Network pharmacology-based strategy combined with molecular docking to explore the potential mechanism of agarwood against recurrent aphthous stomatitis.

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.

Propolis Use in Dentistry: A Narrative Review of Its Preventive and Therapeutic Applications.

Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen. Propolis continues to gain considerable scientific interest due to its potential health benefits. The modern-day use of propolis in pharmaceutical preparations, such as toothpastes, mouthwashes, chewable tablets, mucoadhesive gels, and sprays, is increasing. However, the effectiveness of using propolis-containing pharmaceuticals in dentistry is not clear. The present paper aims to review the literature on the dental applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry and discuss its clinical effectiveness. A literature search was conducted using Scopus, PubMed, and Web of Science databases. In total, 104 studies were included, of which 46 were laboratory studies, 5 animal studies, and 53 human clinical studies. Overall, the laboratory studies revealed a range of antimicrobial effects of propolis on oral pathogens. Clinical investigations of propolis in biofilm and dental caries control as well as adjuvant periodontal therapies reported positive outcomes in terms of plaque control, pathogenic microbial count reduction, and periodontal tissue inflammation control. Additional investigations included the use of propolis for the management of recurrent aphthous stomatitis, oral mucositis, and cavity disinfection after caries removal as well as the development of a range of restorative dental materials. Based on the reported outcomes of the studies, the clinical usage of propolis has potential. However, the majority of the evidence is derived from studies with flaws in their methodological design, making their results and conclusions questionable. As a consequence, properly designed and well-reported clinical studies are required to affirm the effectiveness of propolis for dental applications. Additionally, the safety of propolis and the optimal concentrations and extraction methods for its clinical use warrant further investigation. Utilisation of standardised propolis extracts will help in quality control of propolis-based products and lead to the achievement of reproducible outcomes in research studies.

The effectiveness of fire needle therapy in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is common in clinical practice and imposes both physical and psychological distress on patients. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of fire needle therapy for the treatment of RAS, providing a basis for clinical decision-making. METHODS: Eight databases, in both Chinese and English, were searched from their inception until December 2022. All randomized controlled trials (RCTs) that utilized fire needle therapy, either alone or combined with other treatments for RAS, were considered. Data evaluation and extraction were conducted independently by 2 authors. RESULTS: The revised Cochrane Risk of Bias Version 2 tool was employed to assess the risk of bias in the included RCTs. A meta-analysis was conducted using Review Manager 5.4 and Stata 15.0. Nine RCTs involving 1469 patients were selected for inclusion. The meta-analysis revealed that, compared to a non-fire-needle control group (primarily utilizing vitamin and transfer factor treatments), fire needle therapy for RAS significantly improved the total effective rate (relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.36], P < .00001), reduced the visual analogue scale score (mean difference = -1.68, 95% CI [-1.82, -1.53], P < .0001), diminished the Traditional Chinese Medicine symptom score (standardized mean difference = -1.20, 95% CI [-1.76, -0.65], P < .0001), and shortened the healing time (mean difference = -1.66, 95% CI [-2.73, -0.59], P = .002). Notably, there was no significant difference in the recurrence rate between the groups (relative risk = -0.18, 95% CI [-0.36, 0.01], P = .06). Further subgroup analysis on total efficacy rate was performed based on variables such as experimental group intervention, control group intervention, and duration of therapy to explore potential sources of heterogeneity. CONCLUSION: Fire needle therapy appears to be a clinically effective treatment for RAS, offering benefits such as pain alleviation, symptom improvement based on the Traditional Chinese Medicine parameters, and faster recovery. Nonetheless, the overall quality of the RCTs available raises concerns. Future research, involving high-quality RCTs, is essential to confirm the clinical efficacy and safety of this treatment. Registration number: PROSPERO (CRD42023387973).

The effect of vitamin D supplementation on attacks in PFAPA syndrome patients with low vitamin D levels.

