Systemic and local effect of oxidative stress on recurrent aphthous stomatitis: systematic review.

Recurrent aphthous stomatitis (RAS) is a chronic and recurrent inflammatory disease of the mouth. It is characterised by the appearance of painful ulcers in the oral mucosa. RAS is believed to be a multifactorial disease with genetic predisposition, environmental factors and alterations in the immune system. Oxidative stress, caused by an imbalance between free radicals and the antioxidant system, also appears to be involved in the pathogenesis of RAS. Several risk factors, such as smoking, iron and vitamin deficiency and anxiety, may contribute to the development of the disease. Understanding the underlying mechanisms may help in the prevention and treatment of RAS. We searched PubMed, Scopus and Web of Science databases for articles on oxidative stress in patients with RAS from 2000 to 2023. Studies analysing oxidant and antioxidant levels in the blood and saliva of RAS patients and healthy controls were selected. Of 170 potentially eligible articles, 24 met the inclusion criteria: 11 studies on blood samples, 6 on salivary samples and 7 on both blood and salivary samples. Multiple oxidative and antioxidant markers were assessed in blood and saliva samples. Overall, statistically significant differences were found between RAS patients and healthy controls for most markers. In addition, increased oxidative DNA damage was observed in patients with RAS. Patients with RAS show elevated levels of oxidative stress compared to healthy controls, with a significant increase in oxidative markers and a significant decrease in antioxidant defences in saliva and blood samples.

Oral mucosal diseases and psychosocial factors: progress in related neurobiological mechanisms.

The aetiology of oral mucosal diseases, such as recurrent aphthous ulcer (RAU), oral lichen planus (OLP) and burning mouth syndrome (BMS), involves many factors, and it remains difficult for clinicians to effectively relieve disease symptoms and formulate coping strategies. With the rapid development of psychology, the role of mental and psychological factors in RAU, OLP and BMS has gradually attracted researchers attention, but the specific mechanism has not been completely determined. This narrative review describes the potential neurobiological mechanism of oral mucosal diseases and detailed psychological factors after introducing relevant research into psychological factors and oral mucosal diseases. Future research strategies and innovations needed to understand and treat oral mucosal diseases and psychological factors, as well as how to prevent oral mucosal diseases by regulation of the neuroendocrine system, are also discussed.

The Power of Licorice (Radix glycyrrhizae) to Improve Oral Health: A Comprehensive Review of Its Pharmacological Properties and Clinical Implications.

Licorice (Radix glycyrrhizae) is a plant root extract widely used in various applications, including cosmetics, food supplements, and traditional medicine. It has a long history of medicinal use in different cultures due to its diverse pharmacological properties. Licorice has traditionally been used for treating gastrointestinal problems, respiratory infections, cough, bronchitis, arthritis, and skin conditions. In recent years, the potential therapeutic benefits of licorice for oral health have gained significant interest. This paper aims to provide a comprehensive review of the effects of licorice extracts and their bioactive components on common oral diseases such as dental caries, periodontitis, halitosis, candidiasis, and recurrent aphthous ulcers. The chemical composition of licorice has shown the presence of several bioactive compounds such as glycyrrhizin, glabridin, isoliquiritigenin (ISL), and licochalcone exhibiting various pharmacological activities, including anti-inflammatory, antimicrobial, antioxidative, and immunomodulatory effects. Interestingly, in certain patients, licorice has shown a promising potential to inhibit the spread of viruses, prevent biofilm formation, reduce inflammation, boost immune responses, alleviate pain, and exert antioxidative effects. In this review, we provide a brief overview of the current understanding of licorice's therapeutic benefits in the treatment of oral ailments, emphasising its potential as an alternative treatment option for oral diseases. Further research is warranted to explore its efficacy, safety, and clinical applications using placebo-controlled clinical trials.

Formulation and Evaluation of Prednisolone Sodium Metazoate-Loaded Mucoadhesive Quatsomal Gel for Local Treatment of Recurrent Aphthous Ulcers: Optimization, In Vitro, Ex Vivo, and In Vivo Studies.

