Interleukin-27 augments the inhibitory effects of sorafenib on bladder cancer cells.

Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 µM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration. Finally, the phosphorylation levels of key kinases in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or sorafenib repressed proliferation, migration and invasion but promoted apoptosis, and the effects were all enhanced by the combination of these two drugs in HTB-9 cells. The effect of the combined treatment on bladder cancer cells was verified in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. The combination of IL-27 and sorafenib inhibited proliferation, migration and invasion and promoted apoptosis of bladder cancer cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway might be implicated in the functional effects by down-regulations of MMP-2 and MMP-9.

Genetic background of Escherichia coli isolates from peritoneal dialysis patients with peritonitis and uninfected control subjects.

Escherichia coli is the most common cause of Gram-negative peritonitis resulting in peritoneal function deterioration as well as poor clinical outcome in continuous ambulatory peritoneal dialysis (PD) patients. In this study, we analyzed the phylogenetic background and genetic profile of the E. coli isolates and sought to determine the characteristics of specific bacteria associated with peritonitis. E. coli isolates from 56 episodes of peritonitis in 46 PD patient cases and rectal isolates from 57 matched PD control patient cases were compared for both phylogenetic groups and the presence of virulence factors (VFs). There were no significant differences in terms of demographic data between the peritonitis and control groups. Peritonitis isolates exhibited a significantly greater prevalence of 8 VFs. In multivariate logistic regression analysis, kpsMT II (group 2 capsule synthesis) was the strongest VF predictor of peritonitis (OR = 8.02; 95%CI = 3.18-20.25; P < 0.001), followed by traT (serum-resistance-associated outer membrane protein) (OR = 3.83; 95%CI = 1.33-11.03; P = 0.013). The pathogenic groups of E. coli contained a higher concentration of individual VFs compared to the commensal groups. The prevalence of pathogenic E. coli was much higher in peritoneal isolates than rectal isolates (64.3 vs 31.6%, P = 0.001). Our results indicate that the E. coli peritonitis and rectal isolates are different in PD patients. The specific VFs associated with peritonitis isolates may directly contribute to the pathogenesis of peritonitis.

Analysis of polymorphisms in the FUT1 and TAP1 genes and their influence on immune performance in Pudong White pigs.

FUT1 and TAP1 have been identified as candidate genes that offer resistance against Escherichia coli F18 infection, with the AA genotype in FUT1 and the GG genotype in TAP1 conferring resistance. In order to confirm polymorphisms at FUT1 M307 and TAP1 G729, and evaluate their influence on immunity performance in Pudong White pigs, we performed polymerase chain reaction-restriction fragment length polymorphism analysis, measured immune indices, and compared the results with those observed in Large White pigs. The AA genotype of FUT1 was first discovered in Pudong White pigs and has not been found in other Chinese domestic pig breeds. The frequency of the AA genotype in Pudong White and Large White pigs was 0.018 and 0.052, respectively. The GG genotype of TAP1 was also detected in the two breeds, with a frequency of 0.708 and 0.695, respectively. Chi-square fitness analysis of both genes showed that these loci deviated from Hardy-Weinberg equilibrium in the two breeds (P < 0.05). No significant differences were observed in interleukin-6 (IL-6) and IL-10 levels among the three genotypes at FUT1 and TAP1 in the two breeds (P > 0.05). Individuals for all genotypes of TAP1 in both pig breeds had similar TNF-α levels (P > 0.05), implying that Pudong White pigs may have the same ability for hepatocyte inflammatory response and B cell differentiation as Large White pigs. These differences have a degree of influence on Pudong White pig's immune ability to resist F18 or other infections.