Clinical Effect of Vitamin E Combined with Recombinant Human Epidermal Growth Factor on the Recurrent Oral Ulcer and Effects of Serum Superoxide Dismutase, IL-10, and TNF-α.

Objective: To examine the therapeutic effects of vitamin E combined with recombinant human epidermal growth factor on recurrent oral ulcers as well as on the levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor- (TNF-α), to provide evidence to facilitate medical management. Method: From June 2021 to May 2022, 84 patients with recurrent oral ulcers assessed and treated in our hospital were assigned to the control group and observation group with 42 cases in each group. Vitamin E was administered to the control group, while recombinant human epidermal growth factor and vitamin E were administered to the observation group. The clinical efficacy, serum SOD level, inflammatory factor level (IL-10, TNF-α), immune function index, clinical symptom improvement, pain disappearance time, healing time of ulcer surface, and adverse reactions were examined. Results: Clinical efficacy of the observation group (92.86%) was considerably greater than the control group (73.81%), (P < .05). Following treatment, the observation group had comparatively higher levels of serum SOD and significantly decreased TNF-α and IL-10 concentrations compared to the control group (P < .05). Similarly, post-treatment, the observation group had substantially higher CD3+, CD4+, and CD4+/CD8+ concentrations and lower CD8+ concentrations compared to the normal control (P < .05). In contrast to the control group, the observation group's pain degree score, ulcer diameter, duration for pain relief, and ulcer surface healing time duration were reduced substantially (P < .05). Notably, the incidence of adverse reactions was fairly similar in both groups (P > .05). Conclusion: Vitamin E combined with recombinant human epidermal growth factor has a significant clinical effect on recurrent oral ulcers, can achieve rapid improvement of symptoms in patients, and is relatively safe to be used as a clinical therapy.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Plant extracts used in Brazil for treatment of oral ulcers and mucositis: systematic review / Extratos vegetais utilizados no Brasil para tratamento de úlceras orais e mucosite: revisão sistemática

Objective: To identify and analyze plant extracts used in Brazil for the treatment of oral ulcers and oral mucositis. Material and Methods: A systematic review was registered in PROSPERO (CRD 42018102184) and performed following the PRISMA protocol. The databases searched were PubMed, Web of Science, Scopus, Lilacs, Scielo, the Brazilian Dentistry Library. Manual searches were also performed. Results: Initially, 440 studies were found, of which 392 were excluded after reading the titles and abstracts. A total of 29 articles were read in full and 11 studies were excluded, resulting in 18 articles included in the systematic review. Nine plant species were identified in five clinical trials and 13 in vivo studies, with Chamomila recutita being the most used (33.3% of the studies). Chamomila recutita showed more promising results for analgesic, anti-inflammatory, and healing properties. Calotropis procera latex significantly decreased (p<0.05) inflammatory mediators, such as TNF-α and IL-1ß in oral mucositis induced in rats. Eupatorium laevigatum showed anti-inflammatory activity and analgesic action on oral ulcers. Carapa guianensis Aubl. reduced the severity and painful symptoms of oral mucositis and exhibited better results compared to the use of low power laser. Curcuma longa L accelerated re-epithelialization and resolution of inflammatory processes. Spondias mombin reduced oxidative stress and inflammation caused by oral mucositis and helped on healing it. Extracts of Aloe barbadensis Miller or Aloe vera showed anti-inflammatory action but did not help in the healing process of oral ulcers. Copaifera reticulata Ducke oil did not induce improvement in the healing process, nor did it show an anti-inflammatory effect. Malva sylvestrisdid not show an anti-inflammatory action on oral lesions in humans or rats. The assessment of methodological heterogeneity showed the impossibility of performing a meta-analysis. Risk of bias varied from low to high. Conclusion: The plant species most used and with the best results for the treatment of oral ulcerations and oral mucositis was Chamomilla recutita. Spondias mombin L., Curcuma longa L., Carapa guianensis Aubl and Calotropis procera showed good results in the treatment of oral mucositis, while Eupatorium laevigatum was efficient in the treatment of ulcers of traumatic origin. Malva sylvestris, Copaifera reticulata Ducke, and Aloe barbadensis Miller did not exhibit significant results (AU)

