8 research outputs found

    DataSheet_1_Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice.docx

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    Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials.</p

    Vitality of PCLS evaluated by bronchoconstriction.

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    <p>To induce bronchoconstriction, the untreated slice (a) was incubated with 10<sup>−4</sup> M methacholine (b). Removal of the drug resulted in a reverse effect (c).</p

    Infection of swine PCLS by influenza viruses characterized by immunostaining.

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    <p>PCLS were infected by either porcine H3N2, avian H9N2, or avian H7N7 virus. Cryosections were prepared at 24 h.p.i. and used for detection of infected cells, ciliated cells, and mucus-producing cells. Infected cells were stained with an anti-nucleoprotein antibody (green); ciliated cells were stained using an anti-β-tubulin antibody (red) and mucus-producing cells were stained using an Muc5Ac antibody (red).</p

    Vitality of PCLS evaluated by live (green)/dead (red) staining.

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    <p>Slices were stained with a commercial kit at day 1, 3 and 7 after preparation (upper panels, a–c). For comparison, in the lower panels the live/dead staining is shown for two slices that either had retained full ciliary activity (100%) (d), or had completely lost ciliary activity (0%) (e). The scale bar indicates 50 µm.</p

    Additional file 1: of Host-pathogen interplay at primary infection sites in pigs challenged with Actinobacillus pleuropneumoniae

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    Information about IL8 primers and optimised qPCR assays. More details about the optimisation and validation of qPCR assays for target gene-specific primers in the pig are included. Particularly in the figure is shown that the suitability of the newly designed primers was verified in separate experiments by performing of a cDNA pool. In melt curve and amplification plots samples are shown in green while controls (no reverse transcription control (NRT) and no template control (NTC)) are shown in yellow and orange respectively. Additionally, an agarose gel electrophoresis of the PCR products of undiluted cDNA pool and controls was performed. (DOCX 349 kb
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