This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was conducted to address the impact of independent variables QAS type (X1), QAS to CHO molar ratio (X2), and sonication time (X3). The dependent variables were particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3), entrapment efficiency percent (EE%; Y4) and percent of drug released after 6 h (Q6%: Y5). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases.

Atorvastatin mucoadhesive tablets in the management of recurrent aphthous stomatitis: a randomized clinical study.

BACKGROUND: Aphthous stomatitis is one of the most common oral mucosal diseases. Due to the commonness of recurrent aphthous stomatitis and considering the anti-inflammatory, analgesic, and tissue regenerative properties of atorvastatin and the lack of a study on the effect of statins on minor recurrent aphthous stomatitis, this study investigates the effect of atorvastatin mucoadhesive tablets as a topical treatment on reduction of symptoms and duration of this disease. METHODS: This study is a randomized, double-blinded clinical trial. Patients were divided into two groups, atorvastatin and, placebo; each of the patients received three mucoadhesive tablets daily in the morning, noon, and night. Finally, the patients were examined on days 0 (baseline), 3, 5, and 7 to determine the diameter of the inflammatory halo. The VAS scale was used to evaluate pain intensity for up to 7 days after each meal. The data was entered into SPSS 24 software and analyzed. RESULTS: The halo diameter did not significantly differ between the two groups on baseline (P > 0.05). However, on the study's third, fifth, and seventh days, the difference between the two groups was remarkable, so in the atorvastatin group, the size of the lesions decreased in shorter healing time (P < 0.05). In addition, the patient's pain intensity (VAS) also showed a significant decrease in the atorvastatin group except on the first, second, and seventh days of the study (P < 0.05). CONCLUSION: Atorvastatin mucoadhesive tablets effectively reduce the pain of patients with minor recurrent aphthous stomatitis and reduce the size and healing time of the lesions, so their application should be considered in treating minor recurrent aphthous stomatitis. The present study was approved by the Medical Ethics Committee of Mazandaran University of Medical Sciences with the ethics code IR.MAZUMS.REC.1400.8346. Also, this study received code IRCT20170430033722N4.

Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial.

BACKGROUND: Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU. METHODS: A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14). RESULTS: None of the subjects exhibited allergic reactions or side effects. Their vital signs and blood parameters were stable before and after the 7-day CBD intervention. CBD and TA significantly reduced ulcer size more than placebo at all time points. The erythematous size reduction was higher in the CBD intervention than the placebo on day 2, while TA reduced the erythematous size at all time points. The pain score in the CBD group was lower compared with placebo on day 5, whereas TA reduced pain more than placebo on day 4, 5, and 7. The subjects receiving CBD reported higher satisfaction than placebo. However, the OHIP-14 scores were comparable among the interventions. CONCLUSIONS: Topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without side effects. CBD exerted anti-inflammatory effects in the early stage and an analgesic effect in the late RAU stage. Thus, topical 0.1% CBD might be more appropriate for RAU patients who decline to take topical steroids, except for cases where CBD is contraindicated. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR) Number TCTR20220802004. Retrospectively registered on 02/08/2022.

Detection of the peripheral blood antigens and clinical value in recurrent aphthous ulcer: A cross-section study.

Abstract Background/purpose: Recurrent aphthous ulcer (RAU) is one of the most common diseases of oral mucosa, which is generally believed to be related to immunity, though the etiology is still unclear. It is suspected that allergies are directly related to RAU. So we sought to explore the relationship between hypersensitivity and RAU. Materials and methods: 40 RAU patients who were in ulceration period and 40 people who were in good health were selected from Jan 2016 to Feb 2017, matched in age and sex. The peripheral blood antigens of 40 RAU patients and 40 healthy people was tested, and serum specific IgE (sIgE) with 6 groups of antigens and total IgE (tIgE) analysis was performed to identify IgE-mediated allergic reaction possibly affecting RAU. We then investigated the food intolerance and IgG levels to discover the correlation between non-IgE mediated allergic reaction and RAU. Results: The positive cases and rate of sIgE in RAU group was higher than that of control, but the difference was not statistically significant (P＞0.05). Positive grade of animal fur scraps (EX1), house dust mixed (HX2) and the serum tIgE concentration of the RAU group were significantly higher than the control group (P＜0.05).The number of food intolerance in RAU group was significantly higher than that in control group (P＜0.05). Conclusion: Our findings suggested certain correlation between RAU and anaphylaxis. Daily contact allergens and food intolerance may be one of the causes of RAU. Moreover, this provides reference value for clinical diagnosis and treatment.

