Oral Mucosa Research Articles

Localization of Lesions in Autoimmune Blistering Diseases Is Independent of Site-Specific Target Antigen Expression

Autoimmune blistering diseases (AIBDs) involve autoantibodies targeting proteins in the epidermal/epithelial desmosome (pemphigus) or basement membrane zone (pemphigoid). Despite widespread antigen distribution, lesions exhibit a scattered involvement pattern. This study maps the frequency/severity of AIBD lesions on various body parts and investigates whether differential antigen expression contributes to specific predilection sites. We analyzed affected sites presenting blisters/erosions, erythematous/urticarial lesions, and mucosal lesions in bullous pemphigoid (BP-cohort 1, n = 65; BP-cohort 2, n = 119), pemphigus vulgaris (PV, n = 67), and pemphigus foliaceus (PF, n = 20) patients. To assess antigen expression, we conducted indirect immunofluorescence (IF) staining of 11 AIBD antigens from 13 anatomical sites of 10 body donors without AIBD. In BP, blisters/erosions and erythematous/urticarial lesions predominantly affected arms and legs, while PV/PF patients exhibited frequent involvement of buccal mucosa and back, respectively. IF staining identified significant regional differences in BP180, BP230, and integrin β4 expression, although these variations did not correlate with a higher lesion frequency/severity. Other antigens showed consistent expression across all regions. Our findings suggest that predilection sites for BP and PV/PF are largely unaffected by regional variations in antigen expression but may be influenced by factors like microbiota, mechanical stress, sunlight exposure, local immunity, or genetics.

Effect of Biomechanical Properties of Perioral Soft Tissues on Lip Response to Simulated Protraction of Upper Front Teeth.

Proclination of front teeth in orthodontics and oral rehabilitation may influence lip protrusion and the overall facial profile. We hypothesized that the degree of profile changes is determined by the biomechanical properties of the lips. (1) to investigate the upper lip changes induced by a simulated protraction of upper front teeth; and (2) to assess the relationship between biomechanical properties of the lips and their response to tooth protraction. Thirty-four participants were recruited at the Faculty of Dentistry, University of Otago, New Zealand. Simulated protraction of upper front teeth was achieved by placing a customised stent covering the buccal surface of the maxillary upper incisors and canines, along with the corresponding buccal mucosa and gingiva. Stereophotogrammetry was used to assess lip changes in three dimensions. Biomechanical properties of the lips, including muscle tone, stiffness and elasticity, were measured using a non-invasive digital palpation device. During the simulated protraction of upper front teeth, the upper lip advanced approximately 50% of the stent thickness, with a considerable inter-individual variation in lip displacement. Soft tissue responses were correlated with the biomechanical properties of the lips with significant correlation coefficients ranging from 0.38 to 0.40. Higher lip tone was associated with increased lip displacement, while greater lip elasticity resulted in reduced lip displacement. Multivariate analyses indicated that upper lip displacement was associated with biomechanical properties and ethnicity, but not with age, sex and body mass index. The response of the lips to protraction of front teeth varies largely between individuals and can be partly explained by variations in the biomechanical properties of perioral muscles.

Sebaceous carcinoma of the intraoral origin: a literature review

Abstract Sebaceous carcinoma (SC) is an aggressive cancer arising from sebaceous glands, rarely occurring in the oral cavity (IOSC). With 21 documented cases, it typically affects the buccal and labial mucosa, tongue, and palate. The cause remains unclear, but Fordyce granules, sebaceous structures in oral mucosa, may play a role in malignancy. IOSC often presents as a painless lump, leading to delayed diagnosis and increased risks of recurrence and metastasis. Early detection and treatment are crucial. Wide local excision (WLE) is the primary treatment, while radiotherapy (RT) is an option for patients unfit for surgery, unwilling to undergo it, or requiring palliative care for advanced cases. RT may also be used pre- or postoperatively to reduce recurrence risks. Cryotherapy and chemotherapy are not standard treatments for IOSC. Regular follow-up is essential for long-term management and to monitor for potential recurrence. The current review provides an updated overview of IOSC, focusing on its clinical presentation, risk factors, pathogenesis, diagnostic approaches, treatment strategies, and prognosis, aims to emphasize the importance of early intervention and a multidisciplinary approach to optimize outcomes.