BACKGROUND-AIM: To evaluate the effect of vitamin D supplementation on the frequency and duration of attacks in patients of PFAPA syndrome with low vitamin D levels. METHODS: This retrospective study comprised PFAPA patients with vitamin D deficiency/insufficiency between 2018 and 2023. The frequency and duration of PFAPA attacks before and after vitamin D supplementation were noted. RESULTS: Seventy-one patients were included. Of the 71 patients, 24 (33.8%) had vitamin D insufficiency, and 47 (66.2%) had vitamin D deficiency. In patients with vitamin D insufficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 4.3 ± 1.9/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.5 ± 2.7/year per year and 1.3 ± 0.9 days respectively (p = 0.2, p = 0.2, respectively). In patients with vitamin D deficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 7.4 ± 2.1/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.3 ± 2.4/year and 1.3 ± 0.9 days respectively (p < 0.01, p = 0.04, respectively). When the vitamin D level and the frequency of attacks were compared, the cut-off value of vitamin D was found to be 29.7 nmol/L. CONCLUSIONS: In PFAPA patients with low vitamin D levels, the frequency and duration of PFAPA attacks were reduced with vitamin D supplementation. Especially at vitamin D level cut-off > 29.7 nmol/L, the frequency of attacks reduced significantly.

Anti-inflammatory and tissue repair effect of cinnamaldehyde and nano cinnamaldehyde on gingival fibroblasts and macrophages.

BACKGROUND: Recurrent aphthous stomatitis has a complex and inflammatory origin. Among the great variety of medications it is increasingly common to use herbal medicines due to the adverse side effects of chemical medications. Considering the anti-inflammatory properties of cinnamaldehyde and the lack of studies related to the effectiveness of its nano form; This study investigates the effect of cinnamaldehyde and nano cinnamaldehyde on the healing rate of recurrent aphthous stomatitis lesions. METHODS: In a laboratory experiment, cinnamaldehyde was converted into niosomal nanoparticles. The niosome vesicles diameter and polydispersity index were measured at 25°C using a dynamic light scattering (DLS) Mastersizer 2000 (Malvern Panalytical technologies: UK) and Zetasizer Nano ZS system (Malvern Instruments Worcestershire: UK). After characterizing these particles, the (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) [XTT] assay was used to assess the toxicity of cinnamaldehyde and nano cinnamaldehyde on gingival fibroblast (HGF) and macrophage (THP-1) cells. By determining the release of TNF-α, IL-6, and TGF-ß cytokines using ELISA kits, the level of tissue repair and anti-inflammatory capabilities of these two substances were evaluated. RESULTS: The size and loading rate of the cinnamaldehyde nanoparticles were established after its creation. The optimized nanovesicle exhibited the following characteristics: particle size of 228.75 ± 2.38 nm, PDI of 0.244 ± 0.01, the zeta potential of -10.87 ± 1.09 mV and the drug encapsulation percentage of 66.72 ± 3.93%. PDIs range was between 0.242-0.274. The zeta potential values at 25°C were from -2.67 to -12.9 mV. The results of the XTT test demonstrated that nano cinnamaldehyde exhibited dose-dependent toxicity effects. Moreover, nano cinnamaldehyde released more TGF-ß and had better reparative effects when taken at lower concentrations than cinnamaldehyde. CONCLUSION: Nano cinnamaldehyde and cinnamaldehyde are effective in repairing tissue when used in non-toxic amounts. After confirmation in animal models, it is envisaged that these substances can be utilized to treat recurrent aphthous stomatitis.

Effectiveness of Zhibai Dihuang pill (Chinese herbal formula) in combination with western drugs in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: The pain caused by recurrent aphthous stomatitis (RAS) and the recurrent nature of RAS lead to diminished quality of life for RAS patients. An alternative treatment for RAS is the oral administration of the Chinese herbal medicine Zhibai Dihuang pill (ZBDHP). Our study aims to investigate the clinical efficacy of ZBDHP when used in combination with Western medicine (WM) for the treatment of RAS and its effectiveness in preventing the recurrence of RAS. METHODS: Following the PRISMA 2020 guidelines, we conducted a literature search on 7 electronic databases according to predefined criteria. The methodological quality of randomized controlled trials (RCTs) was evaluated based on the Cochrane Handbook, and data analysis was performed using RevMan 5.3 software. RESULTS: A meta-analysis which included 7 studies and 669 participants in total was carried out in this study. The quantitative analysis revealed that the combined treatment of ZBDHP and WM has witnessed significantly improved overall clinical efficacy (RR = 1.20, 95% CI [1.12, 1.28], P < .05), reduced recurrence rate (RR = 0.24, 95% CI [0.13, 0.45], P < .05), decreased ulcer area (MD = -0.75, 95% CI [-0.91, -0.59], P < .05), and reduced pain visual simulation score (MD = -0.42, 95% CI [-0.52, -0.33], P < .05). No significant heterogeneity was observed among the studies. Qualitative analysis showed that the combination therapy significantly reduced serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10, shortened ulcer healing time and pain disappearance time, with no adverse effects observed. CONCLUSION: It was found that the combination of ZBDHP and WM is more effective in treating RAS than the use of WM alone, which thus provides clinicians with a more optimal treatment option. However, due to limitations in the methodological quality of the included original studies and the small sample size, we hold the opinion that more rigorous and scientific clinical trials are needed to further evaluate the efficacy of ZBDHP in treating RAS.

