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https://www.readbyqxmd.com/read/29792531/the-expression-of-lysophosphatidic-acid-receptor-5-is-necessary-for-the-regulation-of-intestinal-na-h-exchanger-3-by-lysophosphatidic-acid-in-vivo
#1
Kayte A Jenkin, Peijian He, C Chris Yun
Lysophosphatidic acid (LPA) is a bioactive lipid molecule, which regulates a broad range of pathophysiological processes. Recent studies have demonstrated that LPA modulates electrolyte flux in the intestine and its potential as an anti-diarrheal agent has been suggested. Of six LPA receptors, LPA5 is highly expressed in the intestine. Recent studies by our group have demonstrated activation of Na+ /H+ exchanger 3 (NHE3) by LPA5 . However, much of what has been elucidated was achieved using colonic cell lines that were transfected to express LPA5 ...
May 24, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29792287/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-glpg1690-a-novel-autotaxin-inhibitor-to-treat-idiopathic-pulmonary-fibrosis-flora-a-phase-2a-randomised-placebo-controlled-trial
#2
Toby M Maher, Ellen M van der Aar, Olivier Van de Steen, Lisa Allamassey, Julie Desrivot, Sonia Dupont, Liesbeth Fagard, Paul Ford, Ann Fieuw, Wim Wuyts
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. People with IPF have increased concentrations of autotaxin in lung tissue and lysophosphatidic acid (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is a novel, potent, selective autotaxin inhibitor with good oral exposure. We explored the effects of GLPG1690 in patients with IPF. METHODS: This was a randomised, double-blind, placebo-controlled phase 2a study done in 17 centres in Italy, Ukraine and the UK...
May 18, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29778535/lysophosphatidic-acid-receptor-lpa-6-regulates-endothelial-blood-brain-barrier-function-implication-of-hepatic-encephalopathy
#3
Kayo Masago, Yasuyuki Kihara, Keisuke Yanagida, Fumie Hamano, Shinsuke Nakagawa, Masami Niwa, Takao Shimizu
Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#4
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29775162/validation-of-prone-intraoperative-measurements-of-global-spinal-alignment
#5
Max Vaynrub, Brandon P Hirsch, Jared Tishelman, Dennis Vasquez-Montes, Aaron J Buckland, Thomas J Errico, Themistocles S Protopsaltis
OBJECTIVE Verifying the adequacy of surgical correction of adult spinal sagittal deformity (SSD) leads to improved postoperative alignment and clinical outcomes. Traditionally, surgeons relied on intraoperative measurements of lumbar lordosis (LL) correction. However, T-1 pelvic angle (TPA) and its component angles more reliably predict postoperative alignment. While TPA is readily measured on standing radiographs, intraoperative radiographs offer poor resolution of the bicoxofemoral axis. A method to recreate this radiographic landmark by extrapolating preoperative measurements has been described...
May 18, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29760475/computed-tomography-for-evaluating-right-ventricle-and-pulmonary-artery-in-pediatric-tetralogy-of-fallot-correlation-with-post-operative-pulmonary-regurgitation
#6
Yue Gao, Zhi-Gang Yang, Ke Shi, Kai-Yue Diao, Hua-Yan Xu, Ying-Kun Guo
Pulmonary regurgitation (PR) is the most common complication after tetralogy of Fallot (TOF) surgical repair, and long-term PR might result in cardiovascular events. The aim of this study was to assess the influence of pre-operative right ventricle (RV) and pulmonary artery (PA) parameters assessed by dual-source computed tomography on post-operative PR. A total of 41 TOF patients who underwent trans-valve surgical repair were retrospectively recruited. The RV and PA parameters evaluated by pre-operative DSCT were compared between the PR and non-PR groups...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29749484/lysophosphatidic-acid-enhances-neointimal-hyperplasia-following-vascular-injury-through-modulating-proliferation-autophagy-inflammation-and-oxidative-stress
#7
Xuhui Shen, Jianjun Zou, Fuyong Li, Tianhe Zhang, Tongqi Guo
Lysophosphatidic acid (LPA), which is one of the intermediate products of membrane phospholipid metabolism, is a bioactive phospholipid that possesses diverse activities. In the present study, the effects of LPA on neointimal formation following vascular injury were investigated. A carotid artery balloon injury model was employed in the present study, and following vascular injury, rats received an intraperitoneal injection of 1 mg/kg LPA. Subsequently, histopathological alterations were assessed by hematoxylin and eosin staining, the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry, apoptosis was assessed via a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay, and the expression levels of apoptosis‑associated and autophagy‑associated proteins were detected by western blotting...