Objetivo: Identificar e analisar extratos vegetais utilizados no Brasil para o tratamento de úlceras orais e mucosite oral. Material e Métodos: Uma revisão sistemática foi registrada no PROSPERO (CRD 42018102184) e realizada seguindo o protocolo PRISMA. As bases de dados pesquisadas foram PubMed, Web of Science, Scopus, Lilacs, Scielo, Biblioteca Brasileira de Odontologia. Buscas manuais também foram realizadas. Resultados: Inicialmente, foram encontrados 440 estudos, dos quais 392 foram excluídos após a leitura dos títulos e resumos. Um total de 29 artigos oram lidos na íntegra e 11 estudos foram excluídos, resultando em 18 artigos incluídos na revisão sistemática. Nove espécies vegetais foram identificadas em cinco ensaios clínicos e 13 estudos in vivo, sendo a Chamomila recutita a mais utilizada (33,3% dos estudos). A Chamomila recutita apresentou resultados mais promissores quanto às propriedades analgésicas, anti-inflamatórias e cicatrizantes. O látex de Calotropis procera diminuiu significativamente (p<0,05) os mediadores inflamatórios, como TNF-α e IL-1ß, na mucosite oral induzida em ratos. Eupatorium laevigatumapresentou atividade anti-inflamatória e ação analgésica em úlceras orais. Carapa guianensis Aubl. reduziu a gravidade e os sintomas dolorosos da mucosite oral e apresentou melhores resultados em comparação com o uso do laser de baixa potência. Curcuma longa L. acelerou a reepitelização e resolução de processos inflamatórios. Spondias mombinreduziu o estresse oxidativo e a inflamação causadas pela mucosite oral e ajudou na sua cicatrização. Extratos de Aloe barbadensis Miller ou Aloe vera apresentaram ação anti-inflamatória, mas não auxiliaram no processo de cicatrização de úlceras orais. O óleo de Copaifera reticulata Ducke não induziu melhora no processo cicatricial, nem apresentou efeito anti-inflamatório. Malva sylvestris não apresentou ação anti-inflamatória em lesões orais em humanos ou ratos. A avaliação da heterogeneidade metodológica mostrou a impossibilidade de realizar uma meta-análise. O risco de viés variou de baixo a alto. Conclusão: A espécie vegetal mais utilizada e com melhores resultados para o tratamento de ulcerações orais e mucosite oral foi a Chamomilla recutita. Spondias mombin L., Curcuma longa L., Carapa guianensis Aubl e Calotropis procera apresentaram bons resultados no tratamento da mucosite oral, enquanto Eupatorium laevigatum foi eficiente no tratamento de úlceras de origem traumática. Malva sylvestris, Copaifera reticulata Duckee Aloe barbadensis Miller não apresentaram resultados significativos(AU)

Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis.

PURPOSE: To evaluate the effectiveness of photobiomodulation in the treatment of oral mucositis. METHODS: Systematic review and meta-analysis encompassing in the electronic databases: LILACS, MEDLINE, EMBASE, COCHRANE, SCOPUS, WEB OF SCIENCE, and CINAHL and in http://clinicaltrials.gov . Eligibility criteria were randomized, non-randomized, and observational studies that used photobiomodulation for the treatment of oral mucositis. The endpoints were reduction in the severity of oral mucositis, duration of lesions, and pain reduction. For data analysis, the Review Manager 5.4 program was used. RESULTS: A total of 316 studies were identified, 297 in the electronic databases and 19 in http://clinicaltrials.gov . After removing duplicates, 260 studies were selected for title and abstract reading, of which 223 were excluded. A total of 37 studies were chosen for full reading, of which 6 were included in the review, totaling 299 patients. The treatment used was photobiomodulation. The patients were divided into two groups: the laser group used only photobiomodulation or associated with other therapies, and the control group did not use photobiomodulation. For the endpoint reduction in the severity of oral mucositis (OM), the chance of reduction of the OM was greater in the laser group as compared to the control group. For the endpoints duration of OM lesions and pain reduction, it was not possible to carry out a meta-analysis due to the high heterogeneity between studies. In the interpretation of the meta-analysis, the reduction in the severity of oral mucositis was greater in the group that received photobiomodulation. CONCLUSION: Photobiomodulation was effective in the treatment of oral mucositis.

