Fibroblast activation protein (FAP) as a prognostic biomarker in multiple tumors and its therapeutic potential in head and neck squamous cell carcinoma.

Background: Fibroblast activation protein (FAP), a cell surface serine protease, plays roles in tumor invasion and immune regulation. However, there is currently no pan-cancer analysis of FAP. Objective: We aimed to assess the pan-cancer expression profile of FAP, its molecular function, and its potential role in head and neck squamous cell carcinoma (HNSC). Methods: We analyzed gene expression, survival status, immune infiltration, and molecular functional pathways of FAP in The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) tumors. Furthermore, to elucidate the role of FAP in HNSC, we performed proliferation, migration, and invasion assays post-FAP overexpression or knock-down. Results: FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them. In the context of immune infiltration, FAP expression negatively correlated with CD8+ T-cell infiltration in five tumor types and positively with regulatory T-cell infiltration in four tumor types. Our enrichment analysis highlighted FAP's involvement in the PI3K-Akt signaling pathway. In HNSC cells, FAP overexpression activated the PI3K-Akt pathway, promoting tumor proliferation, migration, and invasion. Conversely, FAP knockdown showed inhibitory effects. Conclusion: Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.

The effect of Jiaweidaochi powder on Th1/Th2 in rats with recurrent aphthous ulcer.

OBJECTIVE: To elucidate the effect of Jiaweidaochi powder on the Th1/Th2 ratio in rats with recurrent aphthous ulcers (RAU). DESIGN: 40 Sprague-Dawley rats were included in this study, randomly divided into a control group, a model group, and three treatment groups (0.5 g/ ml, 1 g/ml, 2 g/ml Jiaweidaochi powder). The RAU model of rats was established by autoantigen injection. The effects of Jiaweidaochi powder on the expression of INFG, IL-4, TBX21, and GATA3 mRNA were detected by real-time PCR. The expression of IFN-γ, IL-4, and IFN-γ/IL-4 proteins in oral ulcer tissue and serum of rats were analyzed by Western blot and ELISA, respectively. The proportion of Th1 cells and Th2 cells in RAU rats was analyzed by flow cytometry. RESULTS: Jiaweidaochi powder reduced the number, diameter, and duration of oral ulcers in RAU rats. Real-time PCR showed that middle and high-dose Jiaweidaochi powder decreased the expression of INFG TBX21 mRNA and increased the expression of IL-4 and GATA3 mRNA in the oral tissue of RAU rats. ELISA and western blot confirmed that the expression of IFN-γ protein was significantly decreased, and the level of IL-4 protein was increased both in oral tissue and serum of RAU rats treated with middle or high doses of Jiaweidaochi powder. Flow cytometry found that the Jiaweidaochi powder decreased the proportion of Th1 cells and increased the proportion of Th2 cells in RAU rats. CONCLUSION: This study found that Jiaweidaochi powder promoted the balance of Th1/Th2 in RAU rats, contributing to the healing of RAU.

Fibroblast activating protein promotes the proliferation, migration, and activation of fibroblasts in oral submucous fibrosis.

OBJECTIVES: Fibroblast activating protein (FAP) is associated with various organ fibrosis. However, the expression and molecular function of FAP in oral submucous fibrosis (OSF) is still unclear. MATERIALS AND METHODS: The high-performance liquid chromatography was used to detect the presence of alkaloids in areca nut extract (ANE). Real-time qPCR, Western blot, and Immunohistochemistry assay were used to analyze the expression of FAP mRNA or protein in OSF and normal oral tissue. A chi-squared test analyzed the relationship between FAP protein expression and clinicopathological data of OSF patients. CCK-8, Wound-healing, and Transwell migration assay were employed to assess the effect of the proliferation and migration ability of hOMF cells with FAP overexpression or knockdown. The expression level of a-SMA, FSP1, and P13K-Akt signaling pathways-related protein in hOMF cells transfected with FAP overexpression or knockdown plasmid was verified by western blot assay. RESULTS: The four specific areca alkaloids (Arecoline, Guvacine, Arecaidine, and Guvacoline) were successfully detected in the ANE. The viability of hOMF cells was significantly improved in the 50 µg/mL ANE group and was inhibited in the 5 and 50 mg/mL ANE groups. The expression of FAP was upregulated in OSF tissues, and hOMF cells treated with 50 µg/mL ANE and was related to pathology grade, clinical stage, and history of chewing betel nut. Additionally, FAP may promote the proliferation, migration, and activation of hOMF cells through the P13K-Akt signaling pathway. CONCLUSIONS: This study found that ANE had a bidirectional effect on the viability of hOMF cells, and the FAP gene was a potential therapeutic target in OSF.

Effects of the Screw-Access Hole Diameter on the Biomechanical Behaviors of 4 Types of Cement-Retained Implant Prosthodontic Systems and Their Surrounding Cortical Bones: A 3D Finite Element Analysis.

PURPOSE: To investigate the effect(s) of screw-access hole (SAH) in different diameters on the cement-retained implant prosthodontic systems and surrounding cortical bones. MATERIALS AND METHODS: Twenty finite element models were divided into 4 groups: 2 types of full-contour (FC) crowns (Y-TZP, gold alloy) and 2 types of porcelain-fused-to-metal crowns (based on Co-Cr, Au-Pd alloy). For each group, 5 crowns were simulated by varying the diameter of SAH (0, 1, 2, 3, and 4 mm). A vertical load of 200 N and an oblique load of 100 N (45°s) were applied. All models were analyzed with finite element analysis software. RESULTS: The stress on the occlusal surface of crowns was almost unchanged when the SAH was within 0 to 3 mm, whereas it showed an obvious increase when it reached 4 mm. The stress concentration was also suddenly changed from the loading area to the hole margin under vertical loading. As for the screw, a lower stress level was observed in vertical loading when an FC crown with an SAH within 0 to 1 mm was applied. The stress concentration was constantly located at the beginning of the first thread. Stresses of other components remained almost unchanged. CONCLUSIONS: From the aspect of biomechanics, an FC crown with a 1-mm access hole is recommended when a combined cement- and screw-retained crown was used in the posterior region.