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https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#1
Kuan-Ting Liu, Yao-Hua Liu, Hsin-Liang Liu, Inn-Wen Chong, Meng-Chi Yen, Po-Lin Kuo
Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear...
December 6, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27914477/in-vitro-rescue-of-genital-strains-of-chlamydia-trachomatis-from-interferon-%C3%AE-and-tryptophan-depletion-with-indole-positive-but-not-indole-negative-prevotella-spp
#2
Noa Ziklo, Wilhelmina M Huston, Kuong Taing, Mohammad Katouli, Peter Timms
BACKGROUND: The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan...
December 3, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#3
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#4
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27899931/melatonin-in-plants-and-plant-culture-systems-variability-stability-and-efficient-quantification
#5
Lauren A E Erland, Abhishek Chattopadhyay, Andrew Maxwell P Jones, Praveen K Saxena
Despite growing evidence of the importance of melatonin and serotonin in the plant life, there is still much debate over the stability of melatonin, with extraction and analysis methods varying greatly from lab to lab with respect to time, temperature, light levels, extraction solvents, and mechanical disruption. The variability in methodology has created conflicting results that confound the comparison of studies to determine the role of melatonin in plant physiology. We here describe a fully validated method for the quantification of melatonin, serotonin and their biosynthetic precursors: tryptophan, tryptamine and N-acetylserotonin by liquid chromatography single quadrupole mass spectrometry (LC-MS) in diverse plant species and tissues...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#6
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27889626/absence-of-kynurenine-3-monooxygenase-reduces-mortality-of-acute-viral-myocarditis-in-mice
#7
Hisako Kubo, Masato Hoshi, Akihiro Mouri, Chieko Tashita, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO(-/-) mice and KMO(+/+) mice...
November 23, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27889479/ido1-is-an-integral-mediator-of-inflammatory-neovascularization
#8
Arpita Mondal, Courtney Smith, James B DuHadaway, Erika Sutanto-Ward, George C Prendergast, Arturo Bravo-Nuevo, Alexander J Muller
The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6)...
November 9, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27884595/melatonin-protection-against-age-related-cardiac-pathology
#9
REVIEW
Gaia Favero, Lorenzo Franceschetti, Barbara Buffoli, Moghadasian H Mohammed, Russel J Reiter, Luigi Fabrizio Rodella, Rita Rezzani
Aging is a complex and progressive process that involves physiological and metabolic deterioration in every organ and system. Cardiovascular diseases are one of the most common causes of mortality and morbidity among elderly subjects worldwide. Most age-related cardiovascular disorders can be influenced by modifiable behaviours such as a healthy diet rich in fruit and vegetables, avoidance of smoking, increased physical activity and reduced stress. The role of diet in prevention of various disorders is a well-established factor, which has an even more important role in the geriatric population...
November 21, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27880901/stress-kinase-gcn2-controls-the-proliferative-fitness-and-trafficking-of-cytotoxic-t-cells-independent-of-environmental-amino-acid-sensing
#10
Lee-Ann Van de Velde, Xi-Zhi J Guo, Lidija Barbaric, Amber M Smith, Thomas H Oguin, Paul G Thomas, Peter J Murray
GCN2 is one of four "stress kinases" that block translation by phosphorylating eIF2α. GCN2 is thought to bind uncharged tRNAs to "sense" amino acid availability. In mammals, myeloid cells expressing indoleamine dioxygenases locally deplete tryptophan, which is detected by GCN2 in T cells to cause proliferative arrest. GCN2-deficient T cells were reported to ectopically enter the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed to T cell receptor (TCR) transgenic backgrounds, we found GCN2 is essential for induction of stress target genes such as CHOP...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27878564/the-role-of-b7-family-costimulatory-molecules-and-indoleamine-2-3-dioxygenase-in-primary-sj%C3%A3-gren-s-syndrome-and-systemic-sclerosis
#11
Nóra Legány, László Berta, László Kovács, Attila Balog, Gergely Toldi
B7 costimulatory molecules are present on antigen-presenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a molecule with important immunoregulatory functions. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2 molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28, CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults and 9 SSc and 15 pSS patients using flow cytometry...
