Agata Widera

Natural Killer Cells and Liver Fibrosis

In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified. Here, we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

Urinary cadmium levels in active and retired coal miners

ABSTRACT A meta-analysis, based upon 24 publications, showed a significantly elevated risk for urinary bladder cancer amongst miners. In European underground hard coal mining areas, an increased risk for urinary bladder cancer development was noted among hard coal miners, in particular in three investigations in the greater Dortmund area. However, the cause remains unclear. As cadmium (Cd), which was reported to be a bladder carcinogen in humans and is a constituent of coal, the aim of this study was to determine urinary Cd levels in active and retired hard coal miners and assess whether hard coal miners demonstrated elevated metal levels. In total, 103 retired and 25 active hard coal miners as well as 18 controls without any history of hard coal mining were investigated for urinary Cd levels. Urinary Cd concentrations, in addition to other elements, were analyzed in spot urines by ICP-MS-based multi-element analysis in a Department for Forensic and Clinical Toxicology. Limit of detection (LOD) for Cd was 0.5 μg/L. Reference value for occupationally non-exposed working age population was 0.8 μg/L. In total, 49% of all underground coal miners were exposed to coal dust, 12% to grinded rock, and 39% to both. Urinary Cd levels in retired as well as active coal miners and controls were clearly below the Biological Exposure Index. Urinary Cd concentration is a suitable biomarker to evaluate the metallic load of the body, as the half-life is > than 10 years. The detected urinary Cd levels in retired and active coal miners indicated underground hard coal miners were not apparently exposed to Cd to a occupationally-relevant concentration.

Corrigendum to “Gene networks and transcription factor motifs defining the differentiation of human stem cells into hepatocyte-like cells” [J Hepatol 2015;63:934–942]

IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany; Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, Jena, Germany; University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Robert-Koch-Str. 39, 50931 Cologne, Germany; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom; Takara Bio Europe AB (former Cellartis AB), Arvid Wallgrens Backe 20, 41346 Gothenburg, Sweden; Systems Biology Research Center, School of Bioscience, University of Skövde, Sweden; NovaHep AB, Arvid Wallgrens Backe 20, 41346 Gothenburg, Sweden; Charité University Medicine Berlin, Department of General-, Visceraland Transplantation Surgery, D13353 Berlin, Germany; Center for Liver Cell Research, Department of Pediatrics and Juvenile Medicine, University of Regensburg Hospital, Regensburg, Germany; Eberhard Karls University Tübingen, BG Trauma Center, Siegfried Weller Institut, D72076 Tübingen, Germany; Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile

Highlight report: diagnostic systems for the analysis of immune functions in humans

determine baseline variability. Further studies have been initiated to study the novel immune cell panel in relation to chemical exposure but also stress and age, and it will be included into the Dortmund vital study, a cohort of 500 healthy individuals that will be reevaluated every 5 years. Numerous studies have already addressed the role of immune cells in toxicity induced by chemicals (Godoy et al. 2013; Kadow et al. 2011; Gagnaire et al. 2014; Sánchez-Moreno et al. 2015) or drugs (Schmeits et al. 2015; Volarevic et al. 2015; Wang and Ning 2014; Choi et al. 2015; Chen et al. 2015). However, the hunt for a global diagnostic system to detect compromised immune functions has only just begun.

Highlight report: overview of hepatoprotective compounds

2014; Hammad 2014; Campos et al. 2014; Vitins et al. 2014; Liu et al. 2014; Dias da Silva et al. 2013; Schyschka et al. 2013; Rodrigues et al. 2013; Driessen et al. 2013). Moreover, liver in vitro systems (Chen et al. 2014; Vinken et al. 2014; Godoy et al. 2013; 2015; Ghallab 2014; Reif 2014; Godoy 2011; Ilkavets 2013; Messner et al. 2013) have been intensively applied and systems biology approaches (Schliess et al. 2014; Drasdo et al. 2014a, b; Hoehme et al. 2010) have been introduced to gain a deeper understanding of the mechanisms of hepatotoxicity. Considering this background, the present review of Domitrović and Potočnjak is a must read for anyone interested in how protective compounds can interfere with hepatotoxic mechanisms.