JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation

Intrahepatic mRNA Expression of FAS, FASL, and FOXP3 Genes Is Associated with the Pathophysiology of Chronic HCV Infection.

UNLABELLED:This study aimed to evaluate the relative mRNA expression of Fas receptor (FAS), Fas ligand (FASL), and forkhead box protein 3 (FOXP3) in liver biopsy specimens obtained from patients with viral and non-viral chronic hepatitis and correlate their expression with the fibrosis stage. A total of 51 liver biopsy specimens obtained from HBV (n = 6), HCV (n = 28), and non-viral hepatic disease (NVHD) (n = 9) patients and from individuals with normal liver histology (n = 8) (control-CT) were analyzed. Quantifications of the target genes were assessed using qPCR, and liver biopsies according to the METAVIR classification. The mRNA expression levels of FAS and FASL were lower in the CT group compared to the groups of patients. The increase in the mRNA expression of FAS and FASL was correlated with higher levels of inflammation and disease progression, followed by a decline in tissues with cirrhosis, and it was also associated with increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Higher mRNA expression of FOXP3 was observed in the HCV and NVHD groups, with the peak observed among patients with cirrhosis. The increased FOXP3 mRNA expression was positively correlated with increased FAS and FASL mRNA expression and the AST and ALT levels in all patients. CONCLUSIONS:These results suggest that regardless of the cause, the course of chronic liver disease may be modulated by the analyzed genes and correlated with an increase in regulatory T cells during the liver damage followed by hepatocyte destruction by Fas/FasL system and subsequent non specific lymphocytic infiltrate accumulation

NGF and P75NTR gene expression is associated with the hepatic fibrosis stage due to viral and non-viral causes.

This study evaluated the relative mRNA expression levels of nerve growth factor (NGF) and the p75 neurothrophin receptor (p75NTR) in different histological stages of human liver disease. Fifty-one liver biopsy specimens obtained from patients with hepatitis B virus (n = 6), hepatitis C virus (n = 28), and non-viral hepatitis--(n = 9) and standard histological liver (n = 8) as controls (CT) were subjected to qPCR and histopathological exams. Our data revealed a significant difference in the NGF expression levels between the three patient groups and the Control group. p75NTR expression levels in the HCV and NVH groups were higher than those observed in the HBV and Control groups. In cases of liver cirrhosis, higher p75NTR mRNA expression was observed, whereas NGF was expressed at higher levels in patients with hepatic fibrosis. NGF expression was lower in the F1 liver fibrosis stage, and p75NTR receptor expression continuously and proportionately increased compared to the increase in the degree of fibrosis and was significantly higher in livers in fibrosis stages 3 and 4. The hepatic levels of NGF and p75NTR were decreased and increased, respectively, relative to the stage of inflammatory activity. A positive correlation between p75NTR and NGF gene expression was observed in livers with mild to moderate fibrosis, though not in cases of severe fibrosis and cirrhosis. Conclusion: Our results demonstrate that the course of chronic liver disease can be regulated by NGF and p75NTR, which function by decreasing or inhibiting hepatocyte regeneration and proliferation

mRNA levels of <i>FAS</i>, <i>FASL</i> and <i>FOXP3</i> in the groups without cirrhosis and with cirrhosis.

<p>A-C: Quantification of the <i>FAS</i> receptor, <i>FASL</i> ligand and <i>FOXP3</i> mRNA levels in the groups with fibrosis (without cirrhosis) and the groups with cirrhosis with viral and non-viral liver disease. D-F: Quantification of the <i>FAS</i> receptor, <i>FASL</i> ligand and <i>FOXP3</i> mRNA levels in the groups with hepatic fibrosis (without cirrhosis) and cirrhosis due to viral and non-viral causes.</p

mRNA levels of <i>NGF</i> according to the clinical conditions of liver.

<p>A-D: mRNA levels of <i>NGF</i> and <i>p75</i>^<i>NTR</i> according to the stage of fibrosis (F0 to F4) and inflammatory activity (A0 to A2) in the livers of all individuals with liver disease in the study population.</p

Correlation of <i>FAS</i>, <i>FASL</i> and <i>FOXP3</i> mRNA levels with ALT and AST concentrations.

<p>A, D: Spearman correlation analysis between the <i>FAS</i> receptor mRNA levels and plasma ALT and AST concentrations. B, E: Spearman correlation analysis between the <i>FASL</i> mRNA levels and plasma ALT and AST concentrations. C, F: Spearman correlation analysis between the <i>FOXP3</i> mRNA levels and plasma ALT and AST concentrations, in the chronic liver disease group.</p

Correlation of <i>p75</i>^<i>NTR</i> and <i>NGF</i> mRNA levels with fibrosis and cirrhosis stages.

<p>A, B: Spearman correlation analysis with mild to moderate fibrosis stages and severe fibrosis and cirrhosis stages.</p

Frequency of inflammatory activity levels among the liver fibrosis scores of with viral hepatitis and non-viral hepatic disease.

<p>Frequency of inflammatory activity levels among the liver fibrosis scores of with viral hepatitis and non-viral hepatic disease.</p

mRNA levels of <i>FAS</i>, <i>FASL</i> and <i>FOXP3</i> according to the clinical conditions of liver in the HCV infection.

<p>A-F: mRNA levels of <i>FAS</i>, <i>FASL</i> and <i>FOXP3</i> according to the fibrosis stages (F0 to F4) and inflammatory activity (A0 to A2) in the liver tissue of patients with HCV (METAVIR).</p