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https://www.readbyqxmd.com/read/28445957/peripheral-kynurenine-tryptophan-ratio-is-not-a-reliable-marker-of-systemic-indoleamine-2-3-dioxygenase-a-lesson-drawn-from-patients-on-hemodialysis
#1
Yuanhan Chen, Zhen Xie, Chenggen Xiao, Min Zhang, Zhilian Li, Jianteng Xie, Yusheng Zhang, Xingchen Zhao, Pengfei Zeng, Liyi Mo, Xinling Liang, Wei Shi
Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442882/comparative-analysis-of-immunopathological-features-of-lichen-planopilaris-and-female-patients-with-frontal-fibrosing-alopecia
#2
Emanuella Rd Cerqueira, Neusa Valente, Mírian Nacagami Sotto, Ricardo Romiti
BACKGROUND: Frontal fibrosing alopecia (FFA) is a disorder characterized by progressive cicatricial alopecia (CA). Its classification as a clinical variant of lichen planopilaris (LPP) or as a unique disorder is controversial. The presence of Langerhans cells within the bulge area and the sebaceous epithelium and the presence of lymphocytic infiltrate in this area in CA have led to a series of hypotheses, although limited, about their development. To our knowledge, scarce is the literature demonstrating immunoanalytical studies comparing both disorders...
October 2016: International Journal of Trichology
https://www.readbyqxmd.com/read/28439991/melatonin-a-pleiotropic-molecule-that-modulates-dna-damage-response-and-repair-pathways
#3
REVIEW
Maryam Majidinia, Alireza Sadeghpour, Saeed Mehrzadi, Russel J Reiter, Nasrin Khatami, Bahman Yousefi
DNA repair is responsible for maintaining the integrity of the genome. Perturbations in the DNA repair pathways have been identified in several human cancers. Thus, compounds targeting DNA damage response (DDR) hold great promise in cancer therapy. A great deal of effort, in pursuit of new anticancer drugs, has been devoted to understanding the basic mechanisms and functions of the cellular DNA repair machinery. Melatonin, a widely-produced indoleamine in all organisms is associated with a reduced risk of cancer and has multiple regulatory roles on the different aspects of the DDR and DNA repair...
April 25, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28434116/activation-of-the-serotonin-pathway-is-associated-with-poor-outcome-in-copd-exacerbation-results-of-a-long-term-cohort-study
#4
Marc A Meier, Manuel Ottiger, Alaadin Vögeli, Christian Steuer, Luca Bernasconi, Robert Thomann, Mirjam Christ-Crain, Christoph Henzen, Claus Hoess, Werner Zimmerli, Andreas Huber, Beat Mueller, Philipp Schuetz
BACKGROUND/INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation...
April 22, 2017: Lung
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#5
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#6
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28424423/the-antidepressant-like-effect-of-trans-astaxanthin-involves-the-serotonergic-system
#7
Xi Jiang, Keqi Zhu, Quanyi Xu, Guokang Wang, Jiajia Zhang, Rongrong Cao, Jiang Ye, Xuefeng Yu
The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420185/melatonin-a-full-service-anti-cancer-agent-inhibition-of-initiation-progression-and-metastasis
#8
REVIEW
Russel J Reiter, Sergio A Rosales-Corral, Dun-Xian Tan, Dario Acuna-Castroviejo, Lilan Qin, Shun-Fa Yang, Kexin Xu
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417262/melatonin-inhibits-neural-cell-apoptosis-and-promotes-locomotor-recovery-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway-after-spinal-cord-injury
#9
Zhaoliang Shen, Zipeng Zhou, Shuang Gao, Yue Guo, Kai Gao, Haoyu Wang, Xiaoqian Dang
The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28416039/pig-cognitive-bias-affects-the-conversion-of-muscle-into-meat-by-antioxidant-and-autophagy-mechanisms
#10
Y Potes, M Oliván, A Rubio-González, B de Luxán-Delgado, F Díaz, V Sierra, L Arroyo, R Peña, A Bassols, J González, R Carreras, A Velarde, M Muñoz-Torres, A Coto-Montes
Slaughter is a crucial step in the meat production chain that could induce psychological stress on each animal, resulting in a physiological response that can differ among individuals. The aim of this study was to investigate the relationship between an animal's emotional state, the subsequent psychological stress at slaughter and the cellular damage as an effect. In all, 36 entire male pigs were reared at an experimental farm and a cognitive bias test was used to classify them into positive bias (PB) or negative bias (NB) groups depending on their decision-making capabilities...
April 18, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28414589/progesterone-decreases-in-vitro-indoleamine-2-3-dioxygenase-expression-in-dendritic-and-cd4-cells-from-maternal-fetal-interface-of-rats
#11
Pedro Kastein Faria da Cunha Bianchi, Rafael Magdanelo Leandro, Aline Nayara Poscai, Tulio Yoshinaga, Patrícia Orlandini Gonçalez, José Roberto Kfoury Junior
PROBLEM: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation...
