Polycyclic Aromatic Hydrocarbons (PAHs) are persistent and toxic organic pollutants to which humans are exposed via inhalation, dermal absorption, and ingestion, increasing cancer risk, particularly among smokers and occupationally exposed individuals. This research aims to expand current knowledge by identifying the oral mucosae as an additional gateway for PAHs, owing to their high lipophilicity and the greater permeability of oral mucosae to xenobiotics, a finding that is particularly relevant given the established correlation between tobacco-derived PAHs and oral, head, and neck cancers. Here, ex vivo permeation studies were carefully designed using vertical Franz diffusion cells and porcine buccal and sublingual mucosae, a widely used ex vivo model for permeability studies. Five PAHs congeners were selected as representative of those highlighted from the US EPA as priority control pollutants: fluorene, acenaphthene, phenanthrene, pyrene and benzo(a)pyrene. The studied PAHs were found to permeate the oral mucosae, likely via passive diffusion (permeation∝logP), suggesting a potential relevant contribution to the overall systemic PAHs burden and thus toxicity, especially for individuals with pronounced oromucosal exposure, such as smokers. Additionally, all PAHs exhibited significant retention in the mucosal tissues, suggesting possible loco-regional toxicity. Specifically, the observed BaP accumulation in the buccal and sublingual mucosae (1781.27±397.64 and 1338.78±269.47ng/cm2, respectively) may support its correlation with oral cancers. Despite the experimental model not fully mimic the complexity of living system (e.g., enzymatic activity, active transport processes, blood perfusion, real-life exposure scenario), these findings address a major gap in the literature by identifying the oral mucosae as a previously unrecognized entry route for PAHs, a key point since the oral cavity is part of both the gastrointestinal and respiratory systems, already recognized PAHs exposure routes. The evidence reported here provides both a foundation for further multidisciplinary investigations as well as a rationale for developing cosmetic/medical devices aimed at detoxifying the oral cavity from PAHs. ENVIRONMENTAL IMPLICATION: This study aims to expand knowledge on PAHs permeation and accumulation through oral mucosal tissues. Demonstrating PAHs permeation and accumulation through this route would have major clinical and toxicological implications, including identifying a new exposure route, refining toxicokinetic, elucidating mechanisms linking tobacco-derived PAHs to head and neck carcinogenesis, and guiding preventive interventions to limit oral exposure (e.g., development of PAHs-sequestering cosmetics or medical devices).

The oral in fecal-oral: Exploring the overlooked relationship between saliva and enteric viruses.

Organ-on-a-chip in oral medicine: Emerging approaches and applications.

Dual strategy to enhance domperidone dissolution: mechanochemically synthesized multicomponent salts in orodispersible tablets.

Trends in Buccal Mucosa Cancer Incidence and Mortality in the United States From 2000-2022: A Surveillance, Epidemiology, and End Results (SEER)-Based Study

The buccal route has re-emerged as an alternative non-injectable route for peptide delivery. However, buccal peptide bioavailability is low, necessitating new formulation strategies. Pullulan, a water-soluble carbohydrate polymer, offers potential as a film-forming agent for buccal peptide delivery. Our aim was to co-administer a glucagon-like peptide-1 receptor agonist (GLP-1 RA) model analogue with an epithelial permeation enhancer, sodium glycodeoxycholate (GDC) in a bilayer film using a pullulan-based mucoadhesive layer. A pullulan-carboxymethyl cellulose mucoadhesive layer was selected, along with a backing layer made from an ammonio-methacrylate copolymer (Eudragit® RLPO). Physicochemical characterization confirmed the suitability of the pullulan-based film for buccal application. A Hilltop Chamber comprising an adhesive-backed cotton pad identified an optimal GLP-1 RA:GDC ratio for peptide permeation across ex vivo porcine buccal mucosae. 200mM GDC (94.4mg/mL) enabled ∼6% flux at 3h using a donor concentration of 50mg/mL GLP-1 RA (∼1:2). When these concentrations were incorporated into the prototype pullulan films, GLP-1 RA fluxes across mucosae reached ∼4.5% and ∼2% at 3h for single mucoadhesive-layer and bilayer films, respectively, without overt tissue damage. Integrating GLP-1 RA and GDC into a pullulan-based bilayer film offers a promising carbohydrate polymer platform for enhancing buccal peptide delivery.