November 23, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27876634/individual-and-interactive-sex-specific-effects-of-acute-restraint-and-systemic-ifn-%C3%AE-treatment-on-neurochemistry
#12
Darcy Litteljohn, Chris Rudyk, Sara Razmjou, Zach Dwyer, Shuaib Syed, Shawn Hayley
Compelling evidence supports the involvement of the pro-inflammatory cytokines, IL-6, IFN-α and TNF-α in depression and related stress-associated pathologies. A role has also been suggested for the Th1-type cytokine, IFN-γ, with most mechanistic accounts focusing on the cytokine's capacity to induce indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is surprisingly little evidence directly linking IFN-γ to alterations of brain regional monoamine activity and HPA axis functioning...
November 19, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27870896/m30-antagonizes-indoleamine-2-3-dioxygenase-activation-and-neurodegeneration-induced-by-corticosterone-in-the-hippocampus
#13
Chun-Sing Lam, George Lim Tipoe, Johnny Kong-Ching Wong, Moussa B H Youdim, Man-Lung Fung
Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT)...
2016: PloS One
https://www.readbyqxmd.com/read/27863031/discovery-of-a-novel-scaffold-as-an-indoleamine-2-3-dioxygenase%C3%A2-1-ido1-inhibitor-based-on-the-pyrrolopiperazinone-alkaloid-longamide%C3%A2-b
#14
Zenyu Shiokawa, Emi Kashiwabara, Daisuke Yoshidome, Koichi Fukase, Shinsuke Inuki, Yukari Fujimoto
Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan...
November 11, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27861788/phenotypically-resembling-myeloid-derived-suppressor-cells-are-increased-in-children-with-hiv-and-exposed-infected-with-mycobacterium-tuberculosis
#15
Nelita Du Plessis, Ruschca Jacobs, Andrea Gutschmidt, Zhuo Fang, Paul D van Helden, Manfred B Lutz, Anneke C Hesseling, Gerhard Walzl
Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27860276/regulation-of-kynurenine-biosynthesis-during-influenza-virus-infection
#16
Lana Gaelings, Sandra Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B Lorey, Janne Tynell, Liesbeth Vande Ginste, Ronan Le Goffic, Matthew S Miller, Marika Kuisma, Varpu Marjomäki, Jef De Brabander, Sampsa Matikainen, Tuula A Nyman, Dennis Bamford, Xavier Saelens, Ilkka Julkunen, Henrik Paavilainen, Veijo Hukkanen, Vidya Velagapudi, Denis E Kainov
Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus-host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis...
November 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27859042/hla-g-promotes-myeloid-derived-suppressor-cell-mdsc-accumulation-and-suppressive-activity-during-human-pregnancy-through-engagement-of-the-receptor-ilt4
#17
Natascha Köstlin, Anna-Lena Ostermeir, Bärbel Spring, Julian Schwarz, Alexander Marmé, Christina B Walter, Christian F Poets, Christian Gille
Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27855744/melatonin-natural-health-products-and-supplements-presence-of-serotonin-and-significant-variability-of-melatonin-content
#18
Lauren A E Erland, Praveen K Saxena
STUDY OBJECTIVES: Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin. METHODS: A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin...
November 14, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27836863/checkpoint-proteins-in-pediatric-brain-and-extracranial-solid-tumors-opportunities-for-immunotherapy
#19
Eric K Ring, James M Markert, G Yancey Gillespie, Gregory K Friedman
Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of long term morbidities. While these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27833846/mesenchymal-stromal-cells-derived-from-whole-human-umbilical-cord-exhibit-similar-properties-to-those-derived-from-wharton-s-jelly-and-bone-marrow
#20
Claire Mennan, Sharon Brown, Helen McCarthy, Eleni Mavrogonatou, Dimitris Kletsas, John Garcia, Birender Balain, James Richardson, Sally Roberts
Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time-consuming tissue dissection. MSC can be obtained easily via briefly digesting complete segments of the umbilical cord, likely containing heterogenous or mixed populations of MSC (MC-MSC). MC-MSC are generally less well characterized than WJ-MSC, but nevertheless represent a potentially valuable population of MSC...
November 2016: FEBS Open Bio
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