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https://www.readbyqxmd.com/read/29667084/investigation-of-the-aryl-hydrocarbon-receptor-and-the-intrinsic-tumoral-component-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-primary-brain-tumors
#1
Anthony R Guastella, Sharon K Michelhaugh, Neil V Klinger, Hassan A Fadel, Sam Kiousis, Rouba Ali-Fehmi, William J Kupsky, Csaba Juhász, Sandeep Mittal
INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites...
April 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29666190/tryptophanyl-trna-synthetase-mediates-high-affinity-tryptophan-uptake-into-human-cells
#2
Miki Miyanokoshi, Takumi Yokosawa, Keisuke Wakasugi
The tryptophan (Trp) transport system has a high affinity and selectivity toward Trp, and has been reported to exist in both human and mouse macrophages. Although this system is highly expressed in interferon-γ (IFN-γ)-treated cells and indoleamine 2,3-dioxygenase 1 (IDO1)-expressing cells, its identity remains incompletely understood. Tryptophanyl-tRNA synthetase (TrpRS) is also highly expressed in IFN-γ-treated cells and also has high affinity and selectivity for Trp. Here, we investigated the effects of human TrpRS expression on Trp uptake into IFN-γ-treated human THP-1 monocytes or HeLa cells...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#3
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29651242/discovery-of-novel-inhibitors-of-indoleamine-2-3-dioxygenase-1-through-structure-based-virtual-screening
#4
Guoqing Zhang, Jing Xing, Yulan Wang, Lihao Wang, Yan Ye, Dong Lu, Jihui Zhao, Xiaomin Luo, Mingyue Zheng, Shiying Yan
Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29615752/endothelial-indoleamine-2-3-dioxygenase-1-regulates-the-placental-vascular-tone-and-is-deficient-in-intrauterine-growth-restriction-and-pre-eclampsia
#5
Pablo Zardoya-Laguardia, Astrid Blaschitz, Birgit Hirschmugl, Ingrid Lang, Sereina A Herzog, Liudmila Nikitina, Martin Gauster, Martin Häusler, Mila Cervar-Zivkovic, Eva Karpf, Ghassan J Maghzal, Chris P Stanley, Roland Stocker, Christian Wadsack, Saša Frank, Peter Sedlmayr
Indoleamine 2,3-dioxygenase-1 (IDO1) mediates the degradation of L-tryptophan (L-Trp) and is constitutively expressed in the chorionic vascular endothelium of the human placenta with highest levels in the microvasculature. Given that endothelial expression of IDO1 has been shown to regulate vascular tone and blood pressure in mice under the condition of systemic inflammation, we asked whether IDO1 is also involved in the regulation of placental blood flow and if yes, whether this function is potentially impaired in intrauterine growth restriction (IUGR) and pre-eclampsia (PE)...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29611873/the-role-of-ido-il-10-and-tgf-%C3%AE-in-the-hcv-associated-chronic-hepatitis-liver-cirrhosis-and-hepatocellular-carcinoma
#6
Ruonan Yang, Nan Gao, Qian Chang, Xianchun Meng, Wanhai Wang
Indoleamine-2, 3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10 and TGF-β were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST and total bilirubin (TBil) were collected from clinical databases...
April 3, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29607498/1-l-mt-an-ido-inhibitor-prevented-colitis-associated-cancer-by-inducing-cdc20-inhibition-mediated-mitotic-death-of-colon-cancer-cells
#7
Xiuting Liu, Wei Zhou, Xin Zhang, Yang Ding, Qianming Du, Rong Hu
Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29595533/ido1-expression-is-associated-with-immune-tolerance-and-poor-prognosis-in-patients-with-surgically-resected-esophageal-cancer
#8
Yuki Kiyozumi, Yoshifumi Baba, Kazuo Okadome, Taisuke Yagi, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Yoshihiro Komohara, Hideo Baba
OBJECTIVES: To evaluate the relationship between indoleamine 2, 3-dioxygenase (IDO1) expression and tumoral immune status and clinical outcome in esophageal cancer. SUMMARY BACKGROUND DATA: IDO1 is a primary enzyme that generates immunosuppressive metabolites such as tryptophan and kynurenine. Like the PD-1/PD-L1 pathway, IDO1 plays a major role in tumor immunology and is a potential immune-based therapeutic target. METHODS: The expressions of IDO1, CD8 (a marker of cytotoxic T cells), FOXP3 [a marker of regulatory T cells (Treg)], and PD-L1 in 305 curatively resected esophageal cancers were evaluated by immunostaining...
