Search Results (133)

Background/Objective: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with unclear etiology. Increasing evidence implicates oral microbial dysbiosis in its pathogenesis, but little is known about supragingival plaque communities in relation to clinical subtypes. This cross-sectional case–control study aimed to characterize the supragingival plaque microbiota and microbial interaction networks in erosive OLP (E-OLP), non-erosive OLP (NE-OLP), and healthy controls (HCs), to elucidate microbial patterns associated with disease severity. Methods: Supragingival plaque samples were collected from 90 participants (30 per group) and analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance, and co-occurrence network analyses were performed. Results: E-OLP exhibited pronounced dysbiosis, including the enrichment of pro-inflammatory taxa (e.g., Prevotella, Parvimonas) and depletion of health-associated commensals (e.g., Rothia, Capnocytophaga). Network analysis revealed the stepwise disintegration of microbial community structure from HC to NE-OLP to E-OLP, with reduced connectivity and increased dominance of pathogenic clusters in E-OLP. These microbial alterations aligned with clinical findings, as E-OLP patients showed significantly higher Reticulation/keratosis, Erythema, and Ulceration (REU) scores for erythema and ulceration compared to NE-OLP. Conclusions: Supragingival plaque dysbiosis and ecological disruption are strongly associated with OLP severity and subtype. This study highlights the utility of plaque-based microbial profiling in capturing lesion-proximal dysbiotic signals, which may complement mucosal and salivary analyses in future diagnostic frameworks. Multi-omics approaches incorporating fungal, viral, and metabolic profiling are warranted to fully elucidate host–microbe interactions in OLP. Full article

Background: Oral mucositis (OM) is a common and debilitating complication of cancer therapy, particularly in patients undergoing chemotherapy and radiotherapy. It significantly impairs quality of life and may necessitate the interruption of cancer treatment. This study aimed to evaluate the efficacy and safety of OROSOL, an oral spray device, in managing oral mucositis in pediatric patients undergoing chemotherapy or radiotherapy. Methods: This randomized, double-blind, placebo-controlled clinical trial compared OROSOL to a placebo in children with oral mucositis aged 3 to 17 years. Participants were followed for 28 days with regular medical visits. The primary endpoints were changes in the Oral Assessment Guide (OAG) scores and key symptoms (mucositis score, difficulty in oral feeding, ulceration and erythema, and pain sensation). Safety was assessed via adverse events and local tolerability. Results: Both groups were demographically balanced at baseline (p > 0.6). OROSOL demonstrated significantly greater improvements in the mucositis score beginning on Day 7 (p = 0.0122) and maintained superiority through Day 28 (p = 0.0007). Notable reductions in mucositis severity were observed, with significantly faster relief in the OROSOL group compared to the placebo (p < 0.001 for most timepoints). Oral feeding difficulty also showed a marked decline, with significant improvements starting from Day 5 (p = 0.0153). Ulceration and erythema scores significantly decreased from Day 14 onwards (p = 0.0188). Pain sensation showed a marked reduction from Day 14 (p = 0.0014). No serious adverse events were reported, and tolerability was consistent across all participants. Conclusions: OROSOL has a significant impact on reducing mucositis severity, oral feeding difficulty, ulceration, erythema, and pain. Coupled with its excellent safety profile, it is a valuable therapeutic option. This treatment is particularly beneficial for pediatric patients, ensuring improved comfort and recovery without notable adverse effects. Full article

Glycyrrhiza glabra (licorice) has been used as an herbal medicine for a long time due to its anti-inflammatory, antioxidant, and antimicrobial properties. Additionally, multiple reports have demonstrated its ability to promote wound healing. Several randomized controlled or clinical trials (RCTs) have demonstrated its potentially therapeutic effects in oral mucosal diseases, especially in recurrent aphthous stomatitis (RAS). This systematic review aims to summarize the evidence for Glycyrrhiza glabra in treating RAS. A systematic search was performed across five databases: PubMed (Medline), ScienceDirect, Scopus document, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Library Database of Systematic Reviews. This study was reported following the PRISMA guidelines. RCT study using Glycyrrhiza glabra for treating RAS was included in this study with several reported outcomes like changes in ulcer diameter, pain, and healing periods. Seven RCTs were included, which used Glycyrrhiza glabra in the form of patches, pastes, mucoadhesive tablets, and mouthwashes for treating RAS. Glycyrrhiza glabra treatment in various regimens showed significant improvements in pain, ulcer diameter, and healing time in patients with RAS. This review suggests the potential of Glycyrrhiza glabra as an alternative treatment option for RAS. Full article

