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https://www.readbyqxmd.com/read/28805262/mesenchymal-stem-cells-attenuate-liver-fibrosis-by-suppressing-th17-cells
#1
Neda Milosavljevic, Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Jasmin Nurkovic, Zana Dolicanin, Nemanja Jovicic, Ilija Jeftic, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSCs)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1μL/g intraperitoneally) twice/week for 1 month. MSCs (1x10(6) ), or MSC-conditioned medium (MSC-CM) were intravenously injected 24h after CCl4 and on every 7(th) day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining and RT-PCR. Serum levels of cytokines, IDO and kynurenine were determined by ELISA...
August 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28801236/frailty-status-in-older-adults-is-related-to-alterations-in-indoleamine-2-3-dioxygenase-1-and-guanosine-triphosphate-cyclohydrolase-i%C3%A2-enzymatic-pathways
#2
Diego Marcos-Pérez, María Sánchez-Flores, Ana Maseda, Laura Lorenzo-López, José C Millán-Calenti, Barbara Strasser, Johanna M Gostner, Dietmar Fuchs, Eduardo Pásaro, Vanessa Valdiglesias, Blanca Laffon
BACKGROUND: Frailty is a multidimensional syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalization, and death in the elderly. It is based on the interplay of physiological, psychological, social, and environmental factors. OBJECTIVES: Because aging involves a detrimental immune response, this work aimed to assess the possible role of chronic low-grade immune stimulation on frailty status in the elderly...
August 8, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#3
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28792876/nad-deficiency-congenital-malformations-and-niacin-supplementation
#4
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie
BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#5
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28790848/the-status-of-immunosuppression-in-patients-with-stage-iiib-or-iv-non-small-cell-lung-cancer-correlates-with-the-clinical-characteristics-and-response-to-chemotherapy
#6
Yuan Wang, Guo-Fang Hu, Zhe-Hai Wang
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28789949/reduced-hippocampal-il-10-expression-altered-monoaminergic-activity-and-anxiety-and-depressive-like-behavior-in-female-mice-subjected-to-chronic-social-instability-stress
#7
Ainitze Labaka, Eneritz Gómez-Lázaro, Oscar Vegas, Joana Pérez-Tejada, Amaia Arregi, Larraitz Garmendia
Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity...
August 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28782636/embryo-yolk-sac-membrane-kynurenine-formamidase-of-l-tryptophan-to-nad-pathway-as-a-primary-target-for-organophosphorus-insecticides-opi-in-opi-induced-nad-associated-avian-teratogenesis
#8
Josef Seifert
The objective of this study was to provide in ovo evidence for the proposed role of kynurenine formamidase of l-tryptophan to NAD(+) pathway in embryo yolk sac membranes as a primary target for organophosphorus insecticide (OPI) teratogens in OPI-induced NAD-associated avian teratogenesis. Slices prepared from yolk sac membranes or embryo livers of chicken eggs treated with the OPI dicrotophos and/or methyl parathion were incubated with l-tryptophan. Yolk sac membrane slices metabolized l-tryptophan in the pathway to NAD(+) before that function was established in livers...
August 4, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28762741/suppressive-effect-of-ginsenoside-rg3-against-lipopolysaccharide-induced-depression-like-behavior-and-neuroinflammation-in-mice
#9
An Kang, Tong Xie, Dong Zhu, Jinjun Shan, Liuqing Di, Xiao Zheng
Ginsenoside Rg3 (Rg3), a major active ingredient enriched in red ginseng, possesses well-confirmed immunoregulatory effects. Immune disturbance is a common trigger and aggravating factor of depression. The aim of this study was to explore the effects of Rg3 on lipopolysaccharide (LPS)-induced depression-like behavior in mice and the involvement of immune regulation. Pretreatment with Rg3 (i.g., 20 and 40 mg/kg) effectively ameliorated LPS (i.p., 0.83 mg/kg) induced body weight loss, anorexia, and immobility time in both the tail suspension test and the forced swimming test...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28758944/interactions-between-the-kynurenine-and-the-endocannabinoid-system-with-special-emphasis-on-migraine
#10
REVIEW
Gábor Nagy-Grócz, Ferenc Zádor, Szabolcs Dvorácskó, Zsuzsanna Bohár, Sándor Benyhe, Csaba Tömböly, Árpád Párdutz, László Vécsei
Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28758405/blood-metabolic-signatures-of-body-mass-index-a-targeted-metabolomics-study-in-the-epic-cohort
#11
Marion Carayol, Michael F Leitzmann, Pietro Ferrari, Raul Zamora-Ros, David Achaintre, Magdalena Stepien, Julie A Schmidt, Ruth C Travis, Kim Overvad, Anne Tjønneland, Louise Hansen, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Ursula Bachlechner, Antonia Trichopoulou, Christina Bamia, Domenico Palli, Claudia Agnoli, Rosario Tumino, Paolo Vineis, Salvatore Panico, J Ramón Quirós, Emilio Sanchez-Cantalejo, José María Huerta, Eva Ardanaz, Larraitz Arriola, Antonio Agudo, Jan Nilsson, Olle Melander, Bas Bueno-de-Mesquita, Petra H Peeters, Nick Wareham, Kay-Tee Khaw, Mazda Jenab, Timothy J Key, Augustin Scalbert, Sabina Rinaldi
OBJECTIVE: Metabolomic is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary)...
