Oral diseases最新文献

Objective: This research provides a comprehensive analysis of immunotherapy clinical trials for head and neck squamous cell carcinoma, aiming to enhance future trial designs.

Methods: We analyzed all clinical trials focused on head and neck squamous cell carcinoma immunotherapy registered on ClinicalTrials.gov from January 1st, 2013, to December 31st, 2023, examining general characteristics, methodological features, and types of immunotherapeutic drugs.

Results: The analysis included 727 trials, with 687 interventional (94.50%) and 40 observational (5.50%). Most trials were small-sized (64.37%), single-centered (56.67%), non-blinded (94.76%), and non-randomized (72.93%). Over half of the trials were conducted in North America (55.71%), but trials in Asia increased significantly in the past 5 years (9.88% vs. 32.38%, p < 0.001). Only 20.63% of completed trials updated outcomes, with most results published 6-12 months after primary completion (55.13%). Immune checkpoint inhibitors were the predominant focus, and neoadjuvant immunotherapy was the main regimen in trials with resectable head and neck squamous cell carcinoma (74.83%).

Conclusions: There has been a gradual increase in clinical trials over the past decade, with most being interventional. Delays or absences in outcome submission were prevalent. Novel immunotherapeutic drugs and treatment regimens are a significant focus.

Objective: To compare the demographic and clinical profiles of oral lichen planus (OLP) and oral lichenoid lesions (OLL) diagnosed at a reference center in Southern Brazil from 2010 to 2019.

Methods: This retrospective study included 117 cases of suspected OLP submitted for biopsy. Investigated variables comprised sociodemographic profiles, medical history, harmful habits, clinical characteristics, and histopathological features. Categorical and numerical variables were analyzed using chi-square and Mann-Whitney tests (p < 0.01), respectively.

Results: Applying strict diagnostic criteria, 29% (n = 34) of cases were classified as OLP and 71% (n = 83) as OLL. OLP cases had mainly multifocal manifestations (82.4%), exhibiting a reticular pattern (100%) and primarily occurring on the buccal mucosa (94.1%). Conversely, OLL cases presented both unilateral (48.2%) and multifocal (51.8%) distributions, with a predominantly atrophic-erosive pattern (77.1%) and higher occurrence on the buccal mucosa (69.9%) and tongue (48.2%). OLL patients reported a higher frequency of systemic disorders and medication use (p < 0.01). Hypertension was the most prevalent condition, leading to the frequent use of cardiovascular medications. Two OLL cases without initial dysplasia underwent malignant transformation.

Conclusion: Patient profiles and clinical manifestations of the entities were similar, highlighting the utility of a differential diagnosis, particularly given the apparent association between malignant transformation and OLL cases.

Objectives: The aim of our study was to compare the salivary interleukin-6 (IL-6) concentration and the quality of life (QoL) in patients with oral lichen planus (OLP) or burning mouth syndrome (BMS).

Materials and methods: A total of 160 subjects participated in the cross-sectional study. The unstimulated whole saliva (UWS) was used as a reference for the determination of salivary IL-6 concentration by enzyme-linked immunosorbent assays (ELISAs). QoL was assessed using the Croatian version of the Oral Health Impact Profile Questionnaire (OHIP-CRO14).

Results: The salivary IL-6 concentration showed no statistically significant difference between patients with OLP, patients with BMS or control subjects (p = 0.244). There was a strong/good positive correlation between symptom intensity (pain/burning) and the OHIP-CRO14 dimension "physical pain" (r = 0.720, p < 0.001) and "physical impossibility" (r = 0.372, p = 0.003) in patients with OLP. There was a good positive correlation between symptom intensity (pain/burning) and the OHIP-CRO14 dimension "handicap" (r = 0.353, p = 0.005) in patients with BMS.

Conclusions: Symptom intensity (pain/burning) showed no correlation with salivary IL-6 concentration in patients with OLP or BMS. A slight increase or decrease in salivary IL-6 concentration in OLP or BMS indicates an inflammatory etiopathogenesis of OLP and a loss of neuroprotection in BMS.

