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https://www.readbyqxmd.com/read/28199967/pre-clinical-evaluation-of-small-molecule-loxl2-inhibitors-in-breast-cancer
#1
Joan Chang, Morghan C Lucas, Lidia E Leonte, Marc Garcia-Montolio, Lukram Babloo Singh, Alison D Findlay, Mandar Deodhar, Jonathan S Foot, Wolfgang Jarolimek, Paul Timpson, Janine T Erler, Thomas R Cox
Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumors. Here we tested the anti-tumor properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112368/loxl3-sv2-a-novel-variant-of-human-lysyl-oxidase-like-3-loxl3-functions-as-an-amine-oxidase
#2
Chankyu Jeong, Youngho Kim
Human lysyl oxidase-like 3 (LOXL3) functions as a copper-dependent amine oxidase toward collagen and elastin. The LOXL3 protein contains four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus in addition to the C-terminal characteristic domains of the lysyl oxidase (LOX) family, such as a copper-binding domain, a cytokine receptor‑like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a novel variant of LOXL3 (termed LOXL3-sv2), which lacked the sequences corresponding to exons 4 and 5 of LOXL3...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28111769/suitability-of-combination-of-calcium-propionate-and-chitosan-for-preserving-minimally-processed-banana-quality
#3
Amin Mirshekari, Babak Madani, John B Golding
BACKGROUND: Marketability of fresh-cut banana slices is limited by the rapid rate of fruit softening and browning. However there is no scientific literature on the role of postharvest calcium propionate and chitosan treatment on quality attributes of fresh cut banana and therefore the aim of this research was to investigate these effects. RESULTS: This study showed that the application of calcium propionate plus chitosan (CaP+Chit) treatment retained higher firmness, ascorbic acid content (AA) content, total antioxidant activity (TAA) and total phenolic compounds (TPC) with lower browning, polyphenol oxidase (PPO), peroxidase (POD), polygalacturonase (PG) and pectin methyl esterase (PME) activities and microbial growth compared with the control banana slices after five days of cold storage...
January 23, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28110559/comparing-hydrazine-derived-reactive-groups-as-inhibitors-of-quinone-dependent-amine-oxidases
#4
Ashley A Burke, Elizabeth S Severson, Shreya Mool, Maria J Solares Bucaro, Frederick T Greenaway, Charles E Jakobsche
Lysyl oxidase has emerged as an important enzyme in cancer metastasis. Its activity has been reported to become upregulated in several types of cancer, and blocking its activity has been shown to limit the metastatic potential of various cancers. The small-molecules phenylhydrazine and β-aminopropionitrile are known to inhibit lysyl oxidase; however, issues of stability, toxicity, and poorly defined mechanisms limit their potential use in medical applications. The experiments presented herein evaluate three other families of hydrazine-derived compounds - hydrazides, alkyl hydrazines, and semicarbazides - as irreversible inhibitors of lysyl oxidase including determining the kinetic parameters and comparing the inhibition selectivities for lysyl oxidase against the topaquinone-containing diamine oxidase from lentil seedlings...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28101461/acute-and-subchronic-toxicity-study-of-the-median-septum-of-juglans-regia-in-wistar-rats
#5
Asma Ravanbakhsh, Majid Mahdavi, Ghader Jalilzade-Amin, Shahram Javadi, Masoud Maham, Daryosh Mohammadnejad, Mohammad Reza Rashidi
Purpose: Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#6
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
January 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28080034/mechanism-of-flavoprotein-l-6-hydroxynicotine-oxidase-ph-and-solvent-isotope-effects-and-identification-of-key-active-site-residues
#7
Paul F Fitzpatrick, Fatemeh Chadegani, Shengnan Zhang, Vi Dougherty
The flavoenzyme l-6-hydroxynicotine oxidase is a member of the monoamine oxidase family that catalyzes the oxidation of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during microbial catabolism of nicotine. While the enzyme has long been understood to catalyze oxidation of the carbon-carbon bond, it has recently been shown to catalyze oxidation of a carbon-nitrogen bond [Fitzpatrick, P. F., et al. (2016) Biochemistry 55, 697-703]. The effects of pH and mutagenesis of active site residues have now been utilized to study the mechanism and roles of active site residues...
February 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28068215/tibeticola-sediminis-gen-nov-sp-nov-a-thermophilic-bacterium-isolated-from-hot-spring
#8
Inam Ullah Khan, Firasat Hussain, Ye Tian, Neeli Habib, Wen-Dong Xian, Zhao Jiang, Arshia Amin, Chang-Guo Yuan, En-Min Zhou, Xiao-Yang Zhi, Wen-Jun Li
Two closely related thermophilic bacterial strains, designated YIM 73013T and YIM 73008 were isolated from a sediment sample collected from a hot spring in Tibet, western Tibet province, China. Taxonomic positions of the two isolates were investigated using a polyphasic approach. The novel isolates were Gram-staining negative, aerobic, short rod shaped and motile by means of a polar flagellum. They were oxidase and catalase positive and were able to grow at 30-55 °C (optimum, 37-45 °C), pH 6.0-8.0 (optimum, pH 7...
