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Kynurenine

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https://www.readbyqxmd.com/read/28922389/comprehensive-metabolic-characterization-of-serum-osteocalcin-action-in-a-large-non-diabetic-sample
#1
Lukas Entenmann, Maik Pietzner, Anna Artati, Anke Hannemann, Ann-Kristin Henning, Gabi Kastenmüller, Henry Völzke, Matthias Nauck, Jerzy Adamski, Henri Wallaschofski, Nele Friedrich
Recent research suggested a metabolic implication of osteocalcin (OCN) in e.g. insulin sensitivity or steroid production. We used an untargeted metabolomics approach by analyzing plasma and urine samples of 931 participants using mass spectrometry to reveal further metabolic actions of OCN. Several detected relations between OCN and metabolites were strongly linked to renal function, however, a number of associations remained significant after adjustment for renal function. Intermediates of proline catabolism were associated with OCN reflecting the implication in bone metabolism...
2017: PloS One
https://www.readbyqxmd.com/read/28911850/activation-of-indoleamine-2-3-dioxygenase-pathway-by-olanzapine-augments-antidepressant-effects-of-venlafaxine-in-mice
#2
Jaya Thomas, Razia Khanam, Divya Vohora
Recent clinical studies report antipsychotics as a better option to augment the action of antidepressants in treatment resistant cases. However, the proper mechanisms underlying the antidepressant effect of antipsychotics is still not clear. Indolamine 2, 3 dioxygenase (IDO) pathway is considered to be an important pathway in pro-inflammatory cytokine associated stress-induced depression. The present study investigated the antidepressant effect of venlafaxine, olanzapine and their combinations in chronic forced-swim stress-induced depression in mice...
August 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28905195/experimental-evidences-for-mir-30b-as-a-negative-regulator-of-foxo3-upregulated-by-kynurenine
#3
Zhi-Qing Duan, Yan Li, Lu Li
Molecular constituents regulated by the microenvironment components profoundly influence the propensity of cancer metastasis, a key event of estimating therapeutic actions of anticancer drugs. On one hand, kynurenine (Kyn), one of the microenvironment components, plays key roles in the metastasis of cancer cells in vivo; on the other hand, forkhead box O3 (FOXO3) can serve as a therapeutic target of various anticancer drugs. However, the effect of Kyn on FOXO3 is still not clear. The current study demonstrated that the selected dose of Kyn significantly upregulated the FOXO3 protein rather than FOXO3 messenger RNA (mRNA) in the lung cancer 95D cells...
September 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28901958/pilot-study-of-the-tart-cherry-juice-for-the-treatment-of-insomnia-and-investigation-of-mechanisms
#4
Jack N Losso, John W Finley, Namrata Karki, Ann G Liu, Alfredo Prudente, Russell Tipton, Ying Yu, Frank L Greenway
BACKGROUND: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout...
March 27, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28901950/detecting-drug-target-binding-in-cells-using-fluorescence-activated-cell-sorting-coupled-with-mass-spectrometry-analysis
#5
Kris Wilson, Scott P Webster, John Peter Iredale, Xiaozhong Zheng, Natalie Z M Homer, Nhan Pham, Manfred Auer, Damian James Mole
The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity - the Toxicity-Affinity-Permeability-Selectivity (TAPS) technique...
September 13, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28901278/neuroinflammation-and-the-immune-kynurenine-pathway-in-anxiety-disorders
#6
Yong-Ku Kim, Sang Won Jeon
BACKGROUND: Recently, neuroinflammation and the immune-kynurenine pathway have received increased attention in the psychoimmunology field of major depressive disorder (MDD), while studies related to anxiety disorders have been very limited. OBJECTIVE: This study reviewed possible mechanisms by which stress or inflammation modulate anxiety through tryptophan metabolism and the kynurenine pathway. METHOD: Relevant literature was identified through a search of MEDLINE via PubMed...
September 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28899580/the-interplay-between-cytokines-and-the-kynurenine-pathway-in-inflammation-and-atherosclerosis
#7
Roland Baumgartner, Maria J Forteza, Daniel F J Ketelhuth
The kynurenine pathway (KP) is the major metabolic route of tryptophan (Trp) metabolism. Indoleamine 2,3-dioxygenase (IDO1), the enzyme responsible for the first and rate-limiting step in the pathway, as well as other enzymes in the pathway, have been shown to be highly regulated by cytokines. Hence, the KP has been implicated in several pathologic conditions, including infectious diseases, psychiatric disorders, malignancies, and autoimmune and chronic inflammatory diseases. Additionally, recent studies have linked the KP with atherosclerosis, suggesting that Trp metabolism could play an essential role in the maintenance of immune homeostasis in the vascular wall...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28893581/tryptophan-circuit-in-fatigue-from-blood-to-brain-and-cognition
#8
Masatoshi Yamashita, Takanobu Yamamoto
Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus...
