The existence of microvascular invasion (MVI) formation is one of the most important risk factors predicting poor outcome in hepatocellular carcinoma (HCC) and its mechanism remains largely unknown. Epithelial-Mesenchymal Transition (EMT) has been suggested to be involved in many steps of the invasion-metastasis cascade. To elucidate the possible contribution of EMT to MVI, we initially evaluated the expression of 8 EMT-related transcription factors (TFs) in HCC patients with or without MVI and found that FOXC1 expression was significantly higher in patients with MVI than those without MVI (P < 0.05). Knockdown of FOXC1 expression in HCC cells resulted in a partial conversion of their EMT progresses, mainly regulating the mesenchymal component. Ectopic expression of snail, twist or TGF-β1 could induce expression of FOXC1, but none of the expression of snail, twist, slug or TGF-β was consistently down-regulated in response to FOXC1 silencing, suggesting FOXC1 might operate the downstream of other EMT regulators. In addition, knockdown of FOXC1 expression led to cytoskeleton modification accompanied by decreased ability of cell proliferation, migration, and invasion. Meanwhile, some matrix metalloproteinases (MMPs) and VEGF-A were also simultaneously down-regulated. Together, our findings demonstrate that FOXC1 is one of candidate predictive markers of MVI, and that inhibition of FOXC1 expression can partially reverse EMT program, offering a potential molecular therapeutic target for reducing tumor metastasis in HCC patients.
SUMMARY
Species of the marine benthic dinoflagellate genus Gambierdiscus are the principal cause of Ciguatera fish poisoning. This genus has been recorded from tropical to temperate oceans, although Gambierdiscus species have rarely been found in Chinese waters. Our work revealed the morphological and genetic characteristics of three potentially toxic Gambierdiscus species observed in the temperate to subtropical waters of China. The fine thecal morphology was determined based on light microscopy and scanning electron microscopy analyses, and these species were also characterized by sequencing the D1–D3 and D8–D10 regions of the LSU rDNA. The morphological and genetic data indicated that these three Gambierdiscus species were G. pacificus, G. australes and G. caribaeus. This work provides the first report of these species in Chinese waters, which increases the known species distribution of this genus.
Neutron powder-diffraction studies of the crystal and magnetic structures of the magnetocaloric compound Mn 1.1 Fe 0.9 ͑P 0.8 Ge 0.2 ͒ have been carried out as a function of temperature, applied magnetic field, and pressure. The data reveal that there is only one transition observed over the entire range of variables explored, which is a combined magnetic and structural transformation between the paramagnetic ͑PM͒ and ferromagnetic phases ͑T c Ϸ 255 K for this composition͒. The structural part of the transition is associated with an expansion of the hexagonal unit cell in the direction of the a and b axes and a contraction of the c axis as the FM phase is formed, which originates from an increase in the intralayer metal-metal bond distance. The application of pressure is found to have an adverse effect on the formation of the FM phase since pressure opposes the expansion of the lattice and hence decreases T c . The application of a magnetic field, on the other hand, has the expected effect of enhancing the FM phase and increasing T c . We find that the substantial range of temperature/ field/pressure coexistence of the PM and FM phases observed is due to compositional variations in the sample. In situ high-temperature diffraction measurements were carried out to explore this issue, and reveal a coexisting liquid phase at high temperatures that is the origin of this variation. We show that this range of coexisting phases can be substantially reduced by appropriate heat treatment to improve the sample homogeneity.
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