Network pharmacology and molecular docking-based investigation on traditional Chinese medicine Astragalus membranaceus in oral ulcer treatment.

To analyze the mechanism of Astragalus membranaceus (AM) in molecular level in the oral ulcer (OU) treatment with reference to network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used in screening the AM active components and AM action targets; GeneCards database was used to screen OU targets; the common target were screened by Venny online tool; Cytoscape software was applied to construct the target gene regulation map of AM active components; STRING database was used to construct the protein-protein interaction network and the key targets were screened as per degree value; gene ontology enrichment and KEGG pathway enrichment of interactive genes were calculated through David database. There were 17 active ingredients and 429 target spots in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. There are 606 target genes for OU in GeneCards database. There are 67 common targets, including 10 key targets: IL10, IL6, TNF, IL1B, CXCL8, CCL2, TLR4, IL4, ICAM1, and IFNG. It involves 30 gene ontology terms and 20 KEGG signal channels. The molecular docking results showed that quercetin and kaempferol had a good binding activity with IL6, IL1B, TNF, and CCL2. Network pharmacological analysis shows that AM can regulate multiple signal pathways through multiple targets to treat OU.

Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats.

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.

Efficacy and safety of the compound Chinese herb medicine mouthwash on oral ulcer model in rats.

The present study aimed to evaluate the effect of a mouthwash containing a novel compound Chinese herbal medicine (artemisia capillaris, chrysanthemum, honeysuckle, angelica dahurica and asarum sieboldii) on oral ulcers and analyze sub chronic oral toxicity in rats. For efficacy study, mouthwash was administered on the ulcer area twice daily. Compared with the control group, healing time in the test group was shorter and the ulcer area was smaller. Histological analysis showed less inflammatory cell infiltration in the test group. For sub chronic oral toxicity, mouthwash was administered by oral gavage for 93 consecutive days. There were no significant differences in body weight, food consumption or organ coefficients between the test and control groups. Some parameters of haematology and serum chemistry were statistically different but within normal physiological ranges. No obvious abnormalities were found in the necropsies and histopathological observations. In conclusion, the compound Chinese herbal medicine mouthwash promoted oral ulcer healing in rats with no obvious sub chronic toxicity, providing a potential alternative therapeutic strategy for oral ulcers.

Aplicação da fotobiomodulação laser em úlceras traumáticas na cavidade oral: revisão integrativa da literatura / Laser photobiomodulation application in traumatic ulcers in the oral cavity: integrative literature review

As úlceras traumáticas representam uma condição benigna e recorrente que acomete a cavidade oral, com variação de tamanho e dimensão. Existem inúmeras terapias que podem ser empregadas com o objetivo de promover analgesia e(ou) reparo tecidual. A fotobiomodulação laser (FBML) tem adquirido espaço no manejo dessas lesões, por se tratar de um dispositivo minimamente invasivo e bem tolerado pelo organismo, além de atuar na bioestimulação, o que confere efeito analgésico, anti-inflamatório e cicatricial. Dessa maneira, o estudo tem como objetivo avaliar a aplicação terapêutica da FBML em úlceras traumáticas na cavidade oral. Tratou-se de uma revisão integrativa da literatura, com base na pesquisa de artigos científicos dos últimos nove anos, realizada nas plataformas LILACS, BVS, SciELO, PubMed, e Google Acadêmico, utilizando o cruzamento de Descritores em Ciências da Saúde (DeCS) e empregando o uso dos operador booleano "AND". De forma adicional, a busca livre foi realizada com vistas à complementação da fundamentação teórica. Um total de sete artigos foram incluídos na presente revisão integrativa, o que incluiu estudos em humanos e em modelo animal. Todos os estudos incluídos apresentaram resultados positivos com a utilização da FBML, que demonstrou efeito benéfico através de uma ou duas sessões, com indução do processo de cicatrização, melhora da sintomatologia dolorosa e da inflamação. A FBML foi capaz de melhorar o quadro clínico e histológico das úlceras traumáticas em cavidade oral, através da modulação da percepção da dor e da inflamação, aceleração da cicatrização e consequente regressão das lesões.