April 17, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28412361/structural-insights-into-the-binding-mechanism-of-ido1-with-hydroxylamidine-based-inhibitor-incb14943
#12
You Wu, Tingting Xu, Jinsong Liu, Ke Ding, Jinxin Xu
IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive enzyme, has attracted growing attention as a potential target for cancer immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360 analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical trials for treatment of various types of human cancer. Here, we determined the co-crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode. INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28408139/the-anti-inflammatory-effect-of-melatonin-in-sh-sy5y-neuroblastoma-cells-exposed-to-sublethal-dose-of-hydrogen-peroxide
#13
Chutikorn Nopparat, Varunya Chantadul, Kannika Permpoonputtana, Piyarat Govitrapong
Brain inflammaging is considered as one of the underlying factors of neurodegenerative diseases. The present study aimed to investigate the effects of melatonin, an endogenous indoleamine mainly synthesized by the pineal gland, on hydrogen peroxide (H2O2)-induced inflammaging state in SH-SY5Y cells. Our data showed that p21(Cip1) and p16(INK4a), cell cycle arrest markers, and the number of senescence-associated β-galactosidase (SA-βgal) staining increased significantly in H2O2-treated cells. Melatonin treatment could reverse this effect...
April 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28406643/polyketides-and-anthranilic-acid-possessing-6-deoxy-%C3%AE-l-talopyranose-from-a-streptomyces-species
#14
Sangkeun Son, Sung-Kyun Ko, Mina Jang, Jae Kyoung Lee, Min Cheol Kwon, Dong Hyo Kang, In-Ja Ryoo, Jung-Sook Lee, Young-Soo Hong, Bo Yeon Kim, Jae-Hyuk Jang, Jong Seog Ahn
A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose...
April 13, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#15
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403684/mangiferin-prevents-corticosterone-induced-behavioural-deficits-via-alleviation-of-oxido-nitrosative-stress-and-down-regulation-of-indoleamine-2-3-dioxygenase-ido-activity
#16
Gao-Quan Luo, Ling Liu, Qu-Wen Gao, Xiao-Na Wu, Wei Xiang, Wen-Ting Deng
BACKGROUND: In recent years, a substantial amount of experimental studies have demonstrated that exogenous administration of corticosterone causes anxiety and depressive-like behaviour in rodents which involves hypothalamic-pituitary-adrenal axis dysregulation. Our present study aimed to explore the neuroprotective potential of mangiferin against corticosterone-induced anxiety and depressive-like behaviour. METHODS: Corticosterone (40 mg/kg; subcutaneously) was administered once daily in swiss albino mice for 21 days...
April 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28401366/resistance-to-immunotherapy-clouds-in-a-bright-sky
#17
REVIEW
Gérard Milano
Two major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy...
April 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28398226/melatonin-reduces-angiogenesis-in-serous-papillary-ovarian-carcinoma-of-ethanol-preferring-rats
#18
Yohan Ricci Zonta, Marcelo Martinez, Isabel Cristina C Camargo, Raquel F Domeniconi, Luiz Antonio Lupi Júnior, Patricia Fernanda F Pinheiro, Russel J Reiter, Francisco Eduardo Martinez, Luiz Gustavo A Chuffa
Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28377795/crosstalk-between-tryptophan-metabolism-and-cardiovascular-disease-mechanisms-and-therapeutic-implications
#19
REVIEW
Gang Liu, Shuai Chen, Jin Zhong, Kunling Teng, Yulong Yin
The cardiovascular diseases (CVD) associated with the highest rates of morbidity are coronary heart disease and stroke, and the primary etiological factor leading to these conditions is atherosclerosis. This long-lasting inflammatory disease, characterized by how it affects the artery wall, results from maladaptive immune responses linked to the vessel wall. Tryptophan (Trp) is oxidized in a constitutive manner by tryptophan 2,3-dioxygenase in liver cells, and for alternative cell types, it is catalyzed in the presence of a differently inducible indoleamine 2,3-dioxygenase (IDO1) in the context of a specific pathophysiological environment...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28376268/ahr-mediates-an-anti-inflammatory-feed-back-mechanism-in-human-langerhans-cells-involving-fc%C3%AE%C2%B5ri-and-ido
#20
Susanne Koch, Tim J Stroisch, Julia Vorac, Nadine Herrmann, Nicole Leib, Sylvia Schnautz, Helene Kirins, Irmgard Förster, Heike Weighardt, Thomas Bieber
BACKGROUND: Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. OBJECTIVES: We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC...
April 4, 2017: Allergy
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