BackgroundThe Hepatitis C virus (HCV) core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC), but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells.MethodologyWnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay.Principal FindingsHCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC.Conclusions/SignificanceHCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.

After HIFU ablation, some tumor antigens remained in the tumor debris. This could provide a potential antigen source to stimulate antitumor immune response.

Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long noncoding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up-regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these

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BackgroundLower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited.ObjectivesHuman bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China.MethodsNasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real‐time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software.ResultsPneumonia was the most frequent diagnosis. There was no significant difference between HBoV‐ and HMPV‐positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV‐positive patients had a shorter hospitalization duration than the HBoV‐negative patients (P = .021), and the HMPV‐positive patients had a higher prevalence of fever than the HMPV‐negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses.ConclusionPneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity.