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https://www.readbyqxmd.com/read/28545736/amino-acid-sensing-and-degrading-pathways-in-immune-regulation
#1
Ursula Grohmann, Giada Mondanelli, Maria L Belladonna, Ciriana Orabona, Maria T Pallotta, Alberta Iacono, Paolo Puccetti, Claudia Volpi
Indoleamine 2,3-dioxygenases (IDOs) - belonging in the heme dioxygenase family and degrading tryptophan - are responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD(+)). As such, they are expressed by a variety of invertebrate and vertebrate species. In mammals, IDO1 has remarkably evolved to expand its functions, so to become a prominent homeostatic regulator, capable of modulating infection and immunity in multiple ways, including local tryptophan deprivation, production of biologically active tryptophan catabolites, and non-enzymatic cell-signaling activity...
May 18, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#2
Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute towards a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) pathways...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28540583/circadian-rhythm-in-melatonin-release-as-a-mechanism-to-reinforce-the-temporal-organization-of-the-circadian-system-in-crayfish
#3
Leonor Mendoza-Vargas, Armida Báez-Saldaña, Ramón Alvarado, Beatriz Fuentes-Pardo, Edgar Flores-Soto, Héctor Solís-Chagoyán
Melatonin (MEL) is a conserved molecule with respect to its synthesis pathway and functions. In crayfish, MEL content in eyestalks (Ey) increases at night under the photoperiod, and this indoleamine synchronizes the circadian rhythm of electroretinogram amplitude, which is expressed by retinas and controlled by the cerebroid ganglion (CG). The aim of this study was to determine whether MEL content in eyestalks and CG or circulating MEL in hemolymph (He) follows a circadian rhythm under a free-running condition; in addition, it was tested whether MEL might directly influence the spontaneous electrical activity of the CG...
June 2017: Invertebrate Neuroscience: IN
https://www.readbyqxmd.com/read/28533959/preservation-media-durations-and-cell-concentrations-of-short-term-storage-affect-key-features-of-human-adipose-derived-mesenchymal-stem-cells-for-therapeutic-application
#4
Fengli Zhang, Huaijuan Ren, Xiaohu Shao, Chao Zhuang, Yantian Chen, Nianmin Qi
BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) have shown great potential in the treatment of various diseases. However, the optimum short-term storage condition of ADSCs in 2∼8 °C is rarely reported. This study aimed at optimizing a short-term storage condition to ensure the viability and function of ADSCs before transplantation. METHODS: Preservation media and durations of storage were evaluated by cell viability, apoptosis, adhesion ability and colony-forming unit (CFU) capacity of ADSCs...
2017: PeerJ
https://www.readbyqxmd.com/read/28529635/synthesis-of-5-18-f-fluoro-%C3%AE-methyl-tryptophan-new-trp-based-pet-agents
#5
Benjamin C Giglio, Haiyang Fei, Mengzhe Wang, Hui Wang, Liu He, Huijuan Feng, Zhanhong Wu, Hongjian Lu, Zibo Li
Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of (18)F into the tryptophan aromatic ring...
2017: Theranostics
https://www.readbyqxmd.com/read/28526475/identification-and-preliminary-structure-activity-relationships-of-1-indanone-derivatives-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#6
Dingding Gao, Yingxia Li
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein...
May 10, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28523098/incb24360-epacadostat-a-highly-potent-and-selective-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-for-immuno-oncology
#7
Eddy W Yue, Richard Sparks, Padmaja Polam, Dilip Modi, Brent Douty, Brian Wayland, Brian Glass, Amy Takvorian, Joseph Glenn, Wenyu Zhu, Michael Bower, Xiangdong Liu, Lynn Leffet, Qian Wang, Kevin J Bowman, Michael J Hansbury, Min Wei, Yanlong Li, Richard Wynn, Timothy C Burn, Holly K Koblish, Jordan S Fridman, Tom Emm, Peggy A Scherle, Brian Metcalf, Andrew P Combs
A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28515923/expression-of-cxcr-4-and-ido-in-human-colorectal-cancer-an-immunohistochemical-approach
#8
Masaichi Ogawa, Michiaki Watanabe, Takuo Hasegawa, Kohei Ichihara, Kazuhiko Yoshida, Katsuhiko Yanaga
C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is involved in lymphocyte trafficking. Recent studies have demonstrated that, during pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a key role in suppressing the maternal T-cell response against the fetus. In the present study, the significance of CXCR4 and IDO expression in human colorectal cancer (CRC) has been investigated by immunohistochemical assay, and their association with survival was analyzed...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#9
Tang Tang, Herman S Gill, Annie Ogasawara, Jeff N Tinianow, Alexander N Vanderbilt, Simon-Peter Williams, Georgia Hatzivassiliou, Sharla White, Wendy Sandoval, Kevin DeMent, Mengling Wong, Jan Marik
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[(18)F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET)...
