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Endothelin-1

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https://www.readbyqxmd.com/read/28634054/effect-of-endothelin-1-on-proliferation-migration-and-fibrogenic-gene-expression-in-human-rpe-cells
#1
Dong Qin, Li Zhang, Xuemin Jin, Zhaoxia Zhao, Yanrong Jiang, Zijun Meng
The pathology of the fibrotic proliferative vitreoretinopathy (PVR) membrane represents an excessive wound healing response characterised by cells' proliferation, migration and secretion of extracellular matrix molecules (ECMs). Retinal pigment epithelial (RPE) cells are a major cellular component of the fibrotic membrane. Endothelin-1 (ET-1) has been reported to be involved in the development of PVR in vivo research. However, little is known about the role of ET-1 in RPE cells in vitro. In the present study, we investigated the role of ET-1 in the proliferation, migration and secretion of ECMs (such as type I collagen and fibronectin) in RPE cells in vitro...
June 17, 2017: Peptides
https://www.readbyqxmd.com/read/28632730/phase-2-study-of-combination-spi-1620-with-docetaxel-as-second-line-advanced-biliary-tract-cancer-treatment
#2
Richard Kim, E Gabriela Chiorean, Manik Amin, Caio Max S Rocha-Lima, Jitendra Gandhi, William P Harris, Tao Song, David Portnoy
BACKGROUND: This multicentre, open-label study evaluated the efficacy and safety of SPI-1620, an analogue of endothelin-1, administered in combination with docetaxel as second-line treatment for patients with advanced biliary tract cancer (ABTC). METHODS: Eligible patients received continuous cycles of combination therapy with SPI-1620 (11 μg m(-2)) and docetaxel (75 mg m(-2)) intravenously every 3 weeks until disease progression (PD) or intolerable toxicity...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28631819/protective-effects-of-tannic-acid-on-pressure-overload-induced-cardiac-hypertrophy-and-underlying-mechanisms-in-rats
#3
Li Chu, Pinya Li, Tao Song, Xue Han, Xuan Zhang, Qiongtao Song, Tao Liu, Yuanyuan Zhang, Jianping Zhang
OBJECTIVES: The aim of this study was to examine the cardioprotective effects and latent mechanism of tannic acid (TA) on cardiac hypertrophy. METHODS: Abdominal aortic banding (AAB) was used to induce pressure overload-induced cardiac hypertrophy in male Wistar rats, sham-operated rats served as controls. AAB rats were treated with TA (20 and 40 mg/kg) or captoril. KEY FINDINGS: Abdominal aortic banding rats that received TA showed ameliorated pathological changes in cardiac morphology and coefficients, decreased cardiac hypertrophy and apoptosis, a reduction in over expressions of angiotensin type 1 receptor (AT1 R), angiotensin type 2 receptor (AT2 R), phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β (TGF-β) mRNA, and modified expression of matrix metal proteinase-9 (MMP-9) mRNA in AAB rat hearts...
June 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28628220/importance-of-endothelial-dysfunction-biomarkers-in-patients-with-crimean-congo-hemorrhagic-fever
#4
Mustafa Arslan, Gürdal Yilmaz, Ahmet Mentese, Hülya Yilmaz, S Caner Karahan, Iftihar Koksal
BACKGROUND: The pathogenesis of the Crimean-Congo hemorrhagic fever (CCHF) and the cause of the hemorrhage are not yet fully understood. However, the endothelium plays a key role in the pathogenesis. The purpose of this study was to investigate endothelial dysfunction markers [asymmetrical dimethyl arginine(ADMA), endothelin 1(ET-1), thrombomodulin(TM), von Willebrand factor(vWf) and intercellular adhesion molecule(ICAM-1)] in serum in patients with CCHF and their associations with hemorrhage...
June 19, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28624257/moderate-exercise-training-decreases-inflammation-in-transgenic-sickle-cell-mice
#5
Emmanuelle Charrin, John J Dubé, Philippe Connes, Vincent Pialoux, Samit Ghosh, Camille Faes, Solomon F Ofori-Acquah, Cyril Martin
Chronic systemic inflammation is a pathophysiological feature of sickle cell disease (SCD). Considering that regular exercise exerts multiple beneficial health effects including anti-inflammatory actions, we investigated whether a treadmill training program could minimize the inflammatory state in transgenic sickle cell (SS) mice. To test this hypothesis, SS mice were subjected to a treadmill training protocol of 1h/day, 5days a week for 8weeks. Exercise training increased the percent of venous oxyhemoglobin and sharply decreased the percent of carboxyhemoglobin suggesting that exercise training may limit the proportion of erythrocytes that were deoxygenated in the venous circulation...
