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https://www.readbyqxmd.com/read/28230797/zyz-772-prevents-cardiomyocyte-injury-by-suppressing-nox4-derived-ros-production-and-apoptosis
#1
Ying Wang, Liangjie Zhong, Xinhua Liu, Yi Zhun Zhu
Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a novel flavonoid was isolated from Zanthoxylum bungeanum. Its structure was elucidated as Quercetin-3-O-(6''-O-α-l-rhamnopyransoyl)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (ZYZ-772) for the first time. ZYZ-772 exhibited significant cardio-protective property against CoCl₂ induced H9c2 cardiomyocyte cells injury...
February 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28228756/agonistic-anti-pdgf-receptor-autoantibodies-from-patients-with-systemic-sclerosis-impact-human-pulmonary-artery-smooth-muscle-cells-function-in-vitro
#2
Silvia Svegliati, Donatella Amico, Tatiana Spadoni, Colomba Fischetti, Doreen Finke, Gianluca Moroncini, Chiara Paolini, Cecilia Tonnini, Antonella Grieco, Marina Rovinelli, Armando Gabrielli
One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28225655/mnte-2-pyp-treatment-or-nox4-inhibition-protects-against-radiation-induced-damage-in-mouse-primary-prostate-fibroblasts-by-inhibiting-the-tgf-beta-1-signaling-pathway
#3
Arpita Chatterjee, Elizabeth A Kosmacek, Rebecca E Oberley-Deegan
Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue...
February 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28225041/pvn-blockade-of-p44-42-mapk-pathway-attenuates-salt-induced-hypertension-through-modulating-neurotransmitters-and-attenuating-oxidative-stress
#4
Hong-Li Gao, Xiao-Jing Yu, Kai-Li Liu, Xiao-Lian Shi, Jie Qi, Yan-Mei Chen, Yan Zhang, Juan Bai, Qiu-Yue Yi, Zhi-Peng Feng, Wen-Sheng Chen, Wei Cui, Jin-Jun Liu, Guo-Qing Zhu, Yu-Ming Kang
The imbalance of neurotransmitters and excessive oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether blockade of p44/42 MAPK pathway in the hypothalamic paraventricular nucleus (PVN) ameliorates the development of hypertension through modulating neurotransmitters and attenuating oxidative stress. Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 6 weeks and were treated with bilateral PVN infusion of PD-98059 (0...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216438/porphyromonas-gingivalis-lipopolysaccharide-induces-pro-inflammatory-adipokine-secretion-and-oxidative-stress-by-regulating-toll-like-receptor-mediated-signaling-pathways-and-redox-enzymes-in-adipocytes
#5
Fanny Le Sage, Olivier Meilhac, Marie-Paule Gonthier
Gut microbiota LPS contributes to obesity-related chronic inflammation and oxidative stress, promoting insulin resistance. Periodontal disease also represents a risk factor for type 2 diabetes and is associated with obesity. This study compared the effect of LPS from P. gingivalis periodontopathogen and E. coli enterobacteria on inflammatory adipokine secretion and redox status of 3T3-L1 adipocytes. We found that both LPS activated TLR2- and TLR4-mediated signaling pathways involving MyD88 adaptor and NFκB transcription factor, leading to an increased secretion of leptin, resistin, IL-6 and MCP-1...
February 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28211114/magnesium-lithospermate-b-from-salvia-miltiorrhiza-bunge-ameliorates-aging-induced-renal-inflammation-and-senescence-via-nadph-oxidase-mediated-reactive-oxygen-generation
#6
Chan Hum Park, Sung Ho Shin, Eun Kyeong Lee, Dae Hyun Kim, Min-Jo Kim, Seong-Soo Roh, Takako Yokozawa, Hae Young Chung
The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species...
February 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28199906/aucubin-and-its-hydrolytic-derivative-attenuate-activation-of-hepatic-stellate-cells-via-modulation-of-tgf-%C3%AE-stimulation
#7
Pei-Yu Lv, Han Feng, Wei-Hua Huang, Ying-Ying Tian, Ya-Qin Wang, Yu-Hua Qin, Xiao-Hui Li, Kai Hu, Hong-Hao Zhou, Dong-Sheng Ouyang
Eucommia ulmoides is an important traditional Chinese medicine and has been used as a tonic with a long history. Aucubin is an active component extracted from Eucommia ulmoides, which has liver-protection effects. However the mechanisms are still unclear. To investigate the inhibitory effects and the underlying mechanisms of aucubin on TGF-β1-induced activation of hepatic stellate cells and ECM deposition, Human hepatic stellate cells (LX-2 cells) were incubated with TGF-β1 to evaluate the anti-fibrotic effect of aucubin...
