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Kynurenin

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https://www.readbyqxmd.com/read/29155324/angiotensin-receptor-blocker-irbesartan-reduces-stress-induced-intestinal-inflammation-via-at1a-signaling-and-ace2-dependent-mechanism-in-mice
#1
Maimaiti Yisireyili, Yasuhiro Uchida, Koji Yamamoto, Takayuki Nakayama, Xian Wu Cheng, Tadashi Matsushita, Shigeo Nakamura, Toyoaki Murohara, Kyosuke Takeshita
Stress is associated with pathophysiology of both irritable bowel syndrome (IBS) and hypertension. Angiotensin receptor blockers (ARB) have anti-inflammatory properties via inhibition of angiotensin II (Ang II)/Ang II type I receptor axis (AT1). Inhibition of the classical RAS pathway is also involved in upregulation of angiotensin converting enzyme-2 (ACE2), which activates the Ang-(1-7) /Mas pathway to counteract inflammatory signaling and acts as a partner of the amino acid transporter, B(0)AT-1, to absorb tryptophan for regulation of microbiota-gut-brain axis...
November 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29154397/effects-of-high-ambient-temperature-on-plasma-metabolomic-profiles-in-chicks
#2
Shozo Tomonaga, Hirofumi Okuyama, Tetsuya Tachibana, Ryosuke Makino
Exposure to high ambient temperature is detrimental to the poultry industry. To understand the influence from a metabolic perspective, we investigated the effects of exposure to high ambient temperature on plasma low-molecular-weight metabolite levels in chicks using gas chromatography/mass spectrometry-based non-targeted metabolomic analysis. Heat exposure for 4 days suppressed growth and food intake. Of the 92 metabolites identified, the levels of 29 decreased, whereas the levels of nine increased. We performed an enrichment analysis on the identified metabolites and found 35 candidates for metabolic processes affected by heat exposure...
November 20, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/29153615/inflammation-induced-depression-its-pathophysiology-and-therapeutic-implications
#3
REVIEW
Sang Won Jeon, Yong-Ku Kim
Inflammation is not the only cause of depression and cannot explain its entire pathophysiology, but it is an important pathogenic factor that explains one possible mechanism of depression, with the kynurenine (KYN) pathway of tryptophan at its center. In particular, greater impairment seems to exist in the KYN pathway in inflammation-induced depression related to immunotherapy, autoimmune disease, and infection. In patients with these conditions, immunopharmacology is likely to be an important therapy. To develop this therapy, clear evidence of the immune-KYN pathway must be established via multiple types of experiments...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29153599/lps-induced-cortical-kynurenic-acid-and-neurogranin-nfat-signaling-is-associated-with-deficits-in-stimulus-processing-during-pavlovian-conditioning
#4
A Oliveros, K Wininger, J Sens, M K Larsson, X C Liu, S Choi, A Faka, L Schwieler, G Engberg, S Erhardt, D S Choi
The N-Methyl-d-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT)...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29153034/advances-in-maldi-mass-spectrometry-within-drug-discovery
#5
Dale S Cornett, Michael D Scholle
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
December 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29150070/decreased-expression-of-indolamine-2-3-dioxygenase-in-childhood-allergic-asthma-and-its-inverse-correlation-with-fractional-concentration-of-exhaled-nitric-oxide
#6
Ying Hu, Zhiqiang Chen, Ling Jin, Mei Wang, Wei Liao
BACKGROUND: The tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO...
November 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29146359/determination-of-tryptophan-derivatives-in-kynurenine-pathway-in-fermented-foods-using-liquid-chromatography-tandem-mass-spectrometry
#7
Cemile Yılmaz, Vural Gökmen
This study aimed to develop an analytical method for the determination of tryptophan and its derivatives in kynurenine pathway using tandem mass spectrometry in various fermented food products (bread, beer, red wine, white cheese, yoghurt, kefir and cocoa powder). The method entails an aqueous extraction and reversed phase chromatographic separation using pentafluorophenyl (PFP) column. It allowed quantitation of low ppb levels of tryptophan and its derivatives in different fermented food matrices. It was found that beer samples were found to contain kynurenine within the range of 28...
