Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study.

BACKGROUND: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. METHODS: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. RESULTS: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. CONCLUSION: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Cross Lip Vermilion Flap and Traumatic Upper Lip Avulsion: Reducing Donor Site Morbidity.

Using a cross lip vermilion flap for upper red lip reconstruction in cases other than whistle deformity in patients with cleft lip can lead to donor site morbidity. If the practitioner performs primary closure of the mucosa in lower vermilion after flap harvesting, the width and height of lower lip are reduced, which results in an increased lower incisor tooth show. Using free fat grafting is an effective method for reducing donor site morbidity in the lower lip following cross lip vermilion flap harvest.

A double-layer thin oral film for wet oral mucosa adhesion and efficient treatment of oral ulcers.

Oral ulceration (OU), a prevalent oral mucosal condition causing significant pain and hindering eating and speaking, adversely impacts the patient's quality of life. Topical medications are preferred for their minimal side effects and convenient administration. However, existing formulations generally present discomfort and insufficient drug retention due to the thick formulations and poor adhesion, which considerably restrict their therapeutic effectiveness. In this study, a thin and lightweight double-layer oral film based on FDA approved excipients with excellent adhesion under wet oral conditions and outstanding biocompatibility is successfully developed by a simple method. It consists of an adhesive layer for anchoring in situ to delivery drugs and a hydrophobic layer to isolate the saliva for unidirectional drug delivery. The double-layer oral film with extremely thin appearance (only 0.11 mm thick) offers excellent adhesion (up to 150 min on an SD rat oral ulceration), which was also matched with its drug release time (87.47% release in 2 h). Animal experiments confirmed that the double-layer oral film carrying dexamethasone sodium phosphate achieved satisfactory efficacy in the SD rat oral ulcer model. Hence, this biologically friendly double-layer thin oral film holds great promise for clinical application in topical drug therapy for oral mucosal conditions.

The effect of biopolymer gel derived from sugarcane on healing of traumatic oral ulcers: an experimental study.

PURPOSE: The extracellular polysaccharide (EPS) is produced by the bacterium Zoogloea sp. and plays a positive role in tissue repair. The purpose of this study was to clinically and histologically compare the effects of EPS in the healing of traumatic oral ulcers in rats with the effects of triamcinolone. METHODS: Ulcers were induced in the oral mucous of 45 male Wistar rats, divided into three groups: control group, treated with triamcinolone, and treated with biopolymer gel. In the clinical evaluation, we considered the weight variation of the animals and the size of the lesion area, at baseline and on treatment days 1, 3 and 7. The histological parameters evaluated were the type and intensity of the inflammatory infiltration, the presence of necrosis and foreign body granuloma and the degree of re-epithelialization of the lesion. RESULTS: The reduction of the lesion area was greater in the animals treated with EPS, with no difference in the intensity of the inflammatory infiltration between the groups on days 3 and 7 of treatment. CONCLUSIONS: The results suggest that topical application of EPS in traumatic oral ulcers of rats promotes faster repair than triamcinolone ointment, without increasing the intensity of inflammatory infiltration under the lesion.

Clinical Efficacy of Chlorhexidine Gargle Combined with Recombinant Bovine Basic Fibroblast Growth Factor Gel in the Treatment of Recurrent Oral Ulcers and Its Effects on Inflammatory Factors, Immune Function, and Recurrence Rate.

