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https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#1
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28808570/nitric-oxide-cyclic-gmp-pathway-mediates-the-endothelin-1-upregulation-of-adiponectin-expression-in-rat-cardiomyocytes
#2
Bingyan Guo, Yongjun Li, Xin Jin, Suyun Liu, Chenglong Miao
Endothelin-1 (ET-1) serves an important role in the development of cardiac dysfunction and heart failure. ET-1 and angiotensin II (AngII) comprise a mutually reciprocal signalling network in the myocardium and serve similar or additive roles in the development of heart failure. Our previous study previously demonstrated that AngII upregulated the expression of APN in cardiomyocytes through an AngII receptor type 2/nitric oxide (NO)/cyclic GMP(cGMP)-dependent pathway. The purpose of the present study was to determine the effects of ET-1 and the additive effects of ET-1 and AngII on the gene expression and secretion of APN, and the underlying mechanisms involved...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28800434/enhanced-photothermal-therapy-of-biomimetic-polypyrrole-nanoparticles-through-improving-blood-flow-perfusion
#3
Xuejun Wang, Haichun Li, Xianping Liu, Ye Tian, Huishu Guo, Ting Jiang, Zimiao Luo, Kai Jin, Xinping Kuai, Yao Liu, Zhiqing Pang, Wuli Yang, Shun Shen
In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time...
August 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28797041/repeat-low-level-blast-exposure-increases-transient-receptor-potential-vanilloid-1-trpv1-and-endothelin-1-et-1-expression-in-the-trigeminal-ganglion
#4
Elaine D Por, Melody L Sandoval, Chiquita Thomas-Benson, Teresa A Burke, Allison Doyle Brackley, Nathaniel A Jeske, Jeffery M Cleland, Brian J Lund
Blast-associated sensory and cognitive trauma sustained by military service members is an area of extensively studied research. Recent studies in our laboratory have revealed that low-level blast exposure increased expression of transient receptor potential vanilloid 1 (TRPV1) and endothelin-1 (ET-1), proteins well characterized for their role in mediating pain transmission, in the cornea. Determining the functional consequences of these alterations in protein expression is critical to understanding blast-related sensory trauma...
2017: PloS One
https://www.readbyqxmd.com/read/28790412/determination-of-the-endothelin-1-recognition-sites-of-endothelin-receptor-type-a-by-the-directed-degeneration-method
#5
Seong-Gu Han, Sanghwan Ko, Won-Kyu Lee, Sang Taek Jung, Yeon Gyu Yu
G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770223/plumbagin-alleviates-capillarization-of-hepatic-sinusoids-in-vitro-by-downregulating-et-1-vegf-ln-and-type-iv-collagen
#6
Guiyu Li, Yue Peng, Tiejian Zhao, Jiyong Lin, Xuelin Duan, Yanfei Wei, Jing Ma
Critical roles for liver sinusoidal endothelial cells (LSECs) in liver fibrosis have been demonstrated, while little is known regarding the underlying molecular mechanisms of drugs delivered to the LSECs. Our previous study revealed that plumbagin plays an antifibrotic role in liver fibrosis. In this study, we investigated whether plumbagin alleviates capillarization of hepatic sinusoids by downregulating endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), laminin (LN), and type IV collagen on leptin-stimulated LSECs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28758529/targeting-endothelin-1-receptor-%C3%AE-arrestin1-network-for-the-treatment-of-ovarian-cancer
#7
Laura Rosanò, Roberta Cianfrocca, Rosanna Sestito, Piera Tocci, Valeriana Di Castro, Anna Bagnato
Endothelin-1 receptor (ET-1R)/β-arrestin1 (β-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment. Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein β-arr1, as part of signaling complex, or as a transcription co-activator, promoting precise control of transcription of different genes, including ET-1...
July 31, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28757119/low-plasma-testosterone-is-associated-with-elevated-cardiovascular-disease-biomarkers
#8
Alexander W Pastuszak, Taylor P Kohn, Joel Estis, Larry I Lipshultz
BACKGROUND: The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers. AIM: To determine the relation between T levels and high-sensitivity CV risk biomarkers. METHODS: Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing...
July 27, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28756589/crosstalk-between-the-angiotensin-and-endothelin-system-in-the-cerebrovasculature-after-experimental-induced-subarachnoid-hemorrhage
#9
Stefan Wanderer, Jan Mrosek, Hartmut Vatter, Volker Seifert, Juergen Konczalla
Under physiologic conditions, losartan showed a dose-dependent antagonistic effect to the endothelin-1 (ET-1)-mediated vasoconstriction. This reduced vasoconstriction was abolished after preincubation with an endothelin B1 receptor (ET(B1)-receptor) antagonist. Also, an increased ET(B1)-receptor-dependent relaxation to sarafotoxin S6c (S6c; an ET(B1)-receptor agonist) was detected by preincubation with losartan. Investigations after experimental induced subarachnoid hemorrhage (SAH) are still missing. Therefore, we analyzed losartan in a further pathological setup...
July 29, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28747177/acute-coronary-syndrome-and-acute-kidney-injury-role-of-inflammation-in-worsening-renal-function
#10
Jorge Ortega-Hernández, Rashidi Springall, Fausto Sánchez-Muñoz, Julio-C Arana-Martinez, Héctor González-Pacheco, Rafael Bojalil
BACKGROUND: Acute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting...
