Background Early prediction of severe acute pancreatitis (SAP) plays an important role in timely treatment decisions. Soluble T cell immunoglobulin and mucin domain-3 (sTIM-3) has been applied as a potential biomarker for the prediction of many diseases, while its predictive ability for AP severity remains largely unexplored. In this study, we aimed to identify whether serum sTIM-3 could be used as an indicator of AP severity in the early stage of the disease. Methods A retrospective study was conducted. The enrolled AP patients should meet the 2012 Atlanta guideline and have an onset to admission ≤ 48 h. Results A total of 94 AP patients were enrolled in the current analysis, including 42 (45%), 35 (37%), and 17 (18%) patients were diagnosed as mild AP (MAP), moderately SAP (MSAP), and SAP, respectively. SAP patients had significantly higher the white blood cells (WBCs) count, red blood cells (RBCs) count, C-reactive protein (CRP) level, direct bilirubin level, creatinine and procalcitonin levels compared with MAP and MSAP patients. Among SAP and MSAP patients, significantly higher APACHE II, BISAP, and MCTSI scores were observed compared with MAP patients, and there was significant difference in APACHE II and BISAP scores between SAP and MSAP patients. Stepwise multivariate linear regression analysis showed that the concentrations of serum sTIM-3, as well as the BISAP and MCTSI scores, were significantly associated with the severity of AP. The areas under the ROC curve were 0.914 (95% CI, 0.865-0.963), 0.855 (95%CI, 0.742-0.968) 0.853 (95%CI, 0.768-0.938), and 0.746 (95%CI, 0.633-0.860) for BISAP score, APACHE II score, sTIM-3 level, and MCTSI score, respectively. Conclusions Serum sTIM-3 might be ultimately incorporated into a predictive system for assessing the severity of AP.
Objective: The pathogenesis of acute pancreatitis mainly involves NLRP3 inflammasome-mediated pancreatic cell injury, although regulators of this inflammasome machinery are still not fully identified. Membrane-associated RING-CH 9 (MARCH9) is a member of MARCH-type finger proteins, which regulates innate immunity through catalyzing polyubiquitination of critical immune factors. The aim of present research is to examine the function of MARCH9 in acute pancreatitis.Methods: Cerulein-induced acute pancreatitis was established on pancreatic cell line AR42J and rat model. Reactive oxygen species (ROS) accumulation and NLRP3 inflammasome-dependent cell pyroptosis in pancreas were examined by flow cytometry.Results: MARCH9 was downregulated by cerulein, but overexpressing MARCH9 could inhibit NLRP3 inflammasome activation and ROS accumulation, thus suppressing pancreatic cell pyroptosis and mitigating pancreatic injury. We further uncovered that the mechanism underlying such an effect of MARCH9 is through mediating the ubiquitination of NADPH oxidase-2, whose deficiency reduces cellular ROS accumulation and inflammasome formation. Conclusions:Our results suggested that MARCH9 suppresses NLRP3 inflammasome-mediated pancreatic cell injury through mediating the ubiquitination and degradation of NADPH oxidase-2, which compromises ROS generation and NLRP3 inflammasomal activation.
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