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T cells AND metabolism

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https://www.readbyqxmd.com/read/28738416/conditionally-immortal-slc4a11-mouse-corneal-endothelial-cell-line-recapitulates-disrupted-glutaminolysis-seen-in-slc4a11-mouse-model
#1
Wenlin Zhang, Diego G Ogando, Edward T Kim, Moon-Jung Choi, Hongde Li, Jason M Tenessen, Joseph A Bonanno
Purpose: To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. Methods: We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11-/- C57BL/6 mice...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28738017/distinct-oxysterol-requirements-for-positioning-na%C3%A3-ve-and-activated-dendritic-cells-in-the-spleen
#2
Erick Lu, Eric V Dang, Jeffrey G McDonald, Jason G Cyster
Correct positioning of dendritic cells (DCs) is critical for efficient pathogen encounter and antigen presentation. Epstein-Barr virus-induced gene 2 (EBI2) has been identified as a chemoattractant receptor required for naïve CD4(+)DCIR2(+) DC positioning in response to 7α,25-hydroxycholesterol (7α,25-HC). We now provide evidence that a second EBI2 ligand, 7α,27-HC, is involved in splenic DCIR2(+) DC positioning and homeostasis. Cyp27a1, the enzyme uniquely required for 7α,27-HC synthesis, is expressed by stromal cells in the region of naïve DC localization...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28737753/metabolic-control-of-the-scaffold-protein-tks5-in-tissue-invasive-proinflammatory-t-cells
#3
Yi Shen, Zhenke Wen, Yinyin Li, Eric L Matteson, Jison Hong, Jörg J Goronzy, Cornelia M Weyand
Pathogenic T cells in individuals with rheumatoid arthritis (RA) infiltrate non-lymphoid tissue sites, maneuver through extracellular matrix and form lasting inflammatory microstructures. Here we found that RA T cells abundantly express the podosome scaffolding protein TKS5, which enables them to form tissue-invasive membrane structures. TKS5 overexpression was regulated by the intracellular metabolic environment of RA T cells-specifically, by reduced glycolytic flux that led to deficiencies in ATP and pyruvate...
July 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#4
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28736203/oral-administration-of-visceral-adipose-tissue-antigens-ameliorates-metabolic-disorders-in-mice-and-elevates-visceral-adipose-tissue-resident-cd4-cd25-foxp3-regulatory-t-cells
#5
Xiangyu Chen, Dali Zhang, Xiaoling Chen, Gang Meng, Qian Zheng, Wenli Mai, Yuzhang Wu, Lilin Ye, Li Wang
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4(+)Foxp3(+) Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders...
July 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28736029/protective-role-of-apelin-against-cyclosporine-induced-renal-tubular-injury-in-rats
#6
J S Kim, J W Yang, B G Han, H J Kwon, J H Kim, S O Choi
BACKGROUND: Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. METHODS: Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28735627/inhibition-of-indoleamine-2-3-dioxygenase-activity-by-fatty-acids-and-prostaglandins-a-structure-function-analysis
#7
M Costabile, N K Bassal, J P Gerber, B P Hughes
Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28735466/comparative-metabolic-analysis-in-head-and-neck-cancer-and-the-normal-gingiva
#8
Nadine Fabienne Voelxen, Sebastian Blatt, Pascal Knopf, Maurice Henkel, Christina Appelhans, Leonardo A R Righesso, Andreas Pabst, Jutta Goldschmitt, Stefan Walenta, Andreas Neff, Wolfgang Mueller-Klieser, Thomas Ziebart
OBJECTIVES: Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients. MATERIALS AND METHODS: Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI)...
July 22, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28735358/il-10-and-tgf-%C3%AE-unbalanced-levels-in-neutrophils-contribute-to-increase-inflammatory-cytokine-expression-in-childhood-obesity
#9
Nayara I Medeiros, Rafael T Mattos, Carlos A Menezes, Rafaelle C G Fares, André Talvani, Walderez O Dutra, Fabrício Rios-Santos, Rodrigo Correa-Oliveira, Juliana A S Gomes
PURPOSE: Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. METHODS: We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. RESULTS: We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW)...
