Key pathways and genes in hepatitis B virus-related liver inflammation: Expression profiling and bioinformatics analysis.

Chronic hepatitis B virus infection has become a major public health issue worldwide, which can lead to liver inflammation, fibrosis, and hepatocellular carcinoma. According to the inflammation activity, liver tissues can be divided into 5 grades (G0-G4). However, the mechanism of the development of liver inflammation remains unclear. In our study, expression profiling by microarray and bioinformatics technology was used to systemically identify differentially expressed genes (DEGs) between low grades (G0-G1) and high (G2-G4) grades of liver inflammation. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network construction were performed for further identification of the key functions, pathways, and hub genes that might play important roles in the inflammation development. A total of 1982 DEGs were identified, consisting of 1220 downregulated genes and 762 upregulated genes. GO analysis revealed the DEGs were mainly enriched in GO terms that related to neutrophil activation and degranulation. MAPK1, ITGA2, CDK2, TGFB1, CDKN2A, MTOR, IL6, PCNA, OAS2, and EP300 were hub genes that had the highest centricity and might be potential markers for inflammation development. This study identified the differentially expressed genes between different grades of inflammation, which would enlighten the study that focuses on the mechanism of liver inflammation development.

Prognostic Value of Serum Apolipoprotein B to Apolipoprotein A-I Ratio in Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

INTRODUCTION: The prognosis of advanced hepatocellular carcinoma (HCC) varies in patients receiving transcatheter arterial chemoembolization (TACE). In this study, we aimed to assess the prognostic value of serum apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA-I) in this group of patients. METHODS: The serum lipid levels of HCC patients undergoing TACE were obtained from routine preoperative blood lipid examination. A propensity score-matched (PSM) analysis was used to eliminate the imbalance of baseline characteristics of the high and low ApoB/ApoA-I groups. Then, univariate and multivariate analysis were conducted to evaluate the prognostic value of ApoB/ApoA-I. RESULTS: In 455 HCC patients treated with TACE, ApoB/ApoA-I was positively correlated with AFP, T stage, distant metastasis, and TNM stage (p < 0.05). Patients with high ApoB/ApoA-I had a significantly shorter overall survival (OS) than those with low ApoB/ApoA-I (median OS, 21.7 vs. 39.6 months, p < 0.001). Multivariate analysis indicated that ApoB/ApoA-I was an independent prognostic index for OS (hazard ratio [HR] = 1.42, p = 0.008). After baseline characteristics were balanced, 288 patients were included in the PSM cohort. In this cohort, high ApoB/ApoA-I still predicted inferior OS in both univariate analysis (median OS, 27.6 vs. 39.3 months, p = 0.002) and multivariate analysis (HR = 1.58, p = 0.006). CONCLUSION: Serum ApoB/ApoA-I is a useful biomarker in predicting aggressive clinicopathological characteristics and poor prognosis in HCC patients treated with TACE.

Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.

ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.

Biological characteristics of adipose tissue-derived stem cells labeled with amine-surface-modified superparamagnetic iron oxide nanoparticles.

Cell labeling and tracking are becoming increasingly important areas within the field of stem cell transplantation. The ability to track the migration and distribution of implanted cells is critical to understanding the beneficial effects and mechanisms of stem cell therapy. The present study investigated the effects of amine-surface-modified superparamagnetic iron oxide (SPIO) nanoparticles on the biological properties of human adipose tissue-derived stem cells (hADSCs). Monodisperse hydrophobic magnetite (Fe3 O4 ) nanoparticles were prepared using silicon and surface-modified with amine coating. Cell viability, proliferation, differentiation potential, and surface marker expression were evaluated. The magnetic particles (10-18 nm) displayed high labeling efficiency and stability in hADSCs. SPIO-labeled cells produced a hypointense signal and were effectively visualized by MRI for up to 21 days. The results of MTT proliferation assays and flow cytometry analysis demonstrated that SPIOs were biocompatible, viz. the labeling process did not cause cell death or apoptosis and had no side effects on cell proliferation. In vivo experiments showed that the magnetic particles did not affect liver and kidney function. The successful and stable labeling of hADSCs combined with efficient magnetic tropism demonstrates that SPIOs are promising candidates for hADSC tracking in hADSC-based cell therapy applications.