CD8+ tissue-resident memory T cells induce oral lichen planus erosion via cytokine network.

CD8+ tissue-resident memory T (CD8+ Trm) cells play key roles in many immune-inflammation-related diseases. However, their characteristics in the pathological process of oral lichen planus (OLP) remains unclear. Therefore, we investigated the function of CD8+ Trm cells in the process of OLP. By using single-cell RNA sequencing profiling and spatial transcriptomics, we revealed that CD8+ Trm cells were predominantly located in the lamina propria adjacent to the basement membrane and were significantly increased in patients with erosive oral lichen planus (EOLP) compared to those with non-erosive oral lichen planus (NEOLP). Furthermore, these cells displayed enhanced cytokine production, including IFN-γ (Interferon-gamma, a pro-inflammatory signaling molecule), TNF-α (Tumor Necrosis Factor-alpha, a cytokine regulating inflammation), and IL-17 (Interleukin-17, a cytokine involved in immune response modulation), in patients with EOLP. And our clinical cohort of 1-year follow-up was also supported the above results in RNA level and protein level. In conclusion, our study provided a novel molecular mechanism for triggering OLP erosion by CD8+ Trm cells to secrete multiple cytokines, and new insight into the pathological development of OLP.

Humoral immune disorders affect clinical outcomes of oral lichen planus.

OBJECTIVES: The molecular characteristics of oral lichen planus (OLP) are still unclear, and it is not possible to distinguish the clinical outcome of OLP patients in a short period of time for follow-up. Here, we investigate the molecular characteristics of lesions in patients with stable lichen planus (SOLP) and recalcitrant erosive oral lichen planus (REOLP). METHODS: Our clinical follow-up cohort was split into SOLP and REOLP groups based on the follow-up clinical data. The core modules associated with the clinical information were identified by weighted gene co-expression network analysis (WGCNA). The OLP cohort samples were divided into two groups by molecular typing, and a prediction model for OLP was created by training neural networks with the neuralnet package. RESULTS: We screened 546 genes in five modules. After doing a molecular type of OLP, it was determined that B cells might have a significant impact on the clinical outcome of OLP. In addition, by means of machine learning, a prediction model was developed to predict the clinical regression of OLP with greater accuracy than the existing clinical diagnostic. CONCLUSIONS: Our study revealed humoral immune disorders may make an important contribution to the clinical outcome of OLP.

Detection of the peripheral blood antigens and clinical value in recurrent aphthous ulcer: A cross-section study.

Abstract Background/purpose: Recurrent aphthous ulcer (RAU) is one of the most common diseases of oral mucosa, which is generally believed to be related to immunity, though the etiology is still unclear. It is suspected that allergies are directly related to RAU. So we sought to explore the relationship between hypersensitivity and RAU. Materials and methods: 40 RAU patients who were in ulceration period and 40 people who were in good health were selected from Jan 2016 to Feb 2017, matched in age and sex. The peripheral blood antigens of 40 RAU patients and 40 healthy people was tested, and serum specific IgE (sIgE) with 6 groups of antigens and total IgE (tIgE) analysis was performed to identify IgE-mediated allergic reaction possibly affecting RAU. We then investigated the food intolerance and IgG levels to discover the correlation between non-IgE mediated allergic reaction and RAU. Results: The positive cases and rate of sIgE in RAU group was higher than that of control, but the difference was not statistically significant (P＞0.05). Positive grade of animal fur scraps (EX1), house dust mixed (HX2) and the serum tIgE concentration of the RAU group were significantly higher than the control group (P＜0.05).The number of food intolerance in RAU group was significantly higher than that in control group (P＜0.05). Conclusion: Our findings suggested certain correlation between RAU and anaphylaxis. Daily contact allergens and food intolerance may be one of the causes of RAU. Moreover, this provides reference value for clinical diagnosis and treatment.

SNAI2 promotes the malignant transformation of oral leukoplakia by modulating p-EMT.