The effect of sage (Salvizan gel) compared to triamcinolone acetonide on the treatment of recurrent aphthous stomatitis: a double-blinded randomized clinical trial.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is one of the most common lesions of the oral mucosa. Herbal medicine can be used for the treatment of this disease. The present study aimed to compare the effects of topical application of Sage (Salvizan) and triamcinolone acetonide gels on RAS. METHODS: This double-blind clinical study recruited sixty patients with minor aphthous ulcers. Half of the patients were treated with Salvizan gel, and the other half were treated with oral triamcinolone acetonide gel. The effect of Salvizan topical gel was evaluated and compared with that of oral triamcinolone acetonide gel. Factors such as Pain recovery time, wound healing time, and pain level was evaluated. Data were analyzed by SPSS version 22 using independent t-test, paired t-test, repeated measures ANOVA, and survival analysis, including Kaplan-Meier and Cox regression. RESULTS: The mean duration of pain recovery was 1.5 days for Salvizan and 2.5 days for triamcinolone acetonide (p < 0.001). Moreover, the duration of wound healing was 3.3 days for Salvizan and 6 days for triamcinolone acetonide (p < 0.001). Patients' satisfaction from factors such as taste and smell had no significant difference between the two groups. CONCLUSION: The results of this study showed that Salvizan gel is very effective in the treatment of RAS. It was significantly better than triamcinolone acetonide in the pain recovery and wound healing. These promising results favor herbal treatments and show that they can be used more commonly for treating diseases such as RAS. TRIAL REGISTRATION: This study was approved by the ethics committee of Isfahan University of Medical Sciences (IR.MUI. RESEARCH: REC.1399.834) on 17/03/2021. It was also registered in the Iranian Registry of Clinical Trials (IRCT20100202003251N7).

Effects of honey-lemon spray on recurrent aphthous stomatitis comparing to Triamcinolone ointment: a randomized controlled clinical trial

Recurrent aphthous stomatitis (RAS) is recurrent and painful diseases of the oral mucosa that can be very painful and annoying despite their small size. There is no definitive cure for this disease and the usual treatments are mainly based on pain control. The aim of this study was to investigate the effect of honey-lemon spray (mucotin) in the treatment of recurrent aphthous stomatitis. Methods: This study is a randomized controlled clinical trial conducted in 2020 at Zahedan University of Medical Sciences on 46 RAS patients. The participants were randomly assigned to the intervention (mucotin) or control groups (Triamcinolone ointment) equally (23 patients in each group). Patients were evaluated for the severity of pain and ulcer size. Evaluations were performed on days 0, 2, 7 of the treatment using VAS. Data were analyzed using ANOVA statistical test. Results: The inner aspect of the lower lip was the most common site of RAS in the participants (48.8%) and the lowest site went for hard palate (2.4%). Four items including pain, burning sensation, necrosis area, and erythematous area were evaluated in both groups. There was no significant difference in all parameters before the treatment period (day 0). The mean pain score, burning sensation, necrosis, erythematous areas were not different in days 0, 2 and 7 between groups respectively (p=0.849, p=0.105, p=0.917, p=0.442). Conclusion: Honey-lemon spray (Mucotin) and topical corticosteroid have similar effects in RAS treating, So Mucotin can be used as the first line of treatment for RAS lesions. This herbal medicine has no side effects

Effective licorice gargle juice for aphthous ulcer pain relief: A randomized double-blind placebo-controlled trial.

The aim of this study was to determine the effects of licorice gargle juice on aphthous ulcers, which is a common and painful disease that causes loss of normal mucous tissues and results in inflammatory ulcers in the oral mucosa. A randomized double-blind placebo-controlled trial involving primary care patients suffering from aphthous ulcer was performed. The intervention group received licorice gargle juice for 1 and 2 days. Of the 54 patients that participated in the study, 30 were included in the intervention group and 24 in the placebo group. A 10-point visual analog scale (VAS) was used to assess the patients' self-assessed pain levels before and after treatment. Statistical analyses were performed by using the nonparametric Mann-Whitney test. The licorice gargle juice group had a significantly reduced pain level rate compared with the placebo group at day 1 (mean VAS, 2.47 [95% CI, 1.95-2.98] vs. 4.75 [3.96-5.54]; P<0.001) and day 2 (mean VAS, 1.07 [95% CI, 0.81-1.32] vs. 4.08 [3.23-4.94]; P<0.001).The current study indicates that licorice gargle juice rapidly reduce pain and healing time and thus can improve the quality of life of a patient with aphthous ulcer.

Association Between Behçet's Disease and Depression.

BACKGROUND: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression. OBJECTIVES: To evaluate the association between BD and depression, adjusting for established risk factors for depression. METHODS: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex. RESULTS: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37-2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39-2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18-39 years of age), low and high socioeconomical status, and non-smokers. CONCLUSIONS: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

Network pharmacology and bioinformatics analyses identify the intersection genes and mechanism of Huang Bai for recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. However, there is still no effective treatment method for RAS without side effects. Traditionally, Cortex Phellodendri known as "Huang Bai" was used to treat RAS for antibacterial and anti-inflammatory properties in China. Network pharmacology methods and bioinformatics analysis were utilized to search and fish incorporating target. Network analysis and silico validation were used to discover the pharmacological mechanisms of "Huang Bai" for the treatment of RAS. A total of 25 active ingredients in HB, 200 drug targets, and 578 differentially expressed genes (DEGs) between Recurrent aphthous stomatitis and normal samples were obtained. The Gene Ontology enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 60 significant pathways, most of which involved in the inhibition of inflammation and regulation of immunological response. The functions are dependent on a multi-pathway, particularly the TNF signaling pathway and the HIF-1 signaling pathway. We identified six hub genes in the PPI network, most of which were validated as highly expressed in oral ulcers by DiseaseMeth databases. In addition, molecular docking displayed that the primary molecule combined well with the key targets. "Huang Bai" contains potential anti-RAS active compounds. This study reflects the multi-component multi-target multi-pathway action characteristics of "Huang Bai." Our study provides potential biomarkers or treatment targets for further research.

The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in Human Volunteers.

Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1ß, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-ß levels and significantly downregulated TNF-α and IL-1ß in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to diverse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.

The Comparative Effects of Rhus Coriaria and Triamcinolone in Patients with Recurrent Aphthous Stomatitis: A Single-Blinded Randomized Controlled Clinical Trial.

Background: Recurrent aphthous stomatitis (RAS) is a common oral lesion with unknown etiology. Several treatment strategies are introduced for the treatment of RAS. In this regard, the therapeutic effects of Rhus coriaria, as one of the potential treatments, have recently caught attention. Since the clinical efficacy of Rhus coriaria has not been examined adequately. This study aims at evaluating the therapeutic effects of Rhus coriaria among patients with RAS. Method: s. Twenty-two patients with RAS were divided into two groups (n = 11). The experimental group received three pills of Rhus coriaria daily for 6 days, while the control group received triamcinolone (oral paste) three times a day for 6 days. The pain and size of the lesion were measured on the 1st, 2nd, 3rd, 4th, 5th, and 6th days. The data were analyzed by SPSS 16. In this regard, Student's t-test and Sidak pairwise tests were used for assessment of inter and intragroup comparisons of the pain and the size of the lesion, respectively. Results: Intergroup comparisons indicate that there is no difference between the experimental and the control group (p > 0.05). Whereas, the intragroup analysis of the pain revealed significant changes (p < 0.05) in most of the time points for both groups. Besides, the intragroup analysis of the lesion size, showed significant changes in all the time points in the experimental group (p < 0.05). The results in the control group exhibited the same pattern, except on 1-5, 1-6, 2-6, and 3-6 intervals in the control group. Conclusions: The application of Rhus coriaria could significantly reduce lesion size and pain in patients with RAS. Accordingly, Rhus coriaria can be an effective medication for RAS treatment.

