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.

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.

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).

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.

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.

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.

The efficacy of herbal medicine in the treatment of recurrent aphthous stomatitis: A systematic review of randomized clinical trials.

This systematic review was undertaken with the main aim of assessing the therapeutic effects of herbal medicines in recurrent aphthous stomatitis (RAS). A comprehensive search was performed in PubMed, Scopus, ISI Web of Science, and Google Scholar up to July 2021 to identify randomized clinical trials investigated the effects of herbal medicines on RAS. Thirty-three papers comprising 2,113 patients met the eligibility criteria, of which 30 studies had a high quality based on the Jadad scale. Totally, 22 out of 30 studies which assessed the pain showed that herbal agents significantly decreased the pain compared with the control group or placebo. In 17 out of 25 studies that evaluated ulcer size, herbal agents significantly reduced the size of ulcers compared with the control or placebo groups. In 15 out of 18 studies that assessed the healing time, herbal agents significantly reduced healing time in the intervention groups compared with the placebo or control groups. Few adverse events were reported only in four studies. Findings of the current review indicated medicinal plants and phytochemicals as effective and safe agents that for the treatment of RAS.

Efficacy of hyaluronic acid for recurrent aphthous stomatitis: a systematic review of clinical trials.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a very common oral mucosal disease, and its management is quite challenging with no definitive cure being available so far. Many studies have tried hyaluronic acid (HA) for alleviating signs and symptoms of RAS. The present systematic review sought to assess the available evidence regarding the efficacy of HA in management of RAS. METHODS: Two reviewers independently conducted extensive search in four online databases (PubMed, Scopus, Web of Science, and Google Scholar) and the gray literature, with no restriction to date or language of the publication. All clinical trials that assessed the efficacy of HA in reducing signs and symptoms of RAS were included. Risk of bias was assessed by two reviewers independently, using the Cochrane assessment tool. Due to substantial heterogeneity, no meta-analysis was feasible. RESULTS: Out of the 75 identified articles, nine clinical trials involving 538 RAS patients (259 in HA group) were included. The risk of bias was high in five studies, low in one study, and unclear in three studies. The comparative groups varied greatly across the included studies: triamcinolone (in three studies), chlorhexidine mouthwash, lidocaine, placebo, iodine glycerin, diclofenac, and laser therapy. Overall, the results revealed a good efficacy of HA in alleviating pain and shortening the healing time of RAS, without any reported side effects. Compared to triamcinolone, HA showed superior results in one study, and comparable results in two studies. CONCLUSIONS: The available evidence suggests that HA is a promising treatment option for RAS. However, given the huge heterogeneity of the included studies and high risk of bias in some of these studies, the evidence is inconclusive. Further well-designed clinical trials with standardized methodologies and adequate sample sizes are warranted to discern the efficacy of HA for RAS. CLINICAL RELEVANCE: Hyaluronic acid might be a viable alternative therapeutic option for patients with RAS.

The Clinical Use of Curcumin for the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Clinical Trials.

Recurrent aphthous stomatitis (RAS) lesions are inflammatory painful oral ulcers with uncertain etiology. Curcumin acts as an effective anti-inflammatory and antibacterial agent in the treatment of various oral diseases. This systematic review aimed to assess the effects of curcumin on RAS. A systematic search of the medical databases, PubMed, Scopus, ISI, Science Direct, and Google Scholar was performed up to March 30, 2020, to identify clinical trials assessing the effect of curcumin on aphthous ulcers. Nine studies comprising of 469 participants met all criteria and were analyzed. Treatment with curcumin significantly reduced aphthous ulcer size (seven studies), pain intensity (eight studies), number of aphthous ulcers (three studies), erythematous halo (one study), and erythema and exudate of the aphthous (one study). In four studies, the effect of curcumin on aphthous ulcer was assessed in comparison to the effects of the standard medication, triamcinolone. In all of these studies, curcumin had similar beneficial effects on the aphthous ulcer as measured by ulcer size, number, and pain. Only three studies were categorized as high quality using the Jadad scale. Within the limitations of this review, it can be concluded that curcumin may have a beneficial role in the treatment of recurrent aphthous ulcers. However, more randomized clinical trials are needed to validate these findings.