OBJECTIVE: Snail family transcriptional repressor 2 (SNAI2) is a key regulator of partial epithelial-mesenchymal transition (p-EMT) and is associated with tumorigenesis. Whether SNAI2 promotes oral leukoplakia (OLK) malignant transformation by modulating p-EMT is unclear. MATERIALS AND METHODS: This study utilized two clinical datasets (GSE26549 and GSE85195) from the Gene Expression Omnibus database, cytological experiments, and a 4-nitroquinoline 1-oxide-induced mice model to explore the role of SNAI2 in OLK malignant transformation. RESULTS: The clinical cohort found SNAI2, as a risk factor (HR = 2.50, 95% CI: 1.08-5.79, p = 0.033), could promote OLK malignant transformation (p = 0.012). Cytological experiments indicated that SNAI2 overexpression promoted DOK cell proliferation, invasion, migration, and increase the protein expression of p-EMT relative signatures, whereas SNAI2 silencing has opposite effects. Furthermore, the mice model and clinical datasets demonstrated the expression of SNAI2 and p-EMT relative signatures were increased with OLK malignant transformation. And SNAI2 was strongly correlated with p-EMT. Besides, co-expressed genes of SNAI2 were also enriched in p-EMT relative biological processes and signaling pathways. CONCLUSIONS: p-EMT plays a significant role in promoting the OLK malignant transformation. As an important regulator of p-EMT, SNAI2 could be a target to block the OLK malignant transformation.

The interleukin-6 family in tissues is closely related to the clinical outcomes of oral lichen planus.

OBJECTIVE: We attempted to investigate the role of interleukin-6 (IL-6) family expression in local tissues as it relates to presentations and outcomes in oral lichen planus (OLP), which is a common chronic inflammatory oral disease. MATERIALS AND METHODS: A clinical follow-up cohort of OLP patients was established, and a biological sample library was constructed with categorization into erosive type (EOLP) and nonerosive type (NEOLP). Transcriptome sequencing of the lesions was then performed. A multiple regression model was used to explore the differences in IL-6 family expression among patients with different clinical types and clinical outcomes. RESULTS: OLP tissue transcriptome sequencing showed that IL-6 family expression in EOLP increased significantly. It was also found that IL-6 family factors in the OLP recurrent erosion group were significantly increased compared to the persistent nonerosion group. Based on the multiple regression analysis of the OLP clinical cohort, it was found that the increased expression of the IL-6 family was closely related to the clinical types and clinical outcomes of OLP. CONCLUSION: The high expression of the IL-6 family is closely related to the erosion of local mucosa and poor prognosis of OLP patients. IL-6-related factors may be used as therapeutic targets for OLP patients.

Effect of Marital Status on Upper Digestive Tract Tumor Survival: Married Male Patients Exhibited a Better Prognosis.

Purpose: Marital status has been associated with the outcomes in several types of cancer, but less is known about upper digestive tract tumors (UDTTs). The study aims to explore the effect of marital status on the survival outcomes of UDTT. Methods: We collected patient cases of UDTT using the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. The univariate analyses of overall survival (OS) and cancer-specific survival (CSS) were performed using the Kaplan-Meier method. The multivariate survival analyses were performed using Cox proportional hazard model. Results: A total of 282,189 patients were included, with 56.42, 16.30, 13.33, and 13.95% of patients married, never married, divorced or separated, and widowed, respectively. The significant differences were observed among married, never-married, divorced or separated, and widowed patients with regard to the year of diagnosis, sex, age, race, pathological type, anatomical site, the number of primary tumor, grade, rate of surgery performed, radiotherapy, chemotherapy (p < 0.001). The proportions of patients with 3-year and 5-year OS were 54.22 and 48.02% in the married group, 46.96 and 41.12% in the never-married group, 44.24 and 38.06% in the divorced or separated group, 34.59 and 27.57% in the widowed group, respectively (p < 0.001); the proportions of patients with 3-year and 5-year CSS were 70.76 and 68.13% in the married group, 62.44 and 59,93% in the never-married group, 63.13 and 60.53% in the divorced or separated group, 62.11 and 58.89% in the widowed group, respectively (p < 0.001); all these data indicated married patients exhibited favorable OS and CSS than never-married, divorced or separated, and widowed patients. Men in the married group showed better OS (HR, 1.16; 95%CI: 1.11-1.22) and CSS (HR, 0.96; 95%CI: 0.92-1.23) than those in the never-married group. Conclusion: This study reveals that marital status is an independent prognostic factor for OS and CSS of patients with UDTT. Married male patients with UDTT trend to have a better prognosis.

Predisposition of hypersensitivity in patients with exfoliative cheilitis.

