Search Results (295)

Sphingolipids, essential structural components of biological membranes, form a framework that maintains their stability and fluidity. In addition to their structural function, these lipids and their metabolites participate in regulating multiple cellular processes, including proliferation, differentiation, gene expression, and apoptosis, thereby contributing to the maintenance of oral homeostasis. Dysregulation of sphingolipid metabolism is involved in the pathogenesis of several major oral diseases: oral squamous-cell carcinoma (OSCC), periodontitis, oral candidiasis, Sjögren’s syndrome (SS), and periapical diseases. Accordingly, a deeper understanding of sphingolipid biology may provide new opportunities for developing therapeutic strategies targeting these disorders. This review provides a comprehensive analysis of the structural characteristics and principal metabolic pathways of key sphingolipids (e.g., ceramide, sphingosine-1-phosphate [S1P], and glucosylceramide [GlcCer]), discusses their diverse roles in oral diseases, and summarizes recent advances in pharmacological approaches targeting enzymes involved in sphingolipid metabolism. Full article

Background: Geranium robertianum L. (GR) is a perennial herbaceous plant that belongs to the Geraniaceae family, widely distributed across temperate regions of Europe, Asia, North Africa, and America. It has been used in traditional ethnomedicine for its antibacterial, haemostatic, and anti-allergic properties in the treatment of oropharyngeal conditions, wounds, and inflammatory diseases. Beyond these traditional applications, pharmacological studies have documented several biological activities of its extracts and constituents. Objective: The aim of this review is to evaluate the therapeutic potential of GR by examining the phytochemical composition and the pharmacological properties relevant to dental medicine. Methods: A literature screening was conducted (PubMed, Google Scholar, PubMed Central), with focus on studies concerning phytochemical composition, pharmacological effects, and potential applications of GR and its major bioactive constituents in oral health. Results: Phytochemical analysis reveals that GR is characterized by a rich content of polyphenols, particularly tannins, flavonoids, and phenolic acids, with geraniin, ellagic acid, gallic acid, quercetin, and kaempferol identified as its principal bioactive constituents. Recent studies have confirmed that these constituents are responsible for the plant’s therapeutic potential in oral medicine. These compounds possess a variety of effects, from antibacterial and anti-inflammatory properties to antifungal and antiviral activities, as well as antioxidant, wound-healing, and anticancer benefits relevant to dental medicine. Conclusions: Despite its long-standing traditional use, GR remains largely underexplored in the context of oral health. This gap in the literature highlights GR as a promising phytotherapeutic candidate, calling for further in vitro and in vivo studies in order to investigate its efficacy and establish its mechanism of action in dental medicine. Full article

This study investigated the repurposing potential of clomiphene citrate as a topical therapeutic candidate for tegumentary leishmaniasis (TL) and candidiasis. Comparative in silico analyses were performed to evaluate absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties in comparison with meglumine antimoniate and amphotericin B. In addition, molecular docking was conducted to investigate the interaction of clomiphene with Leishmania spp. arginase and the Sap5 protease of Candida albicans. Clomiphene exhibited a favorable physicochemical profile, characterized by high lipophilicity, moderate skin permeability, and predicted oral bioavailability and intestinal absorption superior to those of the reference drugs. Toxicological predictions also indicated a lower systemic toxicity profile compared with conventional therapies. Molecular docking revealed favorable binding energies and interactions with key residues within the active sites of both targets. Experimental assays demonstrated that clomiphene inhibited the early stages of C. albicans biofilm formation and exhibited potent leishmanicidal activity against L. amazonensis promastigotes, with a high selectivity index in macrophages. Together, these findings indicate that clomiphene citrate represents a promising candidate for further investigation as a potential therapeutic agent against tegumentary leishmaniasis and candidiasis. Full article

