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Kynurenin

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https://www.readbyqxmd.com/read/29332257/kynurenic-acid-and-its-derivatives-are-able-to-modulate-the-adhesion-and-locomotion-of-brain-endothelial-cells
#1
Eszter Lajkó, Bernadett Tuka, Ferenc Fülöp, István Krizbai, József Toldi, Kálmán Magyar, László Vécsei, László Kőhidai
The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood-brain barrier (BBB)] are well established. Cell-extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium...
January 13, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29327354/a-validated-liquid-chromatography-high-resolution-tandem-mass-spectrometry-method-for-the-simultaneous-quantitation-of-tryptophan-kynurenine-kynurenic-acid-and-quinolinic-acid-in-human-plasma
#2
Kathrin Arnhard, Florian Pitterl, Barbara Sperner-Unterweger, Dietmar Fuchs, Therese Koal, Herbert Oberacher
Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent a major link between inflammation and various diseases, including neurodegenerative disorders, depression, schizophrenia, multiple sclerosis, cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) are well regulated under physiological conditions but may be altered as part of the activated immune response. A simple, sensitive and specific liquid chromatography-time of flight mass spectrometry method was developed for determining levels of the four compounds in human plasma samples...
January 12, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29322062/increased-indoleamine-2-3-dioxygenase-activity-is-associated-with-poor-clinical-outcome-in-adults-hospitalized-with-influenza-in-the-insight-flu003plus-study
#3
Sarah L Pett, Ken M Kunisaki, Deborah Wentworth, Timothy J Griffin, Ioannis Kalomenidis, Raquel Nahra, Rocio Montejano Sanchez, Shane W Hodgson, Kiat Ruxrungtham, Dominic Dwyer, Richard T Davey, Chris H Wendt
Background: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up...
January 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29320557/high-ahr-expression-in-breast-tumors-correlates-with-expression-of-genes-from-several-signaling-pathways-namely-inflammation-and-endogenous-tryptophan-metabolism
#4
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
https://www.readbyqxmd.com/read/29317604/beta-defensin-1-aryl-hydrocarbon-receptor-and-plasma-kynurenine-in-major-depressive-disorder-metabolomics-informed-genomics
#5
Duan Liu, Balmiki Ray, Drew R Neavin, Jiabin Zhang, Arjun P Athreya, Joanna M Biernacka, William V Bobo, Daniel K Hall-Flavin, Michelle K Skime, Hongjie Zhu, Gregory D Jenkins, Anthony Batzler, Krishna R Kalari, Felix Boakye-Agyeman, Wayne R Matson, Swati S Bhasin, Taisei Mushiroda, Yusuke Nakamura, Michiaki Kubo, Ravishankar K Iyer, Liewei Wang, Mark A Frye, Rima Kaddurah-Daouk, Richard M Weinshilboum
Major depressive disorder (MDD) is a heterogeneous disease. Efforts to identify biomarkers for sub-classifying MDD and antidepressant therapy by genome-wide association studies (GWAS) alone have generally yielded disappointing results. We applied a metabolomics-informed genomic research strategy to study the contribution of genetic variation to MDD pathophysiology by assaying 31 metabolites, including compounds from the tryptophan, tyrosine, and purine pathways, in plasma samples from 290 MDD patients. Associations of metabolite concentrations with depressive symptoms were determined, followed by GWAS for selected metabolites and functional validation studies of the genes identified...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29317240/toxicity-and-cardiac-effects-of-acute-exposure-to-tryptophan-metabolites-on-the-kynurenine-pathway-in-early-developing-zebrafish-danio-rerio-embryos
#6
Michal Majewski, Natalia Kasica, Anna Jakimiuk, Piotr Podlasz
Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of exposure to tryptophan metabolites might impact the early development of organism. Thus, this study examined the effects of KP exposure in zebrafish embryos starting at the blastula period (4hpf) and the segmentation stage (24hpf)...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29316724/biochemical-and-clinical-impact-of-organic-uremic-retention-solutes-a-comprehensive-update
#7
REVIEW
Raymond Vanholder, Anneleen Pletinck, Eva Schepers, Griet Glorieux
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered...
