9 research outputs found
Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice
The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC500.79 μM) while also showing a reduction of >3 log TCID50/mL for HCoV-229E. The in vivo efficacy of vandetanib was assessed in a mouse model of SARS-CoV-2 infection and statistically significantly reduced the levels of IL-6, IL-10, and TNF-α and mitigated inflammatory cell infiltrates in the lungs of infected animals but did not reduce viral load. Vandetanib also decreased CCL2, CCL3, and CCL4 compared to the infected animals. Vandetanib additionally rescued the decreased IFN-1β caused by SARS-CoV-2 infection in mice to levels similar to that in uninfected animals. Our results indicate that the FDA-approved anticancer drug vandetanib is worthy of further assessment as a potential therapeutic candidate to block the COVID-19 cytokine storm
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Grain-size data from four cores from Walker Lake, Nevada
A number of cores, taken from within and near Walker Lake, Nevada are being studied by various investigators in order to evaluate the late-Pleistocene paleoclimate of the west-central Great Basin. In particular, the cores provide records that can be interpreted in terms of past climate and compared to proposed numerical models of the region`s climate. All of these studies are being carried out as part of an evaluation of the regional paleoclimatic setting of a proposed high-level nuclear waste storage facility at Yucca Mountain, Nevada. Changes in past climate often manifest themselves in changes in sedimentary processes or in changes in the volume of sediment transported by those processes. One fundamental sediment property that can be related to depositional processes is grain size. Grain size effects other physical properties of sediment such as porosity and permeability which, in turn, affect the movement and chemistry of fluids. The purposes of this report are: (1) to document procedures of sample preparation and analysis, and (2) to summarize grain-size statistics for 659 samples from Walker Lake cores 84-4, 84-5, 84-8 and 85-2. Plots of mean particle diameter, percent sand, and the ratio of silt to clay are illustrated for various depth intervals within each core. Summary plots of mean grain size, sorting, and skewness parameters allow comparison of textural data between each core. 15 refs., 8 figs., 3 tabs