Search results for " ACE"

The Volatilomic Footprints of Human HGC-27 and CLS-145 Gastric Cancer Cell Lines

2021

The presence of certain volatile biomarkers in the breath of patients with gastric cancer has been reported by several studies; however, the origin of these compounds remains controversial. In vitro studies, involving gastric cancer cells may address this problem and aid in revealing the biochemical pathways underlying the production and metabolism of gastric cancer volatile indicators. Gas chromatography with mass spectrometric detection, coupled with headspace needle trap extraction as the pre-concentration technique, has been applied to map the volatilomic footprints of human HGC-27 and CLS-145 gastric cancer cell lines and normal Human Stomach Epithelial Cells (HSEC). In total, 27 volat…

Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/β2-Adrenoceptor Agonist Molecule with Long-Lasting Effect…

2019

AZD8871 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M3 receptor (pIC50 in binding assays: 9.5) and shows kinetic selectivity for the M3 (half-life: 4.97 hours) over the M2 receptor (half-life: 0.46 hour). It is selective for the β2-adrenoceptor over the β1 and β3 subtypes (3- and 6-fold, respectively) and shows dual antimuscarinic and β2-adrenoceptor functional activity in isolated guinea pig tissue (pIC50 in electrically stimulated trachea: 8.6; pEC50 in spontaneous tone isolated trachea: 8.8, r…

Chrysophanol- and nepodin-8-O-β-D-glucopyranoside from Rumex acetosella, the cytotoxicity towards drug sensitive and multi- drug resistant T leukaemi…

2016

A historic perspective on the current progress in elucidation of the biologic significance of non-neuronal acetylcholine

2020

The "5th International Symposium on Non-neuronal Acetylcholine: from bench to bedside" was held on September 27-29, 2019 in Hyatt Regency, Long Beach, CA, USA. Approximately 50 scientists from 11 countries over 6 continents participated in this meeting. The major topics included an overall biologic significance of non-neuronal acetylcholine (ACh) and the roles of the non-neuronal cholinergic systems in mucocutaneous, respiratory, digestive, immunologic, endocrine, cardiovascular, musculoskeletal and kidney diseases, and cancer. This meeting facilitated continued work to advance the fundamental science and translational aspects of the interdisciplinary studies on non-neuronal ACh. The progre…

Pharmacological preclinical characterization of LAS190792, a novel inhaled bifunctional muscarinic receptor antagonist /β 2 -adrenoceptor agonist (MA…

2017

LAS190792 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M3 receptor (pIC50: 8.8 in binding assays). It is selective for the β2-adrenoceptor over the β1-and β3-adrenoceptor, and shows a functional potency in a similar range to batefenterol and LABA compounds (pEC50 in spontaneous tone isolated trachea: 9.6). The relaxant potency of LAS190792 in electrically stimulated tissue is similar to batefenterol, with an antimuscarinic activity in presence of propranolol sl…

P/CAF-mediated spermidine acetylation regulates histone acetyltransferase activity

2016

Histones and polyamines are important determinants of the chromatin structure. Histones form the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional regulation. Polyamines, including spermidine, are also targets of both cytoplasmic and nuclear acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report the interplay between polyamines metabolism and levels of histone acetylation, but the molecular basis of this effect is still unclear. In this work, we have analyzed the in vitro effect of spermidine on histone H3 acetylation catalyzed by P/CAF, a highly co…

Combined HAT/EZH2 modulation leads to cancer-selective cell death

2018

Contains fulltext : 197351.pdf (Publisher’s version ) (Open Access) Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro, ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2. Even aggressive models of cancer, …

Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study

2018

International audience; Nicotinic acetylcholine receptors, belonging to the Cys-loop super-family of ligand-gated ion channels (LGICs), are membrane proteins present in neurons and at neuromuscular junctions. They are responsible for signal transmission, and their function is regulated by neurotransmitters, agonists and antagonists drugs. A detailed knowledge of their conformational transition in response to ligand binding is critical to understand the basis of ligand-receptor interaction, in view of new pharmacological approaches to control receptor activity. However, the scarcity of experimentally derived structures of human channels makes this perspective extremely challenging. To contri…

A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study

2017

International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…

Effect of a co-substrate supply in a MBR treating shipboard slop: Analysis of hydrocarbon removal, biomass activity and membrane fouling tendency

2018

The paper reports the main results of an experiment carried out on a membrane bioreactor (MBR) plant designed for the treatment of shipboard slops. With a view of a co-treatment process of the slop with other wastewaters, sodium acetate, as external co-substrate, was supplied (high dosage – Period 1, low dosage – Period 2) to evaluate its effects on hydrocarbons removal. The MBR pilot plant enabled approximately 99% of total petroleum hydrocarbon (TPH) removal during the entire experiment, confirming the robustness of the MBR technology for the treatment of slops. The chromatography/mass spectrometry analysis showed that the removal efficiency for each alkane was close to the value observed…