January 6, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28067251/analgesic-and-anti-inflammatory-effects-of-the-novel-semicarbazide-sensitive-amine-oxidase-inhibitor-szv-1287-in-chronic-arthritis-models-of-the-mouse
#9
Ádám Horváth, Awt Menghis, Bálint Botz, Éva Borbély, Ágnes Kemény, Valéria Tékus, Janka Zsófia Csepregi, Attila Mócsai, Tamás Juhász, Róza Zákány, Dóra Bogdán, Péter Mátyus, Julie Keeble, Erika Pintér, Zsuzsanna Helyes
Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund's adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052533/what-a-difference-a-methyl-group-makes-the-selectivity-of-monoamine-oxidase-b-towards-histamine-and-n-methylhistamine
#10
Aleksandra Maršavelski, Robert Vianello
Monoamine oxidase (MAO) enzymes catalyze the degradation of a very broad range of biogenic and dietary amines including many neurotransmitters in the brain, whose imbalance is extensively linked with the biochemical pathology of various neurological disorders. Although sharing around 70% sequence identity, both MAO A and B isoforms differ in substrate affinities and inhibitor sensitivities. Inhibitors that act on MAO A are used to treat depression, due to their ability to raise serotonin concentrations, while MAO B inhibitors decrease dopamine degradation and improve motor control in patients with Parkinson disease...
January 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28024102/elevated-ischaemia-associated-lysyl-oxidase-activity-in-delayed-graft-failure-6-12%C3%A2-months-after-renal-transplantation
#11
Zhi Chen, Yiyang Li, Hongmei Xu, Fuzhe Ma, Jia Li, Lei Zhao, Ying Xu
What is the central question of this study? What potential biochemical changes are associated with renal parenchyma 6-12 months after renal transplantation and delayed graft failure? What is the main finding and its importance? Tissue fibrosis, mediated by tissue ischaemia-induced induction of hypoxia-inducible factor-1α and fibronectin and consequent activation of lysyl oxidase, is a major underlying pathophysiological mechanism that contributes to delayed graft failure several months after renal transplantation...
February 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28008798/risk-assessment-of-dietary-exposure-to-tryptamine-for-the-austrian-population
#12
Nadja Wüst, Elke Rauscher-Gabernig, Johann Steinwider, Friedrich Bauer, Peter Paulsen
Tryptamine acts as a neuromodulator and vasoactive agent in the human body. Dose-response data on dietary tryptamine are scarce and neither a toxicological threshold value nor tolerable levels in foods have been established so far. This paper reviews dose-response characteristics and toxicological effects of tryptamine as well as tryptamine contents in food, estimates dietary exposure of Austrian consumers, and calculates risk-based maximum tolerable limits for food categories. A dose without effect of 8 mg kg(-1) body weight day(-1) was derived from literature data...
March 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/27998194/use-of-monoamine-oxidase-inhibitors-in-chronic-neurodegeneration
#13
REVIEW
Peter Riederer, Thomas Müller
Neurotransmission by biogenic monoamines is important for brain function. Biogenic amine turnover employs the enzymes catechol-O-methyltransferase and monoamine oxidase in neuronal and glial cells. Inhibition of these enzymes elevates biogenic amine levels in the synaptic cleft. Subtype selectivity of inhibition is lost during long-term use of 'selective' monoamine oxidase inhibitors. Areas covered: This narrative review discusses use of monoamine oxidase inhibitors in the context with chronic neurodegeneration...
February 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27991414/a-description-of-echinorhynchus-baeri-kostylew-1928-acanthocephala-echinorhynchidae-from-salmo-trutta-in-turkey-with-notes-on-synonymy-geographical-origins-geological-history-molecular-profile-and-x-ray-microanalysis
#14
Omar M Amin, Richard A Heckmann, R Paul Evans, Yahya Tepe
A population of Echinorhynchus baeri Kostylew, 1928 with 18-24 rows of 8-10 proboscis hooks each and long fusiform eggs measuring 95-110 × 18-22 μm collected from Salmo trutta (Salmonidae) in a branch of the Murat River in Turkey is described and specimens are designated as neotype. Specimens of two similar populations of E. baeri (E. baeri Kostylew, 1928 and E. sevani Dinnik, 1932) were previously described from Salmo ischchan in Lake Sevan, Armenia. Waters of Lake Sevan and the Murat River were previously joined during the Middle Miocene-Pliocene...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27977122/comparative-analysis-of-the-neurochemical-profile-and-mao-inhibition-properties-of-n-furan-2-ylmethyl-n-methylprop-2-yn-1-amine
#15
Philippe De Deurwaerdère, Claudia Binda, Rémi Corne, Cosima Leone, Aurora Valeri, Massimo Valoti, Rona R Ramsay, Yagamare Fall, José Marco-Contelles
The regulation of brain monoamine levels is paramount for cognitive functions, and the monoamine oxidase (MAO A and B) enzymes play a central role in these processes. The aim of this study was to evaluate whether the procognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both of the classic MAO A and MAO B inhibitors, clorgyline and l-deprenyl, respectively...
