Preliminary in vitro analysis of mechanism of cardiac microvascular endothelial barrier function.

To preliminarily clarify the mechanism of cardiac microvascular endothelial barrier function leading to heart failure, primary HMVEC-D cells were selected and cultured for amplification. The cells were infected with adenovirus vector containing the ADP-ribosylation factor 6 (Arf6) Q67L gene. Full-length and functional fragments of myeloid differentiation primary response 88 and ARF nucleotide-binding site opener genes were established and transfected into HEK293T cells. GTP-Arf6 pull-down experiment, fluorescent quantitative real-time PCR, immuno-coprecipitation, and transendothelial electrical resistance analysis were conducted. Interleukin-1ß (IL-1ß) induced increase in vascular permeability, whereas inhibitor SC514 blocked IL-1ß-induced transfer of nuclear factor-κB into the nucleus, from the cytoplasm. Increase in amount of activated Arf6 promoted reduction in transendothelial electrical resistance. In addition, SecinH3 significantly inhibited increase in vascular permeability, and the progression of heart failure was significantly relieved. Cardiac microvascular endothelial barrier function can lead to heart failure. However, IL-1ß induced increase in vascular permeability, which nullified the function of cardiac microvascular endothelial barrier. These findings are closely related to the activation of the Arf6-VE-cadherin signaling pathway.

Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis.

The aim of this study was to investigate the role of cytokine genes in the susceptibility to Candida infection. A total of 275 consecutive patients diagnosed with Candida infection were selected between May 2010 and May 2011, along with 305 uninfected controls. Genotyping of the IL-1ß gene polymorphisms (IL1ß) rs1143634, IL1ßrs16944, IL8 rs4073, IL10 rs1800872, and IL10 rs1800896 was carried out using a 384-well plate format on the Sequenom MassARRAY platform. Patients with invasive Candida infections were more likely to have had an immunocompromised state, hematopoietic stem cell transplantation, solid organ transplant, solid tumor, chemotherapy within the past three months, neutropenia, surgery within the past 30 days, acute renal failure, liver failure, and/or median baseline serum creatinine. Conditional logistic regression analyses found that individuals with the rs1800896 GG genotype were associated with a higher risk of invasive Candida infections than those carrying the AA genotype (odds ratio = 0.61, 95% confidence interval = 0.37-0.94). From the results of this case-control study, we suggest that the cytokine IL-10 gene rs1800896 polymorphism might play a role in the etiology of invasive Candida infections.