Introduction: The oral cavity is one of the most vital components of the human body, playing a key role in digestion and communication. Stomatitis (Mukhapaka) is a common inflammatory condition of the oral mucosa frequently encountered in the paediatric population. It is characterised by symptoms such as pain, ulceration, and excessive salivation, which often interfere with daily activities such as eating and speaking. In Ayurveda, this condition is associated with the vitiation of Pitta and Kapha doshas. Need of the study: Due to contemporary dietary habits, irregular meal timings, night-time wakefulness, and improper oral hygiene practices, children are increasingly prone to inflammatory oral disorders. Although modern medicine utilises antibiotics and antiinflammatory drugs for treatment, there remains a need for an affordable, safe, and effective Ayurvedic therapeutic approach. Classical Ayurvedic texts mention Krushna Jeerakadi Yoga and Mrudvikadi Lotion as effective treatments; however, their relative efficacy has not yet been established through clinical trials. Aim: To assess the comparative effectiveness of an altered dosage form of Krushna Jeerakadi Yoga (Lotion) and Mrudvikadi Lotion in paediatric patients suffering from Mukhapaka (Stomatitis). Material and Methods: The present study will be a randomised controlled interventional clinical scheduled to be conducted from June 2025 to June 2026 involving 60 children aged 5-16 years diagnosed with Mukhapaka. Participants will be randomly divided into two groups of 30 each. Group A will receive Mrudvikadi Lotion (control group), while Group B will receive the altered dosage form of Krushna Jeerakadi Yoga Lotion (trial group) for seven days. Clinical evaluation will be conducted on the 3rd, 5th, and 7th days, with a final assessment on the 14th day. Outcomes will be measured using the World Health Organisation (WHO) Stomatitis (oral mucositis) Grading Scale along with symptom-relief parameters.

Epulis fissuratum is a benign hyperplastic lesion of the oral mucosa that develops as a result of chronic mechanical irritation, most commonly caused by ill-fitting dentures. This lesion typically occurs in the oral vestibule and is characterized by fibrous folds of mucosa along the denture border. The aim of this case report is to present a clinical case of epulis fissuratum located in the mandibular vestibule and its surgical management. A 62-year-old female patient presented to the Oral Surgery Clinic with a soft tissue mass in the right mandibular vestibular mucosa, associated with local irritation during denture use. Based on clinical examination, a provisional diagnosis of epulis fissuratum was made. The lesion was treated by surgical excision under local anesthesia, and the excised tissue was submitted for histopathological examination. Histopathological analysis confirmed the diagnosis of papillomatosis gingivae and epulis fibromatosis. Following surgery, the wound was sutured, and the patient was instructed on postoperative care and prosthetic rehabilitation. Surgical treatment combined with elimination of etiological factors represents an effective approach for the management of this lesion.

