L'Alerte : journal indépendant : politique, littéraire et commercial

14 décembre 19081908/12/14 (A12)-1908/12/14

Additional file 2: Movie 1. of Integrated ordination of miRNA and mRNA expression profiles

360° rotation of 3D MDS dispersion ellipses of mRNA functional clusters of ALF livers. Labels are shown in the two last frames (38–39) at the end of the rotation cycle. If the media player runs continuously, it should be stopped manually to visualize the labels. The original frame size is 731x712. The player window should be properly resized to optimize the image quality. (SWF 1150 kb

Additional file 3: Movie 2. of Integrated ordination of miRNA and mRNA expression profiles

360° rotation of 3D MDS dispersion ellipses of mRNA functional clusters of control livers. Labels are shown in the two last frames (38–39) at the end of the rotation cycle. If the media player runs continuously, it should be stopped manually to visualize the labels. The original frame size is 731x712. The player window should be properly resized to optimize the image quality. (SWF 1101 kb

Contesting feminist orthodoxies

Additional file 9: Figure S2. The lncRNAs, DBH-AS1, hDREH and hPVT1 were differentially dysregulated in HBV-, HCV-, and HDV-related HCC

MOESM3 of Analysis of long noncoding RNA expression in hepatocellular carcinoma of different viral etiology

Additional file 3: Table S3. Seventeen lncRNAs significantly dysregulated on profiling data in HCC patients

Liver Regeneration Signature in Hepatitis B Virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling

<div><h3>Introduction</h3><p>The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC). The dramatic clinical course of acute liver failure (ALF) has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV)-associated ALF.</p> <h3>Methods and Findings</h3><p>Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7), whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.</p> <h3>Conclusion</h3><p>Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between liver regeneration and liver cancer.</p> </div

Histopathologic features of HBV-associated acute liver failure (ALF) showing the severity of hepatic necrosis in 4 patients.

<p>At the time of liver transplantation there was massive hepatic necrosis (MHN) with no viable hepatocytes in Patient 241, MHN (nearly 100%) with few scattered hepatocytes in Patient 31, and submassive hepatic necrosis (SHN) in Patients 219 (70 to 80% necrosis) and 32 (60% necrosis) (hematoxylin and eosin, x400).</p

Multidimensional scaling.

<p>Three-dimensional (3D) projection of 17 liver specimens from 4 patients with ALF and 10 specimens from individual liver donors by multidimensional scaling using all 11,597 transcripts that passed the filtering criteria. In the 3D projection, each point represents an individual liver specimen, and the distance between points is proportional to the overall dissimilarity of gene expression profiling. The plot illustrates how the gene expression profiles differentiate between ALF and liver donors, as well as among ALF patients. ALF patients with massive hepatic necrosis (MHN) (Patients 241 and 31) and those with submassive hepatic necrosis (SHN) (Patients 219 and 32) form two distinct clusters whose distance from liver donors reflects the extent of liver injury.</p

Liver fibrosis in HBV-associated ALF.

<p>Delicate fibrosis is evident in the zones of collapsed necrotic parenchyma. The mature collagen of portal areas stains dark blue, while the newer collagen stains light blue (Masson’s trichrome, x200).</p

Hierarchical clustering.

<p>Hierarchical cluster analysis of 17 liver specimens from 4 patients with acute liver failure and 10 specimens from individual liver donors using all 11,597 transcripts that passed the filtering criteria. All specimens were grouped into 3 main clusters, which correspond to the 3 liver conditions (ALF with MHN, ALF with SHN and liver donors). The unsupervised nature of the analysis and the 100% correct classification of samples suggest a high specificity and sensitivity of gene expression differences between ALF and normal livers.</p