The relationship between the neutrophil-to-lymphocyte ratio (NLR) and tumours as a prognostic factor has been reported in many studies. In this meta-analysis, we evaluated the prognostic role of the NLR in pancreatic cancer (PC). A systematic search was performed in PubMed and Embase for relevant studies. Data from and characteristics of each study were extracted. A meta-analysis was performed to analyse the prognostic role of the NLR using the hazard ratio (HR) and 95% confidence intervals (95% CI). As a result, a total of 2035 patients in 9 cohorts were included in this meta-analysis. The pooled HR of 1.587 (95% CI: 1.411–1.785, p < 0.01) showed that patients with an elevated NLR were expected to have shorter overall survival (OS) after treatment. This meta-analysis suggests that an elevated NLR can be used as a predictor of survival in patients with pancreatic cancer.
Because the role of Kupffer cells (KCs) in liver transplantation (LT) tolerance is not well understood, we investigated their role in liver allograft acceptance in rats. Male Sprague-Dawley rats were randomly assigned to either an LT group or a transplantation group pretreated with GdCl 3 (Gd group). The rats were postoperatively sacrificed at indicated times for histology and assessment of KC function, nuclear factor kappa B (NF-B) activity, and cytokine production. KCs and T cells (TCs) were isolated from allografts to assess Fas/Fas ligand (FasL) expression. Cytotoxicity of KCs against TCs was monitored by coculturing of 3 H-thymidine TCs with KCs at various effector-to-target ratios. The results were as follows. First, grafts were spontaneously accepted in the LT group with evident apoptosis of TCs; however, inhibition of KCs by pretreatment with GdCl 3 decreased TC apoptosis and shortened the survival of allografts. Second, KCs in the LT group had increased levels of FasL messenger RNA and protein with respect to that in the Gd group. Third, by in vitro cocultivation assays, KCs induced TC apoptosis though elevated expression of FasL, and this process could be blocked by anti-FasL antibody. Fourth, there was a positive correlation between activation of NF-B and FasL expression in KCs and interleukin-4 production in the LT group, and the activation of NF-B was inhibited by pretreatment with GdCl 3 . In conclusion, KC-induced depletion of TCs via the Fas/FasL pathway might play a critical role in LT tolerance. However, the tolerance is abrogated by suppression of FasL and IL-4 expression via inhibition of NF-B activity by GdCl 3 . Liver Transpl 14: 823-836, 2008.
Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
Field and greenhouse studies were conducted to determine the degree to which annual bluegrass (Poa annuaL.) could be controlled by inhibiting seedheads. The materials used were: MH (1,2-dihydro-3,6-pyridazinedione); chlorflurenol (methyl 2-chloro-9-hydroxyfluorene-9-carboxylate), plus methyl 9-hydroxyfluorene-9-carboxylate, and methyl 2,7-dichloro-9-hydroxyfluorene-9-carboxylate; and endothall [7-oxabicyclo (2.2.1) heptane-2,3-dicarboxylic acid]. The effects of these materials on pollen quality and the viability of seed produced by treated plants were also determined. For all chemicals used, multiple applications at low rates resulted in better seedhead inhibition than single treatments at higher rates and their effects lasted longer. However, treatments that inhibited seedheads by an amount predicted to reduce annual bluegrass (more than 75%) often caused objectionable foliar discoloration. Endothall, particularly the granular formulation, caused excessive injury at all rates. All growth regulators reduced the number of seed produced, which affected the number of seeds that germinated from soil that was taken from treated plots. The number of seed found in the soil was sufficient to allow the stand to be self-perpetuating. All treatments reduced the percentage of fertile pollen, however, this reduction was not significant because the germination of seed harvested from treated plants was not reduced significantly. Even though these treatments reduced seedheads significantly, the population of annual bluegrass the following year was not reduced.
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