June 13, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28623618/endothelin-1-decreases-excitability-of-the-dorsal-root-ganglion-neurons-via-etb-receptor
#6
Nandkishor K Mule, Jitendra N Singh, Kunal U Shah, Anil Gulati, Shyam S Sharma
Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623260/qualifying-a-eukaryotic-cell-free-system-for-fluorescence-based-gpcr-analyses
#7
Anne Zemella, Solveig Grossmann, Rita Sachse, Andrei Sonnabend, Michael Schaefer, Stefan Kubick
Membrane proteins are key elements in cell-mediated processes. In particular, G protein-coupled receptors (GPCRs) have attracted increasing interest since they affect cellular signaling. Furthermore, mutations in GPCRs can cause acquired and inheritable diseases. Up to date, there still exist a number of GPCRs that has not been structurally and functionally analyzed due to difficulties in cell-based membrane protein production. A promising approach for membrane protein synthesis and analysis has emerged during the last years and is known as cell-free protein synthesis (CFPS)...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#8
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
June 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28619112/docosahexaenoic-acid-regulates-vascular-endothelial-cell-function-and-prevents-cardiovascular-disease
#9
REVIEW
Kazuo Yamagata
Docosahexaenoic acid (DHA) is present in high concentrations in salmon, herring, and trout. Epidemiologic studies have shown that high dietary consumption of these and other oily fish is associated with reduced rates of myocardial infarction, atherosclerosis, and other ischemic pathologies. Atherosclerosis is induced by inflammation and can lead to acute cardiovascular events and extensive plaque. DHA inhibits the development of inflammation in endothelial cells, alters the function and regulation of vascular biomarkers, and reduces cardiovascular risk...
June 15, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28615922/influence-of-circulating-endothelin-1-and-asymmetric-dimethylarginine-on-whole-brain-circulation-time-in-multiple-sclerosis
#10
Lucia Monti, Lucia Morbidelli, Lorenzo Bazzani, Alessandro Rossi
Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay...
2017: Biomarker Insights
https://www.readbyqxmd.com/read/28613020/integrated-gene-expression-profiling-and-chromatin-immunoprecipitation-followed-by-sequencing-analysis-of-the-c-terminal-binding-protein-in-breast-cancer
#11
Lu Chen, Yang Yang, Liwei Xu, Rui Liu, Yali Wang
AIM: This study explored the possible mechanisms of the transcriptional regulatory activities of C-terminal binding protein (CtBP) and the role of CtBP in the pathogenesis of breast cancer. METHODS: Microarray data of GSE36529, including three CtBP-knockdown breast cancer MCF-7 cell samples, three control knockdown samples and data of CtBP binding profile in MCF-7 cells, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened between CtBP-knockdown MCF-7 cell samples and controls...
June 14, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28611287/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#12
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611127/pulmonary-hypertension-is-associated-with-a-higher-risk-of-heart-failure-hospitalization-and-mortality-in-patients-with-chronic-kidney-disease-the-jackson-heart-study
#13
Senthil Selvaraj, Sanjiv J Shah, Mark J Ommerborn, Cheryl R Clark, Michael E Hall, Robert J Mentz, Saadia Qazi, Jeremy M Robbins, Thomas N Skelton, Jiaying Chen, J Michael Gaziano, Luc Djoussé
BACKGROUND: African Americans develop chronic kidney disease and pulmonary hypertension (PH) at disproportionately high rates. Little is known whether PH heightens the risk of heart failure (HF) admission or mortality among chronic kidney disease patients, including patients with non-end-stage renal disease. METHODS AND RESULTS: We analyzed African Americans participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or urine albumin/creatinine >30 mg/g) and available echocardiogram-derived pulmonary artery systolic pressure (PASP) from the Jackson Heart Study (N=408)...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28608969/effect-of-iloprost-on-biomarkers-in-patients-with-congenital-heart-disease-pulmonary-arterial-hypertension
#14
Xiao-Ye Li, Yu Zheng, Yuliang Long, Xiaochun Zhang, Lei Zhang, Dan Tian, Daxin Zhou, Qian-Zhou Lv
Some biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), galectin-3 (Gal-3), B-type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease-PAH (CHD-PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD-PAH biomarkers and their association with the severity of disease...
