Modulation of RANTES expression by HCV core protein in liver derived cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL).</p> <p>Methods</p> <p>HepG2 and Chang Liver (CHL) cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU) of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis.</p> <p>Results</p> <p>Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter.</p> <p>Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates some interferon response genes and acts as a component of cell defense against viral infection.</p> <p>Conclusion</p> <p>HCV core protein have opposite effects on the expression of RANTES in different cell types <it>in vitro</it>, possibly reflecting a similar scenario in different microenvironments <it>in vivo</it>.</p

Different levels of variability in subtypes 1b and 4a of hepatitis C viruses

We performed genetic and phenic analyses to evaluate nucleotide and amino-acid sequences of the amino-terminus of the E1 protein of HCV genotype 1b (extracted from databank) and 4a (characterised in this study). The non-synonymous (ka) mutation analysis demonstrated that the genome of genotype 1b was not saturated by variations, with a rate of transition/transversion (s/v) of 1.5, which is similar to the expected ratio (i.e., 2.0). The s/v ratio in genotype 4a isolates was lower (0.98), indicating saturation due long-term variability. Moreover, the genotype 1b sequences showed a higher number of ka mutations (s+v) (mean of 2.8 per sequence) than genotype 4a (mean of 1.5). The introduction of ka mutations resulted in a higher degree of amino acid variability in genotype 4a. In the genome of genotype 1b, each nucleotide mutation introduced new amino acids, with a Granthan distance of 3.35-42.5, whereas for genotype 4a the distances ranged from 48.8 to 102.1. The phenic analysis also indicated different and complex patterns of amino-acid substitution. Finally, diverse isoelectric points and hydrophobicity were predicted for the two genotypes, with a higher acidity for genotype 4a E1 proteins

Neoadjuvant chemotherapy for Non-Small-Cell lung cancer: Does it really impact on postoperative outcome after lung resection?

BACKGROUND Although some studies seem to indicate a positive prognostic value of induction chemotherapy in patients with locally advanced Non-Small-Cell Lung Cancer (NSCLC), its impact on postoperative mortality and morbidity is not well established. MATERIALS AND METHODS We reviewed the records of 83 consecutive patients who underwent thoracotomy after induction therapy between 1996 and 2007 (Group 1). Results were compared to those of a control group of 166 patients surgically treated in the same period without prior neoadjuvant therapy (Group 2). RESULTS The two groups were matched for age, sex, histology, comorbidity, respiratory function, and surgical procedure. There was no hospital mortality. Cumulative incidence of major complications was 32% in Group 1 and 37% in Group 2 (p=0.18). The incidence of each complication considered did not significantly differ between the two groups. A higher percentage of patients in Group 1 required blood transfusions (21.7% vs 4.2%, p&lt;0.0001). Multiple logistic regression analysis showed forced expiratory volume in 1 s (FEV1)&lt;75% of predicted (p=0.018) and blood transfusions (p=0.006) to be independent risk factors for major postoperative events in Group 1. DISCUSSION Preoperative chemotherapy did not seem to affect overall morbidity and mortality. Patients with a FEV1B75% of predicted or requiring blood transfusions resulted at increased risk of developing major complications

An insidious cause of spontaneous pneumothorax in an elderly woman

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