July 26, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28738542/protective-effects-of-tannic-acid-on-acute-doxorubicin-induced-cardiotoxicity-involvement-of-suppression-in-oxidative-stress-inflammation-and-apoptosis
#11
Jianping Zhang, Lijing Cui, Xue Han, Yuanyuan Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Ying Zhang, Li Chu
Doxorubicin (DOX) is a highly effective drug, but its cardiotoxicity restricts its therapeutic index. Oxidative stress is the major etiopathological factor in DOX-induced cardiotoxicity. Tannic acid (TA) has various anti-cancer, antioxidant, and anti-inflammatory activities. The purpose of the study was to survey the possible effects of TA against acute DOX-induced cardiotoxicity. Male Sprague-Dawleyrats were randomly divided into five groups: control, DOX (10mg/kg) alone, DOX with TA (20 and 40mg/kg), or DOX withcaptopril (30mg/kg) treatments...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738269/an-anti-inflammatory-effect-of-red-microalga-polysaccharides-in-coronary-artery-endothelial-cells
#12
Oshrat Levy-Ontman, Mahmoud Huleihel, Rachel Hamias, Talya Wolak, Esther Paran
BACKGROUND AND AIMS: Polysaccharides (PSs) produced by the red microalga Porphyridium sp. were reported to exhibit anti-inflammatory bioactivities in the human skin. The primary goal of the present research was to assess whether PSs attenuate inflammatory processes by interfering with tumour necrosis factor-alpha (TNF-α)-induced inflammation, in human coronary artery endothelial cells (HCAECs). METHODS: Functional and inflammatory markers were quantified in TNF-α-stimulated HCAECs, with and without pre-treatment with PSs...
July 16, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28732172/role-of-endothelin-1-and-its-receptors-eta-and-etb-in-the-survival-of-human-vascular-endothelial-cells
#13
Marianne Mikhail, Pierre H Vachon, Pedro D'Orleans-Juste, Danielle Jacques, Ghassan Bkaily
Our previous work showed the presence of endothelin-1 (ET-1) receptors, ETA and ETB, in human vascular endothelial cells (hVECs). In this study, we wanted to verify whether ET-1 via the activation of its receptors ETA and/or ETB (ETAR and ETBR respectively) play a role in the survival of hVECs. Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETBR specific agonist IRL1620. Furthermore, blockade of ETBR with the selective ETBR antagonist A192621 prevented the anti-apoptotic effect of ET-1 in hVECs...
July 21, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#14
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720331/a-novel-antihypertension-agent-sargachromenol-d-from-marine-brown-algae-sargassum-siliquastrum-exerts-dual-action-as-an-l-type-ca-2-channel-blocker-and-endothelin-a-b2-receptor-antagonist
#15
Byong-Gon Park, Woon-Seob Shin, Sangtae Oh, Gab-Man Park, Nam Ik Kim, Seokjoon Lee
We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK(+))-induced basilar artery contraction with EC50 values of 3.52±0.42 and 1.62±0.63μM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC50=9...
July 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28715643/new-insights-into-the-non-hemostatic-role-of-von-willebrand-factor-in-endothelial-protection
#16
Silvia Agostini, Vincenzo Lionetti
During exposure to ischemia and reperfusion (I/R) insult, angiotensin II (AngII)-induced endothelin-1 (ET-1) upregulation in endothelial cells progressively impairs nitric oxide (NO) bioavailability while increasing levels of superoxide anion (O2-) and leading to the onset of endothelial dysfunction. Moreover, the overexpression of ET-1 increases the endothelial and circulating levels of von Willebrand Factor (vWF), a glycoprotein with a crucial role in arterial thrombus formation. Nowadays, the non-hemostatic role of endothelial vWF is emerging; although we not yet know if its increased expression is cause or consequence of endothelial dysfunction...
July 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28713482/comparative-therapeutic-effects-of-minocycline-treatment-and-bone-marrow-mononuclear-cell-transplantation-following-striatal-stroke
#17
Celice C Souza, Michelle Castro da Silva, Rosana Telma Lopes, Marcelo M Cardoso, Lucas Lacerda de Souza, Adriano Guimarães Santos, Ijair Rogério Dos Santos, Edna C S Franco, Walace Gomes-Leal
We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28713274/stimulation-of-adenosine-a2b-receptor-inhibits-endothelin-1-induced-cardiac-fibroblast-proliferation-and-%C3%AE-smooth-muscle-actin-synthesis-through-the-camp-epac-pi3k-akt-signaling-pathway
#18
Sarawuth Phosri, Ajaree Arieyawong, Kwanchai Bunrukchai, Warisara Parichatikanond, Akiyuki Nishimura, Motohiro Nishida, Supachoke Mangmool
Background and Purpose: Cardiac fibrosis is characterized by an increase in fibroblast proliferation, overproduction of extracellular matrix proteins, and the formation of myofibroblast that express α-smooth muscle actin (α-SMA). Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac fibrosis. Overstimulation of endothelin receptors induced cell proliferation, collagen synthesis, and α-SMA expression in cardiac fibroblasts. Although adenosine was shown to have cardioprotective effects, the molecular mechanisms by which adenosine A2 receptor inhibit ET-1-induced fibroblast proliferation and α-SMA expression in cardiac fibroblasts are not clearly identified...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712433/two-year-prognosis-after-acute-coronary-syndrome-in-younger-patients-association-with-feeling-depressed-in-the-prior-year-and-bdi-ii-score-and-endothelin-1
#19
Luba Yammine, Lorraine Frazier, Nikhil S Padhye, Jennifer E Sanner, Matthew M Burg
OBJECTIVE: To examine the effects of depressive symptoms and Endothelin (ET)-1 on 2-year prognosis in younger patients with acute coronary syndrome (ACS). Depression is associated with poor post-ACS prognosis; however, few investigations have focused on younger patients. Importantly, the studies that did emphasize younger patients suggested that the influence of depression on prognosis could be more robust in younger subgroups. The particular links between depression and poor prognosis in younger patients have yet to be definitively determined...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#20
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
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