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https://www.readbyqxmd.com/read/28646338/chemotherapy-induced-gastrointestinal-toxicity-is-associated-with-changes-in-serum-and-urine-metabolome-and-fecal-microbiota-in-male-sprague-dawley-rats
#1
Richard A Forsgård, Vannina G Marrachelli, Katri Korpela, Rafael Frias, Maria Carmen Collado, Riitta Korpela, Daniel Monleon, Thomas Spillmann, Pia Österlund
PURPOSE: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT...
June 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28644754/expression-of-enzymes-related-to-glucose-metabolism-in-non-small-cell-lung-cancer-and-prognosis
#2
Alexandra Giatromanolaki, Efthimios Sivridis, Stella Arelaki, Michael I Koukourakis
Purpose/Aim: Cancer cells are addicted to glycolytic anaerobic pathways, in presence or in absence of a functional Krebs' cycle (phenomenon Warburg). This metabolic predilection relies on both extracellular (impaired vascularization and oxygenation) and intracellular (oncogenic activation of genes) causes. MATERIALS AND METHODS: We investigated the expression and prognostic relevance of enzymes involved in the glucose absorption and metabolism, monocarboxylate transporter (MCT) expression, MCT1 and MCT2, pentose pathway (Glucose-6-phospahte dehydrogenase G6PD), glycogene synthesis (glycogene synthase GYS1), glycolysis (Hexokinase HXKII, phosphofructokinase PFK1, fructose biphosphate aldolase), fate of pyruvate (pyruvate dehydrogenase PDH, phosphorylated pPDH, PDH kinase PDK1, lactate dehydrogenase LDH5 and LDH1) and key Kreb's cycle enzymes (citrate synthase CSynth and isocitrate dehydrogenase IDH)...
June 23, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28636751/using-experimentation-to-understand-the-10-year-snowshoe-hare-cycle-in-the-boreal-forest-of-north-america
#3
C J Krebs, R Boonstra, S Boutin
Population cycles have long fascinated ecologists from the time of Charles Elton in the 1920s. The discovery of large population fluctuations in undisturbed ecosystems challenged the idea that pristine nature was in a state of balance. The 10-year cycle of snowshoe hares (Lepus americanus Erxleben) across the boreal forests of Canada and Alaska is a classic cycle, recognized by fur traders for more than 300 years. Since the 1930s ecologists have investigated the mechanisms that might cause these cycles. Proposed causal mechanisms have varied from sunspots to food supplies, parasites, diseases, predation, and social behaviour...
June 21, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28632748/trimetazidine-therapy-for-diabetic-mouse-hearts-subjected-to-ex-vivo-acute-heart-failure
#4
Emilene Breedt, Lydia Lacerda, M Faadiel Essop
Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1...
2017: PloS One
https://www.readbyqxmd.com/read/28630995/krebs-cycle
#5
Veneta Masson
No abstract text is available yet for this article.
June 20, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#6
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28615447/human-retinal-pigment-epithelium-cells-prefer-proline-as-a-nutrient-and-transport-metabolic-intermediates-to-the-retinal-side
#7
Jennifer R Chao, Kaitlen Knight, Abbi L Engel, Connor Jankowski, Yekai Wang, Megan A Manson, Haiwei Gu, Danijel Djukovic, Daniel Raftery, James B Hurley, Jianhai Du
Metabolite transport is a major function for the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with (13)C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC MS/MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient including glucose, taurine, lipids, vitamins, or other amino acids...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28604247/brucella-central-carbon-metabolism-an-update
#8
T Barbier, A Zúñiga-Ripa, S Moussa, H Plovier, J F Sternon, L Lázaro-Antón, R Conde-Álvarez, X De Bolle, M Iriarte, I Moriyón, J J Letesson
The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle...
June 12, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28602540/deficiencies-in-mitochondrial-dynamics-sensitize-caenorhabditis-elegans-to-arsenite-and-other-mitochondrial-toxicants-by-reducing-mitochondrial-adaptability
#9
Anthony L Luz, Tewodros R Godebo, Latasha L Smith, Tess C Leuthner, Laura L Maurer, Joel N Meyer
Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases...
June 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28599201/serum-metabolome-biomarkers-associate-low-level-environmental-perfluorinated-compound-exposure-with-oxidative-nitrosative-stress-in-humans
#10
Xiaofei Wang, Liangpo Liu, Weibing Zhang, Jie Zhang, Xiaoyan Du, Qingyu Huang, Meiping Tian, Heqing Shen
Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort...
June 6, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28593900/phellinus-rimosus-improves-mitochondrial-energy-status-and-attenuates-nephrotoxicity-in-diabetic-rats
#11
K A Rony, T A Ajith, Tony A Kuttikadan, R Blaze, K K Janardhanan
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation...