Manifestaciones bucales de la enfermedad de Crohn y colitis ulcerosa en adultos mayores / Oral manifestations of Crohn´s disease and ulcerative colitis in of elderly adults

Objetivo: identificar las manifestaciones clínicas bucales de la enfermedad de Crohn y colitis ulcerosa en pacientes adultos mayores. Métodos: se efectuó un estudio descriptivo transversal con un universo de 50 adultos mayores, previamente diagnosticados por los especialistas gastroenterólogos, y prescritos con enfermedad de Crohn y colitis ulcerosa. Estos, confirmados por los hallazgos clínicos, histopatológicos y endoscópicos, remitidos a consulta estomatológica del Policlínico de Especialidades del Hospital Clinicoquirúrgico Universitario "Saturnino Lora Torres" de Santiago de Cuba, entre marzo de 2019 y marzo de 2020, practicándose el examen intrabucal, descripción de las lesiones bucales y su diagnóstico clínico. Para la recolección del dato primario se confeccionó un modelo con las variables: edad, sexo, enfermedad inflamatoria intestinal, localización anatómica, signos y síntomas clínicos orales en ambas patologías. Se creó una base de datos en SPSS versión 22.0 en Windows para el procesamiento y análisis de la información, usándose la técnica estadística descriptiva y agrupándose los datos en frecuencias absolutas y relativas. Resultados: en la serie resaltaron las personas de sexo femenino y el grupo de edades de 60 a 74 años, la pioestomatitis vegetante fue el signo bucal específico más común y la úlcera aftosa recurrente la lesión inespecífica de mayor predominio en ambas patologías. El dolor, el síntoma clínico de mayor afectación y el dorso de lengua el sitio de mayor predilección para su instalación. Conclusiones: las expresiones clínicas bucales más relevantes en pacientes adultos mayores con enfermedad de Crohn y colitis ulcerosa fueron la pioestomatitis vegetante y la úlcera aftosa recurrente.

Objective: Identify the oral clinical manifestations of Crohn´s disease and ulcerative colitis in elderly adults' patients. Methods: a cross-sectional descriptive study was carried out with a universe of 50 older adults previously diagnosed by gastroenterologist specialists, prescribing the presence of Crohn's disease and ulcerative colitis, confirmed by clinical, histopathologica and endoscopic findings, referred to the stomatological consultation of the Specialities Policlinic of the "Saturnino Lora Torres" University Clinical Surgical Hospital of Santiago de Cuba, from March 2019 to the same month of 2020, performing intraoral examination, description of oral lesions and their clinical diagnosis. For the collection of the primary data, a model was made with the variables: age, sex, inflammatory bowel disease, anatomical location, oral clinical signs and symptoms in both pathologies. A database was created in SPSS version 22.0 in Windows for the processing and analysis of the information, using the descriptive statistical technique and grouping the data in absolute and relative frequencies. Results: in the casuistry, females and the age group of 60 to 74 years prevailed, vegetative pyostomatitis was the most common specific oral sign and recurrent aphthous ulcer was the most prevalent non-specific lesion in both pathologies, pain being the most affecting clinical symptom and the back of the tongue is the most preferred site for its installation. Conclusions: the most relevant oral clinical expressions in elderly patients adults with Crohn´s disease and ulcerative colitis were pyostomatitis vegetative and recurrent aphthous ulcer.