May 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28508554/intestinal-epithelial-suppressor-of-cytokine-signaling-3-socs3-impacts-on-mucosal-homeostasis-in-a-model-of-chronic-inflammation
#10
Elisabeth J Shaw, Emily E Smith, Jayde Whittingham-Dowd, Matthew D Hodges, Kathryn J Else, Rachael J Rigby
INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor, limiting intestinal epithelial cell (IEC) proliferation in acute inflammation, and tumour growth, but little is known regarding its role in mucosal homeostasis. Resistance to the intestinal helminth Trichuris muris relies on an "epithelial escalator" to expel the parasite. IEC turnover is restricted by parasite-induced indoleamine 2,3-dioxygenase (IDO). METHODS: Mice with or without conditional knockout of SOCS3 were infected with T...
May 15, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28502732/swimming-exercise-prevents-behavioural-disturbances-induced-by-an-intracerebroventricular-injection-of-amyloid-%C3%AE-1-42-peptide-through-modulation-of-cytokine-nf-kappab-pathway-and-indoleamine-2-3-dioxygenase-in-mouse-brain
#11
Leandro Cattelan Souza, Cristiano R Jesse, Lucian Del Fabbro, Marcelo de Gomes, André Tiago Rossito Goes, Carlos Borges Filho, Cristiane Luchese, Albanin Aparecida Mielniczki Pereira, Silvana Peterini Boeira
Emerging evidence indicates that the activation of indoleamine-2,3-dioxygenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in amyloid-beta (Aβ1-42)-neurotoxicity and Alzheimer's disease (AD) pathogenesis. Physical exercise has been considered an effective intervention in AD, attenuating or limiting their progression. Nevertheless, the neurobiological mechanisms underlying the neuroprotective effects of exercise have not yet been fully elucidated. In present study, we investigated the protective effect of an 8-week swimming training (ST) exercise on cognitive and non-cognitive functions and its role in modulating biomarkers of KYN pathway, before an intracerebroventricular (i...
May 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28500770/the-role-of-melatonin-in-the-neurodevelopmental-etiology-of-schizophrenia-a-study-in-human-olfactory-neuronal-precursors
#12
Tania Galván-Arrieta, Citlali Trueta, Montserrat G Cercós, Marcela Valdés-Tovar, Salvador Alarcón, Julian Oikawa, Horacio Zamudio-Meza, Gloria Benítez-King
Dim light exposure of the mother during pregnancy has been proposed as one of the environmental factors that affect the fetal brain development in schizophrenia. Melatonin circulating levels are regulated by the environmental light/dark cycle. This hormone stimulates neuronal differentiation in the adult brain. However, little is known about its role in the fetal human brain development. Olfactory neuronal precursors (ONPs) are useful for studying the physiopathology of neuropsychiatric diseases because they mimic all the stages of neurodevelopment in culture...
May 13, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28498717/melatonin-as-a-versatile-molecule-to-design-novel-multitarget-hybrids-against-neurodegeneration
#13
Eva Ramos, Javier Egea, Cristóbal de Los Ríos, José Marco-Contelles, Alejandro Romero
Melatonin is an indoleamine produced mainly in the pineal gland. The natural decline of melatonin levels with aging strongly contributes to the development of neurodegenerative disorders. Pleiotropic actions displayed by melatonin prevent several processes involved in neurodegeneration such as neuroinflammation, oxidative stress, excitotoxicity and/or apoptosis. This review focuses on a number of melatonin hybrids resulting from the juxtaposition of tacrine, berberine, tamoxifen, curcumin, N,N-dibenzyl(N-methyl)amine, among others, with potential therapeutic effects for the treatment of neurodegenerative diseases...
