days. Results: LBW piglets exhibited retarded cecal development and lower abundance of hyocholic acid species (p = 0.006). Importantly, bile powder supplementation significantly improved cecal length (p = 0.009) and mucosal thickness (p = 0.020) compared with LBW-CON piglets. Microbial analysis showed that the microbial dysbiosis index was restored to near-normal levels. Transcriptomic analysis revealed impaired extracellular matrix structure and mucus secretion in LBW piglets. Notably, bile powder supplementation markedly upregulated the protein expression of WNT8B (p < 0.001) and the bile acid receptors (i.e., GPBAR1 and FXR), alongside enhanced tight junctions and the goblet cell marker mucin-2 expression (p < 0.05). Conclusions: These findings suggest that specific bile acid supplementation improves gut barrier function and partially supports cecal development in LBW piglets. Full article

Guided bone regeneration membranes are essential for bone formation. While non-resorbable membranes require removal surgery, resorbable membranes such as poly (lactic-co-glycolic acid) PLGA are widely used; however, issues with animal-derived components and degradation control have been identified. A novel bilayer membrane composed of synthetic poly (L-lactic acid-co-ε-caprolactone) (PBM) was developed, offering prolonged degradability and elasticity. This study compared the wound-healing effects of PBM and PLGA membranes in vivo and in vitro experiments. In vivo, maxillary molars were extracted from rats, and membranes were placed over the sockets. Healing was evaluated histologically at 1, 2, 3, 4 and 8 weeks. In vitro, oral epithelial cells and fibroblasts were seeded on both sides of PBM. Adhesion and permeability of the membranes were assessed. In vivo, both groups displayed similar mucosal healing. However, PBM preserved a clear bone-soft tissue boundary. In vitro, the surface of PBM supported significantly greater oral epithelial cell adhesion than the reverse side, with no differences for fibroblasts. Both sides of PBM exhibited better protein permeability compared to PLGA. PBM maintained distinct bone-soft tissue separation in rat extraction sockets, suggesting its potential as an effective space maintainer in guided bone regeneration. Further studies are warranted to investigate the mechanisms underlying these favorable properties. Full article

Background: Anemoside B4 (AB4), the major bioactive saponin from Pulsatilla chinensis, exhibits anti-inflammatory, anti-tumor, anti-apoptotic, and analgesic properties. However, its clinical translation for ulcerative colitis (UC) is constrained by poor epithelial permeability and low oral bioavailability. Objective: This study’s objective was to engineer and optimize thermosensitive rectal in situ gels (ISGs) of AB4, incorporating suitable absorption enhancers to improve mucosal permeation, bioavailability, and therapeutic efficacy against UC. Methods: Screening of effective permeation enhancers was conducted using Caco-2 cell monolayers and Franz diffusion cells. Critical formulation variables such as poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) were optimized, employing single-factor experiments coupled with the Box–Behnken design response surface methodology (BBD-RSM). Comprehensive characterization encompassed in vitro release kinetics, in vivo pharmacokinetics, rectal tissue tolerability, rectal retention time, and pharmacodynamic efficacy in a UC model. Results: We used 2.5% hydroxypropyl-β-cyclodextrin (HP-β-CD) and 1.0% sodium caprate (SC) as the appropriate absorption enhancers, and the amounts of P407, P188, and HPMC were 17.41%, 4.07%, and 0.44%, respectively, to yield the corresponding in situ gels HP-β-CD-AB4-ISG and SC-AB4-ISG. The gel characterization, such as gelation temperature, gelation time, pH, gelation strength, etc., was in accordance with requirements. The ISGs did not stimulate or damage rectal tissue and remained in the rectum for a prolonged period. More importantly, an improvement in bioavailability and alleviation of UC were noted. Conclusion: Absorption enhancer-assisted, poloxamer-based thermosensitive rectal ISGs provide a safe, convenient, and effective platform for targeted delivery of AB4 to the colorectum. This strategy addresses key limitations of oral dosing and warrants further clinical development for UC and related colorectal inflammatory diseases. Full article

Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4⁺ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity. Full article