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https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#1
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastierdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
April 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28409500/tissue-protective-activity-of-selenomethionine-and-d-panthetine-in-b16-melanoma-bearing-mice-under-doxorubicin-treatment-is-not-connected-with-their-ros-scavenging-potential
#2
Rostyslav R Panchuk, Nadia R Skorokhyd, Yuliya S Kozak, Liliya V Lehka, Andrey G Moiseenok, Rostyslav S Stoika
AIM: To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. METHODS: Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears...
April 14, 2017: Croatian Medical Journal
https://www.readbyqxmd.com/read/28396195/treatment-with-salvianolic-acid-b-restores-endothelial-function-in-angiotensin-ii-induced-hypertensive-mice
#3
Wei Chih Ling, Jian Liu, Chi Wai Lau, Dharmani Devi Murugan, Mohd Rais Mustafa, Yu Huang
Salvianolic acid B (Sal B) is one of the most abundant phenolic acids derived from the root of Danshen with potent anti-oxidative properties. The present study examined the vasoprotective effect of Sal B in hypertensive mice induced by angiotensin II (Ang II). Sal B (25mg/kg/day) was administered via oral gavage for 11days to Ang II (1.2mg/kg/day)-infused C57BL/6J mice (8-10weeks old). The vascular reactivity (both endothelium-dependent relaxations and contractions) in mouse arteries was examined by wire myography...
April 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28392886/amifostine-pretreatment-attenuates-myocardial-ischemia-reperfusion-injury-by-inhibiting-apoptosis-and-oxidative-stress
#4
Shao-Ze Wu, Lu-Yuan Tao, Jiao-Ni Wang, Zhi-Qiang Xu, Jie Wang, Yang-Jing Xue, Kai-Yu Huang, Jia-Feng Lin, Lei Li, Kang-Ting Ji
The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28392465/l-carnitine-preserves-cardiac-function-by-activating-p38-mapk-nrf2-signalling-in-hearts-exposed-to-irradiation
#5
Zhigang Fan, Yang Han, Yuanpeng Ye, Chao Liu, Hui Cai
Radiation-induced heart damage (RIHD) is now considered to be one of the causes of mortality in cancer patients undergoing radiotherapy. Cardiac function impairments are clinical manifestations of RIHD. L-carnitine shows protective effects against irradiation and heart disease. This study was aimed to investigate the cardioprotective effects and potential molecular mechanisms of L-carnitine against RIHD. Mouse hearts were exposed to γ-radiation to induce RIHD. L-carnitine at doses of 100mg/Kg and 200mg/Kg was used to treat animals intraperitoneally...
April 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28330665/quantitative-pericardial-delayed-hyperenhancement-informs-clinical-course-in-recurrent-pericarditis
#6
Arnav Kumar, Kimi Sato, Edlira Yzeiraj, Jorge Betancor, Lin Lin, Balaji K Tamarappoo, Deborah H Kwon, Rory Hachamovitch, Allan L Klein
OBJECTIVES: The aim of this study was to evaluate the prognostic value of quantitative assessment of pericardial delayed hyperenhancement (DHE) among patients with recurrent pericarditis (RP). BACKGROUND: Pericardial DHE on cardiac magnetic resonance may persist beyond the acute phase of pericarditis, suggesting continued pericardial inflammation. METHODS: This is a retrospective cohort study of 159 patients with RP who underwent DHE imaging and had a follow-up period of more than 6 months...
March 10, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28270843/liraglutide-directly-protects-cardiomyocytes-against-reperfusion-injury-possibly-via-modulation-of-intracellular-calcium-homeostasis
#7
Shun-Ying Hu, Ying Zhang, Ping-Jun Zhu, Hao Zhou, Yun-Dai Chen
BACKGROUND: Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perform direct protective effects on cardiomyocytes against reperfusion injury. METHODS: In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation (H/R) induction...