April 27, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29747697/low-lpa-gene-kringle-iv-2-repeat-copy-number-association-with-elevated-lipoprotein-a-concentration-as-an-independent-risk-factor-of-coronary-atherosclerotic-heart-disease-in-the-chinese-han-population
#8
Lishan Sun, Ming Zong, Cuncun Chen, Lihong Xie, Fei Wu, Ming Yu, Lieying Fan
BACKGROUND: Lipoprotein (a) [Lp(a)], which is genetically determined by the LPA gene kringle IV type 2 (KIV-2) repeat copy number, has previously been reported in different populations. However, it is uncertain if the same occurs in the Chinese Han population. This study explored the correlation of Lp(a) mass or particle concentration with KIV-2 repeat copy number and application for coronary atherosclerotic heart disease (CAHD) risk assessment. METHODS: A cross-sectional study including 884 subjects was conducted...
May 10, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29743582/synaptic-phospholipids-as-a-new-target-for-cortical-hyperexcitability-and-e-i-balance-in-psychiatric-disorders
#9
Carine Thalman, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, Torfi Sigrudsson, Maria Jelena Hauser, Stefan Tenzer, Ute Distler, Junken Aoki, Andrew J Morris, Gerd Geisslinger, Jochen Röper, Sergei Kirischuk, Heiko J Luhmann, Konstantin Radyushkin, Robert Nitsch, Johannes Vogt
Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses...
May 9, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29732731/double-blind-randomized-8-week-placebo-controlled-followed-by-a-16-week-open-label-extension-study-with-the-lpa1-receptor-antagonist-sar100842-for-patients-with-diffuse-cutaneous-systemic-sclerosis
#10
Yannick Allanore, Oliver Distler, Alexandre Jagerschmidt, Stephane Illiano, Laetitia Ledein, Eric Boitier, Inoncent Agueusop, Christopher P Denton, Dinesh Khanna
BACKGROUND: Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). METHODS: An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15...
May 6, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29732606/influence-of-6-genetic-variants-on-the-efficacy-of-statins-in-patients-with-dyslipidemia
#11
Ruth Cano-Corres, Beatriz Candás-Estébanez, Ariadna Padró-Miquel, Marta Fanlo-Maresma, Xavier Pintó, Pedro Alía-Ramos
BACKGROUND: Patients with dyslipidemia are often treated with statins to reduce lipids and hence cardiovascular risk, but treatment response is variable, partly due to genetic factors. METHODS: We studied the influence of 6 gene variants (APOE c.526C > T (APOE2), APOE c.388T > C (APOE4), SLCO1B1 c.521T > C, CYP3A4 c.-392G > A, HMGCR c.1564-106A > G, and LPA c.3947 + 467T > C) on statin efficacy assessing 2 indicators: the percent reduction in total cholesterol (TC) and non-HDL cholesterol (non-HDL), as well as the achievement of therapeutic goals...