A metagenome-wide association study of the gut microbiota in recurrent aphthous ulcer and regulation by thalidomide.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Evaluation of cinnamaldehyde mucoadhesive patches on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND & OBJECTIVE: The use of herbal medicines to treat common oral diseases increases rapidly. Recurrent aphthous stomatitis is one of the most common oral mucosal diseases, which has an unclear etiology and could lead to severe pain and dysfunction. Cinnamaldehyde is a major component of cinnamon bark oil. Biological properties of cinnamaldehyde, such as antioxidant, antitumor, antifungal, cytotoxic, and anti-mutational characteristics, have been identified. Considering the prevalence of recurrent aphthous stomatitis and the importance of using herbal resources for treatment, the present study aimed to evaluate the effect of mucosal adhesive patches containing Cinnamaldehyde on minor recurrent aphthous stomatitis lesions. MATERIAL & METHODS: In this randomized, double-blind clinical trial, patients were divided into two groups. The intervention group received three daily mucosal adhesive patches to be used in the morning, afternoon, and night. The control group also did the same with a placebo. To evaluate the healing and determine the diameter of the lesions, patients were clinically examined on days zero, 3, 5, and 7. The VAS scale evaluated pain at baseline and after each meal for seven days. The Fisher's exact test, t-test, Shapiro Wilk test, Friedman test, and the Mann-Whitney test were used to analyze the data using the SPSS 20 software. RESULTS: There was no statistically significant difference in the mean diameter of the inflammatory lesion and pain intensity in the two groups in the baseline (p > 0.05). However, the ulcer size was significantly reduced in the cinnamaldehyde group on the third, fifth, and seventh days of the study. Except for baseline, the mean pain intensity significantly decreased in the cinnamaldehyde group compared to the placebo group (p < 0.05). CONCLUSION: Cinnamaldehyde mucoadhesive patches effectively reduced and improved aphthous lesions and pain intensity in patients and can be considered a treatment for RAS. REGISTRATION NUMBER: IRCT20180312039060N2-First registration date: 20/07/2018. The present study was registered as a retrospective study.

Combined signatures of serum proteome and transcriptome in patients with recurrent aphthous ulcer.

OBJECTIVES: Recurrent aphthous ulcer (RAU) is a common oral disease with unclear mechanism. This study aimed to explore the serum signatures of RAU patients via proteomic and transcriptomic analysis. METHODS: This study was based on clinical observation. Part of serum was used for clinical tests, while the rest was processed for isobaric tags for relative and absolute quantitation (ITRAQ) labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) combined with microRNA (miRNA) microarrays. Bioinformatic analysis was then used to obtain significant signatures, which was verified by ELISA, qRT-PCR, and dual-luciferase reporter gene assays. RESULTS: Clinical data showed that triglyceride level, white blood cell count, and neutrophils percentage were increased in RAU group, while lymphocytes percentage was decreased. ITRAQ-2D LC-MS/MS identified 22 upregulated and 33 downregulated proteins in RAU group. Simultaneously, miRNA microarrays identified 64 upregulated and 31 downregulated miRNAs. After integrative bioinformatic analysis and verification, three miRNA-protein pairs, mainly involved in oxidative stress and inflammation responses, were obtained. Additionally, the interaction network indicated the crucial role of complement and coagulation cascade pathway in RAU. CONCLUSIONS: Our study revealed that complement and coagulation cascade pathway, oxidative stress, and inflammation responses may act as vital factors in pathogenesis of RAU.

Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment.

Oral aphthosis is a painful inflammatory process of the oral mucosa. Oral aphthous can appear alone or secondary to numerous distinct disease processes. If recurrence occurs frequently, it is called recurrent aphthous stomatitis. The pathophysiology of oral aphthous ulcers remains unclear but various bacteria are part of its microbiology. Three morphological types hold great importance in literature because these types help manage the illness properly. Google Scholar and PubMed databases were used to retrieve the relevant data and information. Different keywords including "Aphthous", "Aphthosis", "Canker sores", "Aphthous stomatitis", "Aphthous ulcer causes", "Aphthous ulcer AND Microbiota" and "Aphthous ulcer AND treatment". The causes for oral aphthous ulcerations are widespread and ranges from localized trauma to rare syndromes, underlying intestinal disease, or even malignant disease processes. A detailed history and thorough examination of systems can assist the physician or dermatologist in defining whether it is related to a systemic disease process or truly idiopathic. Management of oral aphthous ulcers is challenging. For oral aphthous or recurrent aphthous ulcers from an underlying disease, topical medications are preferred due to their minimum side effects. Systemic medications are necessary if the disease progresses. Within the limitation of research and literature provided, it is safe to say that topical corticosteroids are the first line of treatment. Herein, the author discusses the pathophysiology, types, causes, diagnosis, and appropriate treatment ladder of oral aphthous stomatitis as described in the literature.