January 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28258543/reducing-mitochondrial-bound-hexokinase-ii-mediates-transition-from-non-injurious-into-injurious-ischemia-reperfusion-of-the-intact-heart
#8
Rianne Nederlof, Ebru Gürel-Gurevin, Otto Eerbeek, Chaoqin Xie, G Sjoerd Deijs, Moritz Konkel, Jun Hu, Nina C Weber, Cees A Schumacher, Antonius Baartscheer, Egbert G Mik, Markus W Hollmann, Fadi G Akar, Coert J Zuurbier
Ischemia/reperfusion (I/R) of the heart becomes injurious when duration of the ischemic insult exceeds a certain threshold (approximately ≥20 min). Mitochondrial bound hexokinase II (mtHKII) protects against I/R injury, with the amount of mtHKII correlating with injury. Here, we examine whether mtHKII can induce the transition from non-injurious to injurious I/R, by detaching HKII from mitochondria during a non-injurious I/R interval. Additionally, we examine possible underlying mechanisms (increased reactive oxygen species (ROS), increased oxygen consumption (MVO2) and decreased cardiac energetics) associated with this transition...
March 3, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28245300/anti-inflammatory-and-antioxidative-effects-of-camellia-japonica-on-human-corneal-epithelial-cells-and-experimental-dry-eye-in-vivo-and-in-vitro-study
#9
Hyo Seok Lee, Joo-Hee Choi, Lian Cui, Ying Li, Jee Myung Yang, Je-Jung Yun, Ji Eun Jung, Won Choi, Kyung Chul Yoon
Purpose: To analyze the anti-inflammatory and antioxidative effects of Camellia japonica (CJ) on human corneal epithelial (HCE) cells and its therapeutic effects in a mouse model of experimental dry eye (EDE). Methods: Camellia japonica extracts of varying concentrations (0.001%, 0.01%, and 0.1%) were used to treat HCE cells. Dichlorofluorescein diacetate (DCF-DA) and dihydroethidium (DHE) assays were performed. The production of peroxiredoxin (PRX) 1-6 and manganese-dependent superoxide dismutase (MnSOD) in HCE cells was assessed using Western blot analysis...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28241139/transcription-control-by-the-enl-yeats-domain-in-acute-leukaemia
#10
Michael A Erb, Thomas G Scott, Bin E Li, Huafeng Xie, Joshiawa Paulk, Hyuk-Soo Seo, Amanda Souza, Justin M Roberts, Shiva Dastjerdi, Dennis L Buckley, Neville E Sanjana, Ophir Shalem, Behnam Nabet, Rhamy Zeid, Nana K Offei-Addo, Sirano Dhe-Paganon, Feng Zhang, Stuart H Orkin, Georg E Winter, James E Bradner
Recurrent chromosomal translocations producing a chimaeric MLL oncogene give rise to a highly aggressive acute leukaemia associated with poor clinical outcome. The preferential involvement of chromatin-associated factors as MLL fusion partners belies a dependency on transcription control. Despite recent progress made in targeting chromatin regulators in cancer, available therapies for this well-characterized disease remain inadequate, prompting the need to identify new targets for therapeutic intervention. Here, using unbiased CRISPR-Cas9 technology to perform a genome-scale loss-of-function screen in an MLL-AF4-positive acute leukaemia cell line, we identify ENL as an unrecognized gene that is specifically required for proliferation in vitro and in vivo...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28238401/flavin-containing-enzymes-as-a-source-of-reactive-oxygen-species-in-hema-induced-apoptosis
#11
Helmut Schweikl, Marialucia Gallorini, Markus Forstner, Christine Petzel, Carola Bolay, Karl-Anton Hiller, Amelia Cataldi, Stephanie Krifka, Wolfgang Buchalla
OBJECTIVE: Oxidative stress induced by compounds of dental composites like 2-hydroxyethyl methacrylate (HEMA) due to excess formation of reactive oxygen species (ROS) disturbs vital cell functions leading to apoptosis. The sources of ROS in cells exposed to resin monomers are unknown. The present study investigates functions of flavin-containing ROS and RNS (reactive nitrogen species) producing enzymes in cells exposed to HEMA. METHODS: The formation of oxidative stress in RAW264...