[Relationship between peripheral blood micronutrients and four kinds of oral mucosal diseases in children: clinical analysis of 217 cases].

PURPOSE: To investigate the relationship between peripheral blood micronutrient levels and 4 kinds of oral mucosal diseases (minor recurrent aphthous ulcer, angular cheilitis, cheilitis and geographic tongue) in children aged 0~14 years. METHODS: One hundred and fifty-two children with oral mucosal lesions (COML) and 65 healthy children (health control group, HC) were included. The clinical data of each group were recorded separately to compare whether there existed differences in the levels of serum water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, B12, C), serum fat-soluble vitamins [vitamins A, E, K, 25(OH)D2, 25(OH)D3], zinc and serum calcium. Whether peripheral blood micronutrients were risk factors associated with the onset of COML was analyzed through disorder multiclass logistic regression with SPSS 23.0 software package. RESULTS: Peripheral blood micronutrients differed in children with minor recurrent aphthous ulcers, cheilitis, and geographic tongue (P＜0.05). Compared with HC group, children in minor recurrent aphthous ulcer group had significantly lower levels of vitamin B1, B6, B7, C, A, and 25(OH)D3 (P＜0.05), and relatively higher rates of vitamin B6 (50.00% vs 13.85%), vitamin B7 (36.76% vs 9.23%), 25(OH)D3 (64.71% vs 36.92%) deficiency and vitamin K excess (8.82% vs 0.00%)(P＜0.005). Multiclass logistic regression analysis showed that vitamin B1, vitamin C, vitamin A deficiency, vitamin B5, and vitamin K excess were risk factors for incidence in children with minor recurrent aphthous ulcer, and each element was independent for each other. Compared with HC group, the levels of vitamin B7 and 25(OH)D3 in children with cheilitis were significantly lower(P＜0.05), and the rate of vitamin B7 deficiency was significantly higher (P＜0.005). Multiclass logistic regression analysis showed that vitamin B7 and vitamin A deficiency were risk factors for cheilitis in children, and the two were independent for each other. Compared with the HC group, vitamin K excess rate was significantly higher in children with geographic tongue (7.14% vs 0.00%) (P＜0.005). Multiclass logistic regression analysis showed that vitamin C deficiency and vitamin K excess were risk factors for the incidence of geographic tongue, and the two were independent for each other. Compared with other groups, peripheral blood micronutrients had no correlation with the pathogenesis of angular cheilitis (P＞0.05). CONCLUSIONS: The occurrence of COML is closely related to peripheral blood micronutrient levels, which suggests that children with COML need to monitor vitamin and mineral levels and supplement treatment when necessary.

The clinical efficacy of minocycline mouth rinse on recurrent aphthous stomatitis-A randomized controlled trial.

Introduction: Recurrent aphthous stomatitis (RAS) is one of the most common ulcerative diseases affecting the general population. The present study aimed to evaluate the clinical efficiency of 0.5% minocycline mouth rinse prescribed along with the topical anesthetic gel and vitamin supplement over the topical anesthetic gel and vitamin supplement prescribed alone for treating RAS. Materials and Methods: A total of 60 participants were randomly divided into two groups-experimental group: 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel; and control group: vitamin supplement and topical anesthetic gel alone. The pain symptoms were evaluated using the VAS scores at baseline and first follow-up visits. The data were analyzed using Student's t test. Results: A significant reduction in the pain scores was observed in participants using the 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel on the first follow-up visit (P = < 0.001). Conclusion: The 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel had shown more reduction in the pain symptoms when compared to topical anesthetic gel and vitamin supplement prescribed alone for the treatment of RAS.

The Evaluation of Healing Properties of Galium verum-Based Oral Gel in Aphthous Stomatitis in Rats.

