HGF/c-Met signaling promotes liver progenitor cell migration and invasion by an epithelial-mesenchymal transition-independent, phosphatidyl inositol-3 kinase-dependent pathway in an in vitro model.

Oval cells constitute an interesting hepatic cell population. They contribute to sustain liver regeneration during chronic liver damage, but in doing this they can be target of malignant conversion and become tumor-initiating cells and drive hepatocarcinogenesis. The molecular mechanisms beneath either their pro-regenerative or pro-tumorigenic potential are still poorly understood. In this study, we have investigated the role of the HGF/c-Met pathway in regulation of oval cell migratory and invasive properties. Our results show that HGF induces c-Met-dependent oval cell migration both in normal culture conditions and after in vitro wounding. HGF-triggered migration involves F-actin cytoskeleton reorganization, which is also evidenced by activation of Rac1. Furthermore, HGF causes ZO-1 translocation from cell-cell contact sites to cytoplasm and its concomitant activation by phosphorylation. However, no loss of expression of cell-cell adhesion proteins, including E-cadherin, ZO-1 and Occludin-1, is observed. Additionally, migration does not lead to cell dispersal but to a characteristic organized pattern in rows, in turn associated with Golgi compaction, providing strong evidence of a morphogenic collective migration. Besides migration, HGF increases oval cell invasion through extracellular matrix, a process that requires PI3K activation and is at least partly mediated by expression and activation of metalloproteases. Altogether, our findings provide novel insights into the cellular and molecular mechanisms mediating the essential role of HGF/c-Met signaling during oval cell-mediated mouse liver regeneration.

Ultrastructural analysis of different-made staplers' staples.

AIM: Recently, Chinese-made mechanical staplers with lower price respect to American-made ones have been introduced in clinical practice. In literature, small case series compare the clinical outcomes of different staplers concluding that the new stapler devices perform as well as the American ones. The aim of this study is to compare with an ultrastructural analysis the staples of different staplers in order to verify the existence of differences that might explain significant price disparity and condition clinical outcomes. METHODS: Each stapler was subjected to morphological analysis, energy dispersive X-Ray spectroscopy, metal release assessment followed by inductively coupled plasma mass spectroscopy. P-values were considered statistically significant when <0.05. RESULTS: Autosuture staples have square section whereas the other American one and Chinese made staples have round sections. Roughness index and chips presence before and after ageing tests were comparable for all samples except for Ethicon Endo-Surgery stapler. Energy dispersive X-Ray spectroscopy showed that all staplers are made of pure Titanium but Ethicon Endo-Surgery staples are made with an alloy. Metal release analysis release statistically significant differences between samples in simulated body fluid 20 days solution (P=0.002) and in Aquaregia at 14 days solution. Discussion. Stapling devices have became routinely used in gastrointestinal surgery mainly because of operative time reduction. Recently, new Chinese-made mechanical staplers, with significantly lower prices, have been introduced in clinical practice. In literature, there are some studies that compare clinical outcomes of American-made and Chinese-made staplers on small groups of patients but doesn't exist any work which consider structural differences between traditional and new devices. In our study, for the first time, we propose a comparison between two American-made staplers and three Chinese-made staplers which evaluate morphology, metal composition and chemical staples release. CONCLUSION: Our study suggest that there are some ultrastructural differences between commercially available staplers with no correlation to price disparity. More studies are needed to confirm our results and to verify if our findings could condition clinical outcomes.