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https://www.readbyqxmd.com/read/28551807/prohibitin-signaling-at-the-kidney-filtration-barrier
#1
Christina Ising, Paul T Brinkkoetter
The kidney filtration barrier consists of three well-defined anatomic layers comprising a fenestrated endothelium, the glomerular basement membrane (GBM) and glomerular epithelial cells, the podocytes. Podocytes are post-mitotic and terminally differentiated cells with primary and secondary processes. The latter are connected by a unique cell-cell contact, the slit diaphragm. Podocytes maintain the GBM and seal the kidney filtration barrier to prevent the onset of proteinuria. Loss of prohibitin-1/2 (PHB1/2) in podocytes results not only in a disturbed mitochondrial structure but also in an increased insulin/IGF-1 signaling leading to mTOR activation and a detrimental metabolic switch...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551698/glucose-metabolism-during-rotational-shift-work-in-healthcare-workers
#2
Anu Sharma, Marcello C Laurenti, Chiara Dalla Man, Ron T Varghese, Claudio Cobelli, Robert A Rizza, Aleksey Matveyenko, Adrian Vella
AIMS/HYPOTHESIS: Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose metabolism in humans. METHODS: We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28551194/effects-of-shortening-the-close-up-period-length-coupled-with-increased-supply-of-metabolizable-protein-on-performance-and-metabolic-status-of-multiparous-holstein-cows
#3
T Amirabadi Farahani, H Amanlou, M Kazemi-Bonchenari
This experiment was conducted to compare conventional (CON; 21 d) and shortened (SH; 10 d) close-up period, and evaluate the effect of shortened close-up period combined with feeding different metabolizable protein (MP) levels on dry matter (DM) intake, metabolic status, and performance of dairy cows. Forty-eight multiparous Holstein cows with similar parity, body weight (BW), and previous lactation milk yield were divided into 2 groups. The first group (n = 24) received the far-off diet from -60 to -21 d (CON), and the second group (n = 24) received same far-off diet from -60 to -10 d (SH) relative to expected parturition...
May 24, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28546645/fluorination-at-the-4-position-alters-the-substrate-behavior-of-l-glutamine-and-l-glutamate-implications-for-positron-emission-tomography-of-neoplasias
#4
Thomas M Jeitner, Eva Kristoferson, Juan A Azcona, John T Pinto, Clint Stalnecker, Jon W Erickson, Hank F Kung, Jianyong Li, Karl Ploessl, Arthur J L Cooper
Two 4-fluoro-L-glutamine diastereoisomers [(2S,4R)-4-FGln, (2S,4S)-4-FGln] were previously developed for positron emission tomography. Label uptake into two tumor cell types was greater with [(18)F](2S,4R)-4-FGln than with [(18)F](2S,4S)-4-FGln. In the present work we investigated the enzymology of two diastereoisomers of 4-FGln, two diastereoisomers of 4-fluoroglutamate (4-FGlu) (potential metabolites of the 4-FGln diastereoisomers) and another fluoro-derivative of L-glutamine [(2S,4S)-4-(3-fluoropropyl)glutamine (FP-Gln)]...
December 2016: Journal of Fluorine Chemistry
https://www.readbyqxmd.com/read/28546582/control-of-amino-acid-transport-coordinates-metabolic-reprogramming-in-t-cell-malignancy
#5
K M Grzes, M Swamy, J L Hukelmann, E Emslie, L V Sinclair, D A Cantrell
This study explores the regulation and importance of System L amino acid transport in a murine model of T cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28543637/evidence-of-the-immunomodulatory-role-of-dual-pi3k-mtor-inhibitors-in-graft-survival
#6
Valery Vilchez, Lilia Turcios, D Allan Butterfield, Mihail I Mitov, Cristin L Coquillard, Anthony J Brandon, Virgilius Cornea, Roberto Gedaly, Francesc Marti
The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of Rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative...