January 8, 2018: Toxins
https://www.readbyqxmd.com/read/29315929/wd40-repeat-5a-represses-root-meristem-growth-by-suppressing-auxin-synthesis-through-changes-of-nitric-oxide-accumulation-in-arabidopsis
#8
Wen-Cheng Liu, Si-Qiu Zheng, Zhen-Dong Yu, Xiang Gao, Ran Shen, Ying-Tang Lu
While nitric oxide (NO) is known to regulate root growth, the factor(s) modulating NO during this process have not yet been elucidated. Here, we identified Arabidopsis WD40-REPEAT 5a (WDR5a) as a novel factor that functions in root growth by modulating NO accumulation. The wdr5a-1 mutant accumulated less NO and produced longer roots than the wild type, while the WDR5a overexpression lines had the opposite phenotype. The role of NO was further supported by our observation that the NO donor sodium nitroprusside (SNP) and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) rescued the root meristem growth phenotypes of the wdr5a-1 and WDR5a overexpression lines, respectively...
January 6, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29307018/the-role-of-tryptophan-metabolism-in-postpartum-depression
#9
REVIEW
Kai-Ming Duan, Jia-Hui Ma, Sai-Ying Wang, ZhengDong Huang, YingYong Zhou, HeYa Yu
The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%-20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD...
January 6, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29306989/kynurenine-is-correlated-with-il-1%C3%AE-in-plasma-of-schizophrenia-patients
#10
Helena P G Joaquim, Alana C Costa, Wagner F Gattaz, Leda Leme Talib
The etiology of schizophrenia is still unclear. It is well-known that pro-inflammatory cytokines are higher in schizophrenia patients since the first episode psychosis comparing to healthy controls. Inflammatory downstream cascades influence different cellular pathways, like the displacement of the tryptophan (TRP) metabolism to the production of kynurenine (KYN) instead of serotonin, which results in the generation of several neuro and immunoactive metabolites. The aim of this study was to determine TRP, KYN and IL-1β plasma levels in first-onset schizophrenia (n = 28) and healthy controls (n = 30)...
January 6, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29302770/modulating-tumor-immunology-by-inhibiting-indoleamine-2-3-dioxygenase-ido-recent-developments-and-first-clinical-experiences
#11
Diwakar Davar, Nathan Bahary
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated...
January 4, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29301550/role-of-the-indoleamine-2-3-dioxygenase-kynurenine-pathway-of-tryptophan-metabolism-in-behavioral-alterations-in-a-hepatic-encephalopathy-rat-model
#12
Xi Jiang, Lexing Xu, Lin Tang, Fuhe Liu, Ziwei Chen, Jiajia Zhang, Lei Chen, Cong Pang, Xuefeng Yu
BACKGROUND: This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS: Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29299604/association-of-acylcarnitines-with-left-ventricular-remodeling-in-patients-with-severe-aortic-stenosis-undergoing-transcatheter-aortic-valve-replacement
#13
Sammy Elmariah, Laurie A Farrell, Deborah Furman, Brian R Lindman, Xu Shi, Jordan E Morningstar, Eugene P Rhee, Robert E Gerszten
Importance: Clinical practice guidelines currently endorse a reliance on clinical symptoms of overt left ventricular (LV) failure to time aortic valve replacement for severe aortic stenosis; however, delayed aortic valve replacement can result in irreversible LV injury and adverse outcomes. Blood metabolomic signatures possess prognostic value in heart failure; this study assesses whether they are informative in aortic stenosis. Objective: To evaluate the value of metabolomic signatures in reflecting the extent of maladaptive LV remodeling in patients with end-stage aortic stenosis undergoing transcatheter aortic valve replacement, and to assess whether this procedure reverses metabolomic aberrations...
January 3, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/29287468/effect-of-maize-bran-feruloylated-oligosaccharides-on-the-formation-of-endogenous-contaminants-and-the-appearance-and-textural-properties-of-biscuits
#14
Junqing Huang, Yijinruo Wang, Ling Yang, Xichun Peng, Jie Zheng, Shiyi Ou
Feruloylated oligosaccharides (FOs) have been approved by the US Food and Drug Administration for addition to baked goods. This work investigated the effect of FOs on the formation of endogenous contaminants, antioxidant properties, appearance and texture of biscuits. FOs inhibited the formation of fluorescent AGEs (advanced glycation end-products), protein oxidation products, and dicarbonyl compounds in a dose-dependent manner. Addition of 10 mg/g FOs decreased the levels of fluorescent AGEs, dityrosine, kynurenine, N'-formylkynurenine, 3-deoxyglucosone, glyoxal, and methylglyoxal by 80%, 97%, 56%, 86%, 46%, 54% and 62%, respectively...
