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https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#1
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases and inflammation among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high throughput screening (HTS). A co-crystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28731544/localized-mrs-reliability-of-in-vivo-glutamate-at-3%C3%A2-t-in-shortened-scan-times-a-feasibility-study
#2
J Eric Jensen, Randy P Auerbach, Angela Pisoni, Diego A Pizzagalli
Glutamate is the prime excitatory neurotransmitter in the mammalian brain and has been implicated in a wide range of psychiatric conditions. To improve the applicability and clinical reach of magnetic resonance spectroscopy (MRS), research is needed to develop shortened, yet reliable, MRS scanning procedures for standard 1.5-3-T clinical magnetic resonance imaging (MRI) systems, particularly with young or vulnerable populations unable to tolerate longer protocols. To this end, we evaluated the test-retest reliability of a shortened J-resolved MRS sequence in healthy adolescents (n = 22) aged 12-14 years...
July 21, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28731172/comparison-of-the-neuronal-differentiation-abilities-of-bone-marrow%C3%A2-derived-and-adipose-tissue%C3%A2-derived-mesenchymal-stem-cells
#3
Yani Zheng, Chao Huang, Fang Liu, Haiyan Lin, Xiangqun Yang, Zhiying Zhang
Bone marrow‑derived mesenchymal stem cells (BMSCs) and adipose tissue‑derived mesenchymal stem cells (ADSCs) are able to differentiate into neuron‑like cells when exposed to small molecule compounds, however the specific differences in their neuronal differentiation abilities remain to be fully elucidated. The present study aimed to compare the neuronal differentiation abilities of BMSCs and ADSCs. BMSCs and ADSCs from the same Sprague Dawley rats were isolated and cultured for use. The proliferation capacity was revealed using a cell counting method...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730512/nlrp3-deletion-inhibits-the-non-alcoholic-steatohepatitis-development-and-inflammation-in-kupffer-cells-induced-by-palmitic-acid
#4
Can Cai, Xiwen Zhu, Peizhi Li, Jinzheng Li, Jianping Gong, Wei Shen, Kun He
The cleavage and secretion of pro-inflammatory cytokines IL-1β and IL-18 is regulated by NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Kupffer cells (KCs) are implicated in the pathogenesis of various liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and liver fibrosis. However, the role of NLRP3 played in the non-alcoholic steatohepatitis (NASH) has yet to be evaluated. In the present study, methionine-choline-deficient (MCD) diet was used to establish the mice NASH model...
July 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28729292/amide-proton-transfer-imaging-allows-detection-of-glioma-grades-and-tumor-proliferation-comparison-with-ki-67-expression-and-proton-mr-spectroscopy-imaging
#5
C Su, C Liu, L Zhao, J Jiang, J Zhang, S Li, W Zhu, J Wang
BACKGROUND AND PURPOSE: Prognosis in glioma depends strongly on tumor grade and proliferation. In this prospective study of patients with untreated primary cerebral gliomas, we investigated whether amide proton transfer-weighted imaging could reveal tumor proliferation and reliably distinguish low-grade from high-grade gliomas compared with Ki-67 expression and proton MR spectroscopy imaging. MATERIALS AND METHODS: This study included 42 patients with low-grade (n = 28) or high-grade (n = 14) glioma, all of whom underwent conventional MR imaging, proton MR spectroscopy imaging, and amide proton transfer-weighted imaging on the same 3T scanner within 2 weeks before surgery...
July 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28728374/analysis-of-metabolomic-patterns-in-thoroughbreds-before-and-after-exercise
#6
Hyun-Jun Jang, Duk-Moon Kim, Kyu-Bong Kim, Jeong-Woong Park, Jae-Young Choi, Jin Hyeog Oh, Ki-Duk Song, Suhkmann Kim, Byung-Wook Cho
Objective: Evaluation of exercise effects in racehorse is important in horseracing industry and animal health care. In this study, we compared metabolic patterns between before and after exercise to screen metabolic biomarkers for exercise effects in thoroughbreds. Methods: The concentration of metabolites in muscle, plasma, and urine was measured by 1H NMR spectroscopy analysis and the relative metabolite levels in the three samples were compared between before and after exercise...