May 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28541707/identification-of-a-potent-selective-and-efficacious-phosphatidylinositol-3-kinase-%C3%AE-pi3k%C3%AE-inhibitor-for-the-treatment-of-immunological-disorders
#7
Qingjie Liu, Qing Shi, David Marcoux, Douglas G Batt, Lyndon Cornelius, Lan-Ying Qin, Zheming Ruan, James Neels, Myra Beaudoin Bertrand, Anurag S Srivastava, Ling Li, Robert Joseph Cherney, Hua Gong, Scott H Watterson, Carolyn Weigelt, Kathleen M Gillooly, Kim W McIntyre, Jenny H Xie, Mary T Obermeier, Aberra Fura, Bogdan Sleczka, Kevin Stefanski, R Marcus Fancher, Shweta Padmanabhan, Thatipamula Rp, Ipsit Kundu, Kallem Rajareddy, Rodney Smith, James K Hennan, Dezhi Xing, Jingsong Fan, Paul C Levesque, Qian Ruan, Sidney Pitt, Rosemary Zhang, Donna Pedicord, Jie Pan, Melissa Yarde, Hao Lu, Jonathan Lippy, Christine Goldstine, Stacey Skala, Richard A Rampulla, Arvind Mathur, Anuradha Gupta, Pirama Nayagam Arunachalam, John S Sack, Jodi K Muckelbauer, Mary Ellen Cvijic, Luisa M Salter-Cid, Rajeev S Bhide, Michael A Poss, John Hynes, Percy H Carter, John E Macor, Stefan Ruepp, Gary L Schieven, Joseph A Tino
PI3Kδ plays an important role controlling immune cell function and has therefore been identified as a potential target for the treatment of immunological disorders. This article highlights our work towards the identification of a potent, selective, and efficacious PI3Kδ inhibitor. Through careful SAR, the successful replacement of a polar pyrazole group by a simple chloro or trifluoromethyl group led to improved Caco-2 permeability, reduced Caco-2 efflux, reduced hERG PC activity, and increased selectivity profile while maintaining potency in the CD69 hWB assay...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28541359/potential-antiproliferative-activity-of-polyphenol-metabolites-against-human-breast-cancer-cells-and-their-urine-excretion-pattern-in-healthy-subjects-following-acute-intake-of-a-polyphenol-rich-juice-of-grumixama-eugenia-brasiliensis-lam
#8
L L Teixeira, G R Costa, F A Dörr, T P Ong, E Pinto, F M Lajolo, N M A Hassimotto
The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively...
May 25, 2017: Food & Function
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#9
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539291/-beneficial-effect-of-periodontal-therapy-on-insulin-resistance-and-lipid-metabolism-in-obese-rats-with-periodontitis
#10
Qiao-Xue Chai, Su-Lan Zhong, Jia Ni, Lei Chen, Lei Zhou, Jin-Cai Zhang
OBJECTIVE: To investigate the effect of periodontal therapy in controlling periodontitis and on insulin resistance and lipid metabolism in obese rats with periodontitis. METHODS: Sprague-Dawley rats were randomized into normal group (group C), obese group (group O), periodontitis combined with obesity group (group P) and periodontal treatment group (group T). The obese rats in groups P and T were subjected to ligation of the maxillary second molar with silk thread to induce experimental periodontitis, and the rats in group T received periodontal therapy after the ligation...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28538163/metabolic-signatures-of-t-cells-and-macrophages-in-rheumatoid-arthritis
#11
REVIEW
Cornelia M Weyand, Markus Zeisbrich, Jörg J Goronzy
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors...
May 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28537490/the-magnetic-field-of-magnetic-resonance-imaging-systems-does-not-affect-cells-labeled-with-micrometer-sized-iron-oxide-particles
#12
Martin Kluge, Annekatrin Leder, Karl Herbert Hillebrandt, Benjamin Struecker, Dominik Geisel, Timm Denecke, Rebeka Dalma Major, Anja Reutzel-Selke, Peter Tang, Steffen Lippert, Christian Schmidt, Johann Pratschke, Igor M Sauer, Nathanael Raschzok
INTRODUCTION: Labeling using iron oxide particles enables cell tracking via magnetic resonance imaging (MRI). However, the magnetic field can affect the particle-labeled cells. Here, we investigated the effects of a clinical MRI system on primary human hepatocytes labeled using micrometer-sized iron oxide particles (MPIOs). METHODS: HuH7 tumor cells were incubated with increasing concentrations of biocompatible, silica-based, micron-sized iron oxide-containing particles (sMPIO; 40 - 160 particles/cell)...