Background/Objectives: Oral candidiasis is one of the most prevalent infections among denture wearers and is frequently associated with colonization by Candida albicans. In this context, natural products have been investigated as alternative therapeutic strategies, particularly Punica granatum peel extract and Cinnamomum cassia essential oil, which are recognized for their antimicrobial activity. This study aimed to develop and evaluate a mucoadhesive gel loaded with P. granatum and C. cassia for the treatment of oral candidiasis. Methods: The synergistic potential between the plant materials was assessed using the checkerboard method against C. albicans, and the inhibitory concentration was used as a parameter for the development of the mucoadhesive formulation. The gel was characterized and subsequently evaluated in denture-wearing patients with clinical manifestations of oral candidiasis for 14 days, with the results compared to treatment with nystatin. Results: The combination of plant materials exhibited a synergistic effect, with an inhibitory concentration of 0.1953 mg mL⁻¹ for both components. Clinical evaluation demonstrated a satisfactory therapeutic response in patients treated with the gel, with resolution of symptoms at the end of the treatment period. Statistically significant advantages were also observed regarding ease of application, absence of irritation, and reduced interference with speech and swallowing. In contrast, the group treated with nystatin showed only partial clinical improvement, with additional therapy required in some cases. Conclusions: These findings indicate that the mucoadhesive gel represents a promising topical strategy for the management of oral candidiasis in denture wearers. However, studies with longer follow-up periods are required to consolidate the clinical evidence. Full article

Historically, the study of oral fungal species was limited by the inability to cultivate most of them. However, advances in metagenomic techniques have enabled the direct identification of microbial genomes from human samples, markedly broadening our understanding of the oral mycobiome. This narrative review aims to analyze the available scientific evidence on the composition and dynamics of the oral mycobiome, as well as its influence on the development of local pathological conditions. The oral mycobiome is highly diverse, with emphasis on genus Candida, followed by Cladosporium, Aureobasidium and Saccharomyces. Candida albicans remains the most frequently identified species in both health and diseases state. However, individuals with oral candidiasis present a higher detection of Candida dubliniensis, Candida parapsilosis, Pichia kudriavzevii, Antrodiella micra and Cladosporium sphaerospermum. In dental caries, C. albicans and C. dubliniensis are associated with advanced lesions, whereas Debaryomyces and Rhodotorula may exert protective effects against Streptococcus mutans, a cariogenic bacterium. In periodontitis, an increase in yeast-bacteria interactions is observed. Additionally, C. albicans has been implicated in oral carcinogenesis through multiple mechanisms. These findings highlight the need for a deeper understanding of the oral mycobiome to enable early detection of oral diseases and the development of therapeutic approaches. Full article

Background/Objectives: Cytomegalovirus (CMV) retinitis remains a significant opportunistic infection in patients with advanced human immunodeficiency virus (HIV) infection, particularly with late HIV diagnoses. This three-case series aimed to describe HIV-associated CMV retinitis in newly diagnosed advanced HIV infection with documented concurrent and/or prior infectious conditions, and to highlight the importance of bord systemic screening and multidisciplinary management. Methods: We retrospectively reviewed three male patients diagnosed with HIV-associated CMV retinitis at a tertiary ophthalmology referral center. Clinical findings, CD4-positive T-cell counts, HIV-RNA levels, aqueous humor CMV-DNA results, systemic infectious conditions, treatment and ocular outcomes were summarized. Results: All patients had marked cellular immunodeficiency, with CD4-positive T-cell counts ranging from 46 to 141 cells/µL, and CMV-DNA was detected in aqueous humor in all cases. The infectious burden was substantial: all three patients had syphilis and hepatitis B virus infection, two had oral candidiasis, and individual patients had chlamydia infection, tuberculosis, amebic colitis, or a history of herpes zoster. One patient was initially suspected of having syphilitic uveitis, which illustrates how coinfections may obscure the diagnosis of CMV retinitis. Retinal detachment occurred in two cases and was surgically repaired with anatomical recovery. Conclusions: These cases emphasize that CMV retinitis in newly diagnosed advanced HIV infection should prompt broad infection screening and multidisciplinary evaluation, particularly in the setting of delayed HIV diagnosis and severe immunosuppression. Comprehensive screening for opportunistic and sexually transmitted infections, prompt ocular virological confirmation, and multidisciplinary management are essential in patients with HIV-associated CMV retinitis. Full article