April 7, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28589520/role-of-mitochondria-in-methamphetamine-induced-dopaminergic-neurotoxicity-involvement-in-oxidative-stress-neuroinflammation-and-pro-apoptosis-a-review
#12
Eun-Joo Shin, Hai-Quyen Tran, Phuong-Tram Nguyen, Ji Hoon Jeong, Seung-Yeol Nah, Choon-Gon Jang, Toshitaka Nabeshima, Hyoung-Chun Kim
Methamphetamine (MA), an amphetamine-type psychostimulant, is associated with dopaminergic toxicity and has a high abuse potential. Numerous in vivo and in vitro studies have suggested that impaired mitochondria are critical in dopaminergic toxicity induced by MA. Mitochondria are important energy-producing organelles with dynamic nature. Evidence indicated that exposure to MA can disturb mitochondrial energetic metabolism by inhibiting the Krebs cycle and electron transport chain. Alterations in mitochondrial dynamic processes, including mitochondrial biogenesis, mitophagy, and fusion/fission, have recently been shown to contribute to dopaminergic toxicity induced by MA...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28584880/sulfate-radicals-enable-a-non-enzymatic-krebs-cycle-precursor
#13
Markus A Keller, Domen Kampjut, Stuart A Harrison, Markus Ralser
The evolutionary origins of the tricarboxylic acid cycle (TCA), or Krebs cycle, are so far unclear. Despite a few years ago, the existence of a simple non-enzymatic Krebs-cycle catalyst has been dismissed 'as an appeal to magic', citrate and other intermediates have meanwhile been discovered on a carbonaceous meteorite and do interconvert non-enzymatically. To identify the non-enzymatic Krebs cycle catalyst, we used combinatorial, quantitative high-throughput metabolomics to systematically screen iron and sulfate reaction milieus that orient on Archean sediment constituents...
March 13, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28576319/chloroformate-derivatization-for-tracing-the-fate-of-amino-acids-in-cells-and-tissues-by-multiple-stable-isotope-resolved-metabolomics-msirm
#14
Ye Yang, Teresa W-M Fan, Andrew N Lane, Richard M Higashi
Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment...
July 11, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28559800/key-metabolic-enzymes-underlying-astrocytic-upregulation-of-gabaergic-plasticity
#15
Przemysław T Kaczor, Jerzy W Mozrzymas
GABAergic plasticity is recognized as a key mechanism of shaping the activity of the neuronal networks. However, its description is challenging because of numerous neuron-specific mechanisms. In particular, while essential role of glial cells in the excitatory plasticity is well established, their involvement in GABAergic plasticity only starts to emerge. To address this problem, we used two models: neuronal cell culture (NC) and astrocyte-neuronal co-culture (ANCC), where we chemically induced long-term potentiation at inhibitory synapses (iLTP)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28554536/succinate-increased-in-metabolic-syndrome-activates-gpr91-receptor-signaling-in-urothelial-cells
#16
Abubakr H Mossa, Monica Velasquez Flores, Philippe G Cammisotto, Lysanne Campeau
Metabolic syndrome is associated with overactive bladder syndrome (OAB) and increased circulating levels of succinate, an intermediate of the Krebs cycle. The urothelium is an essential regulator of bladder muscle contraction. This study aimed to determine if GPR91, the succinate receptor, is expressed and functional in the bladder. Urothelial and smooth muscle cells (SMCs) were cultured and characterized. PCR revealed that urothelial cells express GPR91, twice as much as SMCs. Incubation of cells with succinate stimulated phosphorylation of ERK and JNK in urothelial cells...
May 26, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28552342/interplay-between-mitochondrial-metabolism-and-oxidative-stress-in-ischemic-stroke-an-epigenetic-connection
#17
REVIEW
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
The advent of epigenetics brought in a tectonic shift in the understanding of molecular basis of complex diseases like ischemic stroke (IS). Substantial scientific inquiry into the epigenetic basis of neurodegenerative diseases has bolstered the idea that altered carbon flux into central carbon metabolism and disturbed redox states govern the attendant transcriptional profiles through stochastic epigenetic changes. In view of an increasing understanding of the link between mitochondrial energy metabolism, oxidative stress and epigenetics in IS, the hitherto underappreciated 'neuroenergetics' is gaining sustained attention...
May 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28551782/mitochondrial-bioenergetics-and-dysfunction-in-failing-heart
#18
Freya L Sheeran, Salvatore Pepe
Energy insufficiency has been recognized as a key feature of systolic heart failure. Although mitochondria have long been known to sustain myocardial work energy supply, the capacity to therapeutically target mitochondrial bioenergetics dysfunction is hampered by a complex interplay of multiple perturbations that progressively compound causing myocardial failure and collapse. Compared to non-failing human donor hearts, activity rates of complexes I and IV, nicotinamide nucleotide transhydrogenase (NADPH-transhydrogenase, Nnt) and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase and aconitase are markedly decreased in end-stage heart failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28535516/citrate-anticoagulation-during-continuous-renal-replacement-therapy
#19
Davide Ricci, Laura Panicali, Maria Grazia Facchini, Elena Mancini
During extracorporeal dialysis, some anticoagulation strategy is necessary to prevent the coagulation of blood. Heparin has historically been used as an anticoagulant because of its efficacy combined with low cost. However, a variable incidence of hemorrhagic complications (5-30%) has been documented in patients undergoing continuous renal replacement therapy (CRRT) with heparin as an anticoagulant. Citrate has anticoagulation properties secondary to its ability to chelate calcium, which is necessary for the coagulation cascade...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28533563/why-do-the-boreal-forest-ecosystems-of-northwestern-europe-differ-from-those-of-western-north-america
#20
Rudy Boonstra, Harry P Andreassen, Stan Boutin, Jan Hušek, Rolf A Ims, Charles J Krebs, Christina Skarpe, Petter Wabakken
The boreal forest is one of the largest terrestrial biomes on Earth. Conifers normally dominate the tree layer across the biome, but other aspects of ecosystem structure and dynamics vary geographically. The cause of the conspicuous differences in the understory vegetation and the herbivore-predator cycles between northwestern Europe and western North America presents an enigma. Ericaceous dwarf shrubs and 3- to 4-year vole-mustelid cycles characterize the European boreal forests, whereas tall deciduous shrubs and 10-year snowshoe hare-lynx cycles characterize the North American ones...
September 1, 2016: Bioscience
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