BACKGROUND/PURPOSE: Exfoliative cheilitis (EC) is a chronic and reversible inflammatory disease of the lips without definite etiology. Clinically, different types of allergens can be found in exfoliative cheilitis patients, however, few studies have focused on the relationship between exfoliative cheilitis and hypersensitivity. This research aimed to investigate the prevalence of hypersensitivity in EC patients. MATERIALS AND METHODS: A prospective study was conducted in 30 patients with exfoliative cheilitis and 30 healthy controls, matched in age and sex. Laboratory tests included serum total IgE, allergen-specific IgE, and food-specific IgG. RESULTS: Increased serum total IgE level, positive food-specific IgG were seen more frequently in exfoliative cheilitis patients than in healthy control (P < 0.05). Special IgE level to FX5 and the degree of food-specific IgG to wheat were seen higher in exfoliative cheilitis patients than in healthy control (P < 0.05). CONCLUSION: This study suggests that patients with exfoliative cheilitis may have predisposition of hypersensitivity. The detection of allergens should be strengthened in the future clinical work.

Activation of EGFR-Aurora A induces loss of primary cilia in oral squamous cell carcinoma.

OBJECTIVE: Primary cilia, evolutionally conserved organelles involving multiple cell functions, are frequently lost in various cancers. However, little is known about the role of primary cilia in oral squamous cell carcinoma (OSCC). METHODS: Immunofluorescence staining was applied to detect primary cilia in normal, oral leukoplakia (OLK) and OSCC tissues. Differentially expressed ciliary genes of OSCC were screened from the TCGA database. Immunohistochemical analysis was used for validating the correlation between the expression of interested proteins and primary cilia, and their regulatory effect on primary cilia was further proved in vitro and in vivo. RESULTS: A significant decrease in cilia ratio was found in OLK, especially in OSCC. Multiple ciliary genes were abnormally expressed in OSCC and epidermal growth factor receptor (EGFR)-Aurora A signaling was chosen for further study. A parallel increase of EGFR-Aurora A was observed in OLK and OSCC tissues. Moreover, EGFR activation induced obvious cilia absorption by phosphorylating Aurora A. Besides, Aurora A silencing significantly restored ciliary expression and decreased tumor growth in vivo. CONCLUSIONS: The abnormal activation of EGFR-Aurora A leads to the gradual loss of primary cilia in oral mucosa carcinogenesis. Primary cilia have the potential to be new biomarkers and therapeutic targets of oral cancer.

Dexamethasone inhibits BMP7-induced osteogenic differentiation in rat dental follicle cells via the PI3K/AKT/GSK-3ß/ß-catenin pathway.

Impacted third molars are commonly seen in teenagers and young adults and can cause considerable suffering. Preventing eruption of the third molars can reduce pain at the source. Our previous study has shown that dexamethasone (DEX) at a certain concentration can prevent the eruption of third molars without damaging alveolar bone in Sprague-Dawley (SD) rats, but the relevant molecular mechanisms need to be explored. This study aimed to explore the effects of high concentrations of DEX on osteogenic signaling pathways, including BMP/Smad and Wnt/ß-catenin pathways, in rat dental follicle cells (rDFCs) and to elucidate the possible mechanisms. The results showed that BMP7 induced osteogenic differentiation by increasing the activity of ALP and the protein levels of OPN in rDFCs. DEX decreased endogenous BMP7 and phosphorylated Smad1/5/8 expression as well as BMP7-induced osteogenic differentiation. DEX also reduced the mRNA and protein levels of ß-catenin by enhancing the expression of GSK-3ß. In addition, regardless of DEX intervention, overexpression of BMP7 promoted the expression of ß-catenin, while knockdown of BMP7 attenuated it. Further investigation revealed that overexpression of BMP7 attenuated the DEX-mediated inhibition of AKT and GSK-3ß phosphorylation, but knockdown of BMP7 exerted the opposite effects. This study suggests that high concentrations of DEX may inhibit the expression of ß-catenin via the PI3K/AKT/GSK-3ß pathway in a manner mediated by BMP7. The findings further illustrate the possible molecular mechanisms by which DEX prevents tooth development.

The chronological age estimation of third molar mineralization of Han population in southwestern China.

The purpose of the study was to estimate the chronology of third molar mineralization in Han population of southwestern China and find its unique characteristics so that it would provide a reference in several legal cases like forensic age estimation. The study used Demirjian's staging method to study 2192 orthopantomograms of 984 male and 1208 female subjects aged between 8 and 25 years. The statistical data was analyzed by Student's t test and ANOVA. The conclusions of the study are: (1) The chronological mineralization age of third molars of Han population in Southwestern China is similar to the Turkish and the Japanese, was earlier than the Austrian and Han of South China, but later than the Spanish. (2) The mineralization timing of the third molars between two sides in maxilla or mandible has no significant differences in the same gender group. (3) There is no significant difference in mineralization of third molars between male and female, except for tooth 48 in Demirjian's stage E. (4) The mineralization of third molar in maxilla is earlier than mandible.