Search results for "MAC"

Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient…

2020

The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr(-/-)) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemicLdlr(-/-)mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GFLdlr(-/-)mice …

Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice

2016

BACKGROUND:The endocannabinoid 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Despite its high concentration in vascular tissue, the role of 2-AG in atherogenesis has not yet been examined. METHODS:ApoE-deficient mice were sublethally irradiated and reconstituted with bone marrow from mice with a myeloid-specific knockout of the 2-AG synthesising enzyme diacylglycerol lipase α (Dagla) or control bone marrow with an intact 2-AG biosynthesis. After a cholesterol-rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric mice. Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were mea…

Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation

2016

Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3’,4’,5’-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative 1 as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3’,4’,5’-trimethoxybenzoyl moi…

Total coumarins of Hedyotis diffusa induces apoptosis of myelodysplastic syndrome SKM-1 cells by activation of caspases and inhibition of PI3K/Akt pa…

2016

Abstract Ethnopharmacological relevance Hedyotis diffusa is an ethno-medicine used for anti-cancer treatment in the clinic of traditional Chinese medicine (TCM). The total coumarins of Hedyotis diffusa (TCHD) was a selected extract with observed antiproliferative activity, which has not been tested in treatment of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Aim of the study This study aimed to evaluate the apoptosis-inducing effect of TCHD on human MDS cell line (SKM-1) and explore its action mechanism in association with caspase family and PI3K/Akt signaling pathway. Materials and methods The chemical constituents and total coumarins content of TCHD were determined by …

Diversity, evolution, and function of myriapod hemocyanins.

2018

Background Hemocyanin transports O2 in the hemolymph of many arthropod species. Such respiratory proteins have long been considered unnecessary in Myriapoda. As a result, the presence of hemocyanin in Myriapoda has long been overlooked. We analyzed transcriptome and genome sequences from all major myriapod taxa – Chilopoda, Diplopoda, Symphyla, and Pauropoda – with the aim of identifying hemocyanin-like proteins. Results We investigated the genomes and transcriptomes of 56 myriapod species and identified 46 novel full-length hemocyanin subunit sequences in 20 species of Chilopoda, Diplopoda, and Symphyla, but not Pauropoda. We found in Cleidogona sp. (Diplopoda, Chordeumatida) a hemocyanin-…

The Interplay between Metabolism, PPAR Signaling Pathway, and Cancer

2017

Risk Assessment of Hip Fracture Based on Machine Learning

2020

[EN] Identifying patients with high risk of hip fracture is a great challenge in osteoporosis clinical assessment. Bone Mineral Density (BMD) measured by Dual-Energy X-Ray Absorptiometry (DXA) is the current gold standard in osteoporosis clinical assessment. However, its classification accuracy is only around 65%. In order to improve this accuracy, this paper proposes the use of Machine Learning (ML) models trained with data from a biomechanical model that simulates a sideways-fall. Machine Learning (ML) models are models able to learn and to make predictions from data. During a training process, ML models learn a function that maps inputs and outputs without previous knowledge of the probl…

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

2020

Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying …

AMD3100: A Versatile Platform for CXCR4 Targeting 68 Ga-Based Radiopharmaceuticals

2016

International audience; CXCR4 is a G protein-coupled receptor (GPCR), which is overexpressed in numerous diseases, particularly in multiple cancers. Therefore, this receptor represents a valuable target for imaging and therapeutic purposes. Among the different approaches, which were developed for CXCR4 imaging, a CXCR4 antagonist biscyclam system (AMD3100, also called Mozobil), currently used in the clinic for the mobilization of hematopoietic stem cells, was radiolabeled with different radiometals such as 62Zn, 64Cu, 67Ga, or 99mTc. However, cyclam is not an ideal chelator for most of these radiometals, and could lead to the release of the radionuclide in vivo. In the current study, a new …

Dietary polyphenols for managing cancers: What have we ignored?

2020

Abstract Although the chemoprevention and anti-cancer activities of dietary polyphenols have been evidenced through both in vitro and in vivo studies, most of the human clinical trials were unsuccessful or even harmful. Debates on the beneficial roles of dietary polyphenols in cancer therapy are increasing. Many dietary polyphenols studies are conducted by in vitro experiments, but the nature of these studies does not consider the complexity of metabolic processes that are present in vivo. These can often cause instability in the dietary polyphenols, thereby leading to unsuccessful extrapolation into animal or human studies. Dietary polyphenols often have low bioavailability, which is mainl…