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Kynurenin

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https://www.readbyqxmd.com/read/28223212/n-butilydenephthalide-exhibits-protection-against-neurotoxicity-through-regulation-of-tryptophan-2-3-dioxygenase-in-spinocerebellar-ataxia-type-3
#1
Karthyayani Rajamani, Jen-Wei Liu, Cheng-Han Wu, I-Tsang Chiang, Deng-Huwei You, Si-Yin Lin, Dean-Kuo Hsieh, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin-3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28216884/chemical-components-from-aloe-and-their-inhibition-of-indoleamine-2-3-dioxygenase
#2
Ya Nan Sun, Lin Ying Li, Wei Li, Jong Seong Kang, Inkyu Hwang, Young Ho Kim
BACKGROUND: In Korea, Aloe is routinely ingested as a traditional medicine or as a component of health beverages. OBJECTIVE: To research the inhibition of indoleamine 2, 3-dioxygenase (IDO) activities of components from Aloe. MATERIALS AND METHODS: the compounds were isolated by a combination of silica gel and YMC Rp-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-NMR, and MS). All of the isolated compounds were examined for their ability to inhibit IDO, which actively suppresses immune functions by catalyzing the rate limiting reaction in the conversion of tryptophan to kynurenine...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28215897/effects-of-body-condition-monensin-and-essential-oils-on-ruminal-lipopolysaccharide-concentration-inflammatory-markers-and-endoplasmatic-reticulum-stress-of-transition-dairy-cows
#3
C Drong, S Bühler, J Frahm, L Hüther, U Meyer, D von Soosten, D K Gessner, K Eder, H Sauerwein, S Dänicke
Evidence exists that dairy cows experience inflammatory-like phenomena in the transition period. Rumen health and alterations in metabolic processes and gene networks in the liver as the central metabolic organ might be key factors for cows' health and productivity in early lactation. This study made use of an animal model to generate experimental groups with different manifestations of postpartal fat mobilization and ketogenesis. In total, 60 German Holstein cows were allocated 6 wk antepartum to 3 high-body condition score (BCS) groups (BCS 3...
February 16, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28214871/restraint-stress-during-pregnancy-rapidly-raises-kynurenic-acid-levels-in-mouse-placenta-and-fetal-brain
#4
Francesca M Notarangelo, Robert Schwarcz
Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17...
February 18, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28212884/desipramine-decreases-expression-of-human-and-murine-indoleamine-2-3-dioxygenases
#5
Alexandra K Brooks, Tiffany M Janda, Marcus A Lawson, Jennifer L Rytych, Robin A Smith, Cecilia Ocampo-Solis, Robert H McCusker
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential...
February 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28195736/oxidative-fragmentations-and-skeletal-rearrangements-of-oxindole-derivatives
#6
Hendrik F T Klare, Alexander F G Goldberg, Douglas C Duquette, Brian M Stoltz
An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C-H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop-Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis...
February 14, 2017: Organic Letters
https://www.readbyqxmd.com/read/28195169/untargeted-metabolomics-of-colonic-digests-reveals-kynurenine-pathway-metabolites-dityrosine-and-3-dehydroxycarnitine-as-red-versus-white-meat-discriminating-metabolites
#7
Caroline Rombouts, Lieselot Y Hemeryck, Thomas Van Hecke, Stefaan De Smet, Winnok H De Vos, Lynn Vanhaecke
Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187857/adaptive-and-behavioral-changes-in-kynurenine-3-monooxygenase-knockout-mice-relevance-to-psychotic-disorders
#8
Sophie Erhardt, Ana Pocivavsek, Mariaelena Repici, Xi-Cong Liu, Sophie Imbeault, Daniel C Maddison, Marian A R Thomas, Joshua L Smalley, Markus K Larsson, Paul J Muchowski, Flaviano Giorgini, Robert Schwarcz
BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia...
December 16, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28185807/specific-circulating-phospholipids-acylcarnitines-amino-acids-and-biogenic-amines-are-aerobic-exercise-markers
#9
Thomas K Felder, Susanne Ring-Dimitriou, Simon Auer, Selma M Soyal, Ludmilla Kedenko, Mark Rinnerthaler, Janne Cadamuro, Elisabeth Haschke-Becher, Elmar Aigner, Bernhard Paulweber, Wolfgang Patsch
OBJECTIVES: Regular aerobic exercise provides beneficial effects on human health and reduces all-cause mortality. Aerobic exercise has profound metabolic effects, and specific metabolites may reflect physiological changes. We aimed to identify endogenous metabolites that distinguish the trained from the untrained state to increase the spectrum of analytes amenable for hypothesis testing and to expand understanding of putative beneficial pathways. DESIGN: Cross sectional laboratory repeated measures study...
January 24, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/28181858/evaluation-of-immunomodulatory-properties-of-feline-mesenchymal-stem-cells
#10
Maciej Parys, John M Kruger, Vilma Yuzbasiyan-Gurkan
Mesenchymal stem cells (MSC) offer a novel approach to treatment of inflammatory disorders in humans and companion animals. Cats spontaneously develop a wide variety of inflammatory disorders and may potentially benefit from MSC-based therapies. Multiple genes are involved in immunomodulation by MSC and interspecies differences between expressions of these genes exist. The goals of the study were to characterize the expression of genes known to be involved in MSC-based immunomodulation and determine the effect of MSC on proliferation of T-cells in co-culture experiments with PBMC...