PURPOSE: To examine the clinical efficacy of a chlorhexidine gargle combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel in the treatment of recurrent oral ulcers and its effects on inflammatory factors, immune function, and recurrence rate. MATERIALS AND METHODS: Ninety-six patients with recurrent oral ulcers were randomly assigned to two groups: experimental (treatment with chlorhexidine gargle plus rb-bFGF gel) and control (treatment with chlorhexidine gargle alone) (n = 48 cases). The therapeutic efficacy, clinical improvement of symptoms, and recurrence rate within 3 months were compared between the two groups. Serum inflammatory factor and immune factor levels of patients in the two groups were measured before and after treatment. RESULTS: A statistically significantly higher total effective rate was found in patients of the experimental group (95.83%) versus the control group (81.25%) (p < 0.05). The time to onset of pain relief was shortened, the duration of pain relief was prolonged, and VAS scores for pain level were lower in the experimental than the control group (p < 0.05). Among patients in the experimental group, the number of oral ulcers and ulcer area decreased, and faster onset of pain relief and time until normal eating improved in comparison to the control group (p < 0.05). Reduced levels of IL-2, IL-6, IL-8, and TNF-α were observed in the experimental vs the control group (p < 0.05). Elevated levels of CD3+, CD4+, and NKT and reduced levels of CD8+ were found in the experimental group compared to the control group (p < 0.05). The ulcer recurrence rate of patients in the experimental group (8.33%) was notably lower in comparison to the control group (29.17%). CONCLUSION: Chlorhexidine gargle plus rb-bFGF gel can improve the clinical outcome of patients with recurrent oral ulcers. It can reduce the levels of inflammatory factors, improve immune function, and reduce the recurrence rate.

Childhood adverse experiences and clinical manifestations in women with systemic lupus erythematosus.

BACKGROUND: Patients with a history of adverse childhood experiences (ACEs) have a higher incidence of developing autoimmune diseases such as systemic lupus erythematosus. OBJECTIVE: The objective is to associate the ACE with the clinical manifestations of SLE in adult women. METHODS: This is a cross-sectional observational analytical study in a sample of women diagnosed with SLE, whose data were collected through interviews and a review of medical records. The ACE were identified using the Childhood Trauma Questionnaire (CTQ) and were associated with sociodemographic and clinical data, as well as the presence of harm. RESULTS: The sample was composed of 97 women. In this study, significant associations were found between physical abuse and oral ulcers (p = .006) and nephritis (p = .032); between sexual abuse and Sjogren's syndrome (p = .024) and oral ulcers (p = .035); between physical neglect and photosensitivity (p = .024) and oral ulcers (p = .039); and between emotional neglect and diabetes mellitus (p = .033). CONCLUSION: Individuals with a positive history of ACE have significant associations with certain clinical manifestations of SLE and subtypes of ACE, underscoring the importance of preventing childhood trauma to improve adult health. Further studies are needed to elucidate the impact of ACE on adult health.

Oral lichen planus in children: A systematic review / Liquen plano oral en niños: una revisión sistemática

Background: Oral Lichen Planus is a common chronic inflammatory disease of the oral mucosa. The prevalencein adults ranges between 0.5% and 2%, while in children is reported to be about 0,03%. Clinical features of OralLichen Planus could be variable in both adults and children, ranging from painless white hyperkeratotic lesions topainful erythematous atrophic ones.Actually, there are no systematic reviews in the literature on OLP in children, whereby this paper aims to sum-marize all the pathophysiological aspects and identify all cases described in the literature of Oral Lichen Planusin children, reporting their clinical characteristics.Material and Methods: A systematic review of the literature was performed in online databases including PubMed,Scopus, Web of Science, Science Direct, EMBASE. In addition, in order to identify reports not otherwise identifi-able, an analysis of the gray literature was performed on google scholar and in Open Gray.Results: By literature analysis, it emerged that most cases were reported from India. The mean age at time of diag-nosis of the disease was 11 years, ranging from 3 to 17 years. The most frequent pattern was the reticular patternfollowed by plaque-like, erosive, atrophic, sclerosus, and bullous. The buccal mucosa was the most involved oralsite, followed by the tongue, lips and gingiva.Conclusions: Although Oral Lichen Planus in children is rare, it may cause oral discomfort and need to be dif-ferentiated from other oral white lesions and/or chronic ulcers.(AU)

Adhesive hydrogel releases protocatechualdehyde-Fe3+ complex to promote three healing stages for accelerated therapy of oral ulcers.