Background: Oral ulceration with bone sequestration (OUBS) is an uncommon clinical lesion characterized by painful mucosal ulceration associated with exposed and necrotic bone in the oral cavity, often without known factors inducing osteonecrosis. Despite its potential for diagnostic confusion with more serious lesions, such as medication-related osteonecrosis, OUBS remains poorly understood and underreported. Objectives: To systematically review the literature on OUBS and identify its main clinical and radiographic characteristics to assist in early diagnosis and appropriate management. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in the PubMed, Scopus, and Web of Science databases on 27 January 2024, to identify case reports, case series, and observational studies that described OUBS. Data extraction focused on demographic information, lesion location, clinical features, radiographic findings, possible etiological factors, management, and outcomes. The Joanna Briggs Institute (JBI) critical appraisal tools were utilized to assess the quality of the case reports and series. Data were synthesized narratively due to heterogeneity among studies. Results: Fifty-seven patients from 22 studies were included. The male-to-female ratio was 2.5:1, with most cases (71.9%) occurring in males. The mean age was 50.22 ± 11.49 years, with the highest incidence in patients aged 50–59 years (64.9%). Most cases were localized to the mandible (94.7%). Clinically, lesions were shallow ulcers (mean size: 0.75 ± 0.85 cm). Pain was the most common symptom (88.9%). Radiographs revealed no significant maxillary abnormalities, but some cases showed radiopaque areas in the mandible. Surgical interventions were most common (40.4%), with complete healing in 67.7% of cases within 4 weeks. Limitations include the predominance of case reports and series, which limits the strength of evidence. Conclusions: Recognizing OUBS can prevent misdiagnosis and unnecessary interventions. Further studies are needed to clarify its etiology and natural history. Registration: This review was registered on the PROSPERO database (registration number CRD42024541416). Full article

Background and Objectives: Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert immunoregulatory effects in various models of inflammation. This study aimed to evaluate the protective effects of Indoximod in an acetic acid-induced colitis model in rats, focusing on histopathological changes and inflammatory mediators. Materials and Methods: Thirty male Wistar albino rats were randomly assigned to three groups (n = 10 per group): Group 1 (Control) received 0.9% saline oral gavage; Group 2 (Colitis) received intrarectal 4% acetic acid to induce colitis and were then treated with saline; Group 3 (Colitis + Indoximod) received 4% acetic acid followed by oral gavage administration of Indoximod (30 mg/kg) for 15 consecutive days. Histopathological evaluation of colonic tissues was performed using hematoxylin and eosin (H&E) staining. Colonic expression of Toll-like receptor 4 (TLR4) and plasma levels of tumor necrosis factor-alpha (TNF-α), pentraxin-3 (PTX-3), and platelet-activating factor (PAF) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Acetic acid-induced colitis significantly increased mucosal damage, TLR4 expression, and circulating levels of TNF-α, PTX-3, and PAF compared with controls (p < 0.001). Indoximod treatment markedly reduced histological injury and significantly suppressed TLR4 and TNF-α levels (p < 0.01), along with partial reductions in PTX-3 (p < 0.05). However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. Conclusions: Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators. Full article

Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert^®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent, recurrent, and relapsing inflammation of the mucosal layer. Its pathogenesis is complex and not yet fully understood, with current treatments mainly focused on alleviating symptoms through pharmacological methods. Direct drug administration for UC often leads to poor intestinal bioavailability, suboptimal targeting, and an increased risk of resistance. Therefore, there is an urgent need for effective drug delivery systems. Lipid nanoparticles (LNPs) are promising candidates for UC drug delivery due to their high biocompatibility, stability, and customizable properties. Oral administration, as a preferred treatment approach for UC, offers benefits such as convenience, cost-effectiveness, and better patient compliance. However, oral drug delivery systems must navigate the complex gastrointestinal tract to effectively target colonic lesions, posing significant challenges for LNP-based systems. Researchers are exploring ways to enhance oral delivery efficiency by adjusting LNP composition, surface functionalization, and coating. This article reviews recent advancements in oral LNP research aimed at improving drug delivery efficiency for UC treatment and discusses future prospects. Full article

Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. Ramulus Mori alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. Full article