March 27, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/29576845/immunomodulatory-effects-of-diterpene-quinone-derivatives-from-the-roots-of-horminum-pyrenaicum-in-human-pbmc
#9
K Becker, S Schwaiger, B Waltenberger, D Fuchs, C K Pezzei, H Schennach, H Stuppner, J M Gostner
Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN- γ -) dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN- γ -related signaling is strongly sensitive to oxidative triggers...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29565744/il-27-expression-and-responsiveness-in-human-uterine-epithelial-cells-and-fibroblasts-in-vitro-and-the-role-of-estradiol
#10
Mickey V Patel, Zheng Shen, Richard M Rossoll, Charles R Wira
Interleukin (IL)-27 is a pleiotropic cytokine that regulates multiple aspects of innate and adaptive immunity, but whose role in immune protection of the female reproductive tract is unknown. Although not constitutively expressed by human uterine epithelial cells and fibroblasts in culture, IL-27 secretion was upregulated after treatment with the viral ligand poly (I:C) in a type I interferon (IFN)-dependent manner, with higher levels measured in fibroblasts than epithelial cells. Estradiol increased poly (I:C)-induced IL-27 production by fibroblasts, but not epithelial cells...
March 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29563329/deficiency-of-immunoregulatory-indoleamine-2-3-dioxygenase-1in-juvenile-diabetes
#11
Ciriana Orabona, Giada Mondanelli, Maria T Pallotta, Agostinho Carvalho, Elisa Albini, Francesca Fallarino, Carmine Vacca, Claudia Volpi, Maria L Belladonna, Maria G Berioli, Giulia Ceccarini, Susanna Mr Esposito, Raffaella Scattoni, Alberto Verrotti, Alessandra Ferretti, Giovanni De Giorgi, Sonia Toni, Marco Cappa, Maria C Matteoli, Roberta Bianchi, Davide Matino, Alberta Iacono, Matteo Puccetti, Cristina Cunha, Silvio Bicciato, Cinzia Antognelli, Vincenzo N Talesa, Lucienne Chatenoud, Dietmar Fuchs, Luc Pilotte, Benoît Van den Eynde, Manuel C Lemos, Luigina Romani, Paolo Puccetti, Ursula Grohmann
A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29559741/indoleamine-2-3-dioxygenase-in-endometrial-cancer-a-targetable-mechanism-of-immune-resistance-in-mismatch-repair-deficient-and-intact-endometrial-carcinomas
#12
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29558201/inhibition-of-hypoxia-associated-response-and-kynurenine-production-in-response-to-hyperbaric-oxygen-as-mechanisms-involved-in-protection-against-experimental-cerebral-malaria
#13
Marcele F Bastos, Ana Carolina A V Kayano, João Luiz Silva-Filho, João Conrado K Dos-Santos, Carla Judice, Yara C Blanco, Nathaniel Shryock, Michelle K Sercundes, Luana S Ortolan, Carolina Francelin, Juliana A Leite, Rafaella Oliveira, Rosa M Elias, Niels O S Câmara, Stefanie C P Lopes, Letusa Albrecht, Alessandro S Farias, Cristina P Vicente, Claudio C Werneck, Selma Giorgio, Liana Verinaud, Sabrina Epiphanio, Claudio R F Marinho, Pritesh Lalwani, Rogerio Amino, Julio Aliberti, Fabio T M Costa
Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29551031/-brain-derived-neurotrophic-factor-enhances-the-role-of-mesenchymal-stem-cells-in-inhibiting-follicular-helper-t-cells
#14
S N Yang, X Pu, S L Xiang, J P Chen, L Pei
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29548707/inducible-indoleamine-2-3-dioxygenase-1-and-programmed-death-ligand-1-expression-as-the-potency-marker-for-mesenchymal-stromal-cells
#15
Qingdong Guan, Yun Li, Tanner Shpiruk, Swaroop Bhagwat, Donna A Wall
AIM: Establishment of a potency assay in the manufacturing of clinical-grade mesenchymal stromal cells (MSCs) has been a challenge due to issues of relevance to function, timeline and variability of responder cells. In this study, we attempted to develop a potency assay for MSCs. METHODS: Clinical-grade bone marrow-derived MSCs were manufactured. The phenotype and immunosuppressive functions of the MSCs were evaluated based on the International Society for Cellular Therapy guidelines...