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.

The expanding clinical spectrum of autoinflammatory diseases with NOD2 variants: a case series and literature review.

Objective: To assess the impact conferred by NOD2 variants on the clinical spectrum of patients with systemic autoinflammatory diseases (SAIDs) in Greece. Methods: Consecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing (NGS) targeting 26 SAID-associated genes, and carried at least one NOD2 gene variant, were retrospectively studied. The demographic, clinical and laboratory parameters were recorded. Results: In total, 24 rare NOD2 variants in 23/167 patients (14%) were detected. Notably, 18 patients had at least one co-existing variant in 13 genes other than NOD2. Nine patients had juvenile- and 14 adult-onset disease. All patients presented with symptoms potentially induced by the NOD2 variants. In particular, the candidate clinical diagnosis was Yao syndrome (YAOS) in 12 patients (7% of the whole SAID cohort). The clinical spectrum of patients with YAOS (mean episode duration 8 days) was fever (n=12/12), articular symptoms (n=8), gastrointestinal symptoms (n=7; abdominal pain/bloating in 7; diarrhea in 4; oral ulcers in 3), serositis (n=7), and rash (n=5), while the inflammatory markers were elevated in all but one patient. Most of these patients showed a poor response to nonsteroidal anti-inflammatory drugs (n=7/9), colchicine (n=6/8) and/or anti-TNF treatment (n=3/4), while a complete response was observed in 6/10 patients receiving steroids and 3/5 on anti-IL1 treatment. Another 8 patients were diagnosed with either FMF (n=6) or PFAPA syndrome (n=2) presenting with prominent diarrhea (n=7), oral ulcers (n=2), periorbital swelling and sicca-like symptoms (n=1), or maculopapular rash (n=1). One patient had a clinically undefined SAID, albeit characterized by oral ulcers and diarrhea. Finally, one patient presented with chronic relapsing urticaria with periorbital edema and inflammatory markers, and another one had a Crohn-like syndrome with good response to anti-IL-1 but refractory to anti-TNF treatment. Conclusion: NOD2 variants were detected in 1 out of 7 SAID patients and seem to have an impact on disease phenotype and treatment response. Further studies should validate combined molecular and clinical data to better understand these distinct nosological entities.

Oral mucous membrane pemphigoid: updates in diagnosis and management.

Mucous membrane pemphigoid (MMP) is a rare, immune-mediated, vesiculobullous disease that predominantly affects the oral cavity and conjunctiva. In MMP, autoantibodies are directed against hemidesmosomal proteins in the basement membrane zone, most commonly BP180. Clinical signs and symptoms include gingival desquamation, erosions, and ulcerations. Differential diagnoses include other immune-mediated blistering diseases, such as bullous pemphigoid. Definitive diagnosis is reached through history taking, physical examination, tissue biopsy and/or serology testing. MMP, although not curable, is typically managed with topical or systemic corticosteroids, in addition to immunosuppressive therapies and biologic agents in recalcitrant cases. Untreated MMP can lead to life-threatening complications, such as blindness. As a condition that affects the oral cavity, it is important that dentists understand how to recognise, diagnose and manage the disease.

[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.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia on the Tongue.

BACKGROUND: Traumatic Ulcerative Granuloma with Stromal Eosinophilia, commonly known as Eosinophilic Ulcer, is a reactive solitary and self-limiting benign lesion. It manifests as a punched-out ulcer with a distinct surrounding indurated border, often raising concerns about malignancy. METHODS: A 44-year-old male presented with a painless, indurated tongue ulcer evolving over three months. Despite being asymptomatic, the patient underwent an incisional biopsy due to suspicions of oral squamous cell carcinoma. RESULTS: Histological analysis revealed a disrupted epithelial lining, dense necrotic connective tissue, and a fibrino-purulent pseudomembrane. Proximal to the ulcer, a collar-like projection of reactive epithelial tissue hyperplasia was noted, accompanied by mononuclear cells and a predominantly histiocytic infiltrate in the submucosal layer surrounding skeletal muscle fibers. The final diagnosis was Traumatic Ulcerative Granuloma with Stromal Eosinophilia. Remarkably, the lesion spontaneously healed within 2 weeks post-biopsy, with no recurrence over 6 months. CONCLUSION: This case emphasizes considering this benign condition in the differential diagnosis of oral ulcers, highlighting the importance of accurate histopathological evaluation to rule out cancer.

