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Masahiko Terakado, Hidehiro Suzuki, Kazuya Hashimura, Motoyuki Tanaka, Hideyuki Ueda, Hiroshi Kohno, Taku Fujimoto, Hiroshi Saga, Shinji Nakade, Hiromu Habashita, Yoshikazu Takaoka, Takuya Seko
Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1-6. A high throughput screen against LPA1 gave compound 7a as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH)...
October 13, 2016: ACS Medicinal Chemistry Letters
Mauro C Wesseling, Lisa Wagner-Britz, Duc Bach Nguyen, Salome Asanidze, Judy Mutua, Nagla Mohamed, Benjamin Hanf, Mehrdad Ghashghaeinia, Lars Kaestner, Ingolf Bernhardt
BACKGROUND/AIMS: In previous publications we were able to demonstrate the exposure of phosphatidylserine (PS) in the outer membrane leaflet after activation of red blood cells (RBCs) by lysophosphatidic acid (LPA), phorbol-12 myristate-13acetate (PMA), or 4-bromo-A23187 (A23187). It has been concluded that three different mechanisms are responsible for the PS exposure in human RBCs: (i) Ca2+-stimulated scramblase activation (and flippase inhibition) by A23187, LPA, and PMA; (ii) PKCα activation by LPA and PMA; and (iii) enhanced lipid flip flop caused by LPA...
October 24, 2016: Cellular Physiology and Biochemistry
Junyong Zhang, Zuojin Liu, Zhengrong Lian, Rui Liao, Yi Chen, Yi Qin, Jinlong Wang, Qing Jiang, Xiaobo Wang, Jianping Gong
Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed...
October 21, 2016: Scientific Reports
Yue Liao, Chih-Ping Chou, Jimi Huh, Adam Leventhal, Genevieve Dunton
Current knowledge about the relationship of physical activity with acute affective and physical feeling states is informed largely by lab-based studies, which have limited generalizability to the natural ecology. This study used ecological momentary assessment to assess subjective affective and physical feeling states in free-living settings across 4 days from 110 non-physically active adults (Age M = 40.4, SD = 9.7). Light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were measured objectively by an accelerometer...
October 20, 2016: Journal of Behavioral Medicine
Lêniféré Chantal Soro, Sylvie Munier, Yves Pelissier, Lidwine Grosmaire, Rickey Yada, David Kitts, Anin Louise Ocho-Anin Atchibri, Caroline Guzman, Frédéric Boudard, Chantal Menut, Jean Charles Robinson, Patrick Poucheret
ETHNOPHARMACOLOGICAL RELEVANCE: Lippia multiflora is a plant with nutritional and pharmaco-therapeutic properties that is native to central and occidental Africa. The potential effects of plants on health are associated with their chemical composition. Therefore, the present study aimed to identify chemical variations in essential oils of Lippia multiflora as a function of geographic origin and time of annual harvest to determine optimal chemical profiles for ethno-pharmacotherapeutic applications...
October 17, 2016: Journal of Ethnopharmacology
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
October 17, 2016: Neurochemistry International
Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
David R Hodge, Christopher P Salas-Wright, Michael G Vaughn
BACKGROUND: The homeschool population continues to grow in size and now accounts for 3.4% of all students in the United States. OBJECTIVE: Given the heterogeneous nature of the population, this study examines the relationship between different types of homeschoolers and a number of substance use related outcomes. METHODS: To conduct this study, we used pooled data (2002-2013) from the National Survey on Drug Use and Health (NSDUH). Respondents aged 12-17 who reported they had been homeschooled at any time during the previous 12 months were classified as homeschoolers (N = 1,321)...
October 19, 2016: Substance Use & Misuse
Aihua Xu, Md Ahsanul Kabir Khan, Fangzhi Chen, Zhaohui Zhong, Han-Chun Chen, Yuanda Song
Autotaxin (ATX) as an important tumor cell motility-stimulating factor is upregulated in many different types of cancer. ATX, a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, possesses lysophospholipase D activity which hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and mitogen lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors, thereby regulating cell growth, migration, and survival. This study aimed to investigate the differences in gene expression pattern of ATX between cancerous and adjacent normal tissue of human renal cell carcinoma (RCC) and bladder carcinoma (BC) and find the correlation between ATX expression and clinicopathological features of both of these carcinomas...
November 2016: Medical Oncology
Woo Sung Jang, Woong-Han Kim, Sungkyu Cho
BACKGROUND: Left pulmonary artery (LPA) stenosis with acute angulation is a common cause of reoperation after tetralogy of Fallot repair. We therefore investigated surgical outcomes of acute-angle correction angioplasty. METHODS: Between 2005 and 2012, 53 patients underwent operation for LPA stenosis as a concurrent procedure. We divided the patients into two groups according to the LPA ostium angulation: group I (acute angle, acute-angle correction angioplasty, n = 29) and group II (obtuse angle, conventional patch angioplasty, n = 24), encompassing subgroup type I (focal stenosis) and type II (diffuse stenosis)...