February 18, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28226284/does-suboccipital-decompression-and-evacuation-of-intraparenchymal-hematoma-improve-neurological-outcome-in-patients-with-spontaneous-cerebellar-hemorrhage
#12
Katharina A M Hackenberg, Andreas W Unterberg, Carla S Jung, Julian Bösel, Silvia Schönenberger, Klaus Zweckberger
OBJECTIVE: Spontaneous cerebellar hemorrhages (SCH) can lead to life-threatening complications with high mortality rates of 20-50%. Although complications of SCH can be prevented by surgical therapy, there is a lack of consensus concerning the optimal surgical technique for evacuating SCH. METHODS: In this retrospective study 85 patients with SCH were divided into four treatment groups: (1) Decompression and Hematoma Evacuation via suboccipital craniectomy and removal of the posterior arch of C1 (DHE)...
April 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28205171/synthesis-and-live-cell-imaging-of-fluorescent-sterols-for-analysis-of-intracellular-cholesterol-transport
#13
Maciej Modzel, Frederik W Lund, Daniel Wüstner
Cellular cholesterol homeostasis relies on precise control of the sterol content of organelle membranes. Obtaining insight into cholesterol trafficking pathways and kinetics by live-cell imaging relies on two conditions. First, one needs to develop suitable analogs that resemble cholesterol as closely as possible with respect to their biophysical and biochemical properties. Second, the cholesterol analogs should have good fluorescence properties. This interferes, however, often with the first requirement, such that the imaging instrumentation must be optimized to collect photons from suboptimal fluorophores, but good cholesterol mimics, such as the intrinsically fluorescent sterols, cholestatrienol (CTL) or dehydroergosterol (DHE)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28203527/superoxide-increases-angiotensin-ii-at1-receptor-function-in-human-kidney-2-cells
#14
Mohammad Saleem, Indira Pokkunuri, Mohammad Asghar
The redox-sensitive Sp family transcription factor has been linked to the regulation of angiotensin II type 1 receptor (AT1R). However, the exact mechanism of AT1R regulation in renal cells is poorly understood. We tested the specificity of reactive oxygen species (ROS), superoxide vs. hydrogen peroxide (H2O2), and the specific role of Sp3 transcription factor, if any, in the regulation of AT1R in human kidney cells (HK2 cells). Superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC), but not H2O2 treatment, increased fluorescence levels of superoxide probe dihydroethidium (DHE)...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28193034/leveraging-gas-phase-fragmentation-pathways-for-improved-identification-and-selective-detection-of-targets-modified-by-covalent-probes
#15
Scott B Ficarro, Christopher M Browne, Joseph D Card, William M Alexander, Tinghu Zhang, Eunyoung Park, Randall McNally, Sirano Dhe-Paganon, Hyuk-Soo Seo, Ilaria Lamberto, Michael J Eck, Sara J Buhrlage, Nathanael S Gray, Jarrod A Marto
The recent approval of covalent inhibitors for multiple clinical indications has reignited enthusiasm for this class of drugs. As interest in covalent drugs has increased, so too has the need for analytical platforms that can leverage their mechanism-of-action to characterize modified protein targets. Here we describe novel gas phase dissociation pathways which yield predictable fragment ions during MS/MS of inhibitor-modified peptides. We find that these dissociation pathways are common to numerous cysteine-directed probes as well as the covalent drugs, Ibrutinib and Neratinib...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28192190/%C3%AE-7-integrin-and-madcam-1-play-opposing-roles-during-the-development-of-non-alcoholic-steatohepatitis
#16
Hannah K Drescher, Angela Schippers, Thomas Clahsen, Hacer Sahin, Heidi Noels, Mathias Hornef, Norbert Wagner, Christian Trautwein, Konrad L Streetz, Daniela C Kroy
BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. It is unclear how infiltrating leukocytes affect NASH-development. Our study aims to investigate the role of the homing/receptor, pair mucosal addressin cell adhesion molecule-1 (MAdCAM-1)/β7-Integrin, on immune cell recruitment and disease progression in a steatohepatitis model. METHODS: Constitutive β7-Integrin deficient (β7(-/-)) and MAdCAM-1 deficient (MAdCAM-1(-/-)) mice were fed a high fat diet (HFD) for 26weeks or methionine-choline-deficient-diet (MCD) for 4weeks...