Traumatic ulcers represent a benign and recurrent condition that affects the oral cavity, varying in size and dimension. There are numerous therapies that can be used to promote analgesia and/or tissue repair. Laser photobiomodulation (FBML) has gained space in the management of these lesions, as it is a minimally invasive device that is well tolerated by the body, in addition to acting in biostimulation, which confers analgesic, anti-inflammatory and healing effects. Thus, the study aims to evaluate the therapeutic application of FBML in traumatic ulcers in the oral cavity. This was an integrative literature review, based on the research of scientific articles from the last nine years, carried out on the LILACS, BVS, SciELO, PubMed, and Google Scholar platforms, using the intersection of Health Sciences Descriptors (DeCS) and employing the use of the Boolean operator "AND". Additionally, the free search was carried out with a view to complementing the theoretical foundation. A total of seven articles were included in this integrative review, which included studies in humans and in an animal model. All included studies showed positive results with the use of FBML, which demonstrated a beneficial effect through one or two sessions, inducing the healing process, improving pain symptoms and inflammation. FBML was able to improve the clinical and histological picture of traumatic ulcers in the oral cavity, by modulating the perception of pain and inflammation, accelerating healing and consequent regression of the lesions.

Attenuated Total Reflection Fourier Transform Infrared Mapping for the Identification of the Prescribed and Abnormal Ingredients of Herbal Powder Preparations.

Herbal powder preparations (HPPs) are common forms of traditional medicine made by blending the powder of two or more ingredients. The first step to ensure the safety and efficacy of HPPs is to confirm the prescribed ingredients and screen the abnormal ingredients. With the help of attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) imaging or mapping, the particles of different ingredients in an HPP sample can be measured individually. In this way, the overlapped absorption signals of different ingredients in the ATR FT-IR spectrum of the bulk sample can be isolated in the ATR FT-IR spectra of the microscopic particles, which leads to the substantial increase of the specificity and sensitivity of the infrared spectral identification method. The characteristic particles of each ingredient can be identified by the objective comparison of the microscopic ATR FT-IR spectra against the reference spectra based on the correlation coefficients. Since the ATR FT-IR imaging or mapping tests of HPPs are free of the separation preprocess, multiple organic and inorganic ingredients are able to be recognized by a single identification procedure simultaneously rather than by different separation and identification procedures. As an example, the ATR FT-IR mapping method was used in this research to successfully identify three prescribed ingredients and two abnormal ingredients in oral ulcer pulvis, which is a classic HPP for oral ulcer in traditional Chinese medicine. The results show the feasibility of the ATR FT-IR microspectroscopic identification method for the objective and simultaneous identification of the prescribed and abnormal ingredients of HPPs.

The Correlation Between IFNG Gene Methylation and Th1|Th2 Cell Balance in ROU and the Interventional Study of Jiaweidaochi Powder.

