Background Recurrent aphthous stomatitis (RAS) is a chronic oral ulcerative condition with an elusive etiology that is associated with excruciating pain. Psychological factors have been suspected as a possible risk factor in its onset and development. Depression, anxiety, and stress play pivotal roles in how people experience pain. Hence, we aimed to explore the relationship between depression, anxiety, stress, and the severity of pain perceived due to recurrent ulcers in RAS patients. Materials and methods A cross-sectional comparative study was conducted on 248 patients, comprising 124 diagnosed with RAS and 124 healthy subjects without this oral condition. Patients from both of these groups were matched with regard to age and sex and recruited over a period of one year from a dental hospital in Bengaluru, India. Patients with any other oral lesions, painful oral conditions, or systemic and psychological illnesses were excluded. Depression, anxiety, and stress were assessed in these patients using the Depression Anxiety Stress Scale 21 (DASS-21). Utilizing a Visual Analog Scale, ulcer-related pain was assessed in patients with RAS. The data were analyzed using the chi-square test and Pearson\'s correlation test in IBM SPSS Statistics for Windows, Version 26.0 (released 2019, IBM Corp., Armonk, NY). Results The chi-square analysis showed that participants with RAS showed a statistically significant higher prevalence of extreme stress (n = 39, 31.5%), extreme anxiety (n = 82, 66.1%), and depression (n = 38, 30.6%) as opposed to those without this oral condition. A moderately positive correlation was observed in the Pearson\'s test between the severity of pain experienced and stress and anxiety (r = 0.65 and 0.60, respectively, p < 0.05), while a mild positive correlation was observed between the severity of pain and depression (r = 0.35, p < 0.05). Conclusion Depression, anxiety, and stress influenced the severity of pain in these lesions, dictating the need for a holistic approach that integrates psychological interventions in the management of such chronic oral conditions with psychological links.

UNASSIGNED: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach.
UNASSIGNED: The Elsevier\'s Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country.
UNASSIGNED: A list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries.
UNASSIGNED: This report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

OBJECTIVE: The purpose of this study was to determine the therapeutic effect of the Punica granatum (PG) flower on recurrent aphthous stomatitis in comparison with corticosteroid therapy.
METHODS: This cross-over randomized clinical trial was conducted on the patients who had been referred to Shiraz Dental School for their RAS in 2021. All the participants used both P. granatum flower tablets and Triadent a month apart for wash-out time and all compared themselves. In the experimental group, 30 patients received pomegranate flower tablets, three tablets daily, for 6 days. In the control group, oral paste Triadent has been prescribed three times a day for 6 days. The visual analog scale (VAS) and the size of RAS were evaluated on Days 0-6. Data were analyzed by SPSS version 21. The Wilcoxon test was used.
RESULTS: The mean age of participants was 27.8 ± 14.77 years old. In this study, 15 patients (50%) were men and 15 patients (50%) were women. The mean value of VAS after using prescribed treatment in both evaluated groups on all days was significantly different such that the VAS values were lower for PG flower tablets than Triadent (p value < 0.05). The size of oral lesions in participants who used PG flower tablets was significantly less than those who used Triadent on all evaluation days (p value < 0.05) except on Day 1 (p value = 0.29). The descending slope of VAS from Days 1 to 6 for both Triadent and PG flower tablet users was significant and noticeable. (p value < 0.05).
CONCLUSIONS: According to the result of this study, both P. granatum flower tablet and Triadent are useful in reducing the size, period of healing, and VAS of patients with RAS, but the PG flower tablet is more effective.

Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).

