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HUMAN METABOLOM

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https://www.readbyqxmd.com/read/29328914/rewiring-of-the-fruit-metabolome-in-tomato-breeding
#1
Guangtao Zhu, Shouchuang Wang, Zejun Huang, Shuaibin Zhang, Qinggang Liao, Chunzhi Zhang, Tao Lin, Mao Qin, Meng Peng, Chenkun Yang, Xue Cao, Xu Han, Xiaoxuan Wang, Esther van der Knaap, Zhonghua Zhang, Xia Cui, Harry Klee, Alisdair R Fernie, Jie Luo, Sanwen Huang
Humans heavily rely on dozens of domesticated plant species that have been further improved through intensive breeding. To evaluate how breeding changed the tomato fruit metabolome, we have generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes from hundreds of tomato genotypes. The combined results illustrate how breeding globally altered fruit metabolite content. Selection for alleles of genes associated with larger fruits altered metabolite profiles as a consequence of linkage with nearby genes...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29325475/investigation-of-the-mechanisms-of-genkwa-flos-hepatotoxicity-by-a-cell-metabolomics-strategy-combined-with-serum-pharmacology-in-hl-7702-liver-cells
#2
Zhipeng Wang, Yuanyuan Zhang, Quanli Liu, Linjia Sun, Mingming Lv, Peipei Yu, Xiaohui Chen
1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study. 2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed...
January 11, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29322364/changes-in-neutrophil-metabolism-upon-activation-and-aging
#3
Barbara Christine Richer, Natallia Salei, Tamás Laskay, Karsten Seeger
Neutrophil activation is an important mechanism of host defense against pathogens. Chronic inflammation and autoimmunity are often associated with abnormalities in phenotype and functions of neutrophils. Since effector functions of immune cells during inflammation are tightly linked to their metabolic state, changes in neutrophil metabolome upon activation have been investigated in this study. Human neutrophils from healthy blood donors (n = 6) were treated either with tumor necrosis factor α (TNF-α) or lipopolysaccharide (LPS), whereas untreated neutrophils were used as control...
January 10, 2018: Inflammation
https://www.readbyqxmd.com/read/29321378/glutamine-derived-2-hydroxyglutarate-is-associated-with-disease-progression-in-plasma-cell-malignancies
#4
Wilson I Gonsalves, Vijay Ramakrishnan, Taro Hitosugi, Toshi Ghosh, Dragan Jevremovic, Tumpa Dutta, Dhananjay Sakrikar, Xuan-Mai Petterson, Linda Wellik, Shaji K Kumar, K Sreekumaran Nair
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29317762/carnitine-palmitoyltransferase-1c-regulates-cancer-cell-senescence-through-mitochondria-associated-metabolic-reprograming
#5
Yongtao Wang, Yixin Chen, Lihuan Guan, Huizheng Zhang, Yaoyao Huang, Caroline H Johnson, Zeming Wu, Frank J Gonzalez, Aiming Yu, Peng Huang, Ying Wang, Shouhui Yang, Pan Chen, Xiaomei Fan, Min Huang, Huichang Bi
Cellular senescence is a fundamental biological process that has profound implications in cancer development and therapeutics, but the underlying mechanisms remain elusive. Here we show that carnitine palmitoyltransferase 1C (CPT1C), an enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation, plays a major role in the regulation of cancer cell senescence through mitochondria-associated metabolic reprograming. Metabolomics analysis suggested alterations in mitochondria activity, as revealed by the marked decrease in acylcarnitines in senescent human pancreatic carcinoma PANC-1 cells, indicating low CPT1C activity...
January 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29316320/human-microbiota-blood-group-antigens-and-disease
#6
REVIEW
D Rose Ewald, Susan C J Sumner
Far from being just "bugs in our guts," the microbiota interacts with the body in previously unimagined ways. Research into the genome and the microbiome has revealed that the human body and the microbiota have a long-established but only recently recognized symbiotic relationship; homeostatic balance between them regulates body function. That balance is fragile, easily disturbed, and plays a fundamental role in human health-our very survival depends on the healthy functioning of these microorganisms. Increasing rates of cardiovascular, autoimmune, and inflammatory diseases, as well as epidemics in obesity and diabetes in recent decades are believed to be explained, in part, by unintended effects on the microbiota from vaccinations, poor diets, environmental chemicals, indiscriminate antibiotic use, and "germophobia...
