Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-in-Silico Approach Combining In Vitro Experiments and Machine Learning (vol 9, 393, 2018)

A Corrigendum on Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning by Zechendorf E, Vaßen P, Zhang J, Hallawa A, Martincuks A, Krenkel O, Müller-Newen G, Schuerholz T, Simon T-P, Marx G, Ascheid G, Schmeink A, Dartmann G, Thiemermann C and Martin L (2018). Front. Immunol. 9:393. doi: 10.3389/fimmu.2018.00393 In the original article, there was an error in the Author Contributions section. The wording used to declare the contribution of Elisabeth Zechendorf was not clear. The new Author Contributions section appears below. Conception and design: EZ, LM, GD, AS, and CT. In vitro experiments and data analyses: EZ, LM, TS, T-PS, AM, GM-N, OK, GM, and PV. Medical in silico experiments and data analyses: EZ, PV, JZ, GD, AS, LM, AH, and GA. EZ wrote the manuscript. Correction of the manuscript: EZ, PV, LM, CT, GM, GD, T-PS, and AS. All the authors reviewed and finally approved the manuscript. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233

Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis

Background & Aims Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC’s anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis. Methods Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC’s antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses. Results CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05). At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05), and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls). CVC treatment had no notable effect on body or liver/kidney weight. Conclusions CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC’s antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475)

Barrier Tissue Macrophages: Functional Adaptation to Environmental Challenges

Macrophages are found throughout the body, where they have crucial roles in tissue development, homeostasis and remodeling, as well as being sentinels of the innate immune system that can contribute to protective immunity and inflammation. Barrier tissues, such as the intestine, lung, skin and liver, are exposed constantly to the outside world, which places special demands on resident cell populations such as macrophages. Here we review the mounting evidence that although macrophages in different barrier tissues may be derived from distinct progenitors, their highly specific properties are shaped by the local environment, which allows them to adapt precisely to the needs of their anatomical niche. We discuss the properties of macrophages in steady-state barrier tissues, outline the factors that shape their differentiation and behavior and describe how macrophages change during protective immunity and inflammation

Dense SiSiC Ceramics Derived from Different Wood-Based Composites: Processing, Microstructure and Properties

The manufacture of dense SiSiC ceramics from commercial wood-based composites (WBC) via liquid silicon infiltration has been developed in the last years. The process is based on the silicon infiltration of manufactured carbon preforms. An advantage of the carbonization of WBC for the manufacture of SiSiC ceramics is the simple axial pressing process. It is possible to create homogeneous, isotropic and reproducible WBC on the basis of fine grain powders. Fine microstructures and phase compositions of the SiSiC ceramics can be achieved by using particle sizes less than 50 mu-m and additives or by varying the type of wood. So, in a first step different wood powders were homogeneously mixed with phenolic resin, carbon powder and carbon fibers as additives and uni-axially thermal pressed into WBC with the dimensions of 140 x 140 x 10 mm3. After drying up to 110oC the WBC were carbonized up to 1650°C (pyrolysis) to obtain porous carbon preforms for the final siliconization which occurs above the melting point of silicon (greater than 1420°C). The use of C-additives in the WBC results in a reduction of the shrinkage behavior during pyrolysis. Furthermore, it is possible to improve the damage tolerance and the ductility of the SiSiC ceramics. The aim of this study is to create damage tolerant SiC ceramics which can be used for lightweight structures for the application within optical apparatus with high stiffness and low thermal expansion. In this paper the process itself as well as the mechanical, some thermo physical properties of the dense SiSiC ceramics derived from WBC are reported. The microstructure was examined with light microscopy and SEM. The bending strength and fracture behavior, carried out by the three-point short beam flexural test, was correlated with the structure as well as the composition and distribution of the phases

SiC-Keramiken auf der Basis von Holzwerkstoffen

Die Entwicklung von dichten SiC-Keramiken hergestellt durch Flüssigsilicierung von pyrolysierten Holzwerkstoffen ist Ziel eines laufenden DFG-Projektes zwischen der TU München und dem DLR in Stuttgart. Üblicherweise bestehen kommerzielle Holzwerkstoffe aus Fasern, Spänen oder Furnierlagen verschiedener Hart- oder Weichhölzer, die zusammen mit Bindemitteln verpresst werden. Derartige Holzwerkstoffe führten zu inhomogenen SiC-Keramiken mit mäßigen mechanischen und physikalischen Eigenschaften. In zwei Stufen wurden dichte SiC-Keramiken auf der Basis von speziell für die nachfolgende Keramisierung hergestellte Span- und Faserplatten (ca. 140 x 140 mm²) entwickelt. In einem ersten Entwicklungsschritt blieben Holzart und Bindemittelanteil konstant, Bindemittelart, Dichte und Dicke der Platten hingegen wurden variiert. Im zweiten Schritt wurden Bindemittelart und Holzart als Konstanten festgelegt, Bindemittelanteil und Dichte waren variabel. Zunächst wurden die Holzwerkstoffe getrocknet, um die Holzfeuchte zu reduzieren. Mittels anschließendem Hochtemperatur-Prozess, bestehend aus Pyrolyse und Silicierung, wurden biomorphe SiC-Keramiken entwickelt. Die, aus den speziell hergestellten Holzwerkstoffen, entwickelten SiC-Keramiken zeigten ein deutlich homogeneres Gefüge als die kommerziellen Platten. Das wiederum hatte verbesserte Werkstoffeigenschaften zur Folge. Die Dichte der Keramik verbesserte sich auf ca. 3 g/cm³ und die Biegefestigkeit - je nach Ausgangsmaterial - auf 403 MPa