Introduction Recurrent aphthous stomatitis (RAS) is a common ulcer of idiopathic etiology but is recurrent, causing painful ulcers in the non-keratinized mucosa. The disease is commonly seen in people aged 10-40 years. The etiology of RAS has yet to be well established, but several risk factors that lead to the development of RAS have been proven in the literature. With an unknown etiology, developing a definitive cure and maintaining disease remission remains challenging. An epidemiological survey will shed some light on the disease\'s prevalence, which could provide insights into disease management. This study aimed to study the prevalence of aphthous stomatitis among the patients visiting the dental outpatient services of a dental college in South India. The objectives were to discover the different subtypes of aphthous stomatitis and the age predominance of the type of ulcer. Materials and methods The data was collected from the case records of Saveetha Dental College and Hospitals, Chennai, India, dated from June 2019 to June 2023. The age and gender of the patients with RAS were recorded. The details collected were systematically arranged in an Excel sheet (Microsoft Corporation, Redmond, Washington, United States) and further analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States) and chi-square tests were run to check for statistical significance. Results A total of 1,44,056 patients visited the Dental OPD during the study period. Of these, 1115 patients had RAS. When the data was analyzed, there was a three-fold increase in the occurrence of RAS during the coronavirus disease 2019 (COVID-19) pandemic, which was statistically significant (p=0.043). The most commonly affected age group was 26-40 years. Among the clinical variants of RAS, it was found that 82.5% of RAS patients had a minor variant of aphthous stomatitis. Conclusion This study shows the prevalence of different types of aphthous stomatitis, wherein we noticed that the minor clinical variant was the most common, followed by the major variant. The lesions were more commonly seen in women. However, the age group most commonly affected was 26-40 years.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is a frequent chronic disease of the oral cavity that affects 5-25 % of the population with a plethora of predisposing factors. Despite its equivocal etiology, immune alterations, hematologic deficiencies and oxidative stress has been reported to be significant etiologic factors. Stress and obesity are other environmental factors that have been studied to understand associations with RAS.
OBJECTIVE: This study investigated the association of stress, hematologic parameters, oxidative indices and other selected salivary factors in a case control study on RAS Methods: Twenty-two participants each in both case and control groups were recruited with saliva and serum samples collected from them after a self-administered Recent Life Changing Questionnaire (RLCQ). OHI-S and salivary flow rate (SFR) were calculated with selected hematologic parameters and oxidative indices such as Total oxidant (TOS) and anti-oxidant (TAS) levels and their ratio - Oxidative Stress Index (OSI). Anti-oxidative indices of Ferric-Reducing Antioxidant Power (FRAP) and Glutathione Peroxidase Activity (GsPHx) were also estimated.
RESULTS: The RAS group had a significantly higher RLCQ scores at a median of 145 more than the control (57.5). There was no significant in their obesity indices, however there was a significant higher mean in the ESR (p< 0.0001) and Vit B12 (p = 0.0001); OHI-S was also significantly higher in the RAS group with a median of 1.65. Both the salivary and serum TOS were significantly higher in the RAS (10.0 ± 3.8, 15.4 ± 8.9) compared to the control group (7.92 ± 1.49, 9.56 ± 3.5). GsPHx activity was significantly higher in both the saliva and serum in the control group (0.08 ± 0.08, 0.19 ± 0.11) while nil significant difference was found in the FRAP activity. Regression showed most important variables to be the salivary GsPHx activity, followed by serum OSI and GsPHx activity.
CONCLUSIONS: The oxidative indices of TOS, TAS and GsPHx can serve as significant biomarkers in detecting RAS. This further corroborates the role of immune dysregulation in the etiology and predisposition to RAS.

UNASSIGNED: To assess and compare the efficacy of dexamethasone ointment with triamcinolone acetonide, the gel form, in the treatment of minor recurrent aphthous stomatitis (RAS).
UNASSIGNED: This was a randomized clinical trial of 60 patients of either sex with clinically diagnosed RAS who were randomly divided into two groups-the dexamethasone ointment group (Group I) and the triamcinolone acetonide gel group (Group II). Patients were asked to apply the gel three times a day on each ulcer. Estimation of the efficacy of gel was done based on the time required for regression in pain, size, and number of ulcers.
UNASSIGNED: The results showed there was a significant difference in size, pain, number, and duration of ulcers in Group I and Group II within 7 days. However, in both groups, no significant difference was noted in the treatment of RAS.
UNASSIGNED: Dexamethasone ointment was found to be efficient in this treatment and was safe as evaluated using clinical assessments.

