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Kynurenine

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https://www.readbyqxmd.com/read/29778008/plasma-metabolic-changes-in-chinese-hiv-infected-patients-receiving-lopinavir-ritonavir-based-treatment-implications-for-hiv-precision-therapy
#1
Xiaolin Li, Tong Wu, Yongjun Jiang, Zining Zhang, Xiaoxu Han, Wenqing Geng, Haibo Ding, Jing Kang, Qi Wang, Hong Shang
OBJECTIVES: The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. METHODS: 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls...
May 16, 2018: Cytokine
https://www.readbyqxmd.com/read/29777939/variation-of-genes-encoding-kat1-aadat-and-ido1-as-a-potential-risk-of-depression-development
#2
Paulina Wigner, Piotr Czarny, Ewelina Synowiec, Michał Bijak, Monika Talarowska, Piotr Galecki, Janusz Szemraj, Tomasz Sliwinski
Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs -kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan - may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls...
May 16, 2018: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/29775873/psychosocial-stress-and-inflammation-driving-tryptophan-breakdown-in-children-and-adolescents-a-cross-sectional-analysis-of-two-cohorts
#3
Nathalie Michels, Gerard Clarke, Loreto Olavarria-Ramirez, Sonia Gómez-Martínez, Ligia Esperanza Díaz, Ascensión Marcos, Kurt Widhalm, Livia A Carvalho
BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group...
May 15, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29773836/novel-pathway-of-3-hydroxyanthranilic-acid-formation-in-limazepine-biosynthesis-reveals-evolutionary-relation-between-phenazines-and-pyrrolobenzodiazepines
#4
Magdalena Pavlikova, Zdenek Kamenik, Jiri Janata, Stanislav Kadlcik, Marek Kuzma, Lucie Najmanova
Natural pyrrolobenzodiazepines (PBDs) form a large and structurally diverse group of antitumour microbial metabolites produced through complex pathways, which are encoded within biosynthetic gene clusters. We sequenced the gene cluster of limazepines and proposed their biosynthetic pathway based on comparison with five available gene clusters for the biosynthesis of other PBDs. Furthermore, we tested two recombinant proteins from limazepine biosynthesis, Lim5 and Lim6, with the expected substrates in vitro...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773791/single-cell-analysis-of-kynurenine-and-system-l-amino-acid-transport-in-t-cells
#5
Linda V Sinclair, Damien Neyens, George Ramsay, Peter M Taylor, Doreen A Cantrell
The tryptophan metabolite kynurenine has critical immunomodulatory properties and can function as an aryl hydrocarbon receptor (AHR) ligand. Here we show that the ability of T cells to transport kynurenine is restricted to cells activated by the T-cell antigen receptor or proinflammatory cytokines. Kynurenine is transported across the T-cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate the AHR is restricted to T cells that express SLC7A5. We use the fluorescence spectral properties of kynurenine to develop a flow cytometry-based assay for rapid, sensitive and quantitative measurement of the kynurenine transport capacity in a single cell...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29760869/metabolic-alterations-in-urine-extracellular-vesicles-are-associated-to-prostate-cancer-pathogenesis-and-progression
#6
Marc Clos-Garcia, Ana Loizaga-Iriarte, Patricia Zuñiga-Garcia, Pilar Sánchez-Mosquera, Ana Rosa Cortazar, Esperanza González, Verónica Torrano, Cristina Alonso, Miriam Pérez-Cormenzana, Aitziber Ugalde-Olano, Isabel Lacasa-Viscasillas, Azucena Castro, Felix Royo, Miguel Unda, Arkaitz Carracedo, Juan M Falcón-Pérez
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography-mass spectrometry...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29753195/effect-of-l-tryptophan-and-its-metabolites-on-food-passage-from-the-crop-in-chicks
#7
T Tachibana, Y Kadomoto, M S I Khan, R Makino, M A Cline
l-tryptophan (l-Trp), an essential amino acid, is well known as a precursor of 5-hydroxytryptamine (5-HT) and melatonin. In mammals, l-Trp itself has been reported to suppress gastric emptying in mammals. In addition, 5-HT and melatonin are found in the gastrointestinal tract and affect food passage from the digestive tract in mammals. While the function of these factors in mammals is documented, there is little knowledge on their function in the digestive tract of birds. Therefore, the purpose of the present study was to determine if l-Trp and its metabolites affect the crop emptying rate in chicks (Gallus gallus)...