July 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28733845/genome-wide-identification-in-silico-characterization-and-expression-analysis-of-zip-like-genes-from-trichomonas-vaginalis-in-response-to-zinc-and-iron
#10
K G Fernández-Martín, M E Alvarez-Sánchez, V E Arana-Argáez, L C Alvarez-Sánchez, J C Lara-Riegos, J C Torres-Romero
Trace elements such as Zinc and Iron are essential components of metalloproteins and serve as cofactors or structural elements for enzymes involved in several important biological processes in almost all organisms. Because either excess or insufficient levels of Zn and Fe can be harmful for the cells, the homeostatic levels of these trace minerals must be tightly regulated. The Zinc regulated transporter, Iron regulated transporter-like Proteins (ZIP) comprise a diverse family, with several paralogues in diverse organisms and are considered essential for the Zn and Fe uptake and homeostasis...
July 21, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28733763/predictive-value-of-18-f-fdg-pet-ct-in-adults-with-t-cell-lymphoblastic-lymphoma-post-hoc-analysis-of-results-from-the-graall-lysa-llo3-trial
#11
Stéphanie Becker, Thomas Vermeulin, Anne-Ségolène Cottereau, Nicolas Boissel, Pierre Vera, Stéphane Lepretre
PURPOSE: We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). METHODS: This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUVmax), total metabolic tumour volume and total lesion glycolysis were measured at baseline...
July 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28733443/direct-metabolic-interrogation-of-dihydrotestosterone-biosynthesis-from-adrenal-precursors-in-primary-prostatectomy-tissues
#12
Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J Stephenson, Eric A Klein, Nima Sharifi
Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733264/the-impact-of-toxicities-on-first-year-outcomes-after-ex-vivo-cd34-selected-allogeneic-hematopoietic-cell-transplantation-in-adults-with-hematologic-malignancies
#13
Satyajit Kosuri, Diego Adrianzen Herrera, Michael Scordo, Gunjan L Shah, Christina Cho, Sean M Devlin, Molly A Maloy, Jimmy Nieves, Taylor Borrill, Dean C Carlow, Scott T Avecilla, Richard C Meagher, Richard J O'Reilly, Esperanza B Papadopoulos, Ann A Jakubowski, Guenther Koehne, Boglarka Gyurkocza, Hugo Castro-Malaspina, Brian C Shaffer, Roni Tamari, Sergio A Giralt, Miguel-Angel Perales
Factors that impact first year morbidity and mortality in adults undergoing myeloablative allogeneic hematopoietic cell transplantation with ex-vivo CD34+ selection have not been previously reported. We assessed all toxicities ≥ grade 3 from the start of conditioning to date of death, relapse, or last contact in 200 patients during the first year post-transplantation, identifying 1885 individual toxicities among 17 organ-based toxicity groups. The most prevalent toxicities in the 1(st) year were of infectious, metabolic, hematologic, oral/GI, hepatic, cardiac and pulmonary etiologies...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28733206/omics-based-identification-of-the-combined-effects-of-idiosyncratic-drugs-and-inflammatory-cytokines-on-the-development-of-drug-induced-liver-injury
#14
J Jiang, K Mathijs, L Timmermans, S M Claessen, A Hecka, J Weusten, R Peters, J H van Delft, J C S Kleinjans, D G J Jennen, T M de Kok
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733185/fdg-pet-parameters-as-predictors-of-pathologic-response-and-nodal-clearance-in-patients-with-stage-iii-non-small-cell-lung-cancer-receiving-neoadjuvant-chemoradiation-and-surgery
#15
Andrea L Arnett, Ann T Packard, Kristin Mara, Aaron S Mansfield, Dennis A Wigle, Michael G Haddock, Sean S Park, Kenneth R Olivier, Yolanda I Garces, Kenneth W Merrell
OBJECTIVE: Pathologic complete response (pCR) following neoadjuvant chemoradiation (CRT) is associated with improved outcomes in stage III non-small cell lung cancer. Conflicting results exist regarding the value of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pCR. This study evaluated the association between post-CRT FDG-PET and pCR using novel FDG-PET parameters. METHODS AND MATERIALS: This retrospective study included patients treated with CRT and resection...