Background: Network medicine has reshaped how systemic comorbidities are quantified, but the internal comorbidity structure of oral diseases remains undescribed at four-character ICD-10 granularity. Methods: A total of 2,863,671 outpatient visit records from 583,614 patients (2011–2025) were analyzed. Using ICD-10 four-character codes (75 disease nodes), comorbidity networks were constructed for five age strata, with edges selected by relative risk (RR) > 1.5 and Bonferroni-corrected Fisher’s exact tests. Patient-level longitudinal sequences were mined for progression trajectories, and quasi-causal analyses—Cox regression, negative outcome controls, and Baron–Kenny mediation—were used to evaluate pathway directionality and specificity. Results: The all-age network contained 75 nodes and 167 edges (modularity = 0.53), forming eight communities. Network complexity peaked at 18–29 years and declined with age. Dental caries emerged as the strongest hub in the 60+ stratum (degree = 9). Cox regression adjusted for age, sex, and healthcare utilization confirmed pathway directionality (pulpitis → tooth defect: hazard ratio (HR) = 2.65; caries → pulpitis: HR = 2.25), and negative outcome controls confirmed biological specificity. Mediation analysis showed that pulpitis completely mediated the caries → tooth defect association (proportion mediated ≈ 100%; 95% confidence interval (CI), 90–128%). An oral mucosal immune cluster (burning mouth syndrome, lichen planus, candidiasis, and xerostomia) emerged as a clinically actionable community. Conclusions: Oral diseases form biologically coherent, age-evolving comorbidity communities, and pulpitis is the critical mediating intervention point in the caries-to-tooth-defect cascade. The framework provides a reusable network-medicine substrate for age- and sex-specific risk-stratified oral disease management. Full article

Background: Candida albicans is the main etiological agent of oral candidiasis and expresses several virulence-associated traits that contribute to tissue invasion and persistence within the host. Among these, morphogenesis and hydrolytic enzyme secretion are central to fungal pathogenicity. Carvacrol, a phenolic monoterpenoid found in essential oils from aromatic plants, has demonstrated antifungal activity against Candida species, although its effects on virulence phenotypes in clinical isolates remain poorly explored. Therefore, this study investigated the effects of carvacrol on morphogenesis and lipase activity in clinical isolates of C. albicans obtained from oral candidiasis. Methods: Thirteen clinical isolates of C. albicans obtained from the oral mucosa of patients with oral candidiasis and one reference strain (ATCC 90028) were evaluated in the presence and absence of carvacrol (256 μg/mL). The effects of carvacrol on germ tube formation, morphology index, hyphal length, colony filamentation in Spider medium, and lipase activity were analyzed using phenotypic assays. Results: Carvacrol reduced germ tube formation in most of the evaluated strains and decreased the overall morphology index, indicating attenuation of filamentous morphologies. In strains that maintained hyphal growth, treatment with carvacrol significantly reduced hyphal length. In addition, colonies grown in Spider medium supplemented with carvacrol exhibited predominantly smooth morphologies, with reduced filamentous formation. Lipase activity was also inhibited in all evaluated strains in the presence of the compound. Notably, variability in phenotypic response was observed among clinical isolates, particularly in strain 97, which maintained partial filamentation under treatment conditions. Conclusions: Exposure to carvacrol was associated with alterations in morphogenesis- and lipase-associated phenotypes in clinical isolates of C. albicans under inhibitory conditions. Because the experiments were conducted using a concentration corresponding to 2× MIC, the present findings do not allow discrimination between specific modulation of virulence-associated phenotypes and indirect effects associated with growth inhibition. Full article

Background/Objectives: Oral candidiasis is an infection of the oral cavity caused by Candida albicans. Mucoadhesive buccal films could adhere to the buccal mucosa for prolonged periods, improving the therapeutic outcomes of patients with oral candidiasis. This study aimed to develop and evaluate the properties of fluconazole containing sodium alginate/methylcellulose-based buccal films for potential treatment of oral candidiasis. Methods: Drug-polymer compatibility was investigated using FT-IR spectrophotometry. Three optimised fluconazole films (F1 to F3) containing 1–1.6% sodium alginate and methylcellulose (1.6%) were formulated using the solvent-casting method. Their physicomechanical properties were characterised using standard protocols. Drug content and in vitro drug release profiles were evaluated using UV-visible spectroscopy; in vitro/ex vivo mucoadhesion studies were conducted using the shaking water bath technique, and their antifungal activity against Candida albicans was evaluated using the agar ditch method. Results: FT-IR data analysis revealed that sodium alginate, methylcellulose and fluconazole were compatible in the films. The films were off-white, smooth, peelable, thin, with satisfactory pH values, folding endurance, drug content, excellent zones of inhibition against Candida albicans (40 mm), controlled drug release profile (3.6–4.1 mg/cm² after 6 h), and they displayed Korsmeyer–Peppas drug release kinetics. Film F3 containing 1.6% sodium alginate and 1.6% of methylcellulose exhibited superior swelling index (70 ± 1%), tensile strength (0.68 ± 0.04 MPa) and in vitro/ex vivo mucoadhesion time (5.5 ± 0.3 h; 2.3 ± 0.3 h) relative to other studied films. Conclusions: The sodium alginate content of the films influenced their tensile and mucoadhesive properties. Film F3 was the most promising formulation for potential treatment of oral candidiasis. Full article