September 8, 2017: Brain Research
https://www.readbyqxmd.com/read/28879460/vitamin-b6-reduces-neurochemical-and-long-term-cognitive-alterations-after-polymicrobial-sepsis-involvement-of-the-kynurenine-pathway-modulation
#9
Lucinéia Gainski Danielski, Amanda Della Giustina, Mariana Pereira Goldim, Drielly Florentino, Khiany Mathias, Leandro Garbossa, Rosiane de Bona Schraiber, Ana Olívia Martins Laurentino, Marina Goulart, Monique Michels, Karina Barbosa de Queiroz, Markus Kohlhof, Gislaine Tezza Rezin, Jucélia Jeremias Fortunato, Joao Quevedo, Tatiana Barichello, Felipe Dal-Pizzol, Roney S Coimbra, Fabricia Petronilho
Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats...
September 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28875464/changes-in-tryptophan-catabolite-trycat-pathway-patterning-are-associated-with-mild-impairments-in-declarative-memory-in-schizophrenia-and-deficits-in-semantic-and-episodic-memory-coupled-with-increased-false-memory-creation-in-deficit-schizophrenia
#10
Buranee Kanchanatawan, Solaphat Hemrungrojn, Supaksorn Thika, Sunee Sirivichayakul, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, George Anderson, Michael Maes
Evidence indicates that schizophrenia and in particular negative symptoms and deficit schizophrenia are accompanied by neurocognitive impairments and changes in the patterning of the tryptophan catabolite (TRYCAT) pathway. This cross-sectional study was carried out to examine the associations between cognitive functions (as measured with Consortium to Establish a Registry for Alzheimer's disease (CERAD)) and TRYCAT pathway patterning in patients with (n = 40) and without (n = 40) deficit schizophrenia and normal controls (n = 40)...
September 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28871782/antibiotic-treatment-preventing-necrotising-enterocolitis-alters-urinary-and-plasma-metabolomes-in-preterm-pigs
#11
Pingping Jiang, Alessia Trimigno, Jan Stanstrup, Bekzod Khakimov, Nanna Viereck, Søren Balling Engelsen, Per Torp Sangild, Lars Ove Dragsted
Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibiotics-suppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formula-fed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and (1)H NMR, with and without antibiotic treatment immediately after birth...
September 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28869479/kynurenine-pathway-metabolites-in-alzheimer-s-disease
#12
Lasse Melvaer Giil, Øivind Midttun, Helga Refsum, Arve Ulvik, Rajiv Advani, A David Smith, Per Magne Ueland
BACKGROUND: Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines), have been linked to Alzheimer's disease (AD) in small cohorts with conflicting results. OBJECTIVE: To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. METHODS: The study included 65 histopathologically-confirmed AD patients and 65 cognitively-screened controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort...
August 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28867283/kynurenic-acid-is-reduced-in-females-and-oral-contraceptive-users-implications-for-depression
#13
Timothy B Meier, Wayne C Drevets, T Kent Teague, Brent E Wurfel, Sven C Mueller, Jerzy Bodurka, Robert Dantzer, Jonathan Savitz
The incidence of depression is approximately 2-fold greater in women than men but the biological mechanisms underlying this phenomenon remain unclear. One potential mechanism that has been understudied is immune function, which is modulated by sex hormones and differs considerably between males and females. The immune-regulating kynurenine pathway previously has been implicated in the pathogenesis of mood disorders. In particular, a decreased ratio of neuroprotective (kynurenic acid; KynA) to neurotoxic (3-hydroxykynurenine; 3HK and quinolinic acid; QA) kynurenine pathway metabolites has been reported in several mood disorder subtypes...
September 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28851339/comorbid-post-traumatic-stress-disorder-in-alcohol-use-disorder-relationships-to-demography-drinking-and-neuroimmune-profile
#14
Sudan Prasad Neupane, Jørgen G Bramness, Lars Lien
BACKGROUND: This study examined how alcohol use disorder (AUD) patients with post-traumatic stress disorder (PTSD) differed from those without PTSD in terms of demography, drinking patterns and C-reactive protein, inflammatory cytokines, tryptophan metabolism parameters, and brain-derived neurotrophic factor (BDNF). METHODS: A consecutive sample (N = 187) of treatment-receiving AUD individuals were recruited from Nepalese facilities. They underwent fully structured psychiatric interviews...