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy, with unclear mechanisms. This study investigates the regulatory impact of zoledronic acid (ZOL) on osteoclasts and microRNA (miRNA) expression.

Materials and methods: Raw264.7 cells and bone marrow-derived macrophages (BMMs) were used to assess ZOL's effects on proliferation and apoptosis. miRNA array analysis was performed during osteoclastogenesis with ZOL treatment. The role of miR-483-5p was examined using miR-mimics and miR-inhibitors. A rat BRONJ model was established for in vivo validation.

Results: A concentration of 2 μM ZOL, which did not affect cell proliferation or apoptosis, was used in subsequent experiments. ZOL altered the expression of 64 miRNAs (39 upregulated, 25 downregulated). miR-483-5p mimics alleviated ZOL-induced inhibition of osteoclastogenesis, actin ring formation, bone resorption, and differentiation marker expression, whereas inhibitors enhanced these effects. In vivo, Ago-miR-483-5p promoted wound healing in the BRONJ model, while Antago-miR-483-5p impaired it.

Conclusions: ZOL modulates osteoclast function in BRONJ through miR-483-5p inhibition. miR-483-5p may serve as a novel therapeutic target for BRONJ treatment, providing new insights into managing this complication.

Aim: Comparing oral and gut microbiome profiles between patients with and without ulcerative mucositis during allogeneic stem cell transplantation (aSCT).

Materials and methods: Specimens from oral mucosa, saliva, and stool were collected pre-(T0) and post- (T0 +28d ± 14d) aSCT (T1). Microbiome structure differences were analyzed by 16S-rRNA-gene sequencing, and associations to patients' clinical characteristics were investigated.

Results: Ten of 25 included patients developed ulcerations. The α-diversity decreased between T0 and T1, independent of ulcerations. PERMANOVA revealed differences in beta diversity between T1 stool samples from patients with and without ulcerations. At T1, saliva samples of patients with ulcerations showed an increase of Mycoplasma salvarius, while commensals decreased in saliva and mucosal swabs. The gut microbiome of both groups showed an overabundance of Enterococcus spp., associated with inflammatory conditions. Salival α-diversity of older and overweight patients decreased slower, whereas in mucosal swabs mucositis or impaired renal function was associated with a higher decline. Female gender and history of periodontitis were associated with increased stool microbiome changes, while self-reported probiotics intake was related to reduced changes.

Conclusions: Ulcerations appeared in 40% of the patients. Distinct microbial changes, including increased abundance of Mycoplasma salivarius in saliva and decreased abundance of commensals, marked those with ulcerations.

Trial registration: The study was registered in the German Register for Clinical Studies (DRKS00032882).

Objective: To investigate the clinical manifestations of head and neck cancer in patients with Plummer-Vinson syndrome (PVS) and to assess related oral comorbidities.

Materials and methods: Case reports covering head and neck cancer manifestations in patients diagnosed with PVS were included Studies were identified through seven main electronic databases (PubMed/MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, LILACS, and LIVIVO), and a search for gray literature was performed using ProQuest Dissertations and Theses and Google Scholar. Independent reviewers applied predefined eligibility criteria in a two-phase selection process.

Results: Out of a total of 19,183 citations identified, seven met the inclusion criteria. Prevalent symptoms included dysphagia and esophageal webs, with atrophic glossitis and angular cheilitis being common oral manifestations. Most patients presented with long-standing iron deficiency anemia. Head and neck cancers predominantly affected the pharynx and tongue borders, with younger age groups notably affected. The overall risk of bias attributable to the quality of the reports was assessed as "low".

Conclusions: Despite the rarity of PVS-related head and neck cancer, this review underscores its association, particularly in younger patients. A thorough examination of dysphagia and oral manifestations in PVS patients is crucial for early detection and prevention of head and neck cancer.

Objective: To investigate the microarchitecture and crystalline composition of sialoliths and to explore their formation mechanisms.