May 7, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29724718/the-autotaxin-lysophosphatidic-acid-axis-promotes-lung-carcinogenesis
#12
Christiana Magkrioti, Nikos Oikonomou, Eleanna Kaffe, Marios-Angelos Mouratis, Nikos Xylourgidis, Iliana Barbayianni, Petros Megadoukas, Vaggelis Harokopos, Christos Valavanis, Jerold Chun, Alexandra Kosma, Georgios T Stathopoulos, Evangelos Bouros, Demosthenes Bouros, Konstantinos N Syrigos, Vassilis Aidinis
Pathogenesis and progression of lung cancer (LC) are governed by complex interactions between the environment and host genetic susceptibility, which is further modulated by genetic and epigenetic changes. Autotaxin (ATX, ENPP2) is a secreted glycoprotein that catalyzes the extracellular production of lysophosphatidic acid (LPA), a growth-factor-like phospholipid which is further regulated by phospholipid phosphatases (PLPP). LPA's pleiotropic effects in almost all cell types are mediated through at least six, G-protein coupled LPA receptors (LPAR) that exhibit overlapping specificities, widespread distribution, and differential expression profiles...
May 3, 2018: Cancer Research
https://www.readbyqxmd.com/read/29724641/identifying-patterns-of-motor-performance-executive-functioning-and-verbal-ability-in-preschool-children-a-latent-profile-analysis
#13
Suzanne Houwen, Erica Kamphorst, Gerda van der Veer, Marja Cantell
BACKGROUND: A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood. AIMS: To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership. METHODS AND PROCEDURES: The sample consisted of 119 3- to 4-year old children (62 boys; 52%)...
April 30, 2018: Research in Developmental Disabilities
https://www.readbyqxmd.com/read/29721771/oxidative-stress-stimulates-invasive-potential-in-rat-c6-and-human-u-87-mg-glioblastoma-cells-via-activation-and-cross-talk-between-pkm2-enpp2-and-ape1-enzymes
#14
Ravi P Cholia, Monisha Dhiman, Raj Kumar, Anil K Mantha
Maintaining genomic integrity is essential for cell survival and viability. Reactive oxygen species (ROS) overproduction results in oxidative stress leading to the genomic instability via generation of small base lesions in DNA and these unrepaired DNA damages lead to various cellular consequences including cancer. Recent data support the concept "oxidative stress is an indispensable participant in fostering proliferation, survival, and migration" in various cancer cell types including glioblastoma cells...
May 2, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29719665/effect-of-lysophosphatidic-acid-on-the-follicular-development-and-the-expression-of-lysophosphatidic-acid-receptor-genes-during-in-vitro-culture-of-mouse-ovary
#15
Neda Abedpour, Mojdeh Salehnia, Nassim Ghorbanmehr
Lysophosphatidic acid (LPA) known as a serum-derived growth factor, is involved in several cell physiological functions in the female reproductive system including: oocyte maturation, in vitro fertilization and embryo implantation by its transmembrane G protein-coupled receptors. The aim of the present study was to examine the effect of LPA on in vitro follicular development of mouse ovarian tissue. Neonatal mouse ovarian tissues were cultured in five different concentrations of LPA (0, 5, 10, 20 and 40 µM)...
2018: Veterinary Research Forum
https://www.readbyqxmd.com/read/29719272/serum-lipidomic-analysis-for-the-discovery-of-biomarkers-for-major-depressive-disorder-in-drug-free-patients
#16
Eun Young Kim, Jae Won Lee, Min Young Lee, Se Hyun Kim, Hyuck Jun Mok, Kyooseob Ha, Yong Min Ahn, Kwang Pyo Kim
Lipidomic analysis can be used to efficiently identify hundreds of lipid molecular species in biological materials and has been recently established as an important tool for biomarker discovery in various neuropsychiatric disorders including major depressive disorder (MDD). In this study, quantitative targeted serum lipidomic profiling was performed on female subjects using liquid chromatography-mass spectrometry. Global lipid profiling of pooled serum samples from 10 patients currently with MDD (cMDD), 10 patients with remitted MDD (rMDD), and 10 healthy controls revealed 37 differentially regulated lipids (DRLs)...