Retraction: Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa

In November 2020, an alert for a "mysterious disease" among fishermen was issued. Fishermen are particularly subjected to dermatoses due to their constant contact with seawater, fish, crustaceans, and fishing equipment that may contain harmful agents. The study aimed to examine the alert, identify the causative agent and suggest preventive and control measures. This was a cross-sectional study of dermatoses in Dakar (Senegal) from October 11 to November 30, 2020, using quantitative and qualitative methods within a 'One Health' approach." The investigation included bacterio-virological, anatomopathological and toxicological examinations. Data were analyzed using Epi info and QGIS (case mapping), We observed all confidentiality measures during the study. A total of 555 cases were diagnosed with an attack rate of 5.4% among fishermen and no deaths were reported. There was a delay in epidemic detection and notification. The epidemic was most prevalent among people from coastal areas. Average age of cases was 22 ± 9 years, and all were male and artisanal fishermen by profession. Patients presented with fever (16%), cutaneous pain (100%) and mucocutaneous lesions (100%) consisting of vesicles, papules and ulcerations localized on exposed areas of the body, external genitalia and oral mucosa, with severe cases (8%). Toxicology revealed the presence of a toxic alga (V. rugosum) in marine equipments. The notion of a sea trip in the 24-48 hours before the onset of the disease was found in 92%. Majority of cases (74%) did not have full personal protective equipment (PPE). The proportion of people without full protection was 83% among those who developed severe forms. People without full protection were more exposed to severe forms than those with full PPE; (OR = 1.818; 95% CI [0.829 - 3.988]). The investigation has linked the epidemic to a probable algal origin. We need to promote the use of personal protective equipment and improve the early warning and notification system.

"Oral Submucous Fibrosis" (OSF) is a progressive "potentially malignant disorder" which is characterized by fibrosis and epithelial atrophy, resultant to hypoxia. The resulting hypoxic microenvironment is thought to trigger angiogenic responses that promote disease progression and malignant transformation. This study assessed whether hypoxia (HIF-1α) and angiogenesis (CD105) correlate with clinical stages in OSF. A total of 105 tissue samples (30 normal oral mucosa; 75 OSF) were analysed using immunohistochemistry. HIF-1α immunoreactice score and CD105 based microvascular metrics, microvessel density "(MVD)", total vascular area "(TVA)", and mean vascular area "(MVA)" were quantified. HIF-1α expression increased progressively across stages of OSF (p = 0.046). Similarly, CD105 expression, reflected by MVD, TVA, and MVA, demonstrated progressive elevation with disease advancement (p = 0.0001). Both markers demonstrated a positive correlation. (r = _, p < 0.05). The concurrent upregulation of HIF-1α and CD105 across clinical stages underscores a dynamic interrelationship between hypoxia and angiogenesis in OSF. These findings support integrating molecular markers into staging systems to enhance early association with "malignant transformation".

Cardiac metastases are an uncommon clinical entity and are rarely associated with head and neck squamous cell carcinomas, particularly those originating in the buccal mucosa. We report a rare case of a 28-year-old male with previously treated buccal mucosa squamous cell carcinoma who presented with fatigue, dizziness and dyspnoea and was found to have complete atrioventricular block on electrocardiography, prompting further cardiac evaluation. Transthoracic echocardiography demonstrated multiple intracardiac masses with septal involvement, which were further characterised by computed tomography pulmonary angiography and high-resolution computed tomography of the chest, confirming extensive cardiac infiltration. Histopathological examination of metastatic cervical lymph nodes confirmed squamous cell carcinoma. Owing to persistent symptomatic complete atrioventricular block, the patient underwent single-chamber permanent pacemaker implantation following multidisciplinary discussion. This case highlights the importance of considering cardiac metastases in patients with advanced head and neck malignancies presenting with new-onset conduction abnormalities. A focussed review of the literature is also presented.

ABSTRACT Background Naganishia diffluens (formerly Cryptococcus diffluens ) is a non‐neoformans cryptococcal species rarely isolated as a human pathogen. We reported a case of oral cryptococcosis caused by N. diffluens for the first time and reviewed relevant literature. Methods Herein, we present the case of a 31‐year‐old Iranian male with a history of major β‐thalassemia, who presented with non‐hemorrhagic white spots on the buccal mucosa, the mouth, lips, and the tongue's surface. Abdominal ultrasound results of the pelvis and abdomen showed that the patient has significant splenomegaly. Two consecutive samples were collected from the white spots on the patient's tongue to confirm the infection, which was confirmed via PCR Sequencing analysis. Results In both sampling occasions, Naganishia diffluens was isolated as the causative organism. According to a review conducted in PubMed, Web of Science, and Scopus for data analysis of oral cryptococcosis, just 27 reports were described in the literature. Naganishia diffluens can be the causative agent of some infections. Conclusion This is the first report of oral cryptococcosis due to N. diffluens successfully detected by DNA sequencing. However, to understand the precise prevalence of this emerging pathogen, epidemiological surveillance studies are highly recommended.