February 8, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28196727/nrf2-mediates-redox-adaptation-in-nox4-overexpressed-non-small-cell-lung-cancer-cells
#8
Qipeng Wu, Bei Yao, Ning Li, Lei Ma, Yanchao Deng, Yang Yang, Cheng Zeng, Zhicheng Yang, Bing Liu
The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H2O2 enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling...
February 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28188286/hydrogen-sulfide-inhibits-high-glucose-induced-nadph-oxidase-4-expression-and-matrix-increment-by-recruiting-inducible-nitric-oxide-synthase-in-the-kidney-proximal-tubular-epithelial-cells
#9
Hak Joo Lee, Doug Yoon Lee, Meenalakshmi M Mariappan, Denis Feliers, Goutam Ghosh Choudhury, Hanna E Abboud, Yves Gorin, Balakuntalam S Kasinath
High glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species (ROS) generation, and, matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Since hydrogen sulfide (H2S) inhibits high glucose-induced matrix protein increment by activating AMPK in renal cells, we examined if H2S inhibits high glucose induced expression of NOX4 and matrix protein and if H2S nitric oxide (NO) pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells that was inhibited by sodium hydrosulfide (NaHS), a source of H2S...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28185984/hydrogen-sulfide-in-paraventricular-nucleus-attenuates-blood-pressure-by-regulating-oxidative-stress-and-inflammatory-cytokines-in-high-salt-induced-hypertension
#10
Yan-Feng Liang, Dong-Dong Zhang, Xiao-Jing Yu, Hong-Li Gao, Kai-Li Liu, Jie Qi, Hong-Bao Li, Qiu-Yue Yi, Wen-Sheng Chen, Wei Cui, Guo-Qing Zhu, Yu-Ming Kang
Hydrogen sulfide (H2S) is an important gaseous signaling molecule in neuro-modulation, anti-inflammatory, anti-oxidant and anti-hypertensive effects. The paraventricular nucleus (PVN) is a major integrative nucleus in regulating BP and SNA. The aim of this study is to explore whether endogenous or exogenous H2S changed by hydroxylamine hydrochloride (HA) or GYY4137 infused in the PVN affects RSNA and MAP by regulating oxidative stress or the balance between pro-inflammatory cytokines (PICs) and anti-inflammatory cytokines in high salt-induced hypertensive rats...
February 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28185955/endothelial-nox4-based-nadph-oxidase-regulates-atherosclerosis-via-soluble-epoxide-hydrolase
#11
Pingping Hu, Xiaojuan Wu, Alok R Khandelwal, Weimin Yu, Zaicheng Xu, Lili Chen, Jian Yang, Robert M Weisbrod, Kin Sing Stephen Lee, Francesca Seta, Bruce D Hammock, Richard A Cohen, Chunyu Zeng, Xiaoyong Tong
: Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial. OBJECTIVE: Our goal was to investigate the mechanisms of endothelial Nox4 in regulating atherosclerosis. APPROACH AND RESULTS: Atherosclerosis-prone conditions (disturbed blood flow, type I diabetes, and Western diet) downregulated endothelial Nox4 mRNA in arteries. To address whether the downregulated endothelial Nox4 was directly involved in the development of atherosclerosis, we generated mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), driven by the endothelial specific promoter Tie-2, on atherosclerosis-prone genetic background (ApoE deficient mice) to mimic the effect of decreased endothelial Nox4...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#12
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28165467/apx-115-a-first-in-class-pan-nadph-oxidase-nox-inhibitor-protects-db-db-mice-from-renal-injury
#13
Jin Joo Cha, Hye Sook Min, Ki Tae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyun Wook Kim, Ji Eun Lee, Jee Young Han, Gayoung Lee, Hun Joo Ha, Yun Soo Bae, Sae Rom Lee, Sung Hwan Moon, Sung Chan Lee, Ganghyun Kim, Young Sun Kang, Dae Ryong Cha
Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28160092/combined-nox1-4-inhibition-with-gkt137831-in-mice-provides-dose-dependent-reno-and-atheroprotection-even-in-established-micro-and-macrovascular-disease
#14
Stephen P Gray, Jay C Jha, Kit Kennedy, Erik van Bommel, Phyllis Chew, Cedric Szyndralewiez, Rhian M Touyz, Harald H H W Schmidt, Mark E Cooper, Karin A M Jandeleit-Dahm
AIMS/HYPOTHESIS: Oxidative stress is a promising target in diabetes-associated vasculopathies, with inhibitors of NADPH oxidases (NOX), in particular isoforms 1 and 4, shown to be safe in early clinical development. We have explored a highly relevant late-stage intervention protocol using the clinically most advanced compound, the NOX1/4 inhibitor GKT137831, to determine whether end-organ damage can be reversed/attenuated when GKT137831 is administered in the setting of established diabetic complications...
