Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo. We identified 4,517 proteins in exosomes from Panc02 and Panc02-H7 cells via iTRAQ quantitative proteomic analyses, 79 of which were differentially expressed between the two cell lines. Bioinformatics analyses showed that most of the differentially expressed proteins were involved in pancreatic cancer growth, invasion, and metastasis, and that metabolism-related signaling pathways were involved in exosome-mediated intracellular communication. Further studies will be needed to determine whether these proteins are potential pancreatic cancer diagnostic/prognostic markers or novel therapeutic targets.

Hypoxia is a common environmental stress factor and is associated with fibrogenesis. Matrix metalloproteinase-2 (MMP-2), produced by hepatic stellate cells (HSCs), plays an important role in liver fibrogenesis. However, inconsistent results have been reported on the impact of hypoxia on MMP-2 expression and activity in HSCs. We speculated that cell–cell interaction is involved in the regulation of MMP-2 expression and activity at low oxygen level in vivo. Therefore, in this report we investigated the mechanism by which hypoxic hepatocytes regulates MMP-2 expression in HSCs. Our results showed that the conditioned medium from hypoxia-treated rat hepatocytes strongly induced the expression of MMP-2 mRNA and protein in rat HSC-T6 cells. Reduced glutathione neutralized ROS released from hypoxic hepatocytes, leading to reduced MMP-2 expression in HSC-T6 cells. In addition, phospho-IκB-α protein level was increased in HSC-T6 cells treated with hypoxia conditioned medium, and NF-κB signaling inhibitor inhibited MMP-2 expression in HSC-T6 cells. Taken together, our data suggest that ROS is an important factor released by hypoxic hepatocytes to regulate MMP-2 expression in HSCs, and NF-κB signaling is crucially involved in ROS-induced MMP-2 expression in HSCs. Our findings suggest that strategies aimed at antagonizing the generation of ROS in hypoxic hepatocytes and inhibiting NF-κB signaling in HSCs may represent novel therapeutic options for liver fibrosis.

BackgroundThis study aimed to investigate the role of miRNA-339-5p in pancreatic cancer cell invasion and migration.Material/MethodsThe differences between exosomal miRNAs of PANC02 and PANC02-H7 were studied by microarray analysis. We measured miRNA-339-5p expression in different groups; differences in cell invasion and migration were evaluated using the Transwell and wound healing assays and expression of relative proteins (E-cadherin, vimentin and ZNF689) was measured by WB assay. The correlation between miRNA-339-5p and ZNF689 expression was evaluated by luciferase reporter gene assay.ResultsCompared with PANC02 exosome, microarray analysis indicated that miRNA-339-5p mRNA expression was significantly suppressed (P<0.001) in the PANC02-H7 exosome. Supplementation with miR-339-5p mimics led to a significant decrease in the invasion cell number and wound healing rate (P<0.001), with significantly enhanced E-cadherin expression and suppressed vimentin expression (P<0.001). However, transfection of a miR-339-5p inhibitor led to a significant increase in the invasion cell number and wound healing rate (P<0.001), with significantly suppressed E-cadherin expression and increased vimentin expression (P<0.001). Luciferase reporter gene assay demonstrated ZNF689 gene to be the target of miR-339-5p in the PANC02-H7 cell. With miR-339-5p and ZNF689 transfection, the invasion cell number and wound healing rate were significantly increased compared with those in the miR-339-5p group (P<0.001), with significantly increased expression of ZNF689 and vimentin and suppressed E-cadherin expression (P<0.001).ConclusionsmiR-339-5p suppresses the invasion and migration of pancreatic cancer cells via direct regulation of ZNF689 in vitro.

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Purpose – The purpose of this paper is to explore the effects of the camber on gliding and hovering performance of two-dimensional corrugated airfoils. While the flying mechanism of natural flyers remains a myth up to nowadays, the simulation serves as a minor step toward understanding the steady and unsteady aerodynamics of the dragonfly flight. Design/methodology/approach – The lattice Boltzmann method is used to simulate the flow past the cambered corrugated dragonfly airfoil at low Reynolds numbers. For gliding flight, the maximum camber, the distance of the location of maximum camber point from the leading edge and Reynolds number are regarded as control variables; for hovering flight, the maximum camber, the flapping amplitude and trajectory are considered as control variables. Then corresponding simulations are performed to evaluate the implications of these factors. Findings – Greater gliding ratio can be reached by increasing the maximum camber of the dragonfly wing section. When the location of the maximum camber moves backward along the wing chord, large scale flow separation can be delayed. These two effects result in better gliding performances. For hovering performances, it is found that for different flapping amplitudes along an inclined plane, the horizontal force exerted on the airfoils increases with the camber, and the drag growths first but then drops. It is also found that the elliptic flapping trajectory is most sensitive to the camber of the cambered corrugated dragonfly wing section. Originality/value – The effects of the camber on gliding and hovering performance of the cambered dragonfly wing section are explored in detail. The data obtained can be helpful when designing micro aerial vehicles.

Bi 2 O 3 nanosheet was synthesised using China rose petal as a biotemplate for the photodegradation of methylene blue under xenon lamp irradiation. The samples were characterised by thermogravimetric analysis-differential scanning calorimetric analysis, Fourier-transform infrared spectroscopy, nitrogen adsorption, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and ultraviolet-visible diffuse reflectance spectroscopy. The results revealed that the Bi 2 O 3 nanosheet with pure monoclinic phase was successfully synthesised by replication of the petal template with a thickness of about 100 nm, and showed the absorption thresholds wavelength of 480 nm. Moreover, the Bi 2 O 3 nanosheet exhibited 94.84% degradation efficiency of photodegradation of methylene blue in 180 min, which was much more active than that of the commercial α-Bi 2 O 3 due to its high specific surface area of 45.7 m 2 g −1 and wide band gap of 3.10 eV.