April 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29279331/trace-derivatives-of-kynurenine-potently-activate-the-aryl-hydrocarbon-receptor-ahr
#15
Seung-Hyeon Seok, Zhi-Xiong Ma, John B Feltenberger, Hongbo Chen, Hui Chen, Cameron Scarlett, Ziqing Lin, Kenneth A Satyshur, Marissa Cortopassi, Colin R Jefcoate, Ying Ge, Weiping Tang, Christopher A Bradfield, Yongna Xing
Cellular metabolites act as important signaling cues, but are subject to complex unknown chemistry. Kynurenine is a tryptophan metabolite that plays a crucial role in cancer and the immune system. Despite its atypical, non-ligand-like, highly polar structure, kynurenine activates the aryl hydrocarbon receptor (AHR), a PAS family transcription factor that responds to diverse environmental and cellular ligands. The activity of kynurenine increases 100-1000-fold by incubation or long-term storage, and relies on the hydrophobic ligand-binding pocket of AHR, with identical structural signatures for AHR induction before and after activation...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29278387/indoleamine-2-3-dioxygenase-ido-enzyme-links-innate-immunity-and-altered-t-cell-differentiation-in-non-st-segment-elevation-acute-coronary-syndrome
#16
Chiara Zara, Anna Severino, Davide Flego, Aureliano Ruggio, Daniela Pedicino, Ada Francesca Giglio, Francesco Trotta, Claudia Lucci, Domenico D'Amario, Ramona Vinci, Eugenia Pisano, Giulio La Rosa, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo
Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS)...
December 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#17
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29258878/association-of-pre-and-early-post-transplant-serum-amino-acids-and-metabolites-of-amino-acids-and-liver-transplant-outcome
#18
H Oweira, I Lahdou, G Opelz, V Daniel, P Terness, J Schmidt, A Mehrabi, G Fusch, J Schefold, A Zidan, M Sadeghi
The aim of the present study was to investigate association of serum amino (AA) acids and metabolites of AAs with post-transplant outcome in liver transplant recipients. Eighty-nine patients with end-stage liver diseases and available pre- and early post-transplant serum were characterised as patients with (GI) and without one-year mortality (GII) and patients with and without early graft dysfunction (EAD). A panel of pre- and early post-transplant serum levels of AAs and early and metabolites of tryptophan were measured using tandem mass spectrometry...
December 16, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/29258398/pilot-study-of-metabolomics-and-psychoneurological-symptoms-in-women-with-early-stage-breast-cancer
#19
Debra E Lyon, Angela Starkweather, Yingwei Yao, Timothy Garrett, Debra Lynch Kelly, Victoria Menzies, Paweł Dereziński, Susmita Datta, Sreelakshmy Kumar, Colleen Jackson-Cook
Many women with breast cancer experience symptoms of pain, fatigue, and depression, collectively known as psychoneurologic (PN) symptoms, during and after chemotherapy treatment. Evidence that inflammatory dysfunction related to cancer and its treatments contributes to the development and persistence of PN symptoms through several interrelated pathways is accumulating. However, a major limiting factor in more precisely identifying the biological mechanisms underlying these symptoms is the lack of biological measures that represent a holistic spectrum of biological responses...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29248242/plasma-microbiome-modulated-indole-and-phenyl-derived-metabolites-associate-with-advanced-atherosclerosis-and-postoperative-outcomes
#20
Cori A Cason, Kyle T Dolan, Gaurav Sharma, Ming Tao, Rohan Kulkarni, Irene B Helenowski, Brendan M Doane, Michael J Avram, Mary M McDermott, Eugene B Chang, C Keith Ozaki, Karen J Ho
OBJECTIVE: Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. METHODS: Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia...
December 13, 2017: Journal of Vascular Surgery
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