In vitro cytotoxicity (irritant potency) of toothpaste ingredients.

This study aimed to determine the cytotoxicity (irritant potency) of toothpaste ingredients, of which some had known to have sensitizing properties. From the wide variety of toothpaste ingredients, Xylitol, Propylene glycol (PEG), Sodium metaphosphate (SMP), Lemon, Peppermint, Fluoride, Cinnamon, and Triclosan and Sodium dodecyl sulphate (SDS) have been selected for evaluation of their cytotoxic properties. Reconstructed human gingiva (RHG) were topically exposed to toothpaste ingredients at different concentrations. The compound concentration resulting in 50% cell death (EC50) and 10% cell death (EC10) was determined by the MTT assay. Detrimental effects in tissue histology were observed by hematoxylin & eosin staining of tissue sections followed by microscopy. While Xylitol, PEG, and SMP did not appear to affect cell viability or tissue histology, the concentrations of Lemon, Peppermint, Cinnamon and SDS present in toothpastes exceeded the EC50 value and resulted in clear detrimental effects in tissue histology, indicating that they could harm the oral mucosa. Triclosan and Fluoride concentrations in the tested toothpastes exceeded the EC10 value but remained below the EC50 value with no clear detrimental effects in tissue histology. Manufacturers are encouraged to comply with higher standards of quality and safety for toothpaste.

A Decadal Bibliometric Analysis on the Therapeutic Strategies in Oral Lichen Planus.

Oral Lichen Planus (OLP) is a common chronic inflammatory autoimmune illness that mostly affects the oral mucosa but may also affect other mucous membrane. It has higher prevalence in female patients of fourth to sixth decade of life with reticular being the commonest clinical variant. Clinical assessment, patient history, biopsy findings, and immunofluorescence were used to diagnose OLP. This study aimed to assess research publication trends in therapeutic strategies in the treatment of OLP, examining publication growth, country and institution contributions, and collaborative networks. Using the Dimensions and Lens.org databases with Boolean operators combined the keywords a total of 40,046 peer-reviewed international publications were initially assessed. The article was selected from 2014 to December 2023. Through rigorous application of inclusion and exclusion criteria using an advanced search, a subset of 134 papers emerged to meet the high relevance standards. This subset, constituting a representative sample, was selected for in-depth bibliometric analysis. The result shows a clear upward trend in the number of publications, with a notable increase in 2018. After 2018, there is decrease in the number of publications, but it has an upward trend, reaching a peak of 215 in 2022. Chaitanya Nallan CSK leads the list of authors with four publications and a respectable total citation count of 12. Cairo University is the leading institution in this data set, with the 8 number of publications and 11 citations. The analysis revealed that at the top of the list is the "Egyptian Dental Journal" from Egypt, with six publications, four citations, and a link strength of two. In the second position is "BMC Oral Health" from the United Kingdom, with five publications, one citation, and a link strength of three. This study offers valuable insights for future research, clinical practice, and policy decisions.

Characterization of Buccal Mucosa as Barrier for Drug Absorption; A Mechanistic Study via Solvent Uptake and Model Drug Permeation Studies

Characterization of Buccal Mucosa as Barrier for Drug Absorption; A Mechanistic Study via Solvent Uptake and Model Drug Permeation Studies

Efficacy and potentiality of vitamins and micronutrients oral sprays supplementation (review)