March 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29141444/associations-among-obesity-inflammation-and-tryptophan-catabolism-in-pregnancy
#8
Maureen Groer, Dietmar Fuchs, Allyson Duffy, Adetola Louis-Jacques, Amy D'Agata, Teodor T Postolache
OBJECTIVE: To evaluate relationships among obesity in pregnancy and plasma levels of tryptophan (TRP) and kynurenine (KYN), inflammatory markers, and depressed mood. METHODS: Pregnant women ( N = 374) were enrolled, and data were collected at a mean gestation of 20 weeks in this cross-sectional study. Plasma was analyzed for TRP, KYN, neopterin, and nitrite levels. Women completed demographic and mood scales. RESULTS: There was a statistically significant inverse correlation between body mass index (BMI) and TRP and positive correlations between BMI and KYN and the kynurenine/tryptophan (KYN/TRP) ratio...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29128872/prenatal-kynurenine-treatment-in-rats-causes-schizophrenia-like-broad-monitoring-deficits-in-adulthood
#9
Britta Hahn, Carolyn H Reneski, Ana Pocivavsek, Robert Schwarcz
RATIONALE: Elevated brain kynurenic acid (KYNA) levels are implicated in the pathology and neurodevelopmental pathogenesis of schizophrenia. In rats, embryonic treatment with kynurenine (EKyn) causes elevated brain KYNA levels in adulthood and cognitive deficits reminiscent of schizophrenia. OBJECTIVES: Growing evidence suggests that people with schizophrenia have a narrowed attentional focus, and we aimed at establishing whether these abnormalities may be related to KYNA dysregulation...
November 11, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29126954/quantitative-analysis-of-kynurenine-aminotransferase-ii-in-the-adult-rat-brain-reveals-high-expression-in-proliferative-zones-and-corpus-callosum
#10
Chang Song, Sarah M Clark, Chloe N Vaughn, James D Nicholson, Kelley J Murphy, Ta-Chung M Mou, Robert Schwarcz, Gloria E Hoffman, Leonardo H Tonelli
Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking...
November 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29120388/synthesis-and-molecular-modeling-studies-of-n-hydroxyindazolecarboximidamides-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#11
Dong-Ho Lee, Joo-Youn Lee, Jieun Jeong, Miok Kim, Kyung Won Lee, Eunseo Jang, Sunjoo Ahn, Chang Hoon Lee, Jong Yeon Hwang
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N'-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme...
November 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29118088/ido-immune-status-after-chemoradiation-may-predict-survival-in-lung-cancer-patients
#12
Weili Wang, Lei Huang, Jian-Yue Jin, Shruti Jolly, Yong Zang, Huanmei Wu, Li Yan, Wenhu Pi, Lang Li, Andrew L Mellor, Feng-Ming Spring Kong
Host immunity influences the impact of radiotherapy (RT) in cancer but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during and after RT administration and then correlated to overall survival (OS), progression-free survival and disease progression rate in patients...
November 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#13
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109914/revisiting-the-tryptophan-serotonin-deficiency-and-the-inflammatory-hypotheses-of-major-depression-in-a-biopsychosocial-approach
#14
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Robert J Breitenecker, Hans-Bernd Rothenhäusler, Christoph Robier, Maria Baranyi, Simon Theokas, Andreas Meinitzer
Background: The aim of this cross-sectional study was to identify important biopsychosocial correlates of major depression. Biological mechanisms, including the inflammatory and the tryptophan-serotonin deficiency hypotheses of major depression, were investigated alongside health-related quality of life, life satisfaction, and social support. Methods: The concentrations of plasma tryptophan, plasma kynurenine, plasma kynurenic acid, serum quinolinic acid, and the tryptophan breakdown to kynurenine were determined alongside health-related quality of life (Medical Outcome Study Form, SF-36), life satisfaction (Life Satisfaction Questionnaire, FLZ), and social support (Social Support Survey, SSS) in 71 depressive patients at the time of their in-patient admittance and 48 healthy controls...