April 25, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29710848/biofunctionalized-lysophosphatidic-acid-silk-fibroin-film-for-cornea-endothelial-cell-regeneration
#17
Joo Hee Choi, Hayan Jeon, Jeong Eun Song, Joaquim Miguel Oliveira, Rui Luis Reis, Gilson Khang
Cornea endothelial cells (CEnCs) tissue engineering is a great challenge to repair diseased or damaged CEnCs and require an appropriate biomaterial to support cell proliferation and differentiation. Biomaterials for CEnCs tissue engineering require biocompatibility, tunable biodegradability, transparency, and suitable mechanical properties. Silk fibroin-based film (SF) is known to meet these factors, but construction of functionalized graft for bioengineering of cornea is still a challenge. Herein, lysophosphatidic acid (LPA) is used to maintain and increase the specific function of CEnCs...
April 30, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29703846/-lpa-variants-are-associated-with-residual-cardiovascular-risk-in-patients-receiving-statins
#18
Wei-Qi Wei, Xiaohui Li, Qiping Feng, Michiaki Kubo, Iftikhar J Kullo, Peggy L Peissig, Elizabeth W Karlson, Gail P Jarvik, Ming Ta Michael Lee, Ning Shang, Eric A Larson, Todd Edwards, Christian Shaffer, Jonathan D Mosley, Shiro Maeda, Momoko Horikoshi, Marylyn Ritchie, Marc S Williams, Eric B Larson, David R Crosslin, Sarah T Bland, Jennifer A Pacheco, Laura J Rasmussen-Torvik, David Cronkite, George Hripcsak, Nancy J Cox, Russell A Wilke, C Michael Stein, Jerome I Rotter, Yukihide Momozawa, Dan M Roden, Ronald M Krauss, Joshua C Denny
Background -Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with HMG-CoA reductase inhibitors (statins) decreases circulating levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown. Methods -We performed a two-stage genome-wide association study (GWAS) of CHD events during statin therapy. We first identified 3,099 cases who experienced CHD events (defined as acute myocardial infarction or the need for coronary revascularization) during statin therapy and 7,681 controls without CHD events during comparable intensity and duration of statin therapy from four sites in the Electronic Medical Records and Genomics (eMERGE) Network...
April 27, 2018: Circulation
https://www.readbyqxmd.com/read/29700394/stage-specific-effects-of-bioactive-lipids-on-human-ipsc-cardiac-differentiation-and-cardiomyocyte-proliferation
#19
Arun Sharma, Yuan Zhang, Jan W Buikema, Vahid Serpooshan, Orlando Chirikian, Nina Kosaric, Jared M Churko, Elda Dzilic, Alice Shieh, Paul W Burridge, Joseph C Wu, Sean M Wu
Bioactive lipids such as sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) regulate diverse processes including cell proliferation, differentiation, and migration. However, their roles in cardiac differentiation and cardiomyocyte proliferation have not been explored. Using a 96-well differentiation platform for generating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) we found that S1P and LPA can independently enhance cardiomyocyte generation when administered at an early stage of differentiation...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29695520/a-bead-based-flow-cytometric-assay-for-monitoring-yersinia-pestis-exposure-in-wildlife
#20
Jeffrey C Chandler, Laurie A Baeten, Doreen L Griffin, Thomas Gidlewski, Thomas J DeLiberto, Jeannine M Petersen, Ryan Pappert, John W Young, Sarah N Bevins
Yersinia pestis is the causative agent of plague, and is considered a category A priority pathogen due to its potential for high transmissibility and the significant morbidity and mortality it causes in humans. Y. pestis is endemic to the Western United States and much of the world, necessitating programs to monitor for this pathogen on the landscape. Elevated human risk of plague infection has been spatially correlated with spikes in seropositive wildlife numbers, particularly rodent-eating carnivores which are frequently in contact with the enzootic hosts and the associated arthropod vectors of Y...
April 25, 2018: Journal of Clinical Microbiology
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