February 10, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28159361/enhanced-autophagy-by-exenatide-mitigates-doxorubicin-induced-cardiotoxicity
#17
Kyung Hye Lee, Haneul Cho, Sora Lee, Jong Shin Woo, Byung Hyun Cho, Jung Hee Kang, Yun-Mi Jeong, Xian Wu Cheng, Weon Kim
OBJECTIVES: Exenatide is a glucagon-like peptide-1 analogue that mitigates myocardial injury caused by ischemia-reperfusion injury via the survival signaling pathway. We hypothesized that exenatide would provide a protective effect in doxorubicin-induced cardiotoxicity. METHODS: H9c2 cardiomyocytes were pre-treated with exenatide followed by doxorubicin (DOX), and cell viability and intracellular reactive oxygen species (ROS) were subsequently measured. In order to determine the role of autophagy, we performed western blot as well as TUNEL and autophagosome staining...
January 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28116721/measurement-of-superoxide-production-and-nadph-oxidase-activity-by-hplc-analysis-of-dihydroethidium-oxidation
#18
Denise C Fernandes, Renata C Gonçalves, Francisco R M Laurindo
The fluorogenic probe dihydroethidium (DHE) is widely used for detecting intracellular superoxide. DHE oxidation by superoxide generates specifically the compound 2-hydroxyethidium (2-E(+)OH), so that 2-E(+)OH detection confers specificity to superoxide assessment among many other reactive oxygen species. However, DHE oxidation in biological systems leads to formation of other fluorescent products, particularly ethidium, usually formed at higher quantities than 2-E(+)OH. Since both 2-E(+)OH and ethidium are fluorescent, their identification and quantification is possible only after their physical separation by HPLC...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28115273/ablation-of-akt2-prevents-paraquat-induced-myocardial-mitochondrial-injury-and-contractile-dysfunction-role-of-nrf2
#19
Shuyi Wang, Xiaoling Zhu, Lize Xiong, Jun Ren
Paraquat is a quaternary nitrogen herbicide triggering oxidative stress, mitochondrial damage and multi-organ injuries including hearts. To date, effective measure to combat paraquat toxicity is still lacking. Recent evidence has revealed a role for Akt in cardiac homeostasis. To this end, this study was designed to examine the role of Akt2 in acute paraquat exposure-induced cardiac contractile and mitochondrial injury using a unique murine model of Akt2 knockout. Cardiac contractile and intracellular Ca(2+) properties were evaluated...
March 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27997907/improvement-of-huangqi-decoction-on-endothelial-dysfunction-in-5-6-nephrectomized-rats
#20
Shuang Chu, Li Wang, Xiao-Dong Mao, Wen Peng
BACKGROUND/AIMS: Endothelial dysfunction is a major factor in the progression of chronic kidney disease, which correlates with oxidative stress and NO deficiency. Huangqi decoction (HQD) is a potential anti-oxidant ingredient in renoprotection. However, the underlying mechanisms remained identified. Therefore, we investigated whether HQD exhibit improvement in endothelial dysfunction in the 5/6 nephrectomy (Nx) rat model. METHODS: Male Wistar rats (180 - 250 g) were divided into sham, Nx and Nx + HQD (0...
2016: Cellular Physiology and Biochemistry
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