The pathogenesis of recurrent oral ulcers (ROU) is complex, with a long duration of illness and challenging to cure. According to traditional Chinese medicine (TCM),"heat accumulation in the heart-spleen" is one of the main causative factors. Jiaweidaochi powder (JWDCP) is based on the ancient Chinese medicine formula JWDCS, with the addition of Tongcao and gypsum and the removal of Mu Tong. It is generally used to treat "heat accumulation in the heart-spleen." Previous studies have demonstrated that it effectively reduces recurrence rates and is anti-inflammatory in modulating immunity. The ROU rats' model for JWDCP intervention treatment had been established, and histological tests revealed that JWDCP has a therapeutic effect on the pathological changes in the oral mucosa. In addition, the methylation levels of peripheral blood IFNG gene were detected by bisulfite sequencing PCR (BSP), and the methylation levels of the IFNG promoter region in the model group and each dose group were lower than those in the control group. However, no significant methylation differences were observed. Furthermore, the results of enzyme-linked immunosorbent assay (ELISA) and RNA quantitative polymerase chain reaction showed that JWDCP could reduce IFN-γ and IL-4 protein concentrations, with high GATA-3 mRNA production, T-bet mRNAproduction was upgraded, elevated IL-4 mRNA levels, and reduced IFN-γ mRNA levels after treatment (P < 0.001). The expression of transcription factor T-betmRNA and GATA-3 gene mRNA was accompanied by changes in IFN-γmRNA and IL-4mRNA, demonstrating that Th2 type differentiation in RAS suppresses the body's immunity and that the imbalance of transcription factor expression further leads to Th1/Th2 drift. JWDCP is likely to reduce the protein concentration by regulating the imbalance of transcription factors and enhancing antioxidant capacity, thus achieving therapeutic effects. Treatment of recurrent oral ulcer models is not sufficient to reset IFNG methylation levels, correlating with the refractoriness of ROU, further confirming the complexity of epigenetic mechanisms and that epigenetic alterations in specific mediators may persist locally.

Umbrella review: Summary of findings for acupuncture as treatment for radiation-induced xerostomia.

Acupuncture is a common part of complementary medicine. However, traditional Chinese acupuncture has been built on concepts which are not in accordance with science-based medicine. Our aim was to critically assess the evidence presented in systematic reviews (SRs) and meta-analyses (MAs) about the effectiveness of acupuncture on radiotherapy induced xerostomia. A systematic search was conducted in February 2022. We evaluated all SRs/MAs using the AMSTAR-2 instrument. Eight SRs, with 12 controlled studies were included. All SRs summarize that the methodological drawbacks do not allow to give a clear statement about the effectiveness of acupuncture. While objective assessments in most SRs/MAs reported no difference between real and sham acupuncture, some favorable effects on subjective xerostomia symptoms are found. No clinical meaningful effectiveness of acupuncture on xerostomia has been proven so far, but positive subjective findings need to be explored more. While most SRs recommend further studies, studies involving patients with a serious cancer diagnosis are ethically questionable.

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

Effects of Aloe Vera in the Treatment of Oral Ulcers: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

PURPOSE: To analyse the effects of aloe vera on the treatment of oral ulcers. MATERIALS AND METHODS: Relevant studies were identified from PubMed, Embase, ClinicalTrials.gov, SinoMed, Web of Science and Cochrane Library. Randomised controlled trials (RCTs) involving aloe vera (AV) in the treatment of oral ulcers were included. The data were extracted and pooled for meta-analysis to compare the clinical outcomes of patients with oral ulcers in terms of treatment effect, the size of ulcers, Visual Analogue Scale (VAS) for pain, and therapy duration. The standardised mean differences (SMD) with 95% confidence intervals (CI) were determined for the main outcomes, heterogeneity was analysed using the I2 test, and the studies' risk of bias was evaluating using the Cochrane risk of bias assessment tool. RESULTS: The study included 9 trials with a total of 847 participants. Seven trials were included in the meta-analysis. The results indicated no statistically significant differences in pain scores as assessed by the VAS (I2 = 95%, p = 0.89; SMD: -0.12, 95% CI: -1.84, 1.60) and size of ulcers (I2 = 88%, p = 0.60; SMD: -0.29, 95% CI: -1.39, 0.81). Clinical efficacy of the aloe vera group was better compared to control group (I2 = 89%, p = 0.007; RR: 2.25, 95% CI: 1.25, 4.06). Therapy duration was statistically significantly lower following AV gel application in two of the studies (I2 = 0%, p < 0.001; SMD: -1.32, 95% CI: -1.84, -0.79). Considering the results in a systematic manner, AV accelerated tissue epithelialisation and the wound-healing process. CONCLUSION: Compared with other interventions, aloe vera has a better therapeutic effect and shorter healing time. It is comparable with other interventions in relieving pain and reducing ulcer size, but it has higher safety and almost no side effects.

