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Objective: Manganese ion (Mn2+) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. Methods: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway. Moreover, Mn2+ suppressed the development of 4NQO–induced carcinogenesis in the mouse model. In addition, the G‐TA@Mn2+ hydrogel had better anti‐OLK effects. Conclusions: Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway, and the G‐TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Proteasome activator 28γ (PA28γ) upregulation plays a critical role in the carcinogenesis of many malignancies, including oral cancer. We aim to screen the related genes of PA28γ and investigate their function in oral mucosa carcinogenesis. Materials and methods: Bioinformatics analysis was performed to screen the related genes of PA28γ. Immunohistochemical analysis was carried out to validate their correlation in oral squamous cell carcinoma (OSCC) and detect their expression levels in the whole process of oral mucosa carcinogenesis. The Kaplan–Meier method was used for estimating the overall survival, and the Cox models were constructed to predict the prognosis. Results: U2 small nuclear RNA auxiliary factor 1 (U2AF1) was screened out, and the correlation between U2AF1 and PA28γ was further validated in OSCC. The expression levels of PA28γ and U2AF1 were gradually increased from normal to oral potentially malignant disorders (OPMD) to OSCC tissues. Overall survival was significantly shorter in patients with high U2AF1 expression and the combined application of U2AF1 and PA28γ notably improved the accuracy of prognosis prediction. Conclusion: U2AF1 and PA28γ might play pivotal roles in the progression of OPMD, which may provide insights into the development of new therapeutic strategies to prevent OPMD from becoming malignant. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusion Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter‐ and intra‐observer reliability and validity.Retrospective cohort included 209 sets of digital‐photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA).The intraclass correlation coefficient showed the inter‐observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra‐observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min.POLAI is valid for the assessment of oral PV with superior inter‐ and intra‐observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic. [ABSTRACT FROM AUTHOR]