June 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28606996/targeting-endothelin-receptor-signalling-overcomes-heterogeneity-driven-therapy-failure
#15
Michael P Smith, Emily J Rowling, Zsofia Miskolczi, Jennifer Ferguson, Loredana Spoerri, Nikolas K Haass, Olivia Sloss, Sophie McEntegart, Imanol Arozarena, Alex von Kriegsheim, Javier Rodriguez, Holly Brunton, Jivko Kmarashev, Mitchell P Levesque, Reinhard Dummer, Dennie T Frederick, Miles C Andrews, Zachary A Cooper, Keith T Flaherty, Jennifer A Wargo, Claudia Wellbrock
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-high" populations, and because AXL is linked to de-differentiation and invasiveness avoiding an "AXL-high relapse" is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF-induced expression of endothelin 1 (EDN1)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28606962/endothelin-1-promotes-vascular-smooth-muscle-cell-migration-across-the-artery-wall-a-mechanism-contributing-to-vascular-remodelling-and-intimal-hyperplasia-in-giant-cell-arteritis
#16
Ester Planas-Rigol, Nekane Terrades-Garcia, Marc Corbera-Bellalta, Ester Lozano, Marco A Alba, Marta Segarra, Georgina Espígol-Frigolé, Sergio Prieto-González, José Hernández-Rodríguez, Sara Preciado, Rodolfo Lavilla, Maria C Cid
BACKGROUND: Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. OBJECTIVE: To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA...
June 12, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28605810/a-compact-whole-eye-perfusion-system-to-evaluate-pharmacologic-responses-of-outflow-facility
#17
Enhua H Zhou, Michael Paolucci, Thaddeus P Dryja, Ted Manley, Chuanxi Xiang, Dennis S Rice, Ganesh Prasanna, Amy Chen
Purpose: To discover novel therapies that lower IOP by increasing aqueous humor outflow facility, ex vivo ocular perfusion systems provide a valuable tool. However, currently available designs are limited by their throughput. Here we report the development of a compact, scalable perfusion system with improved throughput and its validation using bovine and porcine eyes. Methods: At a fixed IOP of 6 mm Hg, flow rate was measured by flow sensors. We validated the system by measuring the outflow responses to Y-39983 (a Rho kinase inhibitor), endothelin-1 (ET-1), ambrisentan (an antagonist for endothelin receptor A [ETA]), sphigosine-1-phosphate (S1P), JTE-013 (antagonist for S1P receptor 2 [S1P2]), S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide [NO] donor), and 3-Morpholino-sydnonimine (SIN-1, another NO donor)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28604846/identification-of-active-components-in-yixinshu-capsule-with-protective-effects-against-myocardial-dysfunction-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-by-an-integrative-approach
#18
Minyu Zhang, Hongwei Wu, Feifei Guo, Yangyang Yu, Junying Wei, Ya Geng, Shifeng Wang, Shiyou Li, Hongjun Yang
Traditional Chinese medicine (TCM) preparations have significant effects on some refractory diseases; however, these compositions are complex and their mechanisms are unknown. Identification of the active components in these preparations is essential. The mortality rate for heart failure (HF) has been increasing in recent years, and myocardial dysfunction (MD) has been proved to be the pathological basis of HF. Yixinshu Capsule (YXSC) is a multi-component oral drug with therapeutic effects on HF. However, the key active components are still unclear...
June 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28599441/effects-of-silencing-endothelin-1-on-invasion-and-vascular-formation-in-lung-cancer
#19
Zhen-Yu Zhang, Li-Li Chen, Wei Xu, Keshavraj Sigdel, Xing-Tang Jiang
Endothelin-1 (ET-1), which exists not only in the vascular endothelium but is also widely present in various tissues and cells, is an important cardiovascular regulatory factor that serves an important role in maintaining the basal vascular tone and homeostasis in the cardiovascular system. In the present study, the ET-1 gene was silenced by RNA interference, and the effects on lung cancer cell proliferation and tumor cell invasion were then detected by Cell Counting kit-8 and Transwell assays. In addition, the expression of apoptosis, growth and invasion-associated proteins, including RhoA/C, vascular endothelial growth factor, pigment epithelium-derived factor, AKT, E-cadherin and cyclooxygenase-2 was evaluated by western blotting upon silencing ET-1...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28597771/first-in-child-use-of-the-oral-selective-prostacyclin-ip-receptor-agonist-selexipag-in-pulmonary-arterial-hypertension
#20
Lianne M Geerdink, Harald Bertram, Georg Hansmann
Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. Selexipag is a selective prostacyclin receptor agonist with vasodilatory, anti-proliferative, anti-inflammatory, and pro-angiogenic properties. However, no clinical data on its therapeutic use in children with PAH are currently available. Here, we report the case of a 12-year-old girl who presented in World Health Organization (WHO) functional class III and right ventricular (RV) failure with recurrent syncope, dizziness, and progressive fatigue for two years...
April 2017: Pulmonary Circulation
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