July 31, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28758106/neopterin-as-a-biomarker-of-immune-response-in-cancer-patients
#12
REVIEW
Bohuslav Melichar, Martina Spisarová, Marie Bartoušková, Lenka Kujovská Krčmová, Lenka Javorská, Hana Študentová
With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28756310/peroxyl-radical-and-photo-oxidation-of-glucose-6-phosphate-dehydrogenase-generates-cross-links-and-functional-changes-via-oxidation-of-tyrosine-and-tryptophan-residues
#13
Fabian Leinisch, Michele Mariotti, Martin Rykaer, Camilo Lopez-Alarcon, Per Hägglund, Michael J Davies
Protein oxidation is a frequent event as a result of the high abundance of proteins in biological samples and the multiple processes that generate oxidants. The reactions that occur are complex and poorly understood, but can generate major structural and functional changes on proteins. Current data indicate that pathophysiological processes and multiple human diseases are associated with the accumulation of damaged proteins. In this study we investigated the mechanisms and consequences of exposure of the key metabolic enzyme glucose-6-phosphate dehydrogenase (G6PDH) to peroxyl radicals (ROO(•)) and singlet oxygen ((1)O2), with particular emphasis on the role of Trp and Tyr residues in protein cross-linking and fragmentation...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28754152/cerebrospinal-fluid-kynurenine-and-kynurenic-acid-concentrations-are-associated-with-coma-duration-and-long-term-neurocognitive-impairment-in-ugandan-children-with-cerebral-malaria
#14
Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert O Opoka, Paul Bangirana, Carl M Sellgren, Ronny Wickström, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy C John
BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed...
July 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28751584/kynurenines-tryptophan-s-metabolites-in-exercise-inflammation-and-mental-health
#15
REVIEW
Igor Cervenka, Leandro Z Agudelo, Jorge L Ruas
Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28750999/pigmentary-analysis-of-eggs-of-the-silkworm-bombyx-mori
#16
Haiyan Zhang, Ying Lin, Guanwang Shen, Xue Tan, Chao Lei, Wei Long, Hongling Liu, Yandi Zhang, Yinying Xu, Jinxin Wu, Jianjian Gu, Qingyou Xia, Ping Zhao
Ommochromes are major pigments involved in coloration of eggs, eyes, wings, and epidermis of insects. Bombyx mori (silkworm) eggs contain a mixture of ommochrome pigments and their precursors. Here, we analyzed the pigment composition of every egg color strain using egg color mutants (w-2, pe, and re) and wild-type strains (dazao and C108) by using full wavelength scanning and high-performance liquid chromatography. We identified ommochrome pigments and their precursors in pigment extracts from non-diapause eggs and diapause eggs, and found that the quantities of ommochrome precursor 3-hydroxy-kynurenine were much higher in the diapause eggs...
July 24, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28748226/peripheral-kynurenine-3-monooxygenase-deficiency-as-a-potential-risk-factor-for-metabolic-syndrome-in-schizophrenia-patients
#17
Gregory Oxenkrug, Marieke van der Hart, Julien Roeser, Paul Summergrad
Increased predisposition of schizophrenia patients (SP) to development of obesity and insulin resistance suggested common signaling pathway between metabolic syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase (KMO), enzyme catalyzing formation of 3-hydroxykynurenine (3-HK) from kynurenine (Kyn), a tryptophan (Trp) metabolite, might contribute to development of MetS as suggested by non-expression of KMO genes in human fat tissue and elevated serum concentrations of Kyn and its metabolites, kynurenic (KYNA) and anthranilic (ANA) acids, in diabetic patients and Zucker fatty rats (ZFR)...
2017: Integr Clin Med
https://www.readbyqxmd.com/read/28740612/3-hydroxykynurenine-a-tryptophan-metabolite-generated-during-the-infection-is-active-against-trypanosoma-cruzi
#18
Carolina P Knubel, Constanza Insfran, Fernando F Martinez, Cintia Diaz Lujan, Ricardo E Fretes, Martin G Theumer, Laura Cervi, Claudia C Motran
The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28740260/richer-gut-microbiota-with-distinct-metabolic-profile-in-hiv-infected-elite-controllers
#19
Jan Vesterbacka, Javier Rivera, Kajsa Noyan, Mariona Parera, Ujjwal Neogi, Malu Calle, Roger Paredes, Anders Sönnerborg, Marc Noguera-Julian, Piotr Nowak
Gut microbiota dysbiosis features progressive HIV infection and is a potential target for intervention. Herein, we explored the microbiome of 16 elite controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative controls. We found that the number of observed genera and richness indices in fecal microbiota were significantly higher in EC versus naive. Genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were more abundant in EC, whereas Blautia and Anaerostipes were depleted...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738373/neuroprogression-in-schizophrenia-and-psychotic-disorders-the-possible-role-of-inflammation
#20
Norbert Müller
Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e...
2017: Modern Trends in Pharmacopsychiatry
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