October 15, 2016: Annals of Thoracic Surgery
Gretchen Bain, Kristen E Shannon, Fei Huang, Janice Darlington, Lance Goulet, Patricia Prodanovich, Gina L Ma, Angelina M Santini, Adam J Stein, Dave Lonergan, Christopher D King, Imelda Calderon, Andiliy Lai, John H Hutchinson, Jilly F Evans
Autotaxin (ATX) is a secreted glycoprotein that converts lysophosphatidylcholine (LPC) to the bioactive phospholipid lysophosphatidic acid (LPA) and is the major enzyme generating circulating LPA. Inhibition of LPA signaling has profound anti-fibrotic effects in multiple organ systems including the lung, kidney, skin and peritoneum. However, other LPA-generating pathways exist and the role of ATX in localized tissue LPA production and fibrosis remains unclear and controversial. In this study, we describe the preclinical pharmacological, pharmacokinetic and pharmacodynamic properties of a novel small-molecule ATX inhibitor [3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl) thio)-2-fluorobenzoic acid sodium salt] (PAT-505)...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
Zully M Puyén, Joshi Acosta, George Obregon, Edson Pacheco, Hada Ramirez, Alberto Mendoza, Diana Marín, Anthony D Harries
Objective To determine the use and performance of a line probe assay (LPA) compared with conventional culture and drug sensitivity testing (CDST) in patients registered with tuberculosis (TB) under routine program conditions in Peru in 2011-2013. Methods This was a descriptive, operational research, cross-sectional study of sputum specimens from patients with smear-positive pulmonary TB and mycobacterial cultures from patients with smear-negative or positive TB. Drug resistance to rifampicin and/or isoniazid detected by LPA was compared to CDST...
January 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Sung-Hee Hwang, Byung-Hwan Lee, Sun-Hye Choi, Hyeon-Joong Kim, Kyung Jong Won, Hwan Myung Lee, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng...
October 2016: Journal of Ginseng Research
Abhishek Raval, Bhavesh Thakkar, Tarun Madan, Nilesh Oswal, Rajiv Garg, Rhshikesh Umalkar, Komal Shah, Bhumika Maheriya
OBJECTIVES: We aimed to study the feasibility and outcomes of ductal stenting in patients with duct-dependent pulmonary blood flow (PBF). METHODS: Duct-dependent hypoxic patients with confluent pulmonary artery (PA) branches were enrolled for ductal stenting and followed regularly. RESULTS: Sixty patients, with a median age of 12 (1-1095) days and weight of 2.8 (2.2-8.9) kg, were enrolled. Median right PA (RPA) and left PA (LPA) Z-scores were -1...
October 13, 2016: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
Thomas Broggini, Lisa Schnell, Ali Ghoochani, José María Mateos, Michael Buchfelder, Kurt Wiendieck, Michael K Schäfer, Ilker Y Eyupoglu, Nicolai E Savaskan
The Plasticity Related Gene family covers five, brain-specific, transmembrane proteins (PRG1-5, also termed LPPR1-5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. In utero electroporation of PRG3 induced dendritic protrusions and accelerated spine formations in cortical pyramidal neurons...
October 15, 2016: Aging
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
L F S Batista, Y T Utsunomiya, T B F da Silva, R A Dias, T Y Tomokane, A D Pacheco, V L R da Matta, F T Silveira, M Marcondes, C M Nunes, M D Laurenti
A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Thereby we committed to scan 110,165 single-nucleotide polymorphisms (SNPs) aiming to identify chromosomal regions associated to leishmanin skin test (LST), lymphocyte proliferation assay (LPA) and cytokines responses to further understanding the role played by the CMI in the outcome of the natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST-/LPA-, LST+/LPA-, LST-/LPA+ and LST+/LPA+), which were not associated to subclinical infected or diseased dogs...
October 10, 2016: Infection and Immunity
Henry Hui, Kathy A Fuller, Wendy N Erber, Matthew D Linden
Platelets are subcellular blood elements with a well-established role in haemostasis. Upon activation platelets undergo granule exocytosis, resulting in α-granule P-Selectin being expressed on the cell membrane. This allows binding of activated platelets to P-Selectin glycoprotein ligand 1 (PSGL-1) expressing leukocytes, forming leukocyte-platelet aggregates (LPAs). Whole blood flow cytometry (FCM) has demonstrated that elevated circulating LPAs (especially monocyte LPAs) are linked to atherothrombosis in high risk patients, and that activated platelet binding influences monocytes towards a pro-adhesive and pro-atherogenic phenotype...
October 5, 2016: Methods: a Companion to Methods in Enzymology
Stephanie E Chappel, Brad Aisbett, Grace E Vincent, Nicola D Ridgers
Little is currently known about the physical activity patterns of workers in physically demanding populations. The aims of this study were to (a) quantify firefighters' physical activity and sedentary time within (2-h periods) and across planned burn shifts; and (b) examine whether firefighters' activity levels during one shift or 2-h period was associated with their activity levels in the following shift or 2-h period. Thirty-four salaried firefighters (26 men, 8 women) wore an Actical accelerometer for 28 consecutive days...
September 30, 2016: International Journal of Environmental Research and Public Health
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