Management of recurrent aphthous ulcers exploiting polymer-based Muco-adhesive sponges: in-vitro and in-vivo evaluation.

Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.

[Correlation of interleukin-4 gene methylation regulation with the pathogenesis of recurrent aphthous ulcer].

Objetive: To investigate whether the methylation patterns of the interleukin-4 (IL-4) gene promoter changed and whether environmental factors affected the methylation level of IL-4 gene in the peripheral blood of patients with recurrent aphthous ulcer (RAU). Methods: Totally 20 patients, who were diagnosed with RAU, were recruited from May 2018 to May 2019 in the Department of Stomatology， First Hospital of Shanxi Medical University in the study (RAU group), including 12 females and 8 males, with mean age of 16-35 years. During the same period, 20 healthy volunteers matching the age and gender of the RAU group were selected from the medical personnel of the same hospital as the healty control group, including 11 females and 9 males, with mean age of 15-35 years. Peripheral blood samples of two groups were collected and the methylation levels of the IL-4 promoter were detected by bisulfite sequencing PCR (BSP). The IL-4 promoter methylation level of each sample was analyzed by direct sequencing and the IL-4 mRNA level was detected by real-time quantitative PCR. The data obtained were statistically analyzed. Results: The IL-4 gene promoter fragment contained 10 CPG sites from -1400 to -1625 bp. The methylation rates of CPG(-1556), CPG(-1483), CPG(-1479)and 10 CPG sites were significantly higher in RAU group ï¼»(32.0±19.9)%, (53.0±13.4)%, (46.0±19.8)% and (39.3±12.4)%ï¼½ than in healthy control group ï¼»(20.0±3.2)%, (35.5±12.3)%, (28.0±14.4)% and (32.6±5.8)%ï¼½, with statistically significant differences (P<0.05). The relative expression of IL-4 mRNA in the peripheral blood of RAU patients (1.0±0.1) was significantly lower than that of the healthy control group (1.5±0.2) (P<0.01). There was a significant negative correlation between the overall methylation rate of IL-4 gene promoter and the relative expression level of IL-4 mRNA in RAU group (r=-0.494, P<0.05). In the multivariate analysis, smoking, vitamin B12 and folic acid in the RAU group were significantly correlated with the overall methylation rate of the IL-4 gene promoter (P<0.01). Conclusions: The hypermethylation of IL-4 promoter in RAU patients may be related to the reduction of IL-4 gene transcription. Vitamin B12, folic acid and smoking may affect IL-4 gene methylation in peripheral blood of RAU patients.

Lactic acid 5% mouth wash vs Kenalog in Orabase 0.1% for treatment and prophylaxis of recurrent aphthous ulcer.

BACKGROUND: The outcomes of most therapeutic modalities for recurrent aphthous ulcer (RAU) are still unsatisfactory. AIM: To evaluate lactic acid 5% mouth wash vs Kenalog in Orabase for treatment and prophylaxis of RAU. PATIENTS/METHODS: Forty cases with early-onset idiopathic RAU were enrolled in this study. Patients were divided into two equal groups; group A patients had used Kenalog in Orabase twice daily, and group B patients had used lactic acid 5% mouth wash 3 times daily. All patients had used the therapy for 1-2 weeks according to patients' clinical response that was evaluated according to oral clinical manifestations index (OCMI); before therapy, during course of treatments and in follow-up visits. RESULTS: At the ends of both first and second weeks, from beginning of therapy, OCMI was reduced more in group B patients than in group A with statistically significant results. These results revealed that group B achieved more reduction in the size, pain, and healing time of RAU. During the follow-up period, group A showed 40% recurrence rate while group B showed 5% only. CONCLUSIONS: Lactic acid 5% mouth wash is natural, safe, and effective so it is better alternative to corticosteroids for treatment and prophylaxis of RAU without any side effects.

