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https://www.readbyqxmd.com/read/28821279/genetic-deletion-of-mglu2-metabotropic-glutamate-receptors-improves-the-short-term-outcome-of-cerebral-transient-focal-ischemia
#1
Federica Mastroiacovo, Slavianka Moyanova, Milena Cannella, Anderson Gaglione, Remy Verhaeghe, Giovanna Bozza, Michele Madonna, Marta Motolese, Anna Traficante, Barbara Riozzi, Valeria Bruno, Giuseppe Battaglia, David Lodge, Ferdinando Nicoletti
We have recently shown that pharmacological blockade of mGlu2 metabotropic glutamate receptors protects vulnerable neurons in the 4-vessel occlusion model of transient global ischemia, whereas receptor activation amplifies neuronal death. This raised the possibility that endogenous activation of mGlu2 receptors contributes to the pathophysiology of ischemic neuronal damage. Here, we examined this possibility using two models of transient focal ischemia: (i) the monofilament model of middle cerebral artery occlusion (MCAO) in mice, and (ii) the model based on intracerebral infusion of endothelin-1 (Et-1) in rats...
August 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28820947/dysregulated-mitogen-activated-protein-kinase-and-matrix-metalloproteinase-in-ethanol-induced-cavernosal-dysfunction
#2
Jaqueline Jóice Muniz, Leticia Nogueira Leite, Riccardo Lacchini, Jose E Tanus-Santos, Carlos Renato Tirapelli
We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% vol./vol.) for six weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2 or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats...
August 18, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28819824/-update-pulmonary-arterial-hypertension-definitions-diagnosis-therapy
#3
N Sommer, M J Richter, K Tello, F Grimminger, W Seeger, H A Ghofrani, H Gall
The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist...
August 17, 2017: Der Internist
https://www.readbyqxmd.com/read/28819776/tongxinluo-capsule-for-cardiac-syndrome-x-a-systematic-review-and-meta-analysis
#4
Hui-Min Mao, Mi Liu, Hua Qu, Li-Qiong Wang, Da-Zhuo Shi
OBJECTIVE: To evaluate the efficacy and safety of Tongxinluo Capsule (, TXL) for patients with cardiac syndrome X (CSX). METHODS: Randomized controlled trials (RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015...
August 17, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28817788/the-joint-effect-of-the-endothelin-receptor-b-gene-ednrb-polymorphism-rs10507875-and-nitric-oxide-synthase-3-gene-nos3-polymorphism-rs869109213-in-slovenian-patients-with-type-2-diabetes-mellitus-and-diabetic-retinopathy
#5
Dejan Bregar, Ines Cilenšek, Sara Mankoč, Ana Reschner, Danijel Petrovič, Mojca Globočnik Petrovič
Increasing evidence suggests that endothelin and nitric oxide synthase genes and their products exert biological effects on the vasculature via the nitric oxide or endothelin pathway. The aim of the study was to evaluate the association of rs10507875 and rs869109213 (alone or in interaction) with diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). We genotyped the single nucleotide polymorphism rs10507875 of the endothelin receptor B gene (EDNRB) and variable number tandem repeats rs869109213 of the nitric oxide synthase 3 gene (NOS3) in 270 Slovenian patients with DR and T2DM and 256 controls with T2DM without clinical signs of DR...
August 17, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28812426/the-expression-of-etar-in-liver-cirrhosis-and-liver-cancer
#6
Juhong Deng, Yu Huang, Ran Tao, Xiangxue Fan, Hongyue Zhang, Hongyan Kong, Qiqing Song, Jiaquan Huang
BACKGROUND: To investigate the expression of endothelin receptors in liver diseases and discuss its role in the process of liver cirrhosis and liver cancer. RESEARCH DESIGN AND METHODS: We examined the expressions of ETAR, ETBR and α-SMA in tissue samples using western blotting analysis. Furthermore, immunofluorescence was used to locate ETAR expression in hepatic stellate cells (HSCs) and hepatic sinusoidal endothelial cells (HSECs), we calculated the percentage of positive cells and then analyzed its relation with clinical indexes...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28810262/fetal-sheep-mesenteric-resistance-arteries-functional-and-structural-maturation
#7
Julia J Müller, Matthias Schwab, Charles R Rosenfeld, Iwa Antonow-Schlorke, Peter W Nathanielsz, Florian Rakers, Harald Schubert, Otto W Witte, Sven Rupprecht
BACKGROUND: Fetal blood pressure increases during late gestation; however, the underlying vascular mechanisms are unclear. Knowledge of the maturation of resistance arteries is important to identify the mechanisms and vulnerable periods for the development of vascular dysfunction in adulthood. METHODS: We determined the functional and structural development of fetal sheep mesenteric resistance arteries using wire myography and immunohistochemistry. RESULTS: Media mass and distribution of myosin heavy-chain isoforms showed no changes between 0...