Although oral ulcers represent one of the most frequent oral mucosal diseases, the available treatment is not sufficient to provide complete ulcer recovery without side-effects. Therefore, the aim of our study was to prepare a mucoadhesive oral gel based on Galium verum ethanol extract (GVL gel) and reveal its healing effects in the model of aphthous stomatitis in rats. Rats with oral ulcers were divided into the following groups: control (untreated), gel base (ulcer was treated with the gel base, three times per day for 10 days), and GVL gel group (the ulcer was treated with GVL gel in the same way as the gel base). Animals from each group were sacrificed on days 0, 3, 6, and 10 for collecting blood and ulcer tissue samples. Healing properties of oral gel were determined by clinical evaluation, as well as biochemical and histopathological examinations. Our findings suggest a significant decrease in the ulcer size in GVL gel group, with healing effects achieved through the alleviation of oxidative stress, reduction in COX-2 immunopositivity, and increase in collagen content in buccal tissue. Significant ulcer repairing potential of GVL gel highlights this oral mucoadhesive gel as a promising tool for prevention and treatment of RAS.

COMPARATIVE EFFICACY OF 1% CURCUMIN NANOMICELLE GEL AND 2% CURCUMIN GEL FOR TREATMENT OF RECURRENT APHTHOUS STOMATITIS: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL.

OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a highly prevalent painful inflammatory condition. Curcumin is currently used as a medicinal herb with optimal anti-inflammatory properties for many inflammatory conditions. However, due to its low water solubility and consequently low bioavailability, its nanoparticulate formulation has been considered for use. This study aimed to compare the efficacy of topical application of 1% curcumin nanomicelle gel and 2% curcumin gel for treatment of RAS. METHODS: This double-blind randomized clinical trial evaluated 48 RAS patients. The patients randomly received 1% curcumin nanomicelle gel or 2% curcumin gel, and were asked to apply it 3 times/day for 1 week. The severity of pain was measured using a visual analog scale (VAS), and the size of lesions (in millimeters) was measured by a periodontal probe before (baseline), and at 4, and 7 days after treatment. Data were analyzed by repeated measures ANOVA. RESULTS: No significant difference was noted in the pain score (P = .160) or size of lesions (P = .432) between the 2 groups at baseline. At 7 days, the pain score and size of lesions significantly decreased in both groups (P < .05). The reduction in pain score and lesion size was significantly greater in the curcumin nanomicelle gel group at both 4 and 7 days (P < .05). Also, the efficacy index (EI) was higher in curcumin nanomicelle gel group. CONCLUSIONS: The 1% curcumin nanomicelle gel can be effectively used to enhance the healing of RAS.

Recurrent aphthous stomatitis (RAS): guideline for differential diagnosis and management.

AIM: Recurrent aphthous stomatitis (RAS) is a painful and common ulcerative form that can pose a diagnostic challenge. In fact, similar oral ulcers can appear secondary to a variety of well-defined pathological conditions. Thus, the purpose of this work was to update the current knowledge about RAS METHODS: A narrative review is presented aiming to clarify the extensive differential diagnosis of RAS and its management. CONCLUSION: As a first aid in relieving the pain, topical applications of corticosteroids, antibiotics, and analgesics are highly recommended, while systemic therapy of RAS should be used in the case of multiple painful ulcerations compromising the quality of life of the patient. Also, natural anti-inflammatory substances from medicinal herbs, in the form of essential oils and extracts are promising agents in the management of RAS.

Fire needle for recurrent aphthous stomatitis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS), are common inflammatory lesions of the oral mucous, usually round or ovoid, circumscribed by erythematous haloes with a yellow-grey floor and mostly painful. The purpose of this study was to evaluate the efficacy and safety of fire needle in the treatment of RAS. METHODS: PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched by 2 reviewers from the inception until December 2021. The original study that randomized control trials of fire needle for RAS will be selected and is not limited by country or language. In addition, researches in progress, the reference lists and the citation lists of identified publications will be retrieved similarly. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained prior to data extraction. A meta-analysis will be conducted if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager V5.4 software will be using for data synthesis and assessment of the risk of bias according to Cochrane Handbook. RESULTS: This study will provide a comprehensive review of current evidence for the treatment of fire needle on RAS. CONCLUSION: The conclusion of this study will provide a judging basis that whether the treatment of RAS with fire needle is effective. INPLASY REGISTRATION NUMBER: INPLASY2021120118.