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https://www.readbyqxmd.com/read/29430355/microbial-communities-associated-with-the-co-metabolism-of-free-cyanide-and-thiocyanate-under-alkaline-conditions
#1
Lukhanyo Mekuto, Seteno Karabo Obed Ntwampe, John Baptist N Mudumbi
This study focused on the identification of free cyanide (CDO) and thiocyanate (TDO) degrading microbial communities using a culture-dependent and independent approach. Culturable microbial species were isolated from the CDOs (n = 13) and TDOs (n = 18). The CDOs were largely dominated by Bacillus sp. while the TDOs were dominated by Bacillus sp., Klebsiella oxytoca, Providencia sp. and Pseudomonas sp. However, 16S rRNA amplicon gene-sequencing revealed the complexity and diversity of the microbial communities in contrast to the organisms that were detected using culture-dependent technique...
February 2018: 3 Biotech
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#2
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29413421/inflammatory-reprogramming-with-ido1-inhibitors-turning-immunologically-unresponsive-cold-tumors-hot
#3
REVIEW
George C Prendergast, Arpita Mondal, Souvik Dey, Lisa D Laury-Kleintop, Alexander J Muller
We discuss how small-molecule inhibitors of the tryptophan (Trp) catabolic enzyme indoleamine 2,3-dioxygenase (IDO) represent a vanguard of new immunometabolic adjuvants to safely enhance the efficacy of cancer immunotherapy, radiotherapy, or 'immunogenic' chemotherapy by leveraging responses to tumor neoantigens. IDO inhibitors re-program inflammatory processes to help clear tumors by blunting tumor neovascularization and restoring immunosurveillance. Studies of regulatory and effector pathways illuminate IDO as an inflammatory modifier...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#4
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29302770/modulating-tumor-immunology-by-inhibiting-indoleamine-2-3-dioxygenase-ido-recent-developments-and-first-clinical-experiences
#5
Diwakar Davar, Nathan Bahary
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated...
January 4, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#6
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29065237/a-new-polymer-electron-acceptor-based-on-thiophene-s-s-dioxide-unit-for-organic-photovoltaics
#7
Bin Meng, Junhui Miao, Jun Liu, Lixiang Wang
For polymer solar cells (PSCs), efficient polymer electron acceptors are always based on strong electron-withdrawing imide unit or boron-nitrogen coordinative bond (B←N). In this paper, a new polymer electron acceptor based on thiophene-S,S-dioxide (TDO) unit is reported. The polymer electron acceptor, PBDT-TDO, consists of alternating TDO unit and 4,8-bis(alkylthienyl)-2-yl]benzo[1,2-b:4,5-b']dithiophene (BDT) unit. For comparison, a control polymer with alternating BDT unit and thiophene unit has also been synthesized...
October 24, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29030243/the-inhibition-of-the-kynurenine-pathway-prevents-behavioral-disturbances-and-oxidative-stress-in-the-brain-of-adult-rats-subjected-to-an-animal-model-of-schizophrenia
#8
Gislaine Z Réus, Indianara R T Becker, Giselli Scaini, Fabricia Petronilho, Jean P Oses, Rima Kaddurah-Daouk, Luciane B Ceretta, Alexandra I Zugno, Felipe Dal-Pizzol, João Quevedo, Tatiana Barichello
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
October 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28963438/dlx3-promotes-bone-marrow-mesenchymal-stem-cells-proliferation-through-h19-mir-675-axis
#9
Na Zhao, Li Zeng, Yang Liu, Dong Han, Haochen Liu, Jian Xu, Yuxi Jiang, Cuiying Li, Tao Cai, Hailan Feng, Yixiang Wang
The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis...
September 28, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28904628/tibial-derotational-osteotomies-in-two-neuromuscular-populations-comparing-cerebral-palsy-with-myelomeningocele
#10
R M Thompson, S Ihnow, L Dias, V Swaroop
PURPOSE: To review the outcomes of tibial derotational osteotomies (TDOs) as a function of complication and revision surgery rates comparing a cohort of children with myelodysplasia to a cohort with cerebral palsy (CP). METHODS: A chart review was completed on TDOs performed in a tertiary referral centre on patients with myelodysplasia or CP between 1985 and 2013 in patients aged > 5 years with > 2 years follow-up. Charts were reviewed for demographics, direction/degree of derotation, complications and need for re-derotation...