Introduction and Objectives: Buccal carcinoma is a malignancy that occurs in the oral mucosa between the cheeks and teeth. The therapy goals are to eliminate the cancer and maintaining ability to speak, eat, drink, the patient's appearance post therapy. Soft tissue reconstruction is performed to avoid contractures and trismus. Radial forearm flee flap frequently used because of its reliability, versatility, and ease of harvest. A good understanding of management and reconstruction of buccal carcinoma will improve the outcome. Material and Methods: A 52 year old man with chief complaint of posterior left side gum canker sores for three years accompanied by intermittent pain. Physical examination revealed necrotizing reddish lumpy mass on posterior left side oral cavity. Treatment consists of left mandible partial resection, supraomohyoid neck dissection and defect closure reconstruction with radial forearm free flap. Chemotherapy and radiotherapy was done after surgery. Two year follow-up showed no recurrence. Literature search was carried out in PubMed with keywords (buccal) AND (carcinoma) AND (management) AND (surgery). Systematic review with format of population, intervention, comparison, outcome, and time frame was done. Results: Four case reports were relevant to the topic were obtained from 64 literature search results. Conclusion: Primary resection of the lesion and neck dissection are the main option for treating buccal carcinoma. Reconstruction with a radial forearm free flap was chosen to prevent contracture from the lesion. Chemotherapy and radiotherapy can be administered after surgery to improve the outcome without compromising the flap

Abstract Oral lichen planus is a chronic inflammatory disorder of the oral cavity, for which the therapeutic gold standard consists of the topical administration of corticosteroids, such as clobetasol-17-propionate (CLB). Nowadays, there are no commercially available pharmaceuticals intended for CLB delivery within the oral cavity. Then, in clinical practice, the drug is administered via magistral galenic preparations, formulated as adhesive semisolids. As they possess numerous drawbacks (e.g., limited contact time, poor patients’ compliance, inaccurate dosing), the research is still focused on the development of suitable solid buccal drug delivery systems (BDDS). This work aims to: i) combine buccal film and lipid microsystem technologies, thus yielding an innovative composite BDDS and ii) preliminary assess its in vivo effectiveness. Solid Lipid Microparticles containing CLB were designed to possess a softening temperature close to body temperature, thereby facilitating the release of the drug in molecular form by fusion once applied. This lipid matrix, being tissue-affine, may also act as a penetration enhancer. Composite buccal films were then developed to facilitate microparticles administration, converting this powder into a solid mucoadhesive formulation. These Solid Lipid Microparticles-into-Film composites (SiF-composites) resulted homogeneous, highly mucoadhesive and capable of promoting CLB accumulation within the buccal mucosa. The best formulation was subjected to a pilot in vivo evaluation (5 patients per group receiving the SiF-composite or 0.05% CLB in Orafix) resulting in treatment adherence and a reduction in Thongprasom et al. scoring. The preliminary results obtained were extremely promising, thus suggest confirmation through a further larger, randomized double blind clinical trial.

C.E. Credit Practice Quiz for “Extragingival Vascular Lesion on the Buccal Mucosa in an Adult Male: An Approach to Diagnosis”