March 16, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29753175/changes-in-the-tryptophan-kynurenine-axis-in-association-to-therapeutic-response-in-clinically-depressed-patients-undergoing-psychiatric-rehabilitation
#8
B Reininghaus, K Riedrich, N Dalkner, S A Bengesser, A Birner, M Platzer, C Hamm, J M Gostner, D Fuchs, E Z Reininghaus
INTRODUCTION: In recent decades a number of studies have shown an association between the Tryptophan (Trp)-Kynurenine (Kyn) axis and neuropsychiatric disorders. However, the role of the Trp-Kyn pathway on the affective status in a general psychiatric cohort requires clarification. This study aimed to measure peripheral changes in Trp, Kyn and the Kyn/Trp-ratio as well as in the inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukine-6 (IL-6) in individuals undergoing a six-week course of intensive treatment program comparing subgroups of treatment responders and non-responders...
May 6, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29746927/indoleamine-2-3-dioxygenase-1-inhibition-targets-anti-pd1-resistant-lung-tumors-by-blocking-myeloid-derived-suppressor-cells
#9
Ailin Li, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Taylor R Cushman, Mauricio S Caetano, Xiaohong Wang, David R Valdecanas, Sharareh Niknam, Ahmed I Younes, Guang Li, Wendy A Woodward, Maria Angelica Cortez, James W Welsh
Indoleamine 2,3-dioxygenase 1 (IDO1), involved in the catabolism of tryptophan (Trp) to kynurenine (Kyn) is an important regulator of tumor-mediated immunosuppression implicated in resistance to anti-PD1 immunotherapy. We investigated the role of IDO1 in an anti-PD1-resistant lung cancer model (344SQ_R) compared to the parental 344SQ tumors (344SQ_P). IDO1 was overexpressed in tumor-infiltrating leukocytes, and plasma Kyn levels were increased, in 344SQ_R vs. 344SQ_P. The IDO1 inhibitor INCB023843 retarded tumor growth and reduced lung metastases in 344SQ_R...
May 7, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29740359/profiling-of-amino-acids-and-their-derivatives-biogenic-amines-before-and-after-antipsychotic-treatment-in-first-episode-psychosis
#10
Liisa Leppik, Kärt Kriisa, Kati Koido, Kadri Koch, Kärolin Kajalaid, Liina Haring, Eero Vasar, Mihkel Zilmer
Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs)...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29734388/a-prospective-evaluation-of-serum-kynurenine-metabolites-and-risk-of-pancreatic-cancer
#11
Joyce Y Huang, Lesley M Butler, Øivind Midttun, Arve Ulvik, Renwei Wang, Aizhen Jin, Yu-Tang Gao, Per M Ueland, Woon-Puay Koh, Jian-Min Yuan
BACKGROUND: Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. METHODS: A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer...
2018: PloS One
https://www.readbyqxmd.com/read/29734055/kynurenine-pathway-metabolic-balance-influences-microglia-activity-targeting-kynurenine-monooxygenase-to-dampen-neuroinflammation
#12
Allison M Garrison, Jennifer M Parrott, Arnulfo Tuñon, Jennifer Delgado, Laney Redus, Jason C O'Connor
Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown...
April 22, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29731182/effect-of-probiotic-and-prebiotic-vs-placebo-on-psychological-outcomes-in-patients-with-major-depressive-disorder-a-randomized-clinical-trial
#13
Asma Kazemi, Ahmad Ali Noorbala, Kamal Azam, Mohammad Hadi Eskandari, Kurosh Djafarian
BACKGROUND: Disturbance in the equilibrium of the gut microbiota has been involved in the pathophysiology of depression. Probiotics have the potential to healthfully modulate the gut microbiome. Prebiotics could also be effective by stimulation of growth of some bacterial species in the gut microbiota. OBJECTIVE: The aim of this double blind clinical trial, was to compare the effect of supplementation with the probiotic and prebiotic on the Beck Depression Inventory (BDI) score as a primary outcome as well as the kynurenine/tryptophan ratio and tryptophan/branch chain amino acids (BCAAs) ratio as secondary outcomes in patients with major depressive disorder (MDD)...