August 1, 2017: Journal of Children's Orthopaedics
https://www.readbyqxmd.com/read/28809552/characterization-of-2-oxindole-forming-heme-enzyme-mare-expanding-the-functional-diversity-of-the-tryptophan-dioxygenase-superfamily
#11
Yuyang Zhang, Yi Zou, Nelson L Brock, Tingting Huang, Yingxia Lan, Xiaozheng Wang, Zixin Deng, Yi Tang, Shuangjun Lin
3-Substituted 2-oxindoles are important structural motifs found in many biologically active natural products and pharmaceutical lead compounds. Here, we report an enzymatic formation of the 3-substituted 2-oxindoles catalyzed by MarE in the maremycin biosynthetic pathway in Streptomyces sp. B9173. MarE is a homologue of Fe(II)/heme-dependent tryptophan 2,3-dioxygenases (TDOs). Typical TDOs usually catalyze the insertion of two oxygen atoms from O2 into an indole ring to generate N-formylkynurenine (NFK)-like products...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28659861/the-effect-of-systemic-nitroglycerin-administration-on-the-kynurenine-pathway-in-the-rat
#12
Gábor Nagy-Grócz, Klaudia F Laborc, Gábor Veres, Attila Bajtai, Zsuzsanna Bohár, Dénes Zádori, Annamária Fejes-Szabó, Eleonóra Spekker, László Vécsei, Árpád Párdutz
The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#13
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
September 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28637419/pharmacological-inhibitors-of-nad-biosynthesis-as-potential-an-ticancer-agents
#14
Stephanie Lucas, Claire Soave, Ghazal Nabil, Zainab Sabry Othman Ahmed, Guohua Chen, Hossny Awad El-Banna, Q Ping Dou, Jian Wang
BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics through inhibition of cancer metabolism. Nicotinamide Adenine Dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer...
2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28628786/btex-and-naphthalene-degrading-bacterium-microbacterium-esteraromaticum-strain-sbs1-7-isolated-from-estuarine-sediment
#15
Akanit Wongbunmak, Sansanee Khiawjan, Manop Suphantharika, Thunyarat Pongtharangkul
In this study, a non-pathogenic, BTEX-degrading Microbacterium esteraromaticum SBS1-7 was isolated from estuarine sediment in Thailand via an enrichment technique. M. esteraromaticum SBS1-7 was able to degrade all six BTEX components, in both liquid medium and soil slurry system, when BTEX was supplied as an individual component or a mixture. It exhibited a high level of tolerance towards a wide range of hydrocarbons and also utilized alkanes and naphthalene. Detection of metabolites produced during BTEX and naphthalene degradation revealed highly extensive biodegradation pathways used by M...
June 9, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28626554/tuning-the-polarity-of-charge-carriers-using-electron-deficient-thiophenes
#16
Jonathan Z Low, Brian Capozzi, Jing Cui, Sujun Wei, Latha Venkataraman, Luis M Campos
Thiophene-1,1-dioxide (TDO) oligomers have fascinating electronic properties. We previously used thermopower measurements to show that a change in charge carrier from hole to electron occurs with increasing length of TDO oligomers when single-molecule junctions are formed between gold electrodes. In this article, we show for the first time that the dominant conducting orbitals for thiophene/TDO oligomers of fixed length can be tuned by altering the strength of the electron acceptors incorporated into the backbone...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#17
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 to a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO)...
October 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28469468/kynurenine-pathway-of-tryptophan-metabolism-regulatory-and-functional-aspects
#18
REVIEW
Abdulla A-B Badawy
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate)...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28465467/indoleamine-2-3-dioxygenase-1-deficiency-attenuates-ccl4-induced-fibrosis-through-th17-cells-down-regulation-and-tryptophan-2-3-dioxygenase-compensation
#19
Weichao Zhong, Lei Gao, Zhenting Zhou, Haiyan Lin, Chun Chen, Peng Huang, Weiliang Huang, Chuying Zhou, Shaohui Huang, Linghui Nie, Ye Liu, Youming Chen, Daqiao Zhou, Zhiping Lv
Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular rate-limiting enzyme in the metabolism of tryptophan along the kynurenine pathway, subsequently mediating the immune response; however, the role of IDO1 in liver fibrosis and cirrhosis is still unclear. In this study, we investigated the role of IDO1 in the development of hepatic fibrosis and cirrhosis. Patients with hepatitis B virus-induced cirrhosis and healthy volunteers were enrolled. For animals, carbon tetrachloride (CCl4) was used to establish liver fibrosis in wild-type and IDO1 knockout mice...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459584/role-of-the-dark-2ag-state-in-donor-acceptor-copolymers-as-a-pathway-for-singlet-fission-a-dmrg-study
#20
Jiajun Ren, Qian Peng, Xu Zhang, Yuanping Yi, Zhigang Shuai
The mechanism of intramolecular singlet fission in donor-acceptor-type copolymers, especially the role of the dark 2Ag state, is not so clear. In this Letter, the electronic structure of the benzodithiophene (B)-thiophene-1,1-dioxide (TDO) copolymer is calculated by density matrix renormalization group theory with the Pariser-Parr-Pople model. We find that the dark 2Ag state is the lowest singlet excited state and is nearly degenerate with the 1Bu state. So, a fast internal conversion from 1Bu to 2Ag state is highly possible...
May 3, 2017: Journal of Physical Chemistry Letters
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