Hartvigsenringgaard2016

Crosstalk Involving LXR as well as Caveolin-1 Signaling Helps Cholesterol levels Efflux as well as Anti-Inflammatory Paths within Macrophages.

As the presence of nanosized zinc oxide particles (nano-ZnO) in landfill leachate increases, their interaction with coexisting heavy metal ions (HMs) also increases. The interface interaction between nano-ZnO and HMs will influence nano-ZnO stability and therefore affect its bioavailability and environmental impact. In the present study, we investigated the effects of Cu(II), Cr(III), and Cr(VI) ions on the aggregation, sedimentation, and dissolution of nano-ZnO using batch experiments with a view to better understanding their co-effect on the environment. Dynamic light scattering and UV-Vis spectroscopy results show enhanced aggregation of nano-ZnO in the presence of Cr(VI) ions under fresh landfill leachate conditions, in addition to distinct sedimentation of nano-ZnO in the presence of Cr(III) ions in both fresh and aged landfill leachate. In fresh leachate, Cu(II) ions improved the concentration of dissolved Zn from nano-ZnO. However, the effects of Cu(II), Cr(III), and Cr(VI) ions on the aggregation and dissolution of nano-ZnO were markedly reduced in aged landfill leachate. Both acetic and humic acids in landfill leachate significantly affected the stability of nano-ZnO in the presence of HMs. According to the ATR-FTIR results, Cr(III) ions reacted with hydroxyl groups on nano-ZnO to form ZnO-O bonds, which induced chains of nano-ZnO and Cr(III) complexes, and hence the increased of nano-ZnO aggregates. ATR-FTIR shows merely electrostatic adsorption effects between nano-ZnO and Cu(II) or Cr(VI) ions. In brief, the mode of interactions between HMs and nano-ZnO influenced the stability via adsorption and binding effects. The results of the present research provide insight into the potential effects of nano-ZnO on the environment in the presence of HMs in landfill leachate. Aflatoxin B1 (AFB1) is a known carcinogen found in contaminated food and designated by the World Health Organization as a class I carcinogenic substance. AFB1 presents with carcinogenicity, teratogenicity, and mutagenicity, and the liver is the human organ most susceptible to AFB1. Zinc (Zn), which is one of the essential nutrient elements that could protect the cells from biological toxins, heavy metals, hydrogen peroxide, metal chelators and radiation, is assessed in this study for its potential to alleviate AFB1-induced cytotoxicity. Samples were divided into three groups, namely CK, AFB1, and AFB1+Zn. Protein expressions were analyzed by two-way electrophoresis combined with flight mass spectrometry, with 41 differentially expressed proteins identified in the results, mainly related to oxidative stress, cell apoptosis, DNA damage, and energy metabolism. Zn was found to regulate the expression of peroxidases (peroxiredoxin-1, peroxiredoxin-5, peroxiredoxin-6) to relieve AFB1-induced oxidative stress. Moreover, Zn could decrease the expression of pro-apoptotic genes (cleaved-caspase-3, caspase-9, and Bax) and increase the expression of anti-apoptotic genes (Bcl-2 and Bcl-xl) to alleviate the cell apoptosis induced by AFB1. In addition, AFB1 reduced intracellular ATP levels, whereas Zn supplementation boosted ATP levels and maintained homeostasis and a steady state of cellular energy metabolism by modulating AMPK-ACC phosphorylation levels, while many zinc finger proteins changed after AFB1 treatment. These results, therefore, indicate that Zn could alleviate AFB1-induced cytotoxicity by changing the expressions of zinc finger proteins in liver hepatocellular carcinoma (HepG2 cells). Zika Virus (ZIKV), an arbovirus that belongs to the Flaviviridae family, has become a global concern since its outbreak in the Americas in 2015. With symptoms similar to other Flavivirus as Dengue and Yellow Fever viruses, infections by ZIKV have also been related to several neurological complications such as microcephaly in newborns and Guillain-Barre syndrome. Considering the high prevalence of ZIKV infection in certain areas, the risks that the virus poses to fetal brain development, and the fact that there is no vaccine or specific prophylaxis available, an effective treatment capable of preventing the infection is of potential interest. Therefore, in the present investigation, the antiviral activity on ZIKV of a group of xanthenodiones and intermediate ketones involved in their synthesis was evaluated for the first time. It was found that the compound 2-(2,6-dichlorobenzylidene)cyclohexane-1,3-dione 27 was able to completely inhibit the viral infection of Vero cells as well as to significantly reduce viral load in the brains of newborn Swiss mice. this website These effects are related to a direct interaction of the compound with the viral particle, blocking the viral adsorption. INTRODUCTION Several PD-L1 immunohistochemistry (IHC) assays have been developed independently within clinical programs for therapeutic anti-PD-1/PD-L1 antibodies, necessitating assessment of assay comparability. We characterize the Dako PD-L1 IHC 73-10 assay used in clinical trials of avelumab (anti-PD-L1) or bintrafusp alfa (M7824; bifunctional immunotherapy) and compare it with the Dako PD-L1 IHC 22C3 pharmDx assay, an approved companion diagnostic for pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS Formalin-fixed, paraffin-embedded NSCLC tumor samples from a commercial source and from the JAVELIN Solid Tumor phase 1 trial of avelumab (NCT01772004) were stained using the 73-10 and 22C3 IHC assays with a standard protocol. this website RESULTS Both assays displayed expected PD-L1 staining patterns. In 148 commercial NSCLC samples, the 73-10 assay stained ≥1%, ≥50%, and ≥80% of tumor cells PD-L1+ in 64.2%, 36.5%, and 23.6% of samples, respectively, whereas the 22C3 assay stained 20.3% of the samples as ≥50% PD-L1+. In 83 NSCLC clinical trial samples, the 73-10 assay stained 79.5% and 31.3% of the samples as ≥1% and ≥80% PD-L1+, respectively, whereas the 22C3 assay stained 59.0% and 21.7% as ≥1% and ≥50% PD-L1+, respectively. Efficacy of avelumab was similar in the subgroups classified with the 73-10 and 22C3 assays using ≥80% and ≥50% PD-L1+ cutoffs, with objective response rates of 26.9% and 33.3%, respectively. CONCLUSIONS The 73-10 assay showed high sensitivity for PD-L1 staining, and staining was comparable between the ≥80% cutoff of the 73-10 assay and ≥50% cutoff of the 22C3 assay.