Hydrogels (HDs) offer a promising platform for localized and sustained drug delivery. In this study, carboxymethyl chitosan (CMC)—based hydrogels were crosslinked with genipin and evaluated for the controlled release and tissue retention of suramin, a polyanionic drug with anti-inflammatory and antifibrotic properties. The influence of crosslinking density (1%, 3%, and 5%) on drug release, permeation kinetics, and retention was investigated using in vitro synthetic membranes and reconstructed human epithelial tissue models. The 1% genipin HD exhibited the highest cumulative release and drug retention (48.8 ± 6.8 μg/cm² in synthetic membranes; 24.06 ± 7.33 μg/cm² in epithelial models), along with a sustained release profile governed by first-order and Fickian diffusion kinetics. Notably, the 1% crosslinked formulation also demonstrated enhanced transmembrane flux (>140 μg/cm²/h after six hours), suggesting that lower crosslinking density favors both diffusional mobility and depot functionality. In contrast, free suramin solution displayed limited tissue interaction and minimal permeation, highlighting the role of the hydrogel matrix in regulating local bioavailability. These findings demonstrate that CMC–genipin HD can closely modulate drug delivery kinetics through crosslinking density, offering a biocompatible strategy for localized treatment of ulcerated epithelial conditions such as oral mucositis or chronic wounds. Diffusion models included a synthetic multilayer membrane (Strat-M^®) and a reconstructed human epidermis (EpiDerm™) to simulate skin-like barrier properties. Full article

Background: Oral ulcerative mucositis (OUM) is a painful, inflammatory mucosa lesion that impairs quality of life. Despite available treatments, effective agents that promote faster healing and modulate inflammation are still needed. Oxytocin (OT), a neuropeptide with anti-inflammatory and antioxidant properties, may aid wound healing by regulating the remodeling of the extracellular matrix (ECM). This study investigates the effects of OT on oral ulcer healing in rats, focusing on its modulation of the MMP-2/TIMP-2 pathway. Methods: Acetic acid 70% was used as the oral mucosal ulcer inducer. Thirty-six Wistar albino rats were divided into control, oral ulcer + saline, and oral ulcer + OT (intraperitoneally for 15 days) groups. Histopathological, biochemical, and molecular analyses were performed. Buccal mucosa tissue was examined for TNF-α, TIMP-2, and MMP-2 levels via ELISA, while oxidative stress markers and pentraxin-3 (PTX3) were also assessed. Results: OT significantly preserved epithelial integrity and reduced fibrosis compared to the saline group (p < 0.001). TNF-α, MMP-2, PTX3, and malondialdehyde levels were significantly lower, while TIMP-2 levels were elevated in the OT-treated group (p < 0.01). Histopathological analysis confirmed reduced inflammation and enhanced tissue organization. Conclusions: OT accelerates oral ulcer healing by modulating inflammation, oxidative stress, and ECM remodeling via the MMP-2/TIMP-2 pathway. These findings highlight its potential as a therapeutic agent for managing mucosal injuries. Further clinical studies are warranted. Full article

Objectives: Mucositis is a debilitating side effect of cancer therapy that adversely affects quality of life, cost of care, and the outcome of cancer therapy. Oral mucositis-related pain may be treated with numerous modalities but often includes opioids. The effects of opiate treatment on painful UM and its overall influence on the burden of illness (BOI) in cancer patients remain unknown. Methods: This study utilized the 2017 United States (US) National Inpatient Sample (NIS) database. The exposure was opioid treatment for chemo-induced ulcerative mucositis (UM), oral mucositis-induced pain, and the main outcomes included in-hospital mortality and BOI, length of hospital stays (LOS), and total hospital charges. Multivariable regression analysis was used to examine the relationship between outcomes and the key independent variable, opioid use, adjusting for propensity scores. Results: In the propensity score-adjusted analysis, UM patients with opioid treatment had 0.51 times lower total charges (95% CI: 0.42–0.76) and 0.67 times shorter LOS (95% CI: 0.51–0.87) than the UM patients without opioid treatment. However, there was no association between opioid treatment and in-hospital mortality. In the sensitivity analysis, the effect estimates were comparable in the propensity score-adjusted analysis, the decile-adjusted model, and the full model with the non-propensity score estimated method. Conclusions: Cancer patients with chemotherapy-induced UM-prescribed opioid analgesics for treating pain are associated with a lower BOI. Opioid pain medications are commonly provided to cancer survivors; estimating the BOI among them is crucial in supportive care research. Full article