August 16, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#8
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
#9
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/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#10
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhances-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#11
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28805937/new-data-on-hyperpigmentation-disorders
#12
REVIEW
S Schalka
Recently visible light (VL) and vascularization triggered by infrared light (IR) play a role in hyperpigmentation disorders of the skin. The aim of this article is to provide an update on the aetiology of hyperpigmentation disorders and means of prevention against UV, visible (VL) and infrared light (IR). The author conducted a literature review of the most recent data about hyperpigmentation disorders and means of prevention and protection. VL impacts on pigmentation, especially in individuals with phototype III, IV or V and also causes the production of Reactive Oxygen Species (ROS), erythema and DNA damage through ROS production as well as photodermatoses...
September 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28805809/x-ray-structures-of-endothelin-etb-receptor-bound-to-clinical-antagonist-bosentan-and-its-analog
#13
Wataru Shihoya, Tomohiro Nishizawa, Keitaro Yamashita, Asuka Inoue, Kunio Hirata, Francois Marie Ngako Kadji, Akiko Okuta, Kazutoshi Tani, Junken Aoki, Yoshinori Fujiyoshi, Tomoko Doi, Osamu Nureki
Endothelin receptors (ETRs) have crucial roles in vascular control and are targets for drugs designed to treat circulatory-system diseases and cancer progression. The nonpeptide dual-ETR antagonist bosentan is the first oral drug approved to treat pulmonary arterial hypertension. Here we report crystal structures of human endothelin ETB receptor bound to bosentan and to the ETB-selective analog K-8794, at 3.6-Å and 2.2-Å resolution, respectively. The K-8794-bound structure reveals the detailed water-mediated hydrogen-bonding network at the transmembrane core, which could account for the weak negative allosteric modulation of ETB by Na(+) ions...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28802097/heat-shock-protein-47-effects-on-hepatic-stellate-cell-associated-receptors-in-hepatic-fibrosis-of-schistosoma-japonicum-infected-mice
#14
Yumin Zhao, Zhisheng Dang, Shuo Xu, Shigui Chong
The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. japonicum mouse models treated with HSP47 shRNA in vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28800434/enhanced-photothermal-therapy-of-biomimetic-polypyrrole-nanoparticles-through-improving-blood-flow-perfusion
#15
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/28799131/pulmonary-vascular-disease-in-a-failed-fontan-patient-with-down-s-syndrome
#16
Masaya Aoki, Keiichi Hirono, Tomonori Higuma, Yoko Suzuki, Kazuhiko Nakayama, Akio Yamashita, Kazuaki Fukahara, Fukiko Ichida, Noriaki Emoto, Naoki Yoshimura
It is well known that Down's syndrome is a strong risk factor for mortality after Fontan operations. We performed two lung biopsies in a Down's syndrome patient who underwent staged Fontan operations. The pathological findings revealed severe pulmonary arterial hypertrophy and a quantitative real-time polymerase chain reaction revealed the overexpression of endothelin and a decline in the eNOS level at the Fontan operation. Although the preoperative hemodynamic studies revealed that all of the criteria for Fontan had been fulfilled, the patient died of acute cardiac insufficiency, 35 days after the Fontan operation...
August 10, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28797761/tail-vein-injection-of-mmldl-upregulates-mouse-mesenteric-artery-etb-receptors-via-activation-of-the-erk1-2-pathway
#17
Yang Liu, Xiao-Lan Chen, Cang-Bao Xu, Lei Cao, Jie Lin, Gen Chen, Jie Li
Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study investigated the effect of mmLDL on mouse mesenteric artery endothelin type B (ETB) receptors and its molecular mechanism. Mice were injected with normal saline (NS group), mmLDL in the tail vein (mmLDL group), or with both mmLDL and an intraperitoneal injection of the ERK1/2 pathway-specific inhibitor U0126 (mmLDL+U0126 group). The dose-response curve of mesenteric artery contraction induced by sarafotoxin 6c (S6c), the ETB receptor agonist, was measured using a sensitive myograph system...
August 7, 2017: Vascular Pharmacology
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
#18
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/28790817/emerging-pharmaceutical-therapies-for-copd
#19
REVIEW
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28790412/determination-of-the-endothelin-1-recognition-sites-of-endothelin-receptor-type-a-by-the-directed-degeneration-method
#20
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
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