Background The increased rate of apoptosis is one of the major causes of ulcer formation. A variety of factors can influence the rate of apoptosis. Ceramide (CER) is one such factor that has been proposed to play a role in signaling apoptosis induced by extracellular agents. Recurrent aphthous stomatitis (RAS) is a common condition that initially presents in children or adolescents. Multiple recurrent small, round, or ovoid ulcers with erythematous haloes and circumscribed margins are its characteristic features. Its pathogenesis is still a mystery. Ceramide synthase 1 (CERS1) aids in the production of C18 CER. Although the role of CERS1 in aphthous is well understood, its possible intricate role in pathogenesis remains unknown. Aim To evaluate the expression of salivary CERS1 in patients with RAS and healthy individuals. Materials and methods 30 patients were included in the present study. Ethical clearance for this study was obtained, and there were no gender or age limits for enrollment. After obtaining informed consent, 30 salivary samples were collected from patients with RAS (n=15) and from healthy individuals (n=15). Enzyme-linked immunosorbent assay (ELISA) was performed using the CERS1 kit by MyBioSource Inc (San Diego, USA) and the results were recorded. The Chi-square test and Independent t-test were used for statistical analysis with SPSS v23.0 (IBM, Chicago, USA) with a significant p-value of <0.05. Results CERS1 expression was identified in the saliva of all participants. There was a decrease in the salivary CERS1 level in RAS patients (7.6 +/- 2.0 pg/ml) when compared to healthy individuals (8.3 +/- 1.8 pg/ml) but it did not achieve statistical significance. Conclusion We found that salivary CERS1 levels decreased in RAS patients. More research is required to understand CERS1\'s pathogenetic role.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is an inflammatory lesion of the oral mucous lining, accounting for 5 to 25% of the chronic oral lesions. Studies have suggested that RAS patients have increased oxidative stress (OS) and impaired antioxidant capacity, and non-invasive screening using saliva assessment of oxidative stress and antioxidant capacity may be beneficial in RAS.
OBJECTIVE: This study determined total salivary antioxidant concentration and compared it to the total serum antioxidant levels in patients with RAS and controls.
METHODS: This was a case-control study of subjects with RAS and without RAS. Unstimulated mid-morning saliva was collected using the spitting method, and venous blood was collected into a plastic vacutainer. Saliva and blood samples were assayed for total oxidative stress (TOS), total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP) and glutathione.
RESULTS: A total of 46 subjects, 23 with RAS and 23 healthy controls, participated in the study. Twenty-five (54.35%) were males, and 21(45.65) were females aged 17 to 73 years. We identified an increase in salivary and serum TOS (10.06 ± 7.49, 8.26 ± 2.18/ 15.00 ± 8.92, 9.36 ± 3.55µmol/L) and OSI while the TAC (16.85 ± 1.97, 17.07 ± 2.36/17.07 ± 2.36, 2.97 ± 0.29mM/L) and significantly GSH (0.02 ± 0.02, 0.10 ± 0.02/0.10 ± 0.02/0.19 ± 0.11 µmol/ml) were decreased in serum and saliva of the RAS group compared to controls respectively. In addition, there were positive correlations between salivary and serum levels of FRAP r=0.588, p= 0.003 and glutathione r=0.703, p<0.001 in RAS subjects and controls.
CONCLUSIONS: Oxidative stress is associated with RAS, and saliva can be used as a biological marker for glutathione and FRAP.
BACKGROUND: La stomatite aphteuse récurrente (SAR) est une lésion inflammatoire de la muqueuse buccale qui représente 5 à 25 % des lésions buccales chroniques. Des études ont suggéré que les patients atteints de stomatite aphteuse récurrente présentent un stress oxydatif (SO) accru et une capacité antioxydante altérée, et qu’un dépistage non invasif utilisant l’évaluation salivaire du stress oxydatif et de la capacité antioxydante pourrait être bénéfique dans la stomatite aphteuse récurrente.
OBJECTIVE: Cette étude a déterminé la concentration totale d’antioxydants dans la salive et l’a comparée aux niveaux totaux d’antioxydants dans le sérum chez des patients atteints de SRA et chez des témoins.
UNASSIGNED: Il s’agit d’une étude cas-témoins portant sur des sujets atteints ou non du syndrome respiratoire aigu sévère. De la salive non stimulée a été recueillie en milieu de matinée par la méthode du crachat, et du sang veineux a été prélevé dans un vacutainer en plastique. Les échantillons de salive et de sang ont été analysés pour déterminer le stress oxydatif total (TOS), la capacité antioxydante totale (TAC), le pouvoir antioxydant réducteur ferrique (FRAP) et le glutathion.
UNASSIGNED: Au total, 46 sujets, 23 atteints de SRA et 23 témoins sains, ont participé à l’étude. Vingt-cinq (54,35 %) étaient des hommes et 21 (45,65) des femmes âgés de 17 à 73 ans. Nous avons identifié une augmentation des TOS salivaires et sériques (10.06 ± 7.49, 8.26 ± 2.18/ 15.00 ± 8.92, 9.36 ± 3.55µmol/L) et de l’OSI tandis que le TAC (16.85 ± 1.97, 17.07 ± 2.36/17.07 ± 2.36, 2. 97 ± 0.29mM/L) et significativement le GSH (0.02 ± 0.02, 0.10 ± 0.02/0.10 ± 0.02/0.19 ± 0.11 µmol/ml) ont été diminués dans le sérum et la salive du groupe RAS par rapport aux contrôles respectivement. En outre, il y avait des corrélations positives entre les niveaux salivaires et sériques de FRAP r=0,588, p= 0,003 et de glutathion r=0,703, p<0,001 chez les sujets RAS et les témoins.
CONCLUSIONS: Le stress oxydatif est associé au SAPR et la salive peut être utilisée comme marqueur biologique pour le glutathion et la FRAP.
UNASSIGNED: Stomatite aphteuse récurrente, Antioxydants, Salive, Stress oxydatif.

The death of oral keratinocytes is a crucial step in the emergence of recurrent aphthous stomatitis (RAS, also known as aphthae or aphthous ulcers). Since there are no experimental models available to research aphthous ulcers, little is understood about this process. We hypothesize that saliva can be a data bank of information that offers insights on epithelial damage.
In this case-crossover study, we assessed the salivary proteome of patients with RAS (n = 36) in the presence and absence of ulcers using discovery proteomics and bioinformatics. Additionally, we contrasted these patterns with those of healthy individuals (n = 31) who had no prior aphthous ulceration.
Salivary proteome showed that during the ulcerative phase, controlled cell death was downregulated. Due to its ability to distinguish between individuals with and without ulcers, the ATF6B protein raises the possibility that endoplasmic reticulum (ER) stress is responsible for the damage that leads to the death of oral keratinocytes. The high abundance of TRAP1 and ERN1 matches with this biological discovery. The type of death is immunogenic, according to the functional data found in a cell death database.
We identified a cellular process that can lead to the death of oral keratinocytes in the etiopathogenesis process of RAS. Future studies should be conducted to identify what is responsible for the increase in ER stress signaling that would lead to an anti-cell death response.