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Background/Objective: IFNs are a group of cytokines that possess potent antiviral and antitumor activities, while β-catenin pathway is a proliferative pathway involved in carcinogenesis. Interaction between these two pathways has not been well elaborated in hepatocellular carcinoma (HCC). Methods: HCC cell lines, HepG2 and Huh7, were used in this study. β-catenin protein levels and corresponding signaling activities were observed by flow cytometry and luciferase assay, respectively. Cell proliferation was quantified by counting viable cells under microscope, and apoptosis by TUNEL assay. DKK1 and GSK3β levels were determined by flow cytometry. Secreted DKK1 was tested by ELISA. FLUD, S3I and aDKK1 were used to inhibit STAT1, STAT3 and DKK1 activities, respectively. Results: Our findings show that all three types of IFNs, IFNα, IFNγ and IFNλ, are capable of inhibiting β-catenin signaling activity in HepG2 and Huh7 cells, where IFNγ was the strongest (p<0.05). They expressed suppression of cellular proliferation and induced apoptosis. IFNγ expressed greater induction ability when compared to IFNα and IFNλ (p<0.05). All tested IFNs could induce DKK1 activation but not GSK3β in HepG2 and Huh7 cells. IFNs induced STAT1 and STAT3 activation but by using specific inhibitors, we found that only STAT3 is vital for IFN-induced DKK1 activation and apoptosis. In addition, DKK1 inhibitor blocked IFN-induced apoptosis. The pattern of STAT3 activation by different IFNs is found consistent with the levels of apoptosis with the corresponding IFNs (p<0.05). Conclusions: In hepatocellular carcinoma, all three types of IFNs are found to induce apoptosis by inhibiting β-catenin signaling pathway via a STAT3- and DKK1-dependent pathway. This finding points to a cross-talk between different IFN types and β-catenin signaling pathways which might be carrying a biological effect not only on HCC, but also on processes where the two pathways bridge. [ABSTRACT FROM AUTHOR]

Introduction: Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease (HFMD), which is a potentially fatal illness in children. Epidemics of HFMD are seen every year globally and present an increasing threat to public health worldwide. Methodology: To identify potential severity markers for severe HFMD, laboratory findings and levels of eight serum cytokines in 143 EV71- infected patients in Beijing You'an Hospital were analyzed. Patients were grouped by disease severity: Mild (no severe complications) (n = 59), isolated isolated brainstem encephalitis (BE) (n = 47), isolated pulmonary edema (PE) (n = 12), and BE+PE (n = 25). Results: IL-8 levels peaked at day one after admission and were found to be correlated to disease severity, maximal body temperature, and length of hospital stay. Among all tested cytokines, IL-8 was correlated to only IL-6 (p = 0.010). IL-6 and IL-10 were elevated in most patients (98.6% and 70.6%), but not correlated to disease severity (both p > 0.05). IFNγ was only negatively correlated to mild cases (p = 0.025). Conclusions: IL-8 was correlated to disease severity of HFMD. IL-6 and IL-10, although elevated in most HFMD patients, were not correlated to disease severity. [ABSTRACT FROM AUTHOR]