Background: Oral candidiasis is an opportunistic infection caused by Candida albicans (C. albicans), highlighting the need to evaluate candidate substances that ensure both antifungal efficacy and mucosal safety. This study aimed to assess the potential of Sambucus williamsii var. coreana (S. williamsii var. coreana) extract as a naturally derived antifungal agent for topical oral application by investigating its antifungal activity against C. albicans and its cytotoxicity in human keratinocyte (HaCaT) cells. Methods: S. williamsii var. coreana was extracted with 70% ethanol, concentrated, and freeze-dried. The extract was prepared at concentrations of 1–40 mg/mL and applied under 6 h and 24 h exposure conditions. Antifungal activity against cultured C. albicans was evaluated using colony-forming unit (CFU) analysis, while cytotoxicity in HaCaT cells was assessed via the Water-soluble Tetrazolium Salt-1 assay after incubation at 37 °C in 5% CO₂ for 2 h. Statistical significance was analyzed using Student’s t-test, ANOVA, and Tukey’s HSD test (p < 0.05). Results: The S. williamsii var. coreana extract exhibited concentration- and time-dependent antifungal activity. A 99.99% inhibition of C. albicans was observed at 5 mg/mL. No detectable CFUs were observed at 30 mg/mL after 6 h and at 10 mg/mL after 24 h. HaCaT cell viability decreased in a concentration-dependent manner, with the half-maximal inhibitory concentration determined to be 10 mg/mL. Conclusions: The extract of S. williamsii var. coreana exhibited concentration- and time-dependent in vitro antifungal activity against C. albicans. However, the concentration associated with no detectable CFUs overlapped with the cytotoxic concentration range in HaCaT cells, indicating that further studies are required to define an appropriate concentration range for potential oral application. Full article

Objectives: Recurrent vulvovaginal candidiasis (RVVC) is a difficult-to-treat infection, most likely due to the growth of Candida biofilms on the human vaginal epithelium. We assessed in vitro efficacy of conventional antifungals and complementary and alternative medicine (CAM) used in clinical settings, and sought for Candida biofilm-effective single or combination therapies. Methods: Standard broth microdilution assay and XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay were used for antifungal and anti-biofilm efficacies of three conventional antifungals, and selected CAM including boric acid, povidone-iodine, and allicin (garlic extract), against Candida clinical isolates grown at neutral and acidic pHs respectively. Fractional inhibitory concentration (FIC) indices were assessed to evaluate interactions between fluconazole and different CAM. Viable count-based cell enumeration and confocal laser scanning microscopy (CLSM) were performed to confirm the efficacy of single or combination therapies against Candida biofilms. Results: All selected conventional antifungals and CAM showed efficacies against planktonic Candida cells. Acidic vaginal microenvironments provided agent-specific protection to Candida cells against conventional antifungals and the CAM. Synergistic or additive interactions were observed between fluconazole at serum achievable concentrations and povidone-iodide at topically achievable concentrations against all tested Candida strains. Most antifungal agents except caspofungin had very limited activities against Candida biofilms. Combining fluconazole at 8 mg/L with povidone-iodine at 2048 mg/L effectively killed Candida biofilms in an acidic vaginal microenvironment to a level that is comparable to that of caspofungin. Conclusions: We provided robust in vitro evidence supporting the combinational use of oral fluconazole and topical CAM povidone-iodine against Candida biofilms in managing RVVC. Full article