Introduction: Duloxetine hydrochloride (DLX) is a poorly water-soluble antidepressant with low oral bioavailability (~32%) due to acid-mediated degradation in the stomach and extensive first-pass metabolism. Oral fast-dissolving films (ODFs) offer a patient-friendly and effective alternative by promoting rapid drug dissolution in the oral cavity, potentially reducing gastric exposure and improving onset of action. Materials and Methods: In this study, DLX-loaded ODFs were prepared by the solvent casting method and optimized using a 14-run D-optimal mixture design. Hydroxypropyl methylcellulose E15 (HPMC E15), maltodextrin (MD), and propylene glycol (PG) were employed as formulation variables to evaluate their influence on film thickness, disintegration time (DT), and percentage drug release at 30 min (Rel₃₀). Result and discussion: The prepared films demonstrated uniform physicochemical characteristics, with thickness ranging from 0.24±0.013 to 0.55±0.012 mm, DT from 23±2 to 111±4 s, and Rel₃₀ values between 63.30±1.49% and 89.60±1.33%. The optimized formulation (N15), comprising HPMC E15 (109.43 mg), MD (53.23 mg), and PG (637.34 mg), exhibited rapid disintegration (27.61±2.52 s), high drug release (91.18±1.11%), and minimal thickness (0.263±0.013 mm). All formulations showed acceptable content uniformity and near-neutral surface pH. Scanning Electron Microscopy revealed smooth and homogeneous film surfaces, while differential scanning calorimetry and X-ray diffraction confirmed reduced DLX crystallinity within the films. Ex vivo permeation across sheep buccal mucosa resulted in 97.56±7.45 µg/cm² drug permeation within 30 min, indicating partial transmucosal absorption. Conclusion: Overall, the optimized DLX-ODFs demonstrated rapid disintegration, enhanced dissolution, and favourable permeation behaviour, suggesting their potential to improve therapeutic onset and reduce first-pass metabolism compared to conventional oral capsules

The oral mucosa maintains a delicate immunological equilibrium amidst constant microbial and environmental challenges. Within this unique microenvironment, the cytosolic DNA-sensing cGAS-STING signaling pathway has emerged as a central innate immune hub characterized by critical duality across a spectrum of pathologies. While transient STING activation is vital for protective anti-microbial defenses and driving anti-tumor immunity in oral squamous cell carcinoma, chronic, maladaptive signaling-often driven by self-DNA accumulation-fuels pathology in autoimmune and inflammatory conditions. Consequently, emerging therapeutic strategies targeting this pathway involve dichotomous applications, utilizing STING agonists for malignancies versus inhibitors for inflammatory disorders. Safely harnessing the significant therapeutic potential of the cGAS-STING pathway for managing recalcitrant oral diseases urgently requires precise, localized modulation strategies.

Mucosal Margin Shrinkage in Oral Cavity Cancer: A Systematic Review.

To report the prenatal diagnosis and follow-up of a fetus with mosaic tetrasomy 9p without obvious abnormal clinical manifestations. A fetus diagnosed with mosaic T9p at Shaoxing Maternal and Child Health Hospital in February 2022 was selected as the study subject. The amniotic fluid karyotype was 47,XY,+i(9)(p10)[3]/46,XY[97]. CNV-seq revealed a 70.56Mb copy number gain in 9p24.3q21.11 (mosaicism at 6%). After genetic counseling, the parents opted to continue the pregnancy. A 3.9kg male fetus was delivered at full term with normal physical findings at birth. The baby was phenotypically normal and had normal psychomotor and language development at 3 years old, at our last postnatal follow-up. When the child was 3 years old, his physical measurement parameters (height: 97cm; weight: 14kg) and neurodevelopment milestones all met the age standards. His peripheral blood karyotype was 47,XY,+i(9)(p10)[10]/46,XY[90], with CNV-seq analysis indicating a 39.16Mb copy number gain in the 9p24.3p13.1 region (mosaicism at 53%). This discrepancy with the amniotic fluid CNV-seq results was attributed to differences in segmentation algorithms or software. FISH detected T9p mosaicism in oral mucosa (11.2%) and urinary sediment cells (12.7%). A synthesis of data from karyotype analysis, CNV-seq, and FISH collectively substantiates the presence of an acquired alteration within the 9p region, while the evidence does not support the extension of this fragment across the centromere of chromosome 9 into the q arm. The combined use of various methods may be capable of more accurately determining break-points and mosaic levels of T9p during prenatal diagnosis. This enriches the clinical spectrum of T9p mosaicism and provides a basis for prenatal diagnosis and genetic counseling of children with this type of chromosome variation.