Hepatitis C virus (HCV) primarily infects liver tissues, while pathogenesis of extrahepatic tissues has been reported. About 50% of patients with HCV infection suffer from neurological disease. The underlying molecular mechanisms remain unclear. In the present study, we aimed to investigate the induction of CXC chemokine ligand 10 (CXCL10) in human brain microvascular endothelial cells (HBMECs) by HCV infection. CXCL10 and its receptor CXCR3 were constitutively expressed in HBMECs. HCV infection induced CXCL10 elevation in HBMECs. The elevation of CXCL10 in HBMECs was eliminated when HCV infection was blocked by neutralizing antibodies. NF‐κB is a positive regulator for CXCL10 transcription. HCV infection led to an increased phosphorylation of NF‐κB (ser536) in HBMECs, and CXCL10 induced by HCV was slightly decreased when an inhibitor of NF‐κB was added. IL1 beta and IFN gama were also upregulated in HCV infected HBMECs, and could be depressed by inhibitor of NF‐κB. Thus, HCV infection leads to upregulated expression of CXCL10 in HBMECs, which is probably via the phosphorylation of NF‐κB. The findings of this study provide potential mechanisms and novel targets for HCV induced neuroinflammation. J. Med. Virol. 88:1596–1603, 2016. © 2016 Wiley Periodicals, Inc.
Introduction: DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b overexpression can induce colon tumor in mice, and methylation in various CpG islands in these mouse tumors are nonrandom, suggesting at least some specific targeting of Dnmt3b activity. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colorectal cancer. In this study, we examined the relation between DNMT3B expression and CIMP in a large number of colorectal cancers. Materials and Methods: Utilizing 765 colorectal cancers from two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. Using real-time PCR (MethyLight), we quantified DNA methylation in 8 CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1 …
AIM To study expression and clinical significance of urokinase type plasminogen activator (uPA) in medul loblastoma of children. METHODS Expression of uPA in 84 cases of pathologically confirmatory and followed up medulloblastoma of children (46 males, 38 females, aged from 6 to 12 years) was detected with labelled strepatavidin biotin (LSAB). The cases were divided into 3 groups according to survival period of 3, 5, 10 a respectively. Cox regression analysis was used. RESULTS Expression positive rate of uPA was 52% (44/84), and were 71%, 41%, and 20% in group A, B, and C respectively ( P 0.01). Cox regression showed that uPA was in independent prognostic factor affecting survival and it had close negative correlation with the prognosis. CONCLUSION Expression level of uPA was closely related to predicting prognosis of medulloblastoma in children.