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.

Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol: An in vitro study.

OBJECTIVE: To evaluate the anti-inflammatory and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol (CBD). DESIGN: The cellular bioactivities of hemp extract and CBD were determined the inhibition of TNF-α and IL-1ß in LPS-induced murine macrophage (RAW 264.7) cells by using ELISA while wound healing activity in human gingival fibroblast (HGF-1) cells was performed by a scratch test assay. The cytotoxicity was also concerned and evaluated by MTT assay. RESULTS: The hemp extract and CBD significantly decreased TNF-α release by up to 91.05 ± 2.91% and 50.78 ± 7.21% of LPS activity, respectively, in a dose-dependent manner, compared to 10 µg/mL hydrocortisone (61.67 ± 3.79%). The hemp extract and CBD also significantly decreased IL-1ß release, also in dose-dependent response, up to 78.03 ± 3.34% and 85.87 ± 1.11% of LPS activity, respectively, compared to 5 µg/mL hydrocortisone (80.81 ± 3.55%). The mean percentage of closure of the wound area was 27.92 ± 1.21% when exposed to 5 µg/mL hemp extract and 33.49 ± 1.67% when exposed to 0.5 µg/mL CBD, compared to 24.34 ± 2.29% for non-treated control. CONCLUSIONS: Our study demonstrates that both hemp extract and CBD can inhibit TNF-α and IL-1ß production in LPS-induced RAW 264.7 cells and promote wound healing in HGF-1 cells. This is the first to show that short-term exposure to hemp extract and CBD promoted gingival fibroblast wound healing, demonstrating that hemp extract and CBD have potential benefits in the treatment of oral inflammation and ulcers.

Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM).

OBJECTIVES: The effect of photobiomodulation (PBM) treatment on wound healing and macrophage polarization was investigated in vivo. Animal models of oral ulcers were simulated through chemically induced oral ulcers in rats. MATERIALS AND METHODS: PBM treatment using an infrared pulsed laser was used to treat oral ulcers in the animal models. Twelve Sprague-Dawley rats were randomly divided into four groups depending on set absorbed energy: Group 1 (control), Group 2 (30 J), Group 3 (60 J), and Group 4 (100 J). Laser treatment was performed every other day for 8 days after ulcer confirmation. Parameters used were as follows: wavelength 808 nm, power output 50 mW, spot size 10 mm, frequency 10 Hz, and pulse duration 1 millisecond. Ulcers were measured to determine the effect of the treatments over time. Histology, immunostaining, and real-time polymerase chain reaction analyses were performed to evaluate the effect of PBM treatment on macrophage-related (IL-6/IL-10) and wound-healing-related (TNF-α/TGF-ß/MMP-2) cytokine expression. RESULTS: Histological examinations indicate that the PBM treatment stimulated a higher level of wound recovery after 8 days of treatment at 60 J absorbed energy compared to other treatment groups. Analyses of relative gene expression of proinflammatory, anti-inflammatory, and tissue remodeling cytokines indicate that the macrophages in the tissue samples were predominantly characterized as M2 subtypes (alternatively activated), which possibly accounts for the accelerated tissue repair in the animal model of oral ulcer. CONCLUSION: This preliminary study stands as a proof of concept regarding the potential use of infrared laser PBM treatment for oral ulcers which have not been previously investigated upon. PBM treatment affects macrophage polarization and enhances wound healing. Further experimentation will be conducted to expand the understanding of how PBM treatment affects the healing mechanism of ulcers.

