Soluble urokinase plasminogen activator receptor is associated with short-term mortality and enhanced reactive oxygen species production in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a comprehensive syndrome characterized by an acute deterioration of liver function and high short-term mortality rates in patients with chronic liver disease. Whether plasma soluble urokinase plasminogen activator receptor (suPAR) is a suitable biomarker for the prognosis of patients with ACLF remains unknown. METHOD: A prospective cohort of 282 patients with ACLF from three hospitals in China was included. 88.4% of the group was hepatitis B virus-related ACLF (HBV-related ACLF). Cox regression was used to assess the impact of plasma suPAR and other factors on 30- and 90-day mortality. Reactive oxygen species (ROS) production were detected to explore the role of suPAR in regulating neutrophil function in HBV-related ACLF. RESULT: There was no difference in plasma suPAR levels between HBV-related and non-HBV-related ACLF. Patients with clinical complications had higher suPAR levels than those without these complications. A significant correlation was also found between suPAR and prognostic scores, infection indicators and inflammatory cytokines. Cox's regression multivariate analysis identified suPAR ≥ 14.7 ng/mL as a predictor for both day 30 and 90 mortality (Area under the ROC curve: 0.751 and 0.742 respectively), independent of the MELD and SOFA scores in patients with ACLF. Moreover, we firstly discovered suPAR enhanced neutrophil ROS production under E.coli stimulation in patients with HBV-related ACLF. CONCLUSIONS: suPAR was a useful independent biomarker of short-term outcomes in patients with ACLF and might play a key role in the pathogenesis. Trial registration CNT, NCT02965560.

p27(kip1) upregulated by hnRNPC1/2 antagonizes CagA (a virulence factor of Helicobacter pylori)-mediated pathogenesis.

BACKGROUND AND AIMS: Infection by Helicobacter pylori is one of the major contributing factors of chronic active gastritis and peptic ulcer and is closely associated with the occurrence and progression of gastric cancer. CagA protein is a major virulence factor of H. pylori that interacts with SHP-2, a true oncogene, to interfere with cellular signaling pathways; CagA also plays a crucial role in promoting the carcinogenesis of gastric epithelial cells. However, currently, the molecular mechanisms of gastric epithelial cells that antagonize CagA pathogenesis remain inconclusive. METHODS: We showed that AGS gastric cancer cells transfected with CagA exhibited the inhibition of proliferation and increased activity of caspase 3/7 using two-dimensional gel electrophoresis and secondary mass spectrometry (MS/MS). RESULTS: It was found that the AGS gastric cancer cells stably expressing CagA displayed significantly increased the expression of 16 proteins, including hnRNPC1/2. Further analysis revealed that hnRNPC1/2 significantly boosted the expression of the p27(kip1) protein. CONCLUSION: Our data suggested that hnRNPC1/2 upregulates p27(kip1) expression and the subsequent suppression of cell proliferation and induction of apoptosis, thereby providing an important mechanism whereby gastric epithelial cells antagonize CagA-mediated pathogenesis.