Zinc supplementation for prevention and management of recurrent aphthous stomatitis: a systematic review.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a very common oral ulcerative disease with no definitive cure. Growing evidence suggests a significant association between zinc deficiency and RAS. OBJECTIVES: To assess the efficacy of systemic zinc supplementations in the prevention and management of RAS. METHODS: Five databases were searched for all English and Chinese studies published up to November 2020. All clinical trials that assessed the efficacy of zinc supplementations in the management and/or prevention of RAS were included. RESULTS: Seven clinical trials comprising 482 RAS patients (250 in zinc group) fulfilled the inclusion criteria. The follow-up period ranged from three months to one year. Five studies showed significantly better efficacy of zinc in reducing the recurrence rates of RAS, whereas two studies did not report any significant differences compared to the controls. Four studies reported on signs/symptoms of RAS, three of which showed superior outcomes in favour of zinc, while one study reported comparable results. CONCLUSION: Zinc supplementation seems to be efficacious in the management and prevention of RAS. However, further clinical trials with standardized methodologies and adequate follow-up periods are required to confirm the efficacy of zinc supplementations.

Effect of different treatments on recurrent aphthous stomatitis: laser versus medication.

Recurrent aphthous stomatitis (RAS) is a common disease with ulcers in oral cavity which may trigger chewing, speaking, and swallowing difficulties to patients. Treatment of RAS is primarily aimed at pain relief and the promotion of wound healing. However, few agents have been found to have definite effect in the management of RAS and most of the medicinal products may cause adverse reactions or other disadvantages, which makes their clinical usage questionable. The purpose of this randomized controlled clinical trial (RCT) was to assess the clinical effect of diode laser and traditional medication treatment on RAS. In this study, 56 patients were randomly assigned to two groups (n = 28). Laser group was treated using diode laser (810 nm, 1.0 W, CW, irradiation time 20 s for 3 applications) once daily for continuous 3 days. Medication group was treated with triamcinolone acetonide 0.1% three times a day until the lesion was healed. Spontaneous and functional pain level on the third day of treatment was significantly less in the laser group. Significant difference was observed with respect to healing time; however, the order of difference is small albeit of statistical significance. Diode laser with the chosen parameters had better effects on pain relief and no distinct advantage on wound healing comparing with medication. Trial registration number: ChiCTR2000030298; date of registration: 26 February 2020 (retrospectively registered).

Proposal for a new therapeutic high dosage of Pidotimod in children with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: a randomized controlled study.

BACKGROUND: Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. METHODS: 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5-1 mg on need, based on parents/caregivers' decision (group A) or betamethasone 0.5-1 mg on need, based on parents/caregivers' decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment. RESULTS: Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of pharyngitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups. CONCLUSIONS: We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.

The effects of licorice containing diphenhydramine solution on recurrent aphthous stomatitis: A double-blind, randomized clinical trial.

OBJECTIVES: The aim of this study was to compare the efficacy of the diphenhydramine solution (DS) and diphenhydramine-containing glycyrrhiza glabra (DSG) in the treatment of recurrent aphthous stomatitis (RAS). DESIGN: It was a double-blind randomized clinical trial that was conducted from July to September 2018 at the Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran. INTERVENTION: DSG was made by adding 5% hydroethanolic extract of licorice to the diphenhydramine elixir. A total of 70 patients diagnosed with RSA were randomly assigned to the DS and DSG groups, each containing 35 patients. Participants were instructed to swish 3 ml of either solution around their mouth for about three minutes four times a day (at least 20 min before each meal and before bedtime) until the complete healing of the oral lesions. MAIN OUTCOME MEASURES: The primary outcome of this study was to assess the severity of pain prior to the intervention and on the first, third, and fifth days of it. This was done using the visual analog scale (VAS). The duration of wound healing was also measured through photography. The secondary outcome was to record the adverse effects of the intervention. This trial was registered at the Iranian Registry of Clinical Trials under number1 IRCT20180407039213N1. RESULTS: The average pain score before the treatment in the DS and DSG groups was 8. 1 ± 1.17 and 7.97 ± 1.72, respectively, and there was apparently no significant difference between them. However, there was a significant difference between the two groups in terms of the average pain scores on the first (7 ± 1.28 versus 5.31 ± 1.28), third (4.02 ± 1.8 vs. 2.86 ± 1.56) and fifth days (1.71 ± 1.69 vs. 0.54 ± 1.31) of the intervention. Indeed, DSG significantly reduced the average wound healing duration by 1.5 days, as compared to DS (P = 0.0001). No adverse effects were observed with the intervention. CONCLUSION: According to our results, DSG appeared to be more effective in treating RAS than DS alone. TRIAL REGISTRATION: The trial was registered at Iranian Registry of Clinical Trials before the enrolment of the first patient on June 29, 2019 (registration no: IRCT20180407039213N1, http://www.irct.ir/trial/31497).