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Li L.,Soochow University of China | Li L.,Key Laboratory on Technology for Parasitic Disease Prevention and Control | Guo Z.,Soochow University of China | Wang J.,Wuxi Infectious Diseases Hospital | And 3 more authors.
Digestive Diseases and Sciences | Year: 2012

Background: Alpha-fetoprotein detection is currently mainly used in clinic for diagnosis of primary hepatocellular carcinoma (HCC). However, its sensitivity and specificity are not satisfying. Approximately 60-80 % of patients with HCC have an established background of chronic infection with hepatitis B virus (HBV). Aims: To investigate the potential of serum microRNAs (miRNAs) as biomarkers for HBV-related HCC. Methods: This study was divided into two phases: firstly, marker (miR-95, miR-18a, miR-10b, miR125a, and miR-378) detection by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sera from HBV patients with HCC (n = 15) and health subject (n = 15); and, secondly, marker validation by real-time qRT-PCR on HBV patients with HCC (n = 86) or hepatitis or cirrhosis (n = 30), and healthy subject (n = 45). Results: Serum miR-18a was significantly higher in HBV patients with HCC than healthy controls (p<0.01); serum miR-378 was significantly lower in HBV patients with HCC compared to healthy control (p<0.05). Receiver operating characteristic (ROC) curve analyses suggested that serum miR-18a had significant diagnostic value for HBV-related HCC. MiR-18a yielded an area under the curve (AUC) of ROC of 0.881 with 86.1 % sensitivity and 75.0 % specificity in discriminating HBV-related HCC from healthy controls, and an AUC of ROC of 0.775 with 77.2 % sensitivity and 70.0 % specificity in discriminating HBV-related HCC from chronic hepatitis or cirrhosis. Conclusions: Our results suggest that serum miR-18a might serve as a novel and potential noninvasive biomarker for HBV-related HCC screening. © Springer Science+Business Media, LLC 2012.

Zhang B.,Wuxi Infectious Diseases Hospital | Hu M.,Wuxi Infectious Diseases Hospital | Zhang P.,Nanjing Medical University | Cao H.,Wuxi Infectious Diseases Hospital | And 3 more authors.
Brazilian Journal of Medical and Biological Research | Year: 2013

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-b expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-b expression. We also showed that BAFF-activated CD4+T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

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