August 29, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28840775/untargeted-metabolomic-analysis-and-pathway-discovery-in-perinatal-asphyxia-and-hypoxic-ischaemic-encephalopathy
#15
Niamh M Denihan, Jennifer A Kirwan, Brian H Walsh, Warwick B Dunn, David I Broadhurst, Geraldine B Boylan, Deirdre M Murray
Elucidating metabolic effects of hypoxic-ischaemic encephalopathy (HIE) may reveal early biomarkers of injury and new treatment targets. This study uses untargeted metabolomics to examine early metabolic alterations in a carefully defined neonatal population. Infants with perinatal asphyxia who were resuscitated at birth and recovered (PA group), those who developed HIE (HIE group) and healthy controls were all recruited at birth. Metabolomic analysis of cord blood was performed using direct infusion FT-ICR mass spectrometry...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28833866/total-sleep-time-and-kynurenine-metabolism-associated-with-mood-symptom-severity-in-bipolar-disorder
#16
Dahlia Mukherjee, Venkatesh Bassapa Krishnamurthy, Caitlin E Millett, Aubrey Reider, Adem Can, Maureen Groer, Dietmar Fuchs, Teodor T Postolache, Erika F H Saunders
OBJECTIVE: Chronic, low-level inflammation is associated with symptomatic bipolar disorder (BD) and with chronic insomnia. Disrupted sleep is a feature of episodes of both mania and depression. We examined the effect of neopterin, a marker of cellular immune activation, and kynurenine (KYN), an inflammatory byproduct of the serotonin pathway, on the association between total sleep time and depression severity in BD. METHOD: Twenty-one symptomatic BD participants and 28 healthy controls (HC) were recruited and followed during usual clinical care...
August 23, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28831293/3-hydroxykynurenine-and-3-hydroxyanthranilic-acid-enhance-the-toxicity-induced-by-copper-in-rat-astrocyte-culture
#17
Daniela Ramírez-Ortega, Alelí Ramiro-Salazar, Dinora González-Esquivel, Camilo Ríos, Benjamín Pineda, Verónica Pérez de la Cruz
Copper is an integral component of various enzymes, necessary for mitochondrial respiration and other biological functions. Excess copper is related with neurodegenerative diseases as Alzheimer and is able to modify cellular redox environment, influencing its functions, signaling, and catabolic pathways. Tryptophan degradation through kynurenine pathway produces some metabolites with redox properties as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HANA). The imbalance in their production is related with some neuropathologies, where the common factors are oxidative stress, inflammation, and cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28828008/mesenchymal-stem-cells-attenuate-cisplatin-induced-nephrotoxicity-in-inos-dependent-manner
#18
Bojana Simovic Markovic, Marina Gazdic, Aleksandar Arsenijevic, Nemanja Jovicic, Jovana Jeremic, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) are, due to their immunomodulatory characteristics, utilized in therapy of immune-mediated diseases. We used murine model of cisplatin nephrotoxicity to explore the effects of MSCs on immune cells involved in the pathogenesis of this disease. Intraperitoneal application of MSCs significantly attenuated cisplatin nephrotoxicity, decreased inflammatory cytokines TNF-α and IL-17, and increased anti-inflammatory IL-10, IL-6, nitric oxide (NO), and kynurenine in sera of cisplatin-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28827067/increased-tryptophan-metabolism-is-associated-with-activity-of-inflammatory-bowel-diseases
#19
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan, and some of its metabolites, reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome can increase susceptibility of mice to colitis. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features. METHODS: We studied 535 consecutive patients with IBD (211 with ulcerative colitis [UC], 234 with Crohn's disease [CD]; 236 male), enrolled in Germany from August 2013 through April 2014 and followed until July 2016...
August 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28825789/multifunctional-analogs-of-kynurenic-acid-for-the-treatment-of-alzheimer-s-disease-synthesis-pharmacology-and-molecular-modeling-studies
#20
Girdhar Singh Deora, Srinivas Kantham, Stephen Chan, Satish N Dighe, Suresh K Veliyath, Gawain McColl, Marie-Odile Parat, Ross P McGeary, Benjamin P Ross
We report the synthesis and pharmacological investigation of analogs of the endogenous molecule kynurenic acid (KYNA) as multifunctional agents for the treatment of Alzheimer's disease (AD). Synthesized KYNA analogs were tested for their N-methyl-d-aspartate (NMDA) receptor binding, mGluR5 binding and function, acetylcholinesterase (AChE) inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, interference with the amyloid β peptide (Aβ) fibrillation process, and protection against Aβ-induced toxicity in transgenic Caenorhabditis elegans strain GMC101 expressing full-length Aβ42...
September 8, 2017: ACS Chemical Neuroscience
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