Methods: Sixty-six sialolith samples (51 from the submandibular glands and 15 from the parotid glands) were retrospectively collected. Their diameter and quality were measured. Micro-computed tomography, scanning electron microscopy, and polycrystalline X-ray diffractometer (XRD) were utilized to determine their microstructure and crystalline composition.

Results: Stone diameter and weight averaged at 9.6 mm and 0.31 g, respectively. Submandibular stones showed larger size and weight than parotid stones. Microstructurally, the main stones were concentric (n = 51) or mixed (n = 15). Most concentric stones occurred at submandibular glands, while 80% of the mixed stones were parotid stones. Stone surface exhibited three microscopic structures: lamellar, grape-like, and porous, indicating their differences in mineralization process and composition. XRD revealed that all stones contained hydroxyapatite, with 57 containing whitlockite. Concentration of hydroxyapatite in concentric stones was significantly higher than that in mixed stones (p = 0.036) and correlated positively with stone diameter (p = 0.001). The microstructure and crystalline composition of multiple and recurrent stones were similar to that of single stones.

Conclusion: Sialoliths display pronounced diversity in microarchitecture and crystalline composition, reflecting the differences in mineralization process and local microenvironments among stones.

Objective: LepR-expressing cells (LepR⁺ cells), a critical subpopulation of mesenchymal stem cells, have gained increasing attention in the last decade. LepR⁺ cells have been found to play a crucial role in maintaining bone and periodontal homeostasis. This review summarizes current research advances focusing on the role of LepR⁺ cells and their underlying regulatory molecular mechanisms in bones and periodontium, aiming to provide a better understanding of the therapeutic potential of this cell lineage.

Methods: A literature review was conducted based on publications in PubMed over the past 20 years, summarizing the research progress on LepR⁺ cells in bone and periodontal tissues.

Results: Current evidence revealed that LepR⁺ cells possess the ability of self-renewal and multilineage differentiation and are essential for bone turnover and periodontal tissue remodeling. In addition, LepR⁺ cells participate in the processes of bone fracture healing and alveolar socket healing. Moreover, under pathological conditions such as osteoporosis, bone marrow fibrosis, and periodontitis, LepR⁺ cells exhibit enhanced adipogenic or fibrogenic differentiation abilities.

Conclusion: Therapeutic approaches targeting the cell fate of LepR⁺ cells hold the potential to provide novel insights into bone/periodontal repair and regeneration therapy.

Objective: Our study investigated how arecoline-induced extracellular vesicle (EV) secretion suppresses PAX1 protein production through DNA hypermethylation and examined whether PAX1 downregulation enhances cancer stemness and immunosuppression in the tumor microenvironment.

Materials and methods: EVs were isolated from SAS/TW2.6 cancer cell lines using ultracentrifugation and identified using transmission electron microscopy. PAX1 DNA methylation was tested in an ISO17025-certified lab, with and without EV pretreatment. Stemness and epithelial-mesenchymal transition markers were assessed by western blotting and 3D culture. PAX1, IFIT1, and PD-L1 co-expression were examined through immunofluorescence. Flow cytometry detected various T cells.

Results: Arecoline-induced EVs enhanced PAX1 methylation, suppressing its tumor-suppressive function. Reduced PAX1 mRNA in OSCCs was linked to larger tumors, nodal metastasis, late-stage disease, areca quid chewing, and poor survival. Downregulated PAX1 protein negatively correlated with IFIT1 and PD-L1 expression. Reduced PAX1 promoted stemness via the IFIT1 pathway, increasing PD-L1 secretion and aiding immune evasion. PD-L1 expression correlated with Treg and CD8+ T cell levels in OSCC tissues, and the CD4+/CD8+ T cell ratio was lower in OSCC patients than in controls.

Conclusion: Arecoline-induced EV production, which influences PAX1/IFIT1/PD-L1 function, may serve as a reliable biomarker for targeted therapy in OSCC patients.