February 9, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28181189/deficit-but-not-nondeficit-schizophrenia-is-characterized-by-mucosa-associated-activation-of-the-tryptophan-catabolite-trycat-pathway-with-highly-specific-increases-in-iga-responses-directed-to-picolinic-xanthurenic-and-quinolinic-acid
#11
Buranee Kanchanatawan, Sunee Sirivichayakul, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, Heidi Ormstad, George Anderson, Michael Maes
Evidence suggests that activation of the tryptophan catabolite (TRYCAT) pathway is involved in the pathophysiology of schizophrenia. However, no previous study examined whether TRYCAT pathway activation is associated with deficit schizophrenia. We measured IgA responses to TRYCATs, namely quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, and anthranilic acid and 3-OH-kynurenine, in 40 healthy controls and in schizophrenic patients with (n = 40) and without (n = 40) deficit, defined according to the Schedule for the Deficit Syndrome (SDS)...
February 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28179491/increases-in-plasma-tryptophan-are-inversely-associated-with-incident-cardiovascular-disease-in-the-prevenci%C3%A3-n-con-dieta-mediterr%C3%A3-nea-predimed-study
#12
Edward Yu, Miguel Ruiz-Canela, Marta Guasch-Ferré, Yan Zheng, Estefania Toledo, Clary B Clish, Jordi Salas-Salvadó, Liming Liang, Dong D Wang, Dolores Corella, Montse Fitó, Enrique Gómez-Gracia, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Dora Romaguera, Lluis Serra-Majem, Jose V Sorlí, Frank B Hu, Miguel A Martinez-Gonzalez
Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28179106/non-tumor-cell-ido1-predominantly-contributes-to-enzyme-activity-and-response-to-ctla-4-pd-l1-inhibition-in-mouse-glioblastoma
#13
Lijie Zhai, Erik Ladomersky, Carlos R Dostal, Kristen L Lauing, Kathleen Swoap, Leah K Billingham, Galina Gritsina, Meijing Wu, Robert H McCusker, David C Binder, Derek A Wainwright
Glioblastoma (GBM) is the most common malignant brain tumor in adults with a median survival of 14.6months. A contributing factor to GBM aggressiveness is the intratumoral expression of the potently immunosuppressive enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). The enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity. Utilizing the syngeneic, immunocompetent, intracranial GL261 cell GBM model, we previously demonstrated that tumor cell, but not non-tumor cell IDO1, suppresses T cell-mediated brain tumor regression in mice...
February 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28176942/nanomedicine-and-cancer-immunotherapy-focus-on-indoleamine-2-3-dioxygenase-inhibitors
#14
REVIEW
Bilal Zulfiqar, Amnah Mahroo, Kaenat Nasir, Rai Khalid Farooq, Nasir Jalal, Muhammad Usman Rashid, Kashif Asghar
Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially affecting the healthy cells of the body during the process. Nanoparticle-based drug delivery is an emerging approach to stimulate the immune responses against cancer. The inhibition of indoleamine 2,3-dioxygenase (IDO) is a pivotal area of research in cancer immunotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28165296/the-activation-of-the-kynurenine-pathway-in-a-rat-model-with-renovascular-hypertension
#15
Jacek Bartosiewicz, Tomasz Kaminski, Krystyna Pawlak, Malgorzata Karbowska, Anna Tankiewicz-Kwedlo, Dariusz Pawlak
Hypertension is a serious condition that can lead to many health problems. The mechanisms underlying this process are still not fully understood. The kynurenine pathway may be involved in the occurrence and progression of hypertension. The purpose of this study was to examine the activity of peripheral kynurenine pathway in rats with renovascular hypertension in Goldblatt 2K1C model. Hypertension was induced in the experimental groups by constricting the renal artery of the left kidney of the rats. Determination of tryptophan (Trp) and kynurenine pathway metabolites was assessed by high-performance liquid chromatography in plasma and tissues obtained at 4, 8, and 16 weeks after the surgical intervention or sham surgery...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28164545/plasma-zonulin-and-its-association-with-kidney-function-severity-of-heart-failure-and-metabolic-inflammation
#16
Thomas B Dschietzig, Felix Boschann, Jana Ruppert, Franz P Armbruster, Andreas Meinitzer, Dragic Bankovic, Veselin Mitrovic, Christoph Melzer
BACKGROUND: The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. METHODS: Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#17
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155867/kynurenine-pathway-metabolomics-predicts-and-provides-mechanistic-insight-into-multiple-sclerosis-progression
#18
Chai K Lim, Ayse Bilgin, David B Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V Taylor, Alban Bessede, Bruce J Brew, Gilles J Guillemin
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155213/intracerebroventricular-administration-of-streptozotocin-as-an-experimental-approach-to-depression-evidence-for-the-involvement-of-proinflammatory-cytokines-and-indoleamine-2-3-dioxygenase
#19
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Cristini Escobar Viana, Etiara Mattos, Neici Cáceres Silva, Silvana Peterini Boeira
There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28139681/attenuating-nicotine-reinforcement-and-relapse-by-enhancing-endogenous-brain-levels-of-kynurenic-acid-in-rats-and-squirrel-monkeys
#20
Maria E Secci, Alessia Auber, Leigh V Panlilio, Godfrey H Redhi, Eric B Thorndike, Charles W Schindler, Robert Schwarcz, Steven R Goldberg, Zuzana Justinova
Currently-available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). Since the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine...
January 31, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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