Oral manifestations of mpox (monkeypox).

The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving worldwide attention because of its emergence in countries that have never previously documented the illness, resulting in a public health emergency. MPXV is transmitted via human-to-human contact, and sexual contact is especially implicated in spread of the disease. Affected individuals experience fever, headache, malaise, and early lymphadenopathy, followed by a secondary mucotaneous rash. Oral ulcers and perioral papules may be the first evidence of the disease. Although there are numerous articles in medical publications documenting the cutaneous presentations of mpox, there is limited information in the dental literature regarding oral lesions. The objective of this article is to review the oral manifestations of mpox and strategies for management of the disease.

Genetic evidence strengthens the bidirectional connection between oral health status and psychiatric disorders: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies cannot accurately infer the causal associations between oral health status and psychiatric disorders. METHODS: We conducted univariate and multivariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with eight oral health statuses (periodontitis, DMFS, Nteeth, toothache, loose teeth, painful gums, bleeding gums, and mouth ulcers) and four psychiatric disorders (Schizophrenia, Major Depressive Disorder (MDD), anxiety and stress-related disorder (ASRD), and Bipolar Disorder (BIP)) as instrumental variables. Genetic data were sourced from the Gene-lifestyle interactions in dental endpoints (GLIDE), UK Biobank, Psychiatric Genomics Consortium (PGC), and Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The inverse variance-weighted (IVW) approach, supported by a comprehensive sensitivity analysis, was employed. RESULTS: Genetically predicted mouth ulcers were significantly linked to higher MDD (OR = 2.17, 95 % CI: 1.33--3.54, P< 0.01) and BIP risks (OR = 2.25, 95 % CI: 1.22-4.15, P = 0.01). BIP heightened bleeding gums risk (OR = 1.01, 95 % CI: 1.00-1.01, P < 0.01). These associations were adjusted for smoking status and alcohol consumption. Painful gums were significantly associated with MDD risk (OR = 96.48, 95 % CI: 2.66-3495.28, P = 0.01), while MDD raised periodontitis risk (OR = 2.15, 95 % CI: 1.24-3.75, P = 0.01), both confounded by smoking and alcohol. Relatively small effects between several variables, while others could not withstand correction for multiple tests. LIMITATIONS: The sample size and limitation to European populations limits the study generalizability. CONCLUSIONS: This study provide evidence of possible causal relationships between several oral health conditions and mental illness. Focusing on oral health and valuing mental health are important for each other and overall health.

Armillariella tabescens polysaccharide treated rats with oral ulcers through modulation of oral microbiota and activation of the Nrf2/HO-1 pathway.

We identified Armillariella tabescens polysaccharide (PAT-W), a compound isolated from a Chinese medicinal mushroom, as a potential novel oral ulcer (OU) drug. In treating OU rats with PAT-W, especially in the high-dose group, oral mucous tissue TNF-α, IL-1ß, and IL-6 levels were markedly reduced, and pathological morphology and oxidative stress were effectively improved. Western blot analysis showed that the PAT-W channel ameliorated OU mucous tissue damage, which depends on the activation of the Nrf2/HO-1 antioxidant signaling pathway. Furthermore, high-throughput sequencing results showed that PAT-W regulated the maladjustment of the oral microbiota caused by OU. Therefore, based on the new viewpoint of activating the Nrf2/HO-1 pathway and regulating oral microbiota, PAT-W is expected to become a new natural drug for treating oral ulcers and improving patients' quality of life.