February 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28152080/nox1-and-nox4-are-required-for-the-differentiation-of-mouse-f9-cells-into-extraembryonic-endoderm
#15
Benjamin J Dickson, Mohamed I Gatie, Danielle M Spice, Gregory M Kelly
Mouse F9 cells differentiate to primitive endoderm (PrE) when treated with retinoic acid (RA). Differentiation is accompanied by increased reactive oxygen species (ROS) levels, and while treating F9 cells with antioxidants attenuates differentiation, H2O2 treatment alone is sufficient to induce PrE. We identified the NADPH oxidase (NOX) complexes as candidates for the source of this endogenous ROS, and within this gene family, and over the course of differentiation, Nox1 and Nox 4 show the greatest upregulation induced by RA...
2017: PloS One
https://www.readbyqxmd.com/read/28146470/rare-and-low-frequency-coding-variants-alter-human-adult-height
#16
Eirini Marouli, Mariaelisa Graff, Carolina Medina-Gomez, Ken Sin Lo, Andrew R Wood, Troels R Kjaer, Rebecca S Fine, Yingchang Lu, Claudia Schurmann, Heather M Highland, Sina Rüeger, Gudmar Thorleifsson, Anne E Justice, David Lamparter, Kathleen E Stirrups, Valérie Turcot, Kristin L Young, Thomas W Winkler, Tõnu Esko, Tugce Karaderi, Adam E Locke, Nicholas G D Masca, Maggie C Y Ng, Poorva Mudgal, Manuel A Rivas, Sailaja Vedantam, Anubha Mahajan, Xiuqing Guo, Goncalo Abecasis, Katja K Aben, Linda S Adair, Dewan S Alam, Eva Albrecht, Kristine H Allin, Matthew Allison, Philippe Amouyel, Emil V Appel, Dominique Arveiler, Folkert W Asselbergs, Paul L Auer, Beverley Balkau, Bernhard Banas, Lia E Bang, Marianne Benn, Sven Bergmann, Lawrence F Bielak, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Carsten A Böger, Lori L Bonnycastle, Jette Bork-Jensen, Michiel L Bots, Erwin P Bottinger, Donald W Bowden, Ivan Brandslund, Gerome Breen, Murray H Brilliant, Linda Broer, Amber A Burt, Adam S Butterworth, David J Carey, Mark J Caulfield, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y Chu, Massimiliano Cocca, Francis S Collins, James P Cook, Janie Corley, Jordi Corominas Galbany, Amanda J Cox, Gabriel Cuellar-Partida, John Danesh, Gail Davies, Paul I W de Bakker, Gert J de Borst, Simon de Denus, Mark C H de Groot, Renée de Mutsert, Ian J Deary, George Dedoussis, Ellen W Demerath, Anneke I den Hollander, Joe G Dennis, Emanuele Di Angelantonio, Fotios Drenos, Mengmeng Du, Alison M Dunning, Douglas F Easton, Tapani Ebeling, Todd L Edwards, Patrick T Ellinor, Paul Elliott, Evangelos Evangelou, Aliki-Eleni Farmaki, Jessica D Faul, Mary F Feitosa, Shuang Feng, Ele Ferrannini, Marco M Ferrario, Jean Ferrieres, Jose C Florez, Ian Ford, Myriam Fornage, Paul W Franks, Ruth Frikke-Schmidt, Tessel E Galesloot, Wei Gan, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Ayush Giri, Giorgia Girotto, Scott D Gordon, Penny Gordon-Larsen, Mathias Gorski, Niels Grarup, Megan L Grove, Vilmundur Gudnason, Stefan Gustafsson, Torben Hansen, Kathleen Mullan Harris, Tamara B Harris, Andrew T Hattersley, Caroline Hayward, Liang He, Iris M Heid, Kauko Heikkilä, Øyvind Helgeland, Jussi Hernesniemi, Alex W Hewitt, Lynne J Hocking, Mette Hollensted, Oddgeir L Holmen, G Kees Hovingh, Joanna M M Howson, Carel B Hoyng, Paul L Huang, Kristian Hveem, M Arfan Ikram, Erik