A Study to Assess The Efficacy of Local Application of Oral Probiotic in Treating Recurrent Aphthous Ulcer and Oral Candidiasis.

To study the efficacy of local application of oral probiotics in improving oral health in recurrent aphthous ulcer and oral candidiasis. Eighty patients with diagnosis of recurrent aphthous ulcer and oral candidiasis were included in the study. They were divided into group A = 40 patients (patients treated with oral application of probiotic as an adjuvant) and group B = 40 patients (patients treated without probiotic). Both the groups were divided into two subgroups, group AU and group BU for recurrent aphthous ulcer and group AC and BC for oral candidiasis. Clinical signs and symptoms were assessed at the beginning of the study and at the end of the study. Pregnant or lactating women, patients with localised or systemic diseases such as Steven Johnson syndrome, ulcerative colitis, Behcet's syndrome and patients on chemotherapy or radiotherapy were excluded from the study. Bacillus Clausii, was used as a probiotic in our study. Patients in group A showed significant improvement in erythema (p = 0.001), pain reduction (p = 0.0001), decreased oral thrush (p = 0.006) and burning sensation in the mouth (p = 0.005) on day 5, whereas there was no significant difference on day 10 follow up. The study demonstrated the efficacy and rapidity of response to oral probiotic as an adjuvant in treating aphthous ulcer and oral candidiasis. Hence, oral application of probiotics can be used as an adjuvant in treating various oral pathology.

Salivary cortisol and dehydroepiandrosterone as oral biomarkers to determine stress in patients with recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with a multifactorial etiology. Although psychological stress is an exacerbating factor, the role of salivary stress hormones, cortisol, and dehydroepiandrosterone (DHEA) in this oral disease has not been extensively reported. The study aimed to estimate and compare the salivary cortisol and DHEA levels in RAS patients and healthy control group with the aid of ELISA microplate reader. SUBJECTS AND METHODS: Sixty patients were enrolled in our study, which included 30 patients with clinically diagnosed RAS and 30 healthy controls. Two mL of unstimulated whole saliva was collected and salivary cortisol and DHEA levels were measured using ELISA kit, and the values were read by microplate ELISA reader and recorded in both groups. RESULTS AND CONCLUSION: The mean salivary cortisol and DHEA levels were elevated in the RAS patients compared to the healthy controls and were statistically significant. Salivary cortisol and DHEA can serve as oral biomarkers to determine stress in patients with RAS. However, the present study necessitates further studies with larger sample size and an improved protocol to ascertain the actual role of these presumed oral biomarkers as well as anxiety and stress as triggers in the pathogenesis of RAS.

A Randomized, Double-Blind, Placebo-Controlled Trial on Clinical Efficacy of Topical Agents in Reducing Pain and Frequency of Recurrent Aphthous Ulcers.

INTRODUCTION: Recurrent Aphthous Ulcers (RAU) is one of the most common oral ulcerative Disease of the oral mucosa with high recurrence rate. Standard topical treatment options provide symptomatic relief with few have been found to be effective in treating or relieving the symptoms. AIM: The study aimed to evaluate the clinical efficacy of various topical agents in order to find the better treatment modality so as to decrease the number, size, exudate level and discomfort associated with pain with RAU. MATERIALS AND METHODS: The patients diagnosed with minor recurrent aphthous ulcers fulfilling the inclusion and exclusion criteria were enrolled. All the baseline parameters were measured by the principal investigator. The treatment modality was assigned by generating a randomization list by computer software, double-blinded in consecutively numbered sealed envelopes. The topical treatment modalities that were included: 5% Amlexanox, 0.1% Triamcinolone Acetonide, 20% Benzocaine gel, 100 mg Doxycycline hyclatemixed with denture adhesive and normal saline (20:2:1); The study was placebo controlled in which placebo gel 10 gm was used. The size, no of ulcers, pain, erythema and exudate level were measured by the principal investigator at days 1, 4, 8 and 10. All quantitative variables were estimated using measures of central tendency (mean, median) and measures of dispersion (standard deviation). Qualitative or categorical variables were described as frequencies or proportions. Proportions were compared using Post Hoc Test and N Par Tests. Effectiveness was checked using p-value (< 0.005). RESULTS: It was observed that 0.1% Triamcinolone Acetonide and 5% Amlexanox proven to be more efficacious in the reduction of size, Number, Pain, Erythema and Exudate Levels at day 8, (p = .000*) and at day 10 (p =. 000*) as compared to single application of 100 mg Doxycycline Hyclate, 20% Benzocaine gel and the placebo, which was statistically significant. VAS scale was significant for 100 mg Doxycycline Hyclate and 20% Benzocaine gel. CONCLUSION: The selected topical treatment modality can deliver cheap, effective and safe drug therapy which benefits the patient in refining their regular activities and everyday events of life.