April 24, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29728648/salivary-kynurenic-acid-response-to-psychological-stress-inverse-relationship-to-cortical-glutamate-in-schizophrenia
#14
Joshua Chiappelli, Laura M Rowland, Francesca M Notarangelo, S Andrea Wijtenburg, Marian A R Thomas, Ana Pocivavsek, Aaron Jones, Krista Wisner, Peter Kochunov, Robert Schwarcz, L Elliot Hong
Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia...
April 18, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29725904/chronic-mild-stress-alters-kynurenine-pathways-changing-the-glutamate-neurotransmission-in-frontal-cortex-of-rats
#15
David Martín-Hernández, Hiram Tendilla-Beltrán, José L M Madrigal, Borja García-Bueno, Juan C Leza, Javier R Caso
Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29725029/sex-differences-in-hippocampal-memory-and-kynurenic-acid-formation-following-acute-sleep-deprivation-in-rats
#16
Annalisa M Baratta, Silas A Buck, Austin D Buchla, Carly B Fabian, Shuo Chen, Jessica A Mong, Ana Pocivavsek
Inadequate sleep is a prevalent problem within our society that can result in cognitive dysfunction. Elevations in kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation known to impact cognition, in the brain may constitute a molecular link between sleep loss and cognitive impairment. To test this hypothesis, we investigated the impact of 6 hours of sleep deprivation on memory and KP metabolism (brain and plasma) in male and female rats. Sleep-deprived males were impaired in a contextual memory paradigm, and both sexes were impaired in a recognition memory paradigm...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29722898/lw106-a-novel-inhibitor-of-ido1-suppresses-tumor-progression-by-limiting-stroma-immune-crosstalk-and-cancer-stem-cell-enrichment-in-the-tumor-microenvironment
#17
Rong Fu, Yi-Wei Zhang, Hong-Mei Li, Wen-Cong Lv, Li Zhao, Qing-Long Guo, Tao Lu, Stephen J Weiss, Zhi-Yu Li, Zhao-Qiu Wu
BACKGROUND AND PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumors characterized by dysregulated tryptophan metabolism. However, the antitumor efficacy of existing small-molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small-molecule inhibitor of IDO1, LW106, and studied its antitumor effects and the underlying mechanisms in two Tumor models...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29719533/high-indoleamine-2-3-dioxygenase-is-correlated-with-microvessel-density-and-worse-prognosis-in-breast-cancer
#18
Lijuan Wei, Shanshan Zhu, Menghui Li, Fangxuan Li, Feng Wei, Juntian Liu, Xiubao Ren
Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of the essential amino acid tryptophan into kynurenine, is understood to have a key role in cancer immunotherapy. IDO has also received more attention because of its non-immune functions including regulating angiogenesis. The purpose of this study was to investigate the effects of IDO on microvessel density (MVD), and to explore its prognostic role in breast cancer. We showed IDO expression was positively correlated with MVD labeled by CD105 (MVD-CD105) rather than MVD labeled by CD31 (MVD-CD31) in breast cancer specimens...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29716602/lower-plasma-trans-4-hydroxyproline-and-methionine-sulfoxide-levels-are-associated-with-insulin-dysregulation-in-horses
#19
Ákos Kenéz, Tobias Warnken, Karsten Feige, Korinna Huber
BACKGROUND: Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targeted metabolomics approach to identify novel metabolites associated with insulin dysregulation...
May 2, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29712976/impact-of-hiv-and-type-2-diabetes-on-gut-microbiota-diversity-tryptophan-catabolism-and-endothelial-dysfunction
#20
Hedda Hoel, Malene Hove-Skovsgaard, Johannes R Hov, Julie Christine Gaardbo, Kristian Holm, Martin Kummen, Knut Rudi, Felix Nwosu, Jørgen Valeur, Marco Gelpi, Ingebjørg Seljeflot, Per Magne Ueland, Jan Gerstoft, Henrik Ullum, Pål Aukrust, Susanne Dam Nielsen, Marius Trøseid
HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene...
April 30, 2018: Scientific Reports
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