The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles ...(PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (
n=109) and in healthy controls (
n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.
This experiment studied the effect of nano-multilayer structures of boron carbide film with silicon carbide (SiC) layers on oxidation behavior and hardness. The multilayer films were deposited at ...450°C using an unbalanced dual-gun magnetron sputtering system with stoichiometric B4C and SiC targets. The period of the multilayer system (the thickness of one pair of boron carbide and SiC layers) with a constant film thickness was varied between 2.3nm and 22.1nm. The structures of these multilayer thin films were amorphous irrespective of the period. A remarkable hardness enhancement, frequently observed in crystalline nano-multilayer thin film systems, did not appear. The maximum hardness of the multilayer thin film was measured to be about 36GPa, similar to that of the monolithic boron carbide film deposited under the same condition. Oxidation was, however, greatly reduced by the insertion of the SiC layers. Oxidation was rarely observed at temperatures up to 1200°C, the maximum experimental temperature, whereas significant oxidation was observed at around 700°C in the case of the boron carbide monolithic film.
•Investigation of oxidation behavior of silicon carbide - boron carbide nanomultilayers•Significant reduction of oxidation of BC films by SiC layer insertion up to 1200°C•Negligible decrease of the hardness of the film caused by the multilayer formation•BC/SiC nanomultilayer coating as a candidate for cutting tool application used especially at high temperature
Inclusions in a brush are entropically disfavored, as they constrain the surrounding brush chains and limit possible chain conformations. As a result, polymer brushes can be used in lubrication or as ...biological coatings against toxic molecules. Here, we study the interaction of nanoparticles with a brush using self-consistent field theory (SCFT). For a large particle compressing a brush, we reproduce the linear scaling of the repulsive potential with the particle radius found previously using SCFT. Also, we find that this linearity gives way to a nonlinear (parabolic or cubic) dependence on the particle size for particles inserted deeply into the brush, consistent with earlier particle-based simulations. The insertion of particles disrupts the brush, changing polymer–particle interactions for subsequent nanoparticles, thus introducing effective particle–particle interactions mediated by the brush. When the grafting point is mobile in the plane of the grafting surface, our results suggest that the brush promotes clustering of inclusions. In contrast, inclusions tend to be dispersed when the grafting point is fixed. Finally, we discuss the biological implications of these findings: interactions of antimicrobial peptides with bacterial lipopolysaccharides and clustering of integrin on cancerous cell membranes.
Hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that controls transcriptional activation of a number of genes responsive to the low cellular oxygen tension, including vascular ...endothelial growth factor (VEGF), erythropoietin, and glycolytic enzymes. The stability and activity of HIF-1α are regulated by binding to various proteins such as pVHL, p53, and p300/CBP. Here, using the yeast two-hybrid screening system, we found that HIF-1α interacts with Jab1 (Jun activation domain-binding protein-1), which is a coactivator of AP-1 transcription factor and fifth subunit of COP9 signalosome complex. The interaction of Jab1 with HIF-1α was confirmed by GST pull-down assay and also reproduced in vivo in HEK 293 cells, where endogenous Jab1 was coimmunoprecipitated with the overexpressed HIF-1α. Moreover, Jab1-enhanced transcriptional activity of HIF-1 under hypoxia led to increase the expression of VEGF, a major HIF-1 target gene. Furthermore, Jab1 increased HIF-1α protein levels, which was due to the enhanced HIF-1α stability. The binding of HIF-1α and p53 tumor suppressor protein, negative regulator of HIF-1α stability, was interfered in a Jab1-dependent manner. Taken together, these results indicate that Jab1 should be considered as a novel regulator of HIF-1α stability via direct interaction.
Abstract Background and aim Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum ...FABP4 levels and the progression of metabolic syndrome in healthy adults. Methodsand results A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS ( P < 0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P < 0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations ( P < 0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71–12.23 for highest tertile vs. lowest tertile, P < 0.001) Conclusion Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.
The effects of subinhibitory concentrations (sub-MICs) of antibacterial agents on the biofilm-forming ability of Staphylococcus aureus require further study.
To investigate the effects of sub-MICs of ...chlorhexidine and mupirocin on biofilm formation in clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates.
MRSA isolates were collected from patients with bloodstream infections at a tertiary care hospital. The basal level of biofilm formation and biofilm induction by sub-MICs of chlorhexidine and mupirocin were evaluated by measuring biofilm mass stained with Crystal Violet.
Of the 112 MRSA isolates tested, 63 (56.3%) and 44 (39.3%) belonged to sequence type (ST)5 and ST72 lineages, respectively, which are the predominant healthcare- and community-associated clones in South Korea. ST5 isolates were more likely to have chlorhexidine MIC ≥4 (73.0% vs 29.5%), resistance to mupirocin (23.8% vs 0%), agr dysfunction (73.0% vs 9.1%), and qacA/B gene (58.7% vs 2.3%) compared to ST72 isolates. The basal level of biofilm formation ability was frequently stronger in ST72 isolates compared to ST5 isolates (77.3% vs 12.7%). Sub-MICs of chlorhexidine and mupirocin promoted biofilm formation in 56.3% and 53.6%, respectively, of all isolates. Biofilm induction was more prevalent in ST5 isolates (85.7% for chlorhexidine, 69.8% for mupirocin) than in ST72 isolates (15.9% for chlorhexidine, 27.3% for mupirocin).
Sub-MICs of chlorhexidine and mupirocin promoted biofilm formation in half of the clinical MRSA isolates. Our results suggest that ST5 MRSA biofilm can be induced together with some other bacterial virulent factors following exposure to chlorhexidine, which might confer a survival advantage to this clone in the healthcare environment.
RUNX3 is silenced by histone modification and hypoxia-inducible factor (HIF)-1α is stabilized under hypoxia, but little is known of cross-talk between RUNX3 and HIF-1α under hypoxia. In the present ...study, the authors investigated the effect of RUNX3 on HIF-1α stability in gastric cancer cells. RUNX3 overexpression was found to downregulate HIF-1α stability under normoxic and hypoxic conditions. Furthermore, the activity of a luciferase reporter containing five copies of vascular endothelial growth factor (VEGF) promoter hypoxia-responsive element (5 × HRE) and the amount of secreted VEGF, were diminished in RUNX3-expressing but increased in RUNX3-knockdown cells. When expression of RUNX3 was recovered using epigenetic reagents the expressions of HIF-1α and VEGF were clearly suppressed under hypoxic conditions. RUNX3 also significantly attenuated the half-life of HIF-1α protein, and induced the cytosolic localization and ubiquitination of HIF-1α. In addition, RUNX3 directly interacted with the C-terminal activation domain of HIF-1α and prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1α and PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF-1α. Furthermore, RUNX3 overexpression significantly inhibited hypoxia-induced angiogenesis in vitro and in vivo. Taken together, these results suggest that RUNX3 destabilizes HIF-1α protein by promoting the proline hydroxylation of HIF-1α through binding to HIF-1α/PHD2. RUNX3 appears to be a novel suppressor of HIF-1α and of hypoxia-mediated angiogenesis in gastric cancer cells.
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