Introduction. Modern pharmaceutical development enables to introduce into practice more than ever new active ingredients delivery systems and forms enhancing actives activity compared to traditional approach (methods). A nowadays pace of life often providing improper feeding and micronutrients intake imbalance leads to necessary administration of micronutrient additional doses in the form of different pharmacies. Over the last years vitamins and minor nutrient elements spray forms are becoming more attractive for introduction into pharmaceutical practice. These dosage forms are characterized by the production availability, usability, easy dosage and sufficiently high bioavailability for both normal patients and ones having gastrointestinal tract diseases and other problems connecting with the food consumption and digestion.Text. Drug delivery by oral mucosa attracts more attention due to its potential advantages compared to other methods. Until recently this administration way was considered mainly for topical application. However, in recent years number of developments connecting with oral cavity application as a portal for delivery of drugs active ingredients, vitamins and micronutrients into systemic blood has kept steadily growing. Diverse forms of oral drugs for sublingual and buccal administration have been developed by many scientific and clinical teams. Spray forms among them are of particular interest as the most economically viable and easy to use. Most of these developments deal with vitamins D and B12, which arises from the acutest problems of their deficiency among global population, on the one hand, and low bioavailability due to negative effects by dietary intake, gastrointestinal tract health condition and other factors, on the other hand. Other micronutrients such as thiamin, niacin, pyridoxin, ascorbic acid, coenzyme Q and iron are examined and launched into the market in an oral spray form for sublingual application.Conclusion. The current results of development and comparison study of micronutrients oral forms, in particular, randomized controlled trial data indicate a sublingual administration efficiency which either is similar to or exceeds traditional administration ways.

Significant risk factors for oral mucosa cancer in the Altai Krai population

Relevance. Squamous cell carcinoma of the head and neck, including oral and oropharyngeal cancer, ranks as the seventh most common cancer worldwide, contributing to over 660,000 new cases and 325,000 deaths annually. Understanding the interplay of adverse factors, their association with disease development, and the creation of mathematical risk prediction models can play a crucial role in enhancing screening efforts and advancing primary prevention of malignant neoplasms.Objective. This study aimed to identify significant risk factors for oral mucosa cancer in the Altai Krai population and to develop a mathematical model for disease risk assessment.Material and methods. The study included 184 patients diagnosed with oral mucosa cancer, along with a control group of 416 healthy volunteers with no history or current diagnosis of oncological diseases. A total of 39 potential risk factors were analyzed across all participants. Statistical analyses were conducted to identify region-specific risk factors for Altai Krai. Binary logistic regression and ROC analysis were used to construct the risk prediction model.Results. Comparative analysis between the patient group and the control group revealed differences in 19 of the 39 evaluated factors. However, the final risk prediction model identified five key factors significantly influencing disease development. Advanced age, smoking status, the number of cigarettes smoked, and alcohol consumption were found to substantially increase the risk of oral mucosa cancer, while engagement in intellectual work-related activities was associated with a reduced risk. The resulting formula demonstrated high predictive accuracy, with an Area Under the ROC Curve (AUC) of 0.91, a standard error of 0.024, and a 95% confidence interval of 0.856–0.955 (z-statistic: 17.50; significance level: P (area = 0.5) < 0.001). Both the sensitivity and specificity of the model were high.Conclusion. The developed risk assessment model shows great promise for helping screen and diagnose oral cancer in the Altai Krai population. This tool could give dentists and healthcare providers a simple, practical way to identify individuals at risk early by using well-established risk factors.

The impact of vapes and electronic cigarettes on the oral mucosa: a literature review

Relevance. Over the past few years, electronic cigarettes have gained popularity as an alternative means of nicotine consumption. In Russia, the number of individuals using vapes has reached 4.2 million. According to studies by Russian addiction specialists, 8.5% of adolescents aged 13–15 in Russia use electronic cigarettes, with prevalence rates of 10.3% among boys and 6.8% among girls. The oral tissues, particularly the mucosa, are the first point of contact with electronic cigarettes, directly exposed to the adverse effects of vape liquid components.Objective. To investigate the effects of vapes on oral health, with a particular focus on the oral mucosa and associated structures.Materials and methods. A total of 37 sources were selected for analysis, including 16 articles from the eLibrary database, 5 from CyberLeninka, and 4 from databases such as Wiley, Taylor & Francis Online, and ScienceDirect. The search was conducted using the query "the impact of vapes on the oral mucosa" and keywords such as "electronic cigarette", "vapes," "oral health," "oral mucosa", and "smoking," in both Russian and English. Preference was given to materials published between 2014 and 2023 that directly addressed the topic, described conducted studies, and provided conclusions. Additionally, a manual search was performed within the reference lists of relevant articles to identify suitable publications.Results. A review of the literature revealed that electronic cigarettes adversely affect oral health, causing irritation of the mucosa and periodontium, salivary gland disorders, demineralization of dental hard tissues, and alterations in the pH of oral fluids.Conclusion. The impact of vapes on oral health remains insufficiently studied. Further experiments and long-term analyses are necessary to more accurately assess the effects of vape chemical components on oral tissues.