May 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28498425/gene-silencing-of-indoleamine-2-3-dioxygenase-hinders-tumor-growth-through-angiogenesis-inhibition
#14
Jinfeng Pan, Keng Yuan, Shanshan Peng, Yanqin Huang, Yujuan Zhang, Yinying Hu, Yuanyuan Feng, Yanmei Shi, Yanling Liu, Hongmei Wang, Nanjin Zhou, Weiping Min
The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in various types of tumors, but the relationship between IDO1 and tumor angiogenesis needs further delineation. We aimed to clarify the relationship between tumor angiogenesis and IDO1 expression, and to explore the possibility of IDO1-targeting molecular therapy for lung cancer. For the first time, we found that silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro cancer cell invasion and migration. We further demonstrated that knockdown of IDO1 decreased the formation of vasculogenic mimicry...
April 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28490020/maternal-inflammation-results-in-altered-tryptophan-metabolism-in-rabbit-placenta-and-fetal-brain
#15
Monica Williams, Zhi Zhang, Elizabeth Nance, Julia L Drewes, Wojciech G Lesniak, Sarabdeep Singh, Diane C Chugani, Kannan Rangaramanujam, David R Graham, Sujatha Kannan
Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28488390/mesenchymal-stem-cells-protect-from-acute-liver-injury-by-attenuating-hepatotoxicity-of-liver-nkt-cells-in-inos-and-ido-dependent-manner
#16
Marina Gazdic, Bojana Simovic Markovic, Ljubica Vucicevic, Tamara Nikolic, Valentin Djonov, Nebojsa Arsenijevic, Vladimir Trajkovic, Miodrag L Lukic, Vladislav Volarevic
The effects of mesenchymal stem cells (MSCs) on phenotype and function of natural killer T (NKT) cells, is not understood. We used concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced liver injury to evaluate effects of MSCs on NKT-dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A- and α-GalCer-mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated influx of inflammatory (T-bet(+) TNF-α, IFN-γ producing and GATA3(+) , IL-4-producing) liver NKT cells and down-regulated TNF-α, IFN-γ and IL-4 levels in the sera...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28488123/ido-pten-expressing-tregs-and-control-of-antigen-presentation-in-the-murine-tumor-microenvironment
#17
REVIEW
David H Munn, Madhav D Sharma, Theodore S Johnson, Paulo Rodriguez
The tumor microenvironment is profoundly immunosuppressive. This creates a major barrier for attempts to combine immunotherapy with conventional chemotherapy or radiation, because the tumor antigens released by these cytotoxic agents are not cross-presented in an immunogenic fashion. In this Focused Research Review, we focus on mouse preclinical studies exploring the role of immunosuppressive Tregs expressing the PTEN lipid phosphatase, and the links between PTEN+ Tregs and the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO)...
May 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28485810/expression-of-indoleamine-2-3-dioxygenase-in-pregnant-mice-correlates-with-cd4-cd25-foxp3-t-regulatory-cells
#18
L-L Yu, Y-H Zhang, F-X Zhao
OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) initiated tryptophan degradation in the placenta has a role in the prevention of allogeneic fetus rejection by T-cells. The present study aimed to investigate the relationship between IDO and CD4+CD25+Foxp3+ T cells in pregnant mice. MATERIALS AND METHODS: The percentage of CD4+CD25+Foxp3+ T cells in peripheral blood mononuclear cells (PBMC) and IDO mRNA levels were detected in pregnant mice. The non-pregnant mice were used as control in this study...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28481310/effects-of-melatonin-and-its-analogues-on-pancreatic-inflammation-enzyme-secretion-and-tumorigenesis
#19
REVIEW
Jolanta Jaworek, Anna Leja-Szpak, Katarzyna Nawrot-Porąbka, Joanna Szklarczyk, Michalina Kot, Piotr Pierzchalski, Marta Góralska, Piotr Ceranowicz, Zygmunt Warzecha, Artur Dembinski, Joanna Bonior
Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N¹-acetyl-N¹-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28481005/mesenchymal-stem-cells-attenuate-acute-liver-injury-by-altering-ratio-between-il-17-producing-and-regulatory-nkt-cells
#20
Neda Milosavljevic, Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Jasmin Nurkovic, Zana Dolicanin, Valentin Djonov, Miodrag L Lukic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune-mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and NKT cells, major interleukin (IL)-17 producing cells in acute liver injury, is still unknown. By using two well established murine models of neutrophil and NKT cell mediated acute liver failure (induced by Carbon tetrachloride (CCl4 ) and alphagalactoceramide (α-GalCer)), we investigated molecular and cellular mechanisms involved in MSC-mediated modulation of IL-17 signaling during acute liver injury...
May 8, 2017: Liver Transplantation
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