January 9, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29299125/serum-metabolomic-profiling-of-human-gastric-cancer-and-its-relationship-with-the-prognosis
#7
Daguang Wang, Wei Li, Qi Zou, Lei Yin, Yechao Du, Jingkai Gu, Jian Suo
Objective: This study was aimed to investigate serum metabolites in gastric cancer (GC) patients and their relationships with the prognosis of GC in order to find potential specific serum biomarkers for GC. Methods: Blood samples of 125 GC patients of unifocal GC at initial stage and 38 healthy people recruited in our hospital from September 2008 to August 2009 were analyzed by using high performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (HPLCESI/Q-TOFMS)...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29299119/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#8
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stephanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombes, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombes
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296929/red-blood-cell-metabolism-in-down-syndrome-hints-on-metabolic-derangements-in-aging
#9
Rachel Culp-Hill, Connie Zheng, Julie A Reisz, Keith Smith, Angela Rachubinski, Travis Nemkov, Eric Butcher, Ross Granrath, Kirk C Hansen, Joaquín M Espinosa, Angelo D'Alessandro
Red blood cells (RBCs) are the most abundant cell in the human body. During their ∼120-day life span in the circulatory system, RBCs release oxygen to all human tissues while being exposed to tissue metabolic activity. Owing to the relative simplicity of their intrinsic metabolism and the abundance of metabolite transporters in RBC membranes, the metabolism of mature erythrocytes indirectly mirrors systemic metabolic homeostasis and its alterations as a function of physiological factors, such as aging. Trisomy 21 (T21), the etiological factor of Down syndrome (DS), has been shown to cause chronic autoinflammation, promoting alterations in RBC life span, size (macrocytosis), and redox homeostasis...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296771/red-blood-cells-in-hemorrhagic-shock-a-critical-role-for-glutaminolysis-in-fueling-alanine-transamination-in-rats
#10
Julie A Reisz, Anne L Slaughter, Rachel Culp-Hill, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Erik D Peltz, Kirk C Hansen, Anirban Banerjee, Angelo D'Alessandro
Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295987/discovery-of-human-cell-selective-effector-molecules-using-single-cell-multiplexed-activity-metabolomics
#11
David C Earl, P Brent Ferrell, Nalin Leelatian, Jordan T Froese, Benjamin J Reisman, Jonathan M Irish, Brian O Bachmann
Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29291405/enhanced-glycometabolism-as-a-mechanism-of-nqo1-potentiated-growth-of-nsclc-revealed-by-metabolomic-profiling
#12
Xuefang Cheng, Fang Liu, Huiying Liu, Guangji Wang, Haiping Hao
NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, has been considered as a potential poor prognostic biomarker and a promising therapeutic target for patients with non-small cell lung cancer (NSCLC) due to its frequent overexpression and significantly increased activity in NSCLC. Previous studies have shown that depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. However, the underlying mechanisms whereby NQO1 potentiates proliferation have not been fully understood...
December 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29290782/hypothesis-induction-of-biomarkers-for-detection-of-colonic-neoplasms
#13
Michael Bordonaro, Darina Lazarova
The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29290411/cmpf-a-metabolite-formed-upon-prescription-omega-3-acid-ethyl-ester-supplementation-prevents-and-reverses-steatosis
#14
Kacey J Prentice, Stacy G Wendell, Ying Liu, Judith A Eversley, Sonia R Salvatore, Haneesha Mohan, Sydney L Brandt, Andrew C Adams, X Serena Wang, David Wei, Garret A FitzGerald, Timothy B Durham, Craig D Hammond, Kyle W Sloop, Carsten Skarke, Francisco J Schopfer, Michael B Wheeler
Prescription ω-3 fatty acid ethyl ester supplements are commonly used for the treatment of hypertriglyceridemia. However, the metabolic profile and effect of the metabolites formed by these treatments remain unknown. Here we utilized unbiased metabolomics to identify 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) as a significant metabolite of the ω-3-acid ethyl ester prescription Lovaza™ in humans. Administration of CMPF to mice before or after high-fat diet feeding at exposures equivalent to those observed in humans increased whole-body lipid metabolism, improved insulin sensitivity, increased beta-oxidation, reduced lipogenic gene expression, and ameliorated steatosis...
December 19, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29289672/a-multi-omics-analysis-reveals-metabolic-reprogramming-in-thp-1-cells-upon-treatment-with-the-contact-allergen-dncb
#15
Franz Mussotter, Sarah Potratz, Jan Budczies, Andreas Luch, Andrea Haase
Dendritic cell (DC) activation by contact allergens