Paraneoplastic pemphigus involved oral mucosa only: a case report and literature review

Paraneoplastic pemphigus (PNP) is a rare and potentially fatal autoimmune disease that primarily affects the mucocutaneous tissues. Here we present the clinical features of a patient with the lichenoid variant of PNP involving the oral mucosa only. The patient exhibited clinical manifestations resembling both lichen planus and pemphigus, yet these lesions remained unresponsive to corticosteroid therapy. A chest computed tomography (CT) scan revealed Castleman disease. Following surgical removal of the tumor, the patient’s oral mucosa healed completely, with no recurrence observed in a 4-year follow-up period. These findings emphasize the importance of considering PNP as a potential diagnosis in patients with refractory oral erosions displaying lichen planus-like and pemphigus-like features, particularly when unresponsive to corticosteroid therapy. A thoracic-abdominal-pelvic CT scan is recommended to facilitate accurate diagnosis and appropriate treatment.

Mucoadhesive Drug Delivery System

Mucoadhesive drug delivery systems engage with the mucus layer on the mucosal epithelial surface, interacting with mucin molecules and prolonging the duration of the dosage form at the absorption site. Mucoadhesive drug delivery systems are components of controlled drug delivery systems as well as novel drug delivery systems. Administering drugs through the absorptive mucosa in various readily accessible body cavities such as ocularnasal, buccal, rectal, and vaginal mucosa presents notable benefits compared to peroral administration for systemic effects. Mucoadhesive drug delivery systems extend the duration the dosage form remains at the application or absorption site. They promote close interaction between the dosage form and the underlying absorption surface, thereby enhancing the drug's therapeutic effectiveness.

Bullous Lichen Planus Treated with Adalimumab: A Case Report

Introduction: Bullous lichen planus is a rare variant of lichen planus that is characterized by vesiculo-bullous lesions developing in the setting of pre-existing LP lesions with a burning and painful feeling. Bullous lichen planus treatment is difficult since so few examples of the condition have been documented in the literature. Case Presentation: A 46-year-old female, presented to our outpatient clinic with pruritic violaceous bullae involving lower extremities and oral mucosa for 8 years. After extensive investigations a diagnosis of bullous lichen planus was made and successfully treated with adalimumab after failure of other treatment options. Conclusion: Adalimumab may represent a promising, efficacious, and safe monotherapy option for the management of bullous lichen planus. The therapeutic value of this novel off-label use should be assessed in controlled clinical trials.

Para-Phenylenediamine-Induced Lichenoid Eruption With Involvement of the Oral Mucosa and Subsequent Contact Leukoderma.

Para-Phenylenediamine-Induced Lichenoid Eruption With Involvement of the Oral Mucosa and Subsequent Contact Leukoderma.

The Cell Cycle Regulatory Proteins p16, CDK4, and PTEN Are Unsuitable as Biomarkers in Oral Melanocytic Lesions.

Melanocytic neoplasms are rare in the oral cavity and represent a diagnostic challenge due to the overlap between benign and malignant lesions. However, their pathogenesis is not fully elucidated. The aim of this study was to evaluate the expression of the cell cycle-related proteins p16, CDK4, and PTEN in oral melanocytic nevi and melanomas. A total of 42 cases of melanocytic nevi and five cases of melanoma underwent immunohistochemical analysis. Cases were scored as 0, 1 (< 5% of positive cells), 2 (6%-50% of positive cells), and 3 (> 50% of positive cells). Statistical significance was set at p ≤ 0.05. Two cases of melanocytic nevi were totally negative for p16 and 95.2% of cases scored 1. For CDK4, 47.6% of the cases scored 2 and 52.4% scored 3. For PTEN, 97.6% of the cases scored 3 and only one case showed a score of 2. All melanoma cases were classified with a score of 2 for p16, and for CDK4 and PTEN, all cases exhibited a score of 3. PTEN and CDK4 were higher expressed when compared to p16 both in melanocytic nevi and melanomas (p < 0.001), and melanocytic nevi showed low expression of p16 when compared to melanomas (p < 0.0001). The findings suggest that these cell cycle-related proteins are not useful biomarkers in melanocytic lesions of the oral mucosa and support the apparent biological distinction between oral and cutaneous lesions.

Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9, SPARC, and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy.

Application of Microneedles for High-Molecular-Weight Dextran Penetration Across the Buccal Mucosa

Objectives: This work aimed at investigating the effect of different microneedle-based strategies on the permeation of high-molecular-weight model molecules (fluorescently labeled dextrans (FDs), 70 and 150 kDa) across the buccal mucosa. Methods: Two different approaches were evaluated: (1) stainless steel microneedles (MNs) of 500 µm height used for tissue pre-treatment; and (2) soluble microneedles of different lengths (150, 500, and 800 µm), made of polyvinylpyrrolidone and FDs, prepared using the solvent casting technique. Porcine esophageal epithelium was used as a model for the buccal mucosa. Results: The application of soluble MNs promoted high-molecular-weight dextran transport across pig esophageal epithelium. The transport was proportional to MN length, with a minimum of 500 µm, regardless of the molecular weight of the FDs. The use of solid MNs of the same length to pre-treat the tissue, followed by the application of a solution of the permeant, did not produce the same effect in terms of onset of permeation, which was found to be much slower. Conclusions: The results obtained show that by applying soluble MNs of appropriate length (500 and 800 µm), the transport of high-molecular-weight dextrans (70 and 150 kDa) across and into the mucosal tissue occurs very rapidly. The multiphoton microscopy analysis confirmed the presence of holes in the tissue and the presence of fluorescein-labeled dextrans.

Efficacy of Tocopherol vs. Chlorhexidine in the Management of Oral Biopsy Site: A Randomized Clinical Trial

Background/Objectives: Chlorhexidine digluconate (CHX) is widely regarded as the gold standard for oral mucosa antiseptic treatments but has been associated with delayed healing, scar formation, microbiome alterations, and fibroblast toxicity. Tocopherol, with its ability to accelerate tissue healing and minimal side effects, has emerged as a potential alternative. This randomized clinical trial aimed to compare the efficacy of topical tocopherol acetate and 0.2% chlorhexidine in managing postoperative pain and wound healing following oral cavity biopsies. Methods: Seventy-seven patients undergoing oral biopsies were divided into two groups: the test group (tocopherol acetate) and the control group (0.2% chlorhexidine). Pain was assessed using VAS (Visual Analogue Scale) scores on days 1 and 6 postoperatively, and wound healing was evaluated through measurements of the biopsy site’s height and width from standardized photographs analyzed with ImageJ. Painkiller use was also documented. The study followed CONSORT (Consolidated Standards of Reporting Trials) guidelines, with ethical approval from the Padua Ethics Committee and registration on ISRCTN. Results: No significant differences were found between the groups in VAS scores, wound dimensions, or painkiller use (p &gt; 0.05). However, significant pain reduction within each group was observed (p &lt; 0.0001). Conclusions: Tocopherol acetate showed comparable efficacy to chlorhexidine, suggesting it could be a viable alternative for postoperative care in oral surgery.

Mandibular hybrid odontogenic tumor.