May 24, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28537488/capturing-human-na%C3%A3-ve-pluripotency-in-the-embryo-and-in-the-dish
#13
Ludovic Zimmerlin, Tea Soon Park, Elias T Zambidis
Although human embryonic stem cells (hESC) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to post-implantation lineage-primed murine epiblast stem cells (EpiSC) than to naïve pre-implantation ICM-derived mouse embryonic stem cells (ESC). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESC and human induced pluripotent stem cells (hiPSC) appear to lack many of the defining hallmarks of naïve mouse ESC...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28537232/-cd47-receptor-as-a-primary-target-for-cancer-therapy
#14
N M Ratnikova, Y N Lezhnin, E I Frolova, J E Kravchenko, S P Chumakov
Recently, a number of new highly efficient antibody-based anticancer therapeutics have emerged. These receptor-binding antibodies have beneficial toxicity profiles associated with relatively mild side effects. Therefore, the search for novel surface proteins that are present on cancer cells and play important metabolic or defensive roles has intensified. Additionally, the therapeutic stimulation of patient's immune system in order to aim its components, specifically, phagocytes and cytotoxic T-lymphocytes, at tumor cells is gaining traction...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28537058/unusual-suspects-in-the-development-of-obesity-induced-inflammation-and-insulin-resistance-nk-cells-inkt-cells-and-ilcs
#15
REVIEW
Beatriz Dal Santo Francisco Bonamichi, Jongsoon Lee
The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils...
May 22, 2017: Diabetes & Metabolism Journal
https://www.readbyqxmd.com/read/28535598/antarctic-seals-molecular-biomarkers-as-indicators-for-pollutant-exposure-health-effects-and-diet
#16
K Lehnert, L Weirup, K C Harding, T Härkönen, O Karlsson, J Teilmann
Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden...
May 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28535458/mtor-signaling-in-the-differentiation-and-function-of-regulatory-and-effector-t-cells
#17
REVIEW
Hu Zeng, Hongbo Chi
The mechanistic target of rapamycin (mTOR) signaling pathway integrates environmental signals and cellular metabolism to regulate T cell development, activation and differentiation. Recent studies reveal the importance of exquisite control of mTOR activity for proper T cell function, and detailed molecular mechanisms that regulate mTOR signaling in different T cell subsets. Here, we review the latest advances in our understanding of the mTOR pathway and its regulation in the differentiation and function of regulatory T cells and effector T cells...
May 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28535369/packing-on-the-pounds-in-response-to-bacterial-growth-conditions
#18
Sabih Rashid, Lesley T MacNeil
Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C. elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28533395/integrative-modeling-of-gene-and-genome-evolution-roots-the-archaeal-tree-of-life
#19
Tom A Williams, Gergely J Szöllősi, Anja Spang, Peter G Foster, Sarah E Heaps, Bastien Boussau, Thijs J G Ettema, T Martin Embley
A root for the archaeal tree is essential for reconstructing the metabolism and ecology of early cells and for testing hypotheses that propose that the eukaryotic nuclear lineage originated from within the Archaea; however, published studies based on outgroup rooting disagree regarding the position of the archaeal root. Here we constructed a consensus unrooted archaeal topology using protein concatenation and a multigene supertree method based on 3,242 single gene trees, and then rooted this tree using a recently developed model of genome evolution...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533125/markers-of-immune-mediated-inflammation-in-the-brains-of-young-adults-and-adolescents-with-type-1-diabetes-and-fatal-diabetic-ketoacidosis-is-there-a-difference
#20
William H Hoffman, Carol M Artlett, Dallas Boodhoo, Mary G F Gilliland, Luis Ortiz, Dries Mulder, David H T Tjan, Alvaro Martin, Alexandru Tatomir, Horea Rus
Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0...
May 19, 2017: Experimental and Molecular Pathology
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