The expression levels of ciRS-7 were comparable between HCC and matched non-tumor tissues. However, the highly ciRS-7 expression in HCC tissues was significantly correlated with hepatic MVI, AFP level and younger age and thus partly related with the deterioration of HCC. Especially, ciRS-7 was one of the independent factors of hepatic MVI. These data suggested that ciRS-7 may be a promising biomarker of hepatic MVI and a novel therapy target for restraining MVI.

The Hand gene family encodes highly conserved basic helix-loop-helix (bHLH) transcription factors that play crucial roles in cardiac and vascular development in vertebrates. In Drosophila, a single Hand gene is expressed in the three major cell types that comprise the circulatory system: cardioblasts, pericardial nephrocytes and lymph gland hematopoietic progenitors, but its function has not been determined. Here we show that Drosophila Hand functions as a potent transcriptional activator, and converting it into a repressor blocks heart and lymph gland formation. Disruption of Hand function by homologous recombination also results in profound cardiac defects that include hypoplastic myocardium and a deficiency of pericardial and lymph gland hematopoietic cells, accompanied by cardiac apoptosis. Targeted expression of Hand in the heart completely rescued the lethality of Hand mutants, and cardiac expression of a human HAND gene, or the caspase inhibitor P35, partially rescued the cardiac and lymph gland phenotypes. These findings demonstrate evolutionarily conserved functions of HAND transcription factors in Drosophila and mammalian cardiogenesis, and reveal a previously unrecognized requirement of Hand genes in hematopoiesis.

The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.

Summary The gene networks regulating heart morphology and cardiac integrity are largely unknown. We previously reported a role for the heterotrimeric G protein γ subunit 1 (Gγ1) in mediating cardial-pericardial cell adhesion in Drosophila. Here we show G-oα47A and Gβ13F cooperate with Gγ1 to maintain cardiac integrity. Cardial-pericardial cell adhesion also relies on the septate junction (SJ) proteins Neurexin-IV (Nrx-IV), Sinuous, Coracle, and Nervana2, and which together function in a common pathway with Gγ1. Furthermore, Gγ1 signaling is required for proper SJ protein localization, and loss of at least one SJ protein, Nrx-IV, induces cardiac lumen collapse. These results are surprising because the embryonic heart lacks SJs and suggest that SJ proteins perform non-canonical functions to maintain cardiac integrity in Drosophila. Our findings unveil the components of a previously unrecognized network of genes that couple G-protein signaling with novel structural constituents of the heart.

Vulnerability of parents enrolled in an EDP did not increase after hospital discharge. Physical well-being of the baby was the most important issue for both groups. EDP parents requested less paediatric support and scored higher in the Well-being verbatim.

No abstract

Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR‐203 adenovirus was administered to induce hepatic miR‐203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR‐203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non‐tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR‐203 overexpression further promoted the regeneration of the non‐tumorous liver by upregulating Ki67 expression and enhancing IL‐6/SOCS3/STAT3 pro‐proliferative signals. Importantly, miR‐203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR‐203 overexpression reversed the epithelial–mesenchymal transition induced by hepatectomy through targeting IL‐1β, Snail1 and Twist1. In conclusion, our results suggested that miR‐203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial–mesenchymal transition.

No abstract