Aplicação do laser de baixa intensidade no tratamento do eritema multiforme: relato de caso / Low intensity laser application in the treatment of erythema multiforme: case report

Objetivo: Este trabalho tem como objetivo relatar um caso de Eritema Multiforme (EM) menor desencadeado por amoxicilina oral, tratado a partir de aplicação de laser de baixa intensidade na região afetada pela doença. Relato de caso: Paciente de 12 anos, atendido no Hospital Metropolitano Odilon Behrens (HMOB), apresentando úlceras em mucosa jugal, lábios e língua, disfagia, dislalia e febre, recebeu diagnóstico clínico de EM e tratamento com aplicação de laser vermelho de baixa intensidade, emitindo em 660nm, com potência de 100mW, sendo aplicado uma dose de 33 J/cm², em pontos com distância aproximada de 1 cm entre eles. Houve resolução das lesões em 7 dias após instituição do tratamento. Conclusão: O presente trabalho mostrou que a Terapia de Fotobiomodulação (TF) com laser de baixa intensidade associado à substituição do medicamento detectado como causa foram fundamentais para a resolução do EM, evidenciando as propriedades bioestimulantes do laser nas lesões ulceradas de mucosa bucal.

Aim: This paper aims to report a case of minor Erythema Multiforme (EM) triggered by oral amoxicillin, treated with low-level laser applications in the region affected by the disease. Case report: A 12-year-old patient, treated at the Metropolitan Hospital Odilon Behrens, presenting ulcers in the buccal mucosa, lips, tongue, dysphagia, dyslalia, and fever, received a clinical diagnosis of EM and treatment with low-intensity red laser applications, emitted at 660 nm, with a power of 100 mW, with a dose of 33 J/cm² being applied, in points with an approximate distance of 1 cm between them. The lesions resolved within 7 days after treatment were instituted. Conclusion: This present paper shows a successful therapeutic, non-pharmacological alternative for the management of EM, showing the bio stimulating properties of laser in ulcerated lesions of the oral mucosa.

Treatment Following Erythema Multiforme in the Oral Mucosa After qHPV Vaccine with Low-Level Laser Therapy: case Report / Tratamiento del Eritema Multiforme en la Mucosa Oral Después de la Vacuna Contra el qHPV con Terapia con Láser de Baja Potencia: reporte de un Caso

Erythema multiforme (EM) is a mucocutaneous condition of uncertain etiology, although the hypersensitivity reaction to a wide variety of agents may be related to the onset of the lesions. In about half of the affected patients it is possible to identify a previous infection. This article aims to report a case of EM in the oralmucosa after qHPV vaccine (Gardasil®), to highlight the diagnostic process and the proposed treatment. Female patient, 16 years old, after 10 days of receiving the first dose of the qHPV vaccine. On physical examination, she presented multiple ulcers and hemorrhagic crusts to the touch, based on the clinical picture and the history of the disease, a diagnostic hypothesis was EM. Low-level laser therapy (LLLT) was chosen as an alternative treatment, since the exercises applied were not successful. The patient was followed up, reported decreased pain and burn and, after one year of treatment, there was no recurrence of the lesions. Laser treatment showed an effective treatment alternative, in addition to the low cost and ease of application.

El eritema multiforme (EM) es una afección mucocutánea de etiología incierta, aunque la reacción de hipersensibilidad a una amplia variedad de agentes puede estar relacionada con la aparición de las lesiones. En aproximadamente la mitad de los pacientes afectados es posible identificar una infección previa. Este artículo tiene como objetivo informar un caso de EM en la mucosa oral después de la vacuna qHPV (Gardasil®), para resaltar el proceso de diagnóstico y el tratamiento propuesto. Paciente de 16 años, después de 10 días de recibir la primera dosis de la vacuna qHPV. En el examen físico, presentó múltiples úlceras y costras hemorrágicas al tacto, según el cuadro clínico y la historia de la enfermedad, una hipótesis diagnóstica fue EM. La terapia con láser de baja potencia (TLBP) se eligió como un tratamiento alternativo, ya que los ejercicios aplicados no tuvieron éxito. La paciente fue seguida, informó disminución del dolor y las quemaduras y, después de un año de tratamiento, no hubo recurrencia de las lesiones. El tratamiento con láser mostró una alternativa de tratamiento efectivo, además del bajo costo y la facilidad de aplicación.

Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease.

PURPOSE: To determine the immediate pain-relieving effect of photobiomodulation therapy (PBMt) in patients with oral ulcers of chronic graft-versus-host disease (cGVHD) refractory to first line therapy with topical corticosteroids. METHODS: This retrospective study included all patients who underwent PBMt for pain relief of refractory oral cGVHD lesions. PBMt was applied using an intraoral approach to all sites with mucosal lesions, using a 940 nm InGaAsP diode laser device, with the following parameters: pulsed modulation (duty cycle of 50%), power 0.7 W, illuminated spot size 7.1 cm2, irradiance 98.6 mW/cm2, and irradiation time 90 s per point. Pain was self-assessed using a 0-to-10 scale immediately before and after PBMt. RESULTS: Data from eleven patients with a total of 56 PBMt sessions were analyzed. In 48 (85.7%) sessions, the patients reported less pain immediately after treatment, with a reduction of ≥ 50% of the initial pain level in 43 (76.8%) sessions. Mean pre- and post-treatment pain levels were 5.20 ±2.7 and 1.38 ±2.1, respectively (p < 0.001), i.e., a post-treatment reduction of 73.4% of the initial pain level. The benefits of the treatment remained for a mean of 6.50 ±5.4 days (range of 2 to 14 days). No adverse effects were reported. CONCLUSIONS: PBMt seems to be a promising treatment modality for refractory oral cGVHD lesions as a rapid pain reliever with relatively long-lasting effects.

HPLC/MSn Profiling and Healing Activity of a Muco-Adhesive Formula of Salvadora persica against Acetic Acid-Induced Oral Ulcer in Rats.

Salvadora persica L. (S. persica, Siwak) is an ethnic plant that is widely used for improving oral hygiene. This study aimed to provide a phytochemical profiling of S. persica ethyl acetate fraction (SPEAF) and to evaluate the healing activity of a muco-adhesive formula of the fraction against acetic acid-induced oral ulcers in rats. HPLC-ESI-QTOF-MS-MS analysis of SPEAF resulted in the tentative identification of 56 metabolites containing fatty acids (23%), urea derivatives (10.5%) and sulphur compounds (10%), in addition to several amides, polyphenols and organic acids (6.5%, 5% and 2%, respectively). For the first time, 19 compounds were identified from S. persica. In vitro and in vivo experiments indicated that the extract is non-toxic. SPEAF exhibited superior healing activities compared to both the negative and positive control groups on days 7 and 14 of tongue ulcer induction. This was confirmed by histopathological examinations of haematoxylin and eosin-stained (H&E) and Masson's trichrome-stained tongue sections. Moreover, SPEAF showed potent anti-inflammatory activities, as evidenced by the inhibited expression of interleukin-6 (IL-6) and tumour necrosis alpha (TNF-α). Moreover, SPEAF exhibited potent antioxidant activity, as it prevented malondialdehyde (MDA) accumulation, reduced glutathione (GSH) depletion and superoxide dismutase (SOD) exhaustion. SPEAF significantly enhanced hydroxyproline tongue content and upregulated collagen type I alpha 1 (Col1A1) mRNA expression. SPEAF also improved angiogenesis, as shown by the increased mRNA expression of the angiopoietin-1 (Ang-1). In conclusion, S. persica has a wide range of secondary metabolites and ameliorates acetic acid-induced tongue ulcers in rats. This can be attributed, at least partly, to its anti-inflammatory, antioxidant, procollagen and angiogenic activities. These findings provide support and validity for the use of S. persica as a traditional and conventional treatment for oral disorders.