Aberrant expression of Fos-related antigen-1 (Fra1) is commonly elevated in various malignant cancers and is strongly implicated in invasion and metastasis. However, the molecular mechanisms underlying its dysregulation in human glioma remain poorly understood. In the present study, we demonstrate that up-regulation of Fra1 plays a crucial role in the glioma aggressiveness and epithelial–mesenchymal transition (EMT) activated by Wnt/β-catenin signal pathway. In glioma cells, activation of Wnt/β-catenin signalling by Wnt3a administration obviously induced EMT and directly activated the transcription of Fra1. Phenotype experiments revealed that up-regulation of Fra1 induced by Wnt/β-catenin signalling drove the EMT of glioma cells. Furthermore, it was found that the cisplatin resistance acquired by Wnt/β-catenin signalling activation depended on increased expression of Fra1. Analysis of clinical specimens verified a positive correlation between Fra1 and β-catenin as well as a poor prognosis in glioma patients with double-high expressions of them. These findings indicate that an aberrant Wnt/β-catenin signalling leads to the EMT and drug resistance of glioma via Fra1 induction, which suggests novel therapeutic strategies for the malignant disease.

Pulp regeneration is to replace the inflamed/necrotic pulp tissue with regenerated pulp-like tissue to rejuvenate the teeth. Self-assembling peptide hydrogels RADA16-I (Ac-(RADA16-I) 4 -CONH 2 ) can provide a three-dimensional environment for cells. The stem cell factor (SCF) plays a crucial role in homing stem cells. Combining these advantages, our study investigated the effects of SCF-RADA16-I on adhesion, proliferation, and migration of human dental pulp stem cells (DPSCs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs). The β-sheet and grid structure were observed by circular dichroism (CD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Cytoskeleton staining, living cell staining, cell viability, cell migration, angiogenesis, and western blot assays were performed, and the results indicated that all the SCF groups were superior to the corresponding non-SCF groups in cell adhesion, proliferation, migration, and angiogenesis. RADA16-I provided a three-dimensional environment for DPSCs. Besides, the SCF promoted HUVECs to form more vascular-like structures and release more vascular endothelial growth factor A. In summary, the SCF-loaded RADA16-I scaffold improved adhesion, proliferation, and migration of DPSCs and the formation of more vascular-like structures of HUVECs. SCF-RADA16-I holds promise for guided pulp regeneration, and it can potentially be applied widely in tissue engineering and translational medicine in the future.

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Facial nerves are fragile and easily injured, for example, by traffic accidents or operations. Facial nerve injury drastically reduces the quality of life in affected patients, and its treatment presents clinical challenges. A promising therapeutic strategy includes nerve conduits with appropriate fillers capable of guiding nerve regeneration. In this study, a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) assembled via electrospinning and molecular self-assembly was first used to mimic the architecture of the native fibrin cable, which is similar to the nerve extracellular matrix (ECM). AFG as a substrate in chitosan tubes (CST) was used to bridge a 7 mm-long gap in a rabbit buccal branch facial nerve defect model. The results showed that AFG and CST showed good compatibility to support the adhesion, activity, and proliferation of Schwann cells (SCs). Further morphological, histological, and functional analyses demonstrated that the regenerative outcome of AFG-prefilled CST was close to that of autologous nerve grafts and superior to that of CST alone or CSTs prefilled with random fibrin nanofiber hydrogel (RFG), which indicated that AFG-prefilled CST markedly improved axonal regeneration with enhanced remyelination and functional recovery, thus showing great potential for clinical application for facial nerve regeneration treatments.