December 30, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27924150/increasing-n-butanol-production-with-saccharomyces-cerevisiae-by-optimizing-acetyl-coa-synthesis-nadh-levels-and-trans-2-enoyl-coa-reductase-expression
#16
Virginia Schadeweg, Eckhard Boles
BACKGROUND: n-Butanol can serve as an excellent gasoline substitute. Naturally, it is produced by some Clostridia species which, however, exhibit only limited suitability for industrial n-butanol production. The yeast Saccharomyces cerevisiae would be an ideal host due to its high robustness in fermentation processes. Nevertheless, n-butanol yields and titers obtained so far with genetically engineered yeast strains are only low. RESULTS: In our recent work, we showed that n-butanol production via a clostridial acetoacetyl-CoA-derived pathway in engineered yeast was limited by the availability of coenzyme A (CoA) and cytosolic acetyl-CoA...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/27893774/multivalent-interactions-of-human-primary-amine-oxidase-with-the-v-and-c22-domains-of-sialic-acid-binding-immunoglobulin-like-lectin-9-regulate-its-binding-and-amine-oxidase-activity
#17
Heli Elovaara, Vimal Parkash, Ruth Fair-Mäkelä, Outi M H Salo-Ahen, Gabriela Guédez, Eva Bligt-Lindén, Janne Grönholm, Sirpa Jalkanen, Tiina A Salminen
Sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on leukocyte surface is a counter-receptor for endothelial cell surface adhesin, human primary amine oxidase (hAOC3), a target protein for anti-inflammatory agents. This interaction can be used to detect inflammation and cancer in vivo, since the labeled peptides derived from the second C2 domain (C22) of Siglec-9 specifically bind to the inflammation-inducible hAOC3. As limited knowledge on the interaction between Siglec-9 and hAOC3 has hampered both hAOC3-targeted drug design and in vivo imaging applications, we have now produced and purified the extracellular region of Siglec-9 (Siglec-9-EC) consisting of the V, C21 and C22 domains, modeled its 3D structure and characterized the hAOC3-Siglec-9 interactions using biophysical methods and activity/inhibition assays...
2016: PloS One
https://www.readbyqxmd.com/read/27851736/an-oxidative-n-demethylase-reveals-pas-transition-from-ubiquitous-sensor-to-enzyme
#18
Mary Ortmayer, Pierre Lafite, Binuraj R K Menon, Tewes Tralau, Karl Fisher, Lukas Denkhaus, Nigel S Scrutton, Stephen E J Rigby, Andrew W Munro, Sam Hay, David Leys
The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases. The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine...
November 24, 2016: Nature
https://www.readbyqxmd.com/read/27822966/mitochondrial-dna-phylogeny-of-camel-spiders-arachnida-solifugae-from-iran
#19
Hassan Maddahi, Mahsa Khazanehdari, Mansour Aliabadian, Haji Gholi Kami, Amin Mirshamsi, Omid Mirshamsi
In the present study, the mitochondrial DNA phylogeny of five solifuge families of Iran is presented using phylogenetic analysis of mitochondrial cytochrome c oxidase, subunit 1 (COI) sequence data. Moreover, we included available representatives from seven families from GenBank to examine the genetic distance between Old and New World taxa and test the phylogenetic relationships among more solifuge families. Phylogenetic relationships were reconstructed based on the two most probabilistic methods, Maximum Likelihood (ML) and Bayesian inference (BI) approaches...
November 8, 2016: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/27815088/-13-c-kinetic-isotope-effects-on-the-reaction-of-a-flavin-amine-oxidase-determined-from-whole-molecule-isotope-effects
#20
José R Tormos, Marina B Suarez, Paul F Fitzpatrick
A large number of flavoproteins catalyze the oxidation of amines. Because of the importance of these enzymes in metabolism, their mechanisms have previously been studied using deuterium, nitrogen, and solvent isotope effects. While these results have been valuable for computational studies to distinguish among proposed mechanisms, a measure of the change at the reacting carbon has been lacking. We describe here the measurement of a (13)C kinetic isotope effect for a representative amine oxidase, polyamine oxidase...
December 15, 2016: Archives of Biochemistry and Biophysics
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