Background/Aims: Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth. Methods: The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined. Results: The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2. Conclusion: Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy.

Pathological retinal angiogenesis is one of the most common causes of blindness, with limited treatment options being currently available. Epidermal growth factor (EGF)-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) has been reported to serve an important role in embryonic vasculogenesis and tumor angiogenesis; however, its implication in retinal angiogenesis has yet to be elucidated. The present study aimed to investigate the putative roles of EDIL3 in retinal endothelial cells. RNA interference was used to disrupt the expression of EDIL3 in human retinal endothelial cells (HRECs) in vitro, and the resulting effects were examined. Cell proliferation was assessed using cell counting kit-8 reagent, Cell migration was investigated using a transwell chamber and a tube formation assay was used to study angiogenic capability in vitro. Flow cytometry was used to detect the cell cycle distribution and western blotting was used to study protein expression. The present results demonstrated that silencing EDIL3 expression significantly impaired the proliferative, migratory and tube forming capabilities of HRECs. Furthermore, EDIL3 knockdown was revealed to induce cell cycle arrest at the G1 phase. Western blot analysis suggested that the possible mechanisms underlying the antiproliferative effects of EDIL3 silencing may involve the inhibition of EGF receptor-mediated pathways, and the suppression of cyclin D1 and cyclin E1 expression in HRECs. In conclusion, the findings of the present study suggested that EDIL3 may be implicated in retinal angiogenesis, and may have potential as a novel therapeutic target for the treatment of pathological angiogenesis.

Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistochemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-β signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.

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In some long and untrimmed videos, locating the important and key segments can be a very challenging task for temporal action detection. Current methods make remarkable progress when it comes to RGB images. The aim of this paper is to develop a method with the assistance of dynamic model of human body skeletons to address this problem. To this end, we propose a Feature Pyramid Graph Convolutional Network (FP-GCN). The introduced model contains a Feature Encoding Module to encode skeleton data with graph convolutional networks, a Feature Pyramid Module to exploit the inherent pyramidal hierarchy and an Action Detection Module to generate the final prediction results of the detection. We experiment our approach on NTU RGB+D and THUMOS14 datasets and obtain a satisfactory result.