Ingelsson, Anne U Jackson, Jan-Håkan Jansson, Gail P Jarvik, Gorm B Jensen, Min A Jhun, Yucheng Jia, Xuejuan Jiang, Stefan Johansson, Marit E Jørgensen, Torben Jørgensen, Pekka Jousilahti, J Wouter Jukema, Bratati Kahali, René S Kahn, Mika Kähönen, Pia R Kamstrup, Stavroula Kanoni, Jaakko Kaprio, Maria Karaleftheri, Sharon L R Kardia, Fredrik Karpe, Frank Kee, Renske Keeman, Lambertus A Kiemeney, Hidetoshi Kitajima, Kirsten B Kluivers, Thomas Kocher, Pirjo Komulainen, Jukka Kontto, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Jennifer Kriebel, Helena Kuivaniemi, Sébastien Küry, Johanna Kuusisto, Martina La Bianca, Markku Laakso, Timo A Lakka, Ethan M Lange, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Eric B Larson, I-Te Lee, Terho Lehtimäki, Cora E Lewis, Huaixing Li, Jin Li, Ruifang Li-Gao, Honghuang Lin, Li-An Lin, Xu Lin, Lars Lind, Jaana Lindström, Allan Linneberg, Yeheng Liu, Yongmei Liu, Artitaya Lophatananon, Jian'an Luan, Steven A Lubitz, Leo-Pekka Lyytikäinen, David A Mackey, Pamela A F Madden, Alisa K Manning, Satu Männistö, Gaëlle Marenne, Jonathan Marten, Nicholas G Martin, Angela L Mazul, Karina Meidtner, Andres Metspalu, Paul Mitchell, Karen L Mohlke, Dennis O Mook-Kanamori, Anna Morgan, Andrew D Morris, Andrew P Morris, Martina Müller-Nurasyid, Patricia B Munroe, Mike A Nalls, Matthias Nauck, Christopher P Nelson, Matt Neville, Sune F Nielsen, Kjell Nikus, Pål R Njølstad, Børge G Nordestgaard, Ioanna Ntalla, Jeffrey R O'Connel, Heikki Oksa, Loes M Olde Loohuis, Roel A Ophoff, Katharine R Owen, Chris J Packard, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Aniruddh P Patel, Alison Pattie, Oluf Pedersen, Peggy L Peissig, Gina M Peloso, Craig E Pennell, Markus Perola, James A Perry, John R B Perry, Thomas N Person, Ailith Pirie, Ozren Polasek, Danielle Posthuma, Olli T Raitakari, Asif Rasheed, Rainer Rauramaa, Dermot F Reilly, Alex P Reiner, Frida Renström, Paul M Ridker, John D Rioux, Neil Robertson, Antonietta Robino, Olov Rolandsson, Igor Rudan, Katherine S Ruth, Danish Saleheen, Veikko Salomaa, Nilesh J Samani, Kevin Sandow, Yadav Sapkota, Naveed Sattar, Marjanka K Schmidt, Pamela J Schreiner, Matthias B Schulze, Robert A Scott, Marcelo P Segura-Lepe, Svati Shah, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Timothy D Spector, Elizabeth K Speliotes, John M Starr, Valgerdur Steinthorsdottir, Heather M Stringham, Michael Stumvoll, Praveen Surendran, Leen M 't Hart, Katherine E Tansey, Jean-Claude Tardif, Kent D Taylor, Alexander Teumer, Deborah J Thompson, Unnur Thorsteinsdottir, Betina H Thuesen, Anke Tönjes, Gerard Tromp, Stella Trompet, Emmanouil Tsafantakis, Jaakko Tuomilehto, Anne Tybjaerg-Hansen, Jonathan P Tyrer, Rudolf Uher, André G Uitterlinden, Sheila Ulivi, Sander W van der Laan, Andries R Van Der Leij, Cornelia M van Duijn, Natasja M van Schoor, Jessica van Setten, Anette Varbo, Tibor V Varga, Rohit Varma, Digna R Velez Edwards, Sita H Vermeulen, Henrik Vestergaard, Veronique Vitart, Thomas F Vogt, Diego Vozzi, Mark Walker, Feijie Wang, Carol A Wang, Shuai Wang, Yiqin Wang, Nicholas J Wareham, Helen R Warren, Jennifer Wessel, Sara M Willems, James G Wilson, Daniel R Witte, Michael O Woods, Ying Wu, Hanieh Yaghootkar, Jie Yao, Pang Yao, Laura M Yerges-Armstrong, Robin Young, Eleftheria Zeggini, Xiaowei Zhan, Weihua Zhang, Jing Hua Zhao, Wei Zhao, Wei Zhao, He Zheng, Wei Zhou, Jerome I Rotter, Michael Boehnke, Sekar Kathiresan, Mark I McCarthy, Cristen J Willer, Kari Stefansson, Ingrid B Borecki, Dajiang J Liu, Kari E North, Nancy L Heard-Costa, Tune H Pers, Cecilia M Lindgren, Claus Oxvig, Zoltán Kutalik, Fernando Rivadeneira, Ruth J F Loos, Timothy M Frayling, Joel N Hirschhorn, Panos Deloukas, Guillaume Lettre
Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28138709/trpm8-downregulation-by-angiotensin-ii-in-vascular-smooth-muscle-cells-is-involved-in-hypertension
#17
Fang Huang, Min Ni, Jing-Ming Zhang, Dong-Jie Li, Fu-Ming Shen
Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive...
January 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28138033/targeted-treatment-of-metastatic-breast-cancer-by-plk1-sirna-delivered-by-an-antioxidant-nanoparticle-platform
#18
Jingga Morry, Worapol Ngamcherdtrakul, Shenda Gu, Moataz Reda, David J Castro, Thanapon Sangvanich, Joe W Gray, Wassana Yantasee
Metastatic breast cancer is developed in about 20-30% of newly diagnosed early stage breast cancer patients despite treatments. Herein, we report a novel nanoparticle platform with intrinsic anti-metastatic properties for the targeted delivery of Polo-like kinase 1 siRNA (siPLK1). We first evaluated it in a triple negative breast cancer (TNBC) model, which shows high metastatic potential. PLK1 was identified as the top therapeutic target for TNBC cells and tumor initiating cells in a kinome-wide screen. The platform consists of a 50-nm mesoporous silica nanoparticle (MSNP) core coated layer-by-layer with bioreducible cross-linked PEI and PEG polymers, conjugated with an antibody for selective uptake into cancer cells...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28132925/combined-nadph-and-the-nox-inhibitor-apocynin-provides-greater-anti-inflammatory-and-neuroprotective-effects-in-a-mouse-model-of-stroke
#19
Yuan-Yuan Qin, Mei Li, Xing Feng, Jian Wang, Lijuan Cao, Xi-Kui Shen, Jieyu Chen, Meiling Sun, Rui Sheng, Feng Han, Zheng-Hong Qin
Our previous study has reported that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) protected neurons against ischemia/reperfusion-induced brain injury. NADPH can either act as a co-enzyme to produce GSH or a substrate of NADPH oxidase (NOX) to generate ROS. This study was designed to elucidate the effects of co-treatment with NADPH and NOX inhibitor apocynin on ischemia/reperfusion-induced brain inflammation and neuronal injury. The results showed that both NADPH and apocynin markedly attenuated ischemia/reperfusion-induced increases in the levels of NOX2, NOX4 and ROS...
January 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28132913/nebivolol-prevents-ethanol-induced-reactive-oxygen-species-generation-and-lipoperoxidation-in-the-rat-kidney-by-regulating-nadph-oxidase-activation-and-expression
#20
Gabriel T do Vale, Natália A Gonzaga, Janaina A Simplicio, Carlos R Tirapelli
We studied whether the β1-adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O2(-)) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response...
January 26, 2017: European Journal of Pharmacology
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