Hybrid Odontogenic Tumors (HOT) are defined by the presence of two or more independent odontogenic tumors that originate from and affect the same maxillofacial site. The present study is the first case report of a mandibular HOT consisting of Ameloblastoma, Calcifying Epithelial Odontogenic Tumor, and Ameloblastic Fibroma. A 37-year-old otherwise healthy male presented with the chief complaint of swelling in the right mandibular body. On extraoral examination, mild facial asymmetry and stable occlusion were observed. Intraoral examination was significant for an erythematous, sessile, and indurated swelling in the buccal gingiva and mucosa, with ulceration in the lower right cervical pre-molar region. The computed tomography scan indicated a mandibular osteolytic, multilocular, and expansile lesion with areas of bone fenestration extending from the lower left lateral incisor to the right second molar. The patient underwent resection of the lesion through an intraoral approach with a 1cm safety margin. Reconstruction was performed with a microvascularized fibula flap to restore function and achieve an acceptable cosmetic result. The patient is currently at a ten-year follow-up without recurrence. Understanding the pathogenesis and pathophysiology of these complex lesions is necessary to improve comprehension, treatment, and surgical outcomes. Despite the rarity of hybrid lesions, they should be considered in the differential diagnosis, especially in large odontogenic pathologies. Due to microscopic variability, they require multiple biopsies and a thorough examination of the specimens to confirm the co-existence of two or more entities.

Aloin remodels the cell wall of Candida albicans to reduce its hyphal virulence against oral candidiasis

Aloe vera (L.) Burm.f. is a traditional Chinese medicine known for treating various ailments, including fungal infections. Aloin is one of the major components from A. vera, but its antifungal mechanism and therapeutic potential against oral candidiasis are not clear. This study aimed to examine the mechanism of aloin against Candida albicans and its inhibitory activity against oral candidiasis. In this study, we for the first time found that aloin could induce the formation of abnormal hyphae with smaller hyphal diameters and fewer branching points in C. albicans including 11 clinical isolates without growth inhibition. The transcriptome and further cell wall contents analysis indicated that aloin remodeled the cell wall to increase the contents of β-1,3-glucan and furtherly showed an antagonistic effect with micafungin. Aloin also significantly inhibited the cell damage of oral epithelial cells and oral candidiasis in mice infected by C. albicans due to its inhibitory actions on the hyphal development and expressions of virulence factors, including candidalysin (coded by ECE1). Our results suggest that aloin is a promising antifungal agent for controlling candidiasis and targeting hyphal development and pathogenesis represents a practical strategy for developing new antifungal drugs.Key points• Aloin remodels the C. albicans cell wall to form avirulent hyphae.• Aloin inhibits C. albicans infections in oral epithelial cells and mouse mucosa without toxicity.• Aloin is a promising antifungal agent with therapeutic potential against C. albicans infections.Graphical

Clinical patterns and outcomes of patients affected by primary malignant melanoma of the oral mucosa: A European multicenter retrospective chart review.

The purpose of this European multicenter study was to describe and assess the characteristics, diagnosis, management, and recurrence of oral malignant melanoma at different European oral and maxillofacial surgery centers. This study was based on a systematic computer-assisted database that allowed the recording of data for all primary oral mucosal melanomas treated in the involved surgical units across Europe between January 1, 2003 and December 31, 2022. The following data were recorded for each patient: gender, age, site, TNM staging, metastases, symptoms, imaging features, histopathological features, treatment, complications, recurrence, follow up, and survival. A total of 29 patients (15 females, 14 males) with a primary oral mucosal malignant melanoma fulfilled the inclusion criteria. The mean age was 64.4 years. The most frequent primary site was the vestibular and crestal maxillary gum. Nineteen patients had been diagnosed with a T3 oral melanoma, nine patients with a T4a oral melanoma, and one patient with a T4b neoplasm. Three patients had distant metastases at diagnosis. Clinically, the most frequently observed clinical features were hyperpigmentation, nodular appearance, ulceration, and hemorrhage. Among the 27 surgical cases, radical/clear margins were obtained in 24 cases, non-radical/invaded margins were obtained in two cases, while in one case a non-specific result of margin positivity was found. The overall 2-year survival was 62%. The 2-year disease-free survival was 52%. Oral mucosal melanoma is an aggressive and often asymptomatic malignancy. The overall long-term survival for patients with oral mucosal melanoma is poor, with a high rate of distant metastasis, independently from the performed treatment. Prevention and early diagnosis could be crucial to improving the disease-free survival of patients with oral mucosal melanomas.