June 27, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28727427/high-throughput-synthesis-and-structure-of-zeolite-zsm-43-with-two-directional-8-ring-channels
#7
Tom Willhammar, Jie Su, Yifeng Yun, Xiaodong Zou, Mobae Afeworki, Simon C Weston, Hilda B Vroman, William W Lonergan, Karl G Strohmaier
The aluminosilicate zeolite ZSM-43 (where ZSM = Zeolite Socony Mobil) was first synthesized more than 3 decades ago, but its chemical structure remained unsolved because of its poor crystallinity and small crystal size. Here we present optimization of the ZSM-43 synthesis using a high-throughput approach and subsequent structure determination by the combination of electron crystallographic methods and powder X-ray diffraction. The synthesis required the use of a combination of both inorganic (Cs(+) and K(+)) and organic (choline) structure-directing agents...
July 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28725667/data-on-lipocalin-2-and-phosphatidylinositol-3-kinase-signaling-in-a-methionine-and-choline-deficient-model-of-non-alcoholic-steatohepatitis
#8
Anastasia Asimakopoulou, Erawan Borkham-Kamphorst, Eddy Van de Leur, Ralf Weiskirchen
The data presented in this brief report support the research article "Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis" [1, doi: 10.1016/j.bbadis.2017.04.006]. We tested whether the absence of Lipocalin-2 (LCN2) could dysregulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K-PKB) pathway and hepatic homeostasis in Non-Alcoholic-Steatohepatitis (NASH). The article highlights the role of LCN2 in hepatic homeostasis.
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28725583/positron-emission-tomography-pet-in-primary-prostate-cancer-staging-and-risk-assessment
#9
REVIEW
Sandra Bednarova, Maria L Lindenberg, Maria Vinsensia, Chiara Zuiani, Peter L Choyke, Baris Turkbey
Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28724959/hepatic-metabolic-effects-of-curcuma-longa-extract-supplement-in-high-fructose-and-saturated-fat-fed-rats
#10
Fabrice Tranchida, Zo Rakotoniaina, Laetitia Shintu, Léopold Tchiakpe, Valérie Deyris, Mehdi Yemloul, Pierre Stocker, Nicolas Vidal, Odile Rimet, Abel Hiol, Stefano Caldarelli
The metabolic effects of an oral supplementation with a Curcuma longa extract, at a dose nutritionally relevant with common human use, on hepatic metabolism in rats fed a high fructose and saturated fatty acid (HFS) diet was evaluated. High-resolution magic-angle spinning NMR and GC/MS in combination with multivariate analysis have been employed to characterize the NMR metabolite profiles and fatty acid composition of liver tissue respectively. The results showed a clear discrimination between HFS groups and controls involving metabolites such as glucose, glycogen, amino acids, acetate, choline, lysophosphatidylcholine, phosphatidylethanolamine, and β-hydroxybutyrate as well as an increase of MUFAs and a decrease of n-6 and n-3 PUFAs...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724646/association-between-microbiota-dependent-metabolite-trimethylamine-n-oxide-and-type-2-diabetes
#11
Zhilei Shan, Taoping Sun, Hao Huang, Sijing Chen, Liangkai Chen, Cheng Luo, Wei Yang, Xuefeng Yang, Ping Yao, Jinquan Cheng, Frank B Hu, Liegang Liu
Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent.Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms.Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped...
July 19, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28724545/magnetic-resonance-spectroscopy-in-preterm-infants-association-with-neurodevelopmental-outcomes
#12
Reina Hyodo, Yoshiaki Sato, Miharu Ito, Yuichiro Sugiyama, Chikako Ogawa, Hisashi Kawai, Toshiki Nakane, Akiko Saito, Akihiro Hirakawa, Hiroyuki Kidokoro, Jun Natsume, Masahiro Hayakawa
OBJECTIVE: To compare magnetic resonance spectroscopy (MRS) metabolite ratios in preterm infants at term-equivalent age with those in term infants and to evaluate the association between MRS metabolites and neurodevelopmental outcomes at 18 months corrected age in preterm infants. DESIGN: We studied infants born at a gestational age <37 weeks and weighing <1500 g during 2009-2013 using MRS at term-equivalent age. Infants with major brain abnormalities were excluded...
