Search results for "Raf"

Frequent Ultrafine Particle Formation and Growth in the Canadian Arctic Marine Environment

2017

Abstract. The source strength and capability of aerosol particles in the Arctic to act as cloud condensation nuclei have important implications for understanding the indirect aerosol-cloud effect within the polar climate system. It has been shown in several Arctic regions that ultrafine particle (UFP) formation and growth is a key contributor to aerosol number concentrations during the summer. This study uses aerosol number size distribution measurements from ship-board measurement expeditions aboard the research icebreaker CCGS Amundsen in the summers of 2014 and 2016 throughout the Canadian Arctic to gain a deeper understanding of the drivers of UFP formation and growth within this marine…

New 3-Aryl-2-(2-Thienyl)acrylonitriles with High Activity against Hepatoma Cells

2021

New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, whil…

Interleukin-22 in Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

2016

International audience; Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in …

Gamma-Delta CAR-T Cells Show CAR-Directed and Independent Activity Against Leukemia

2020

Autologous T cells engineered to express a chimeric antigen receptor (CAR) against the CD19 antigen are in the frontline of contemporary hemato-oncology therapies, leading to high remission rates in B-cell malignancies. Although effective, major obstacles involve the complex and costly individualized manufacturing process, and CD19 target antigen loss or modulation leading to resistant and relapse following CAR therapy. A potential solution for these limitations is the use of donor-derived γδT cells as a CAR backbone. γδT cells lack allogenecity and are safely used in haploidentical transplants. Moreover, γδT cells are known to mediate natural anti-tumor responses. Here, we describe a 14-da…

“Out of the can”: a draft genome assembly, liver transcriptome, and nutrigenomics of the european sardine, sardina pilchardus

2018

Clupeiformes, such as sardines and herrings, represent an important share of worldwide fisheries. Among those, the European sardine (Sardina pilchardus, Walbaum 1792) exhibits significant commercial relevance. While the last decade showed a steady and sharp decline in capture levels, recent advances in culture husbandry represent promising research avenues. Yet, the complete absence of genomic resources from sardine imposes a severe bottleneck to understand its physiological and ecological requirements. We generated 69 Gbp of paired-end reads using Illumina HiSeq X Ten and assembled a draft genome assembly with an N50 scaffold length of 25,579 bp and BUSCO completeness of 82.1% (Actinoptery…

Environmental epigenetics in zebrafish

2017

Abstract It is widely accepted that the epigenome can act as the link between environmental cues, both external and internal, to the organism and phenotype by converting the environmental stimuli to phenotypic responses through changes in gene transcription outcomes. Environmental stress endured by individual organisms can also enforce epigenetic variations in offspring that had never experienced it directly, which is termed transgenerational inheritance. To date, research in the environmental epigenetics discipline has used a wide range of both model and non-model organisms to elucidate the various epigenetic mechanisms underlying the adaptive response to environmental stimuli. In this rev…

Inhibition of cell migration and induction of apoptosis by a novel class II histone deacetylase inhibitor, MCC2344.

2020

Epigenetic modifiers provide a new target for the development of anti-cancer drugs. The eraser histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that targets various non-histone proteins such as transcription factors, nuclear receptors, cytoskeletal proteins, DNA repair proteins, and molecular chaperones. Therefore, it became an attractive target for cancer treatment. In this study, virtual screening was applied to the MicroCombiChem database with 1162 drug-like compounds to identify new HDAC6 inhibitors. Five compounds were tested in silico and in vitro as HDAC6 inhibitors. Both analyses revealed 1-cyclohexene-1-carboxamide, 2-hydroxy-4,4-dimethyl-N-1-naphthalenyl-6-oxo- (MC…

Microenvironment modulation and enhancement of antilymphoma therapy by the heparanase inhibitor roneparstat

2018

RE: Regorafenib Also Can Cause Osteonecrosis of the Jaw

2016

Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation

2018

Abstract Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effec…