2017: PeerJ
https://www.readbyqxmd.com/read/29103054/is-the-enzyme-acmsd-a-novel-therapeutic-target-in-parkinson-s-disease
#15
Keerthi Thirtamara-Rajamani, Peipei Li, Martha L Escobar Galvis, Viviane Labrie, Patrik Brundin, Lena Brundin
 Several large genome wide association studies have identified a locus in close proximity to the gene encoding the enzyme aminocarboxymuconate-semialdehyde-decarboxylase (ACMSD) to be associated with the risk for Parkinson's disease (PD), tentatively suggesting that this enzyme might influence PD pathogenesis. Further support for this comes from the recent identification of a disease-segregating stop codon mutation in ACMSD in a family with Parkinsonism, and a missense mutation in the ACMSD gene predicted to disrupt enzyme function in an individual with typical PD...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29102224/an-endogenous-tryptophan-photo-product-ficz-is-potentially-involved-in-photo-aging-by-reducing-tgf-%C3%AE-regulated-collagen-homeostasis
#16
Mika Murai, Gaku Tsuji, Akiko Hashimoto-Hachiya, Yoshihito Kawakami, Masutaka Furue, Chikage Mitoma
BACKGROUND: Persistent ultraviolet (UV) radiation in the form of sunlight causes photo-aging of the skin by reducing the production of type I collagen, the major constituent of the extracellular matrix of the dermis. Transforming growth factor (TGF)-β transforms dermal fibroblasts into α2-smooth muscle actin (ACTA2)-expressing myofibroblasts. Myofibroblasts produce a precursor form of type I collagen, type I procollagen (collagen I), consisting of pro-alpha1 (produced by the COL1A1 gene) and pro-alpha2 chains (produced by the COL1A2 gene)...
October 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29090837/biological-plausibility-of-the-gut-brain-axis-in-autism
#17
Alex Vasquez
Organic abnormalities with neuroinflammatory and psychiatric consequences involving abnormal kynurenine and purine metabolism, neurotransmitter and cytokine imbalances, and altered levels of nutrients and metabolites are noted in autism, and many of these abnormalities-specifically including increased intestinal permeability, microbial metabolites, and heightened serum levels of endotoxin-originate from the gut.
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29080891/prenatal-dynamics-of-kynurenine-pathway-metabolism-in-mice-focus-on-kynurenic-acid
#18
Nick Goeden, Francesca M Notarangelo, Ana Pocivavsek, Sarah Beggiato, Alexandre Bonnin, Robert Schwarcz
The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or saline on embryonic day 18...
October 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29080383/clinical-significance-of-tryptophan-catabolism-in-hodgkin-lymphoma
#19
Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida
Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients' affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88...
October 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/29076586/cancer-and-normal-adipose-derived-mesenchymal-stem-cells-ascs-do-they-have-differential-effects-on-tumor-and-immune-cells
#20
Mahboobeh Razmkhah, Zahra Mansourabadi, Maryam Al-Sadat Mohtasebi, Abdol-Rasoul Talei, Abbas Ghaderi
Adipose-derived mesenchymal stem cells (ASCs) are known to have immunomodulatory properties through soluble factors or by direct cell-to-cell contact. This study aimed to assess the expression of HLA-G and IDO activity in breast cancer and normal ASCs and to see if ASC is capable of modulating both tumor cells and immune system cells in vitro. ASCs were enzymatically isolated from 15 breast cancer patients and 10 normal individuals. Then they were cultured, and the impact of their conditioned media on the movement of the MDA-MB-231 breast cancer cell line was studied in wound healing scratch assay...
October 27, 2017: Cell Biology International
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