133 research outputs found
Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis
BACKGROUND: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. METHODS: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. RESULTS: FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)). CONCLUSIONS: These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients
Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis
Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in
local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the
development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN)
induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation,
proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the
transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGESeq
approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary
human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand.
Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene
Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of
immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators,
negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly
downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is
altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature
dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the
suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different
mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome
sequencing of stimulated/restimulated iDCs identified numerous genes with altered expression to date not associated
with role in chronic inflammation, underlying the relevance of our in vitro model for further characterization of IFNprimed
iDCs
Quasi-local formulation of the mirror TBA
We present a method of removing all infinite sums from the various forms of
the mirror TBA equations and the energy formula of the AdS/CFT spectral
problem. This new formulation of the TBA system is quasi-local because
Y-functions that are connected by the TBA equations are at most next to nearest
neighbors with respect to the Y-system diagram of AdS/CFT.Comment: 13 pages, LaTe
Hybrid-NLIE for the AdS/CFT spectral problem
Hybrid-NLIE equations, an alternative finite NLIE description for the
spectral problem of the super sigma model of AdS/CFT and its gamma-deformations
are derived by replacing the semi-infinite SU(2) and SU(4) parts of the AdS/CFT
TBA equations by a few appropriately chosen complex NLIE variables, which are
coupled among themselves and to the Y-functions associated to the remaining
central nodes of the TBA diagram. The integral equations are written explicitly
for the ground state of the gamma-deformed system. We linearize these NLIE
equations, analytically calculate the first correction to the asymptotic
solution and find agreement with analogous results coming from the original TBA
formalism. Our equations differ substantially from the recently published
finite FiNLIE formulation of the spectral problem.Comment: 63 pages, 1 figur
Addition of vardenafil into storage solution protects the endothelium in a hypoxia-reoxygenation model
OBJECTIVE: Based upon the well known protective effect of intracellular cyclic guanosine monophosphate (cGMP) accumulation, we tested the hypothesis that storage solution enriched with optimal concentration of the phosphodiestherase-5 inhibitor vardenafil could provide better protection of vascular grafts against reperfusion injury after long-term cold ischaemic storage. METHODS: Isolated thoracic aorta obtained from rats underwent 24-h cold ischaemic preservation in physiological saline or vardenafil (10(-11) M)-supplemented saline solution. Reperfusion injury was simulated by hypochlorite (200 muM) exposure for 30 minutes. Endothelium-dependent vasorelaxation was assessed, and histopathological and molecular-biological examination of the aortic tissue were performed. RESULTS: Compared with the control group, the saline group showed significantly attenuated endothelium-dependent maximal relaxation (Rmax) to acetylcholine after hypoxia-reoxygenation, which was significantly improved by vardenafil supplementation (Rmax control: 98 +/- 1%; saline: 48 +/- 6%; vardenafil: 75 +/- 4%; p < .05). Vardenafil treatment significantly reduced DNA strand breaks (control: 10.6 +/- 6.2%; saline: 72.5 +/- 4.0%; vardenafil: 14.2 +/- 5.2%; p < .05) and increased cGMP score in the aortic wall (control: 8.2 +/- 0.6; saline: 4.5 +/- 0.3; vardenafil: 6.7 +/- 0.6; p < .05). CONCLUSIONS: Our results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction induced by cold storage warm reperfusion, which can be effectively reversed by pharmacological phosphodiesterase-5 inhibition
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