764 research outputs found

    Hypoxia up-regulates SERPINB3 through HIF-2\u3b1 in human liver cancer cells.

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    SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells. Exposure of HepG2 and Huh7 cells to hypoxia up-regulated SERPINB3 transcription, protein synthesis and release in the extracellular medium. Hypoxia-dependent SERPINB3 up-regulation was selective (no change detected for SERPINB4) and operated through hypoxia inducible factor (HIF)-2\u3b1 (not HIF-1\u3b1) binding to SERPINB3 promoter, as confirmed by chromatin immuno-precipitation assay and silencing experiments employing specific siRNAs. HIF-2\u3b1-mediated SERPINB3 up-regulation under hypoxic conditions required intracellular generation of ROS. Immuno-histochemistry (IHC) and transcript analysis, performed in human HCC specimens, revealed co-localization of the two proteins in liver cancer cells and the existence of a positive correlation between HIF-2\u3b1 and SERPINB3 transcript levels, respectively. Hypoxia, through HIF-2\u3b1-dependent and redox-sensitive mechanisms, up-regulates the transcription, synthesis and release of SERPINB3, a molecule with a high oncogenic potential

    SerpinB3 as hepatic marker of post-resective shear stress

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    Post-resective liver failure is a frequent complication of liver surgery and it is due to portal hyperperfusion of the remnant liver and to arterial vasoconstriction, as buffer response of the hepatic artery. In this context, splenectomy allows a reduction of portal flow and increases the survival chance in preclinical models. SerpinB3 is over-expressed in the liver in oxidative stress conditions, as a mechanism of cell defense to provide survival by apoptosis inhibition and cell proliferation. In this study, the expression of SerpinB3 was assessed as predictor of liver damage in in vivo models of major hepatic resection with or without splenectomy. Wistar male rats were divided into 4 groups: group A received 30% hepatic resection, group B > 60% resection, group C > 60% resection with splenectomy and group D sham-operated. Before and after surgery liver function tests, echo Doppler ultrasound and gene expression were assessed. Transaminase values and ammonium were significantly higher in groups that underwent major hepatic resection. Echo Doppler ultrasound showed the highest portal flow and resistance of the hepatic artery in the group with > 60% hepatectomy without splenectomy, while the association of splenectomy determined no increase in portal flow and hepatic artery resistance. Only the group of rats without splenectomy showed higher shear-stress conditions, reflected by higher levels of HO-1, Nox1 and of Serpinb3, the latter associated with an increase of IL-6. In conclusion, splenectomy controls inflammation and oxidative damage, preventing the expression of Serpinb3. Therefore, SerpinB3 can be considered as a marker of post-resective shear stress

    Focusing on the role of abiotic and biotic drivers on cross-taxon congruence

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    Diversity patterns can show congruence across taxonomic groups. Consistent diversity patterns allow the identification of indicator surrogates potentially representative of unobserved taxa or the broader biodiversity patterns. However, the effective use of biodiversity surrogates depends on underlying mechanisms driving the strength of the relationship among taxonomic groups. Here, we explored congruence patterns in community composition among taxa occupying different trophic levels, accounting for abiotic and biotic factors: vascular plants and six groups of ground-dwelling arthropods (pseudoscorpions, spiders, darkling beetles, rove beetles, ground beetles and ants) were chosen as potential indicator surrogates. We evaluated the cross-taxon relationships using Mantel test; subsequently, we investigated if these relationships could partially depend on abiotic drivers, using partial Mantel tests; then, we evaluated the partial contributions of abiotic and biotic drivers in explaining these relationships through a series of variation partitioning analyses. Our results showed that a consistent cross-taxon congruence pattern was evident across almost all group pairs: pseudoscorpions, spiders, ground beetles and vascular plants showed the largest number of significant correlations with other taxa. Environmental gradients resulted as drivers of cross-taxon congruence, shaping composition patterns. However, they were not the only ones. Biotic drivers account for part of cross-taxon congruence among vascular plants and arthropod predators (i.e., pseudoscorpions and spiders, but also ground beetles), as well as among taxa at high trophic levels. Almost all strictly predatory taxa, known as biological control agents, emerged as the best predictors of plant community composition even when the role of environmental factors was considered. Spiders/ants and spiders/ground beetles showed close relationships and congruent composition patterns, irrespective of environmental parameters. Relationships among taxa might be driven by several complex biotic interactions (e.g., non-trophic and trophic interactions, direct and indirect interactions). Bottom-up and top-down forces, consumptive and non-consumptive interactions may play a role in influencing the community composition of taxa and driving the observed relationships. Future studies should broaden knowledge about the role of these forces and interactions in determining the congruence across taxa. The multi-trophic perspective in cross-taxon studies can be promising for identifying biodiversity surrogates and their application in conservation planning

    Ultrabithorax confers spatial identity in a context-specific manner in the Drosophila postembryonic ventral nervous system.

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    BACKGROUND: In holometabolous insects such as Drosophila melanogaster, neuroblasts produce an initial population of diverse neurons during embryogenesis and a much larger set of adult-specific neurons during larval life. In the ventral CNS, many of these secondary neuronal lineages differ significantly from one body segment to another, suggesting a role for anteroposterior patterning genes. RESULTS: Here we systematically characterize the expression pattern and function of the Hox gene Ultrabithorax (Ubx) in all 25 postembryonic lineages. We find that Ubx is expressed in a segment-, lineage-, and hemilineage-specific manner in the thoracic and anterior abdominal segments. When Ubx is removed from neuroblasts via mitotic recombination, neurons in these segments exhibit the morphologies and survival patterns of their anterior thoracic counterparts. Conversely, when Ubx is ectopically expressed in anterior thoracic segments, neurons exhibit complementary posterior transformation phenotypes. CONCLUSION: Our findings demonstrate that Ubx plays a critical role in conferring segment-appropriate morphology and survival on individual neurons in the adult-specific ventral CNS. Moreover, while always conferring spatial identity in some sense, Ubx has been co-opted during evolution for distinct and even opposite functions in different neuronal hemilineages

    The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): A post-hoc between-sex analysis

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    Background: Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods: All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 at inclusion and follow-up visit. Results: Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O'Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions: Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth
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