March 13, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29547726/expression-of-indoleamine-2-3-dioxygenase-1-as-transcript-and-protein-in-the-healthy-and-diseased-equine-endometrium
#16
Sandra Schöniger, Hilke Gräfe, Franziska Richter, Heinz-Adolf Schoon
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) acts immunomodulatory and restricts bacterial growth. In the uterus of women and mice, it likely contributes to tissue homeostasis and disease pathogenesis. Pregnancy failure in mares is often caused by endometritis and endometrosis. The pathogenesis of nonsuppurative endometritis and endometrosis is still uncertain. To the authors' knowledge, no information on IDO1 expression in the equine endometrium is published. Aim of this study was to examine the presence of IDO1 as transcripts and proteins in the healthy and diseased endometrium of 25 mares and to determine its cellular expression...
March 5, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29545920/hypoxia-enhances-indoleamine-2-3-dioxygenase-production-in-dendritic-cells
#17
Xiang Song, Yan Zhang, Li Zhang, Wengang Song, Lixin Shi
Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2 ) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29543650/tryptophan-catabolites-along-the-indoleamine-2-3-dioxygenase-pathway-as-a-biological-link-between-depression-and-cancer
#18
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29531094/immune-modulating-enzyme-indoleamine-2-3-dioxygenase-is-effectively-inhibited-by-targeting-its-apo-form
#19
Micah T Nelp, Patrick A Kates, John T Hunt, John A Newitt, Aaron Balog, Derrick Maley, Xiao Zhu, Lynn Abell, Alban Allentoff, Robert Borzilleri, Hal A Lewis, Zeyu Lin, Steven P Seitz, Chunhong Yan, John T Groves
For cancer cells to survive and proliferate, they must escape normal immune destruction. One mechanism by which this is accomplished is through immune suppression effected by up-regulation of indoleamine 2,3-dioxygenase (IDO1), a heme enzyme that catalyzes the oxidation of tryptophan to N -formylkynurenine. On deformylation, kynurenine and downstream metabolites suppress T cell function. The importance of this immunosuppressive mechanism has spurred intense interest in the development of clinical IDO1 inhibitors...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29531009/-communication-melatonin-hyperhomocysteinemia-thioretinaco-ozonide-adenosylmethionine-and-mitochondrial-dysfunction-in-aging-and-dementia
#20
Kilmer S McCully
The indoleamine hormone melatonin is synthesized by the pineal gland, controls circadian rhythm, and is dependent upon adenosyl methionine for enzymatic synthesis of melatonin from N-acetyl serotonin. Pineal melatonin secretion declines dramatically with aging and dementia. Elevated plasma homocysteine is a risk factor for atherosclerosis and Alzheimer's disease, and the marked decline in adenosyl methionine with aging leads to dysregulation of methionine metabolism and hyperhomocysteinemia. Thioretinaco ozonide is a disulfonium complex formed from thioretinamide, cobalamin, and ozone, which binds the alpha and gamma-phosphate groups of adenosine triphosphate (ATP) and oxygen in the process of oxidative phosphorylation within mitochondria...
January 2018: Annals of Clinical and Laboratory Science
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