July 19, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28723716/refining-the-management-of-patients-with-hepatocellular-carcinoma-integrating-11c-choline-pet-ct-scan-into-the-multidisciplinary-team-discussion
#13
Ezio Lanza, Matteo Donadon, Paolo Felisaz, Antonio Mimmo, Arturo Chiti, Guido Torzilli, Luca Balzarini, Egesta Lopci
OBJECTIVE: The aim of this study was to report the impact of C-choline PET/CT on the management of patients with hepatocellular carcinoma (HCC) and incorporate into a refined algorithm combining diagnostic imaging and multidisciplinary team (MDT) discussion. PATIENTS AND METHODS: From February 2010 to February 2016, the charts of all patients discussed in the liver MDT were revised. Suspected or confirmed HCC lesions or Barcelona Clinic Liver Cancer stages A, B or C with a C-choline PET/CT performed in our hospital were included in the analyses...
July 18, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28723518/mid-term-outcomes-following-salvage-lymph-node-dissection-for-prostate-cancer-nodal-recurrence-status-post-radical-prostatectomy
#14
Fabio Zattoni, Avinash Nehra, Christopher R Murphy, Laureano Rangel, Lance Mynderse, Val Lowe, Eugene Kwon, R Jeffrey Karnes
BACKGROUND: Patients with oligometastatic prostate cancer lymph node recurrence can be treated with many options including salvage lymph node dissection (sLND). OBJECTIVE: Evaluation of outcomes of sLND and identification of clinicopathologic features in predicting further biochemical and radiological relapse after sLND for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Between November 1, 2009 and March 31, 2015, 117 patients with biochemical recurrence (BCR) after radical prostatectomy (RP) underwent sLND by a single surgeon after a standardized 11C-choline positron emission tomography/computed tomography...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#15
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28723110/portable-sensor-for-the-detection-of-choline-and-its-derivatives-based-on-silica-isoporous-membrane-and-gellified-nanointerfaces
#16
Lisiqi Xie, Xiao Huang, Bin Su
A portable amperometric ion sensor was fabricated by integrating silica isoporous membrane (SIM) and organogel composed of polyvinyl chloride and 1,2-dichloroethane (PVC-DCE) on a 3D-printed polymer chip. The detection of ionic species in aqueous samples could be accomplished by adding a microliter of sample droplet to the sensor and by identifying the ion-transfer potential and current magnitude at the water/organogel interface array templated by SIM. Thanks to the ultrasmall channel size (2-3 nm in diameter), high channel density (4 × 10(8) μm(-2)), and ultrathin thickness (80 nm) of SIM, the ensemble of nanoscopic water/organogel (nano-W/Gel) interface array behaved like a microinterface with two back-to-back hemispherical mass diffusion zones...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722769/promoter-iv-bdnf-deficiency-disturbs-cholinergic-gene-expression-of-chrna5-chrm2-and-chrm5-effects-of-drug-and-environmental-treatments
#17
Kazuko Sakata, Abigail E Overacre
Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28721304/imaging-features-of-paget-s-disease-on-11-c-choline-pet-ct
#18
Cameron E Leitch, Ajit H Goenka, Benjamin M Howe, Stephen M Broski
The purpose of this study was to investigate the appearance of Paget's disease (PD) on (11)C choline PET/CT and correlate these findings to serum alkaline phosphatase (ALP) level and skeletal scintigraphy. With IRB approval, our institutional (11)C choline PET/CT database (9/2005-6/2015) was searched for patients with PD. Site of osseous involvement, CT appearance, and multiple semi-quantitative measures were measured and correlated with ALP and degree of uptake on bone scan. Our search identified 10 males (mean age 79...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28721046/brain-metabolite-values-in-children-with-breath-holding-spells
#19
Mustafa Calik, Dilek Sen Dokumaci, Suna Sarikaya, Mahmut Demir, Ilhan Isik, Halil Kazanasmaz, Cemil Kaya, Hasan Kandemir
Breath-holding spells are benign, paroxysmal events with apnea and postural tone changes after a crying episode in infants. The objective of this study was to investigate the pathologies in brain metabolite values in the absence of seizure in children with breath-holding spells by using magnetic resonance spectroscopy (MRS). Brain MRS examination was performed on 18 children with breath-holding spells and 13 neurologically normal children who were included as the control group. There was no significant difference in terms of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), and myoinositol (mI) levels and also in terms of NAA/Cr, Cho/Cr, and mI/Cr ratios between the patients and the control group (all P>0...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28718809/maternal-choline-supplementation-alters-fetal-growth-patterns-in-a-mouse-model-of-placental-insufficiency
#20
Julia H King, Sze Ting Cecilia Kwan, Jian Yan, Kevin C Klatt, Xinyin Jiang, Mark S Roberson, Marie A Caudill
Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/- (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/- female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10...
July 18, 2017: Nutrients
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