April 19, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28732510/protective-and-therapeutic-role-of-2-carba-cyclic-phosphatidic-acid-in-demyelinating-disease
#16
Shinji Yamamoto, Kota Yamashina, Masaki Ishikawa, Mari Gotoh, Sosuke Yagishita, Kensuke Iwasa, Kei Maruyama, Kimiko Murakami-Murofushi, Keisuke Yoshikawa
BACKGROUND: Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death...
July 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28732499/association-between-serum-osteocalcin-and-glucose-lipid-metabolism-in-chinese-han-and-uygur-populations-with-type-2-diabetes-mellitus-in-xinjiang-two-cross-sectional-studies
#17
Yuan Chen, Qiang Zhao, Guoli Du, Yancheng Xu
BACKGROUND: Recent studies have shown osteocalcin (OC) plays an important role in regulating glucose and lipid metabolism. Thus, the aim of this study was to investigate the association of OC with glucose and lipid metabolism in patients with type 2 diabetes mellitus (T2DM) in the Chinese Han and Uygur population. METHODS: A total of 1397 T2DM patients (705 Han and 692 Uygur T2DM patients) were enrolled in the present study. Lipid profile, glucose metabolic indices and total OC (TOC) were measured...
July 21, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28731268/-13-c-metabolic-flux-profiling-of-pichia-pastoris-grown-in-aerobic-batch-cultures-on-glucose-revealed-high-relative-anabolic-use-of-tca-cycle-and-limited-incorporation-of-provided-precursors-of-branched-chain-amino-acids
#18
Meng Zhang, Xiao-Wei Yu, Yan Xu, Paula Jouhten, G V T Swapna, Ralf W Glaser, John F Hunt, Gaetano T Montelione, Hannu Maaheimo, Thomas Szyperski
Carbon metabolism of Crabtree negative yeast Pichia pastoris was profiled using (13) C NMR to delineate regulation during exponential growth and to study the import of two precursors for branched-chain amino acid biosynthesis, α-ketoisovalerate and α-ketobutyrate. Cells were grown in aerobic batch cultures containing (i) only glucose, (ii) glucose along with the precursors, or (iii) glucose and Val. The study provided the following new insights. First, (13) C flux ratio analyses of central metabolism reveal an unexpectedly high anaplerotic supply of the tricarboxylic acid cycle for a Crabtree negative yeast, and show that a substantial fraction of glucose catabolism proceeds through the pentose phosphate pathway...
July 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28730764/mtor-deregulation-in-oral-cavity-squamous-cell-carcinoma
#19
Nicholas S Mastronikolis, Evangelos Tsiambas, Theodoros A Papadas, Panagiotis P Fotiades, Athanasios T Papadas, Stylianos N Mastronikolis, Ioannis Kastanioudakis, Vasileios Ragos
Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF)...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729055/novel-1-2-dihydroquinazolin-2-ones-design-synthesis-and-biological-evaluation-against-trypanosoma-brucei
#20
ThanhTruc Pham, Madeline Walden, Christopher Butler, Rosario Diaz-Gonzalez, Guiomar Pérez-Moreno, Gloria Ceballos-Pérez, Veronica Gomez-Pérez, Raquel García-Hernández, Henry Zecca, Emma Krakoff, Brian Kopec, Ogar Ichire, Caden Mackenzie, Marika Pitot, Luis Miguel Ruiz, Francisco Gamarro, Dolores González-Pacanowska, Miguel Navarro, Amy B Dounay
In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability...
July 11, 2017: Bioorganic & Medicinal Chemistry Letters
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