Background: Agarwood has been widely used for the treatment of gastrointestinal diseases. Our research group has suggested that agarwood alcohol extracts (AAEs) provide good gastric mucosal protection. However, the exact mechanisms underlying this effect remain unclear. Objectives: This study aimed to investigate the ameliorative effect of agarwood chromone on gastric ulcers and its mechanism. Methods: Network pharmacology was used to predict the disease spectrum and key therapeutic targets of 2-(2-phenylethyl)chromone (CHR1) and 2-(2-(4-methoxyphenyI)ethyl)chromone (CHR2). Mice were orally administered CHR1 (20 and 40 mg/kg) and CHR2 (20 and 40 mg/kg) and the positive drug omeprazole as an enteric-coated capsule (OEC, 40 mg/kg) orally. After 7 days of pretreatment with the CHRs, gastric ulcers were induced using absolute ethanol (0.15 mL/10 g). The ulcer index, gastric histopathology, biochemical parameters, and inflammatory and apoptotic proteins were evaluated. Finally, binding of the core compounds to the key targets was verified via molecular docking and visualized. Results: The pharmacological results show that the CHRs reduced the gastric occurrence and ulcer inhibition rates by up to more than 70% in a dose-dependent manner. The CHRs decreased the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), and improved the severity of the pathological lesions in the gastric tissue. The expression of ATP-binding box transporter B1 (ABCB1), arachidonic acid-5-lipoxygenase (ALOX5), nuclear factor kappa B (NF-κB), cysteinyl aspartate specific proteinase 3 3 (Caspase3), and cysteinyl aspartate specific proteinase 9 (Caspase9) was inhibited, but the expression of B-cell lymphoma-2 (Bcl-2) was enhanced. The CHRs bound stably to the key targets via hydrogen bonding, van der Waals forces, etc. These results demonstrate that agarwood chromone compounds exert alleviative effects against the occurrence and development of gastric ulcers by inhibiting the NF-κB and caspase pathways. The CHRs have a therapeutic effect on gastric ulcers through anti-inflammation and anti-apoptosis mechanisms. Conclusions: This study suggests that agarwood may have a potential role in drug development and the prevention and treatment of gastrointestinal inflammation, and tumors. Full article

Ulcerative colitis (UC) pathogenesis is strongly linked to gut microbiota dysbiosis and compromised intestinal barrier integrity. Emerging evidence suggests that targeted dietary interventions may restore microbial homeostasis and ameliorate colitis progression. In this study, we evaluated the therapeutic potential of Fu Brick tea (FBT) using a dextran sulfate sodium (DSS)-induced murine colitis model. The results indicated that oral administration of FBT extract significantly improved the disease index, reduced inflammatory response, protected intestinal barrier protein (e.g., ZO-1), and maintained intestinal structure integrity. Furthermore, FBT intake increased the diversity of gut microbiota, promoted the growth of beneficial bacteria (e.g., Akkermansia), inhibited the proliferation of harmful bacteria (e.g., Desulfovibrioceae, Escherichia, and Helicobacter), restored intestinal homeostasis, and alleviated colitis symptoms including diarrhea. These findings position FBT as a promising nutraceutical candidate for UC management via multi-target modulation of mucosal immunity and microbial ecology. Full article

Background/Objectives: Ulcerative colitis (UC) is a part of inflammatory bowel disease (IBD) and it is characterized by colonic-mucosal chronic inflammation with intermittent clinical activity. Personalized medicine is becoming more and more a relevant method of approach in this field, and the identification of potential concerns in a single patient may contribute to the improvement of the clinical approach. Mesalamine represents the cornerstone of therapy for mild–moderate disease forms, but non-adherence to medical therapy represents a critical health problem, although it is underestimated by many physicians, with evident consequences in terms of disease-related complications. The aim of the present study is to evaluate the magnitude of non-adherence to oral mesalamine in UC patients performing a systematic review and meta-analysis of literature. Methods: A literature search in PubMed and Cochrane databases was performed for studies reporting the non-adherence rate to oral mesalamine in adult UC patients, and eligible studies have been selected for evaluation. The type of study (trial vs. observational), geographic area, sample size, method of adherence assessment, and non-adherence rate were considered. Results: From a total of 464 articles, 34 studies were included in the meta-analysis after selection. Sixteen studies (47%) are observational, and eighteen (53%) are clinical trials. A total of 12/34 (35%) studies are from North America, 14/34 (41%) from Europe, 4/34 (12%) from Asia, with 4/34 (12%) from mixed areas of the world. The mean non-adherence rate was 32%, but with a consistent variability among the studies. In particular, the non-adherence rate was significantly higher in observational studies vs. clinical trials (47 vs. 20%, p < 0.001), and in North American vs. European and Asian studies (54 vs. 23 vs. 4%, respectively, p < 0.001). Conclusions: The non-adherence rate to oral mesalamine is variably reported in the literature due to the inhomogeneity of available studies, but it represents a consistent problem, often neglected, that deserves future research. A personalized approach by a physician to a single patient can improve the effectiveness of medical therapy and the management of UC patients. Full article

Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45–74%) and dysgeusia (32–59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues. Full article