Digestive candidiasis is a major opportunistic infection among people living with HIV (PLHIV). In Gabon, data on antifungal resistance remain limited. This study aimed to characterise Candida colonisation and antifungal resistance according to anatomical site and species in Libreville. In this cross-sectional study, 108 PLHIV provided paired oral and stool samples. Candida spp. was identified using conventional phenotypic methods. Antifungal susceptibility to azoles and polyenes was assessed by disc diffusion following CLSI guidelines. Resistance burden was classified by drug class and by cumulative number of antifungal agents involved. Digestive colonisation was detected in 97 (89.8%) participants. Oral and intestinal colonisation rates were 78.7% and 66.7%, respectively, with dual-site involvement in 55.6%. Among resistant isolates, Candida albicans accounted for 55.2% (oral) and 48.9% (intestinal), while non-albicans Candida represented 29.8% and 44.4%, respectively. Multidrug resistance was significantly higher in intestinal than oral isolates (36.2% vs. 11.8%; OR = 4.99; 95% CI: 2.04–12.16; p < 0.01). Resistance was predominantly azole-driven, with complex cumulative resistance profiles in intestinal isolates. The intestinal tract showed resistance profiles consistent with a preferential accumulation of MDR Candida populations in PLHIV. Site-specific resistance patterns underscore the importance of targeted sampling and antifungal stewardship strategies in resource-limited settings. Full article

Background: Oral lichen planus (OLP) is a chronic T-cell-mediated inflammatory disorder classified by the World Health Organization as a potentially malignant disorder. Diagnosis remains challenging due to clinical and histopathological overlap with other oral white lesions, including lichenoid reactions, frictional keratosis, and malignancy. Objectives: This systematic search with narrative review aimed to synthesize current diagnostic criteria, characterize key differential diagnoses, and provide an evidence-based diagnostic framework for clinicians. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Embase through December 2025. Following a systematic screening process, eligible manuscripts were narratively summarized and a clinical case illustration was demonstrated. Results: Twenty-nine of 214 peer-reviewed studies (including systematic reviews, guidelines, and cohort studies) were summarized. Diagnostic standards have evolved toward the American Academy of Oral & Maxillofacial Pathology (AAOMP) 2016 criteria, which emphasize mandatory clinicopathological associations. Key differential diagnoses include reactive lesions (frictional keratosis), infectious conditions (chronic hyperplastic candidiasis), and other lichenoid patterns. Malignant transformation rates are approximately 1.43%, increasing to 5.13% in the presence of dysplasia, necessitating long-term surveillance. An 81-year-old case exemplifies the value of a stepwise diagnostic approach, in which initial management focuses on the elimination of local irritants and a period of clinical observation, followed by histopathological confirmation of oral lichen planus through biopsy when necessary. Conclusions: Accurate OLP diagnosis requires integrating clinical presentation with histopathological findings. A systematic diagnostic algorithm—incorporating local factor elimination, selective biopsy, and long-term monitoring—is essential to distinguish OLP from its mimics and manage the risk of malignant transformation effectively. Full article

Background/Aim: This study aims to assess the prevalence of self-reported oral ulcers and their associated factors among patients with type 2 diabetes mellitus (T2DM) in Bangladesh. Materials and Methods: A hospital-based cross-sectional study was conducted among 260 patients with T2DM attending outpatient dental services at three tertiary hospitals in Dhaka. Data were collected using a semi-structured questionnaire covering sociodemographic characteristics, behavioral and dietary factors, medical history, and self-reported oral mucosal conditions. Associations between oral ulcers and potential risk factors were analyzed using Chi-square and Fisher’s exact tests. Results: Most participants were middle-aged (50–59 years), female, of low educational status and married, with a high prevalence of regular tooth-brushing but low use of oral hygiene aids such as mouthwash. Traumatic ulcers (21.5%) and oral lichen planus (19.6%) were the most frequently observed oral mucosal lesions followed by recurrent aphthous ulcers, oral lichenoid reactions, and oral candidiasis. Traumatic ulcers and oral lichenoid reactions showed associations with sharp teeth, dentures or braces, and amalgam restorations, while lichen planus and aphthous ulcers were significantly associated with smoking, systemic conditions such as hypertension, and coexisting oral lesions such as oral candidiasis. Multivariable logistic regression showed that sharp teeth, denture or brace use, amalgam restorations, and tobacco-related habits were associated with oral lesions. Conclusions: Oral ulcers and related mucosal lesions were found to be common among patients with T2DM in Bangladesh, with traumatic ulcers being most frequent and several local and behavioral factors showing significant associations. Full article

Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance—a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC. Full article