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3 Publications matching the given criteria: (Clear all filters)
Project: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)3
Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression

Abstract (Expand)

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male …e, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of ‘rest-and-jump genes’ that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30–48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.

Authors: Ahmed Ghallab, Maiju Myllys, Adrian Friebel, Julia Duda, Karolina Edlund, Emina Halilbasic, Mihael Vucur, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe, Reham Hassan, Michael Burke, Erhan Genc, Lynn Johann Frohwein, Ute Hofmann, Christian H. Holland, Daniela González, Magdalena Keller, Abdel-latif Seddek, Tahany Abbas, Elsayed S. I. Mohammed, Andreas Teufel, Timo Itzel, Sarah Metzler, Rosemarie Marchan, Cristina Cadenas, Carsten Watzl, Michael A. Nitsche, Franziska Kappenberg, Tom Luedde, Thomas Longerich, Jörg Rahnenführer, Stefan Hoehme, Michael Trauner, Jan G. Hengstler

Date Published: 1st Oct 2021

Publication Type: Journal

Guided interactive image segmentation using machine learning and color based data set clustering

Abstract

Not specified

Authors: Adrian Friebel, Tim Johann, Dirk Drasdo, Stefan Hoehme

Date Published: 18th May 2020

Publication Type: Misc

A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers

Abstract (Expand)

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct … morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.

Authors: Geert Peeters, Charlotte Debbaut, Wim Laleman, Adrian Friebel, Diethard Monbaliu, Ingrid Vander Elst, Jan R Detrez, Tim Vandecasteele, Tim Johann, Thomas De Schryver, Luc Van Hoorebeke, Kasper Favere, Jonas Verbeke, Dirk Drasdo, Stefan Hoehme, Patrick Segers, Pieter Cornillie, Winnok H De Vos

Date Published: 28th Dec 2016

Publication Type: Not specified

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