ABSTRACT
OBJECTIVES: To evaluate the role and biological function of nucleic acid binding protein 2 (NABP2) in hepatocellular carcinoma (HCC). METHODS: Our study was based on comprehensive bioinformatics methods and functional analysis experiments using HCC cells to reveal the expression of NABP2, the prognostic role of NABP2, the relationship between NABP2 and the infiltration of immune cells and the expression of immune-related cytokines, potential effective drugs against HCC, and the biological function of NABP2 in HCC. RESULTS: Our results indicated that NABP2 expression was markedly elevated in HCC, which suggested a worse prognosis and shorter survival time in HCC patients. Moreover, NABP2 was an independent prognostic factor and was associated with cancer-related signal pathways in HCC. Further functional analysis showed that knockdown of NABP2 dramatically inhibited proliferation and migration, and promoted apoptosis of HCC cells. Subsequently, we identified NABP2-related genes and NABP2-related clusters. Next, we constructed a NABP2-related risk signature based on differentially expressed genes that were responsible for NABP2-related clusters. We found that the risk signature was an independent prognostic factor for patients with HCC that was associated with dysregulated immune infiltration. Finally, drug sensitivity analysis revealed eight potentially effective drugs for beneficial treatment options for HCC patients with high-risk scores. CONCLUSIONS: These findings indicated that NABP2 is a prognostic biomarker and therapeutic target for HCC, and a NABP2-related risk signature could guide clinicians to judge the prognosis and suggest drug treatments for HCC patients.
ABSTRACT
Tenofovir alafenamide (TAF) is one of the most potent first-line nucleot(s)ide analogs for treating chronic hepatitis B virus (HBV) infections. To date, no cases of TAF drug resistance and/or suboptimal response have been reported. To our knowledge, this is the first report of two adult male patients presenting a suboptimal response response to TAF monotherapy. Our study indicates long-term observations and extensive data are needed to further evaluate the efficacy and safety of TAF, and highlights the need for the development of robust novel direct-acting antivirals and immune therapies for HBV.
ABSTRACT
Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or 18F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked 18F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease.