Salivary metabolomics profile of patients with recurrent aphthous ulcer as revealed by liquid chromatography-tandem mass spectrometry.

Objective We compared the salivary nontargeted metabolite profiles between patients with recurrent aphthous ulcer (RAU) and healthy individuals to investigate the metabolic alterations associated with RAU. Methods Saliva samples were collected from 45 patients with RAU and 49 healthy individuals, and the salivary metabolites were quantified using liquid chromatography-tandem mass spectrometry. The metabolomic profiles were then analyzed using multivariate and univariate statistical methods, and enrichment of the metabolites in various biological pathways was assessed. Results In total, 206 significant differentiating metabolites (Wilcoxon test, false discovery rate [FDR] of <0.05) were identified between patients with RAU and healthy individuals. These metabolites were implicated in tryptophan metabolism, steroid hormone biosynthesis, and other metabolic pathways. Two commonly circulating steroids, estrone sulfate and dehydroepiandrosterone sulfate, were significantly lower in the saliva of patients with RAU (Wilcoxon test, FDR < 0.05, power > 0.9). Principal component analysis and partial least-squares discriminant analysis revealed metabolic perturbations involving RAU, and receiver operating characteristic curve analysis with several metabolites showed good diagnostic ability for RAU. Conclusions The results of this study indicate that patients with RAU are characterized by metabolic imbalances. Psychogenic factors, endocrinopathies, and immunosuppression may contribute to the onset of RAU.

[Soluble programmed death-1 and soluble programmed death ligand 1 protein expression and immune status in patients with recurrent aphthous ulcer].

OBJECTIVE: This study aims to investigate the possible role and significance of soluble programmed death-1 (sPD-1)  /soluble programmed death ligand 1 (sPD-L1) in the immune pathogeneses of recurrent aphthous ulcer (RAU). METHODS: A total of 30 RAU cases (18 cases of minor RAU, 5 cases of major RAU, and 7 cases of herpetiform ulcers) were enrolled in this study. A total of 18 healthy people served as controls. Lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD16⁺+56⁺) were investigated by flow cytometric analysis. Humoral immunity (IgG, IgA, IgM, C3, and C4) was explored by nephelometry immunoassay. The sPD-1 and sPD-L1 protein levels in the sera of RAU patients were investigated by enzyme-linked immunosorbent assay. The correlations of the sPD-1 and sPD-L1 protein levels with the immune status and clinical characteristics of the RAU patients were analyzed by SPSS 19.0. RESULTS: The number of CD4+ T cells decreased and the levels of IgM antibodies increased in the RAU patients relative to those in the normal controls (P<0.05). The sPD-1 and sPD-L1 protein levels in the RAU patients were significantly higher than those in the control group (P<0.05). Meanwhile, the sPD-1 and sPD-L1 protein levels in the patients with minor and major RAU were significantly higher than those in the control group (P<0.05). By contrast, no significant difference was found in the patients with herpetiform RAU (P>0.05). Positive correlations were noted between the sPD-1 protein level and the CD19+ cell frequency or C4 level (r1=0.389, P1=0.034; r2=0.382, P2=0.037). CONCLUSIONS: Cellular immune hypofunction and humoral immunity disorders were found in the RAU patients. The PD-1/PD-L1 signaling pathway, which might be influenced by the involvement of sPD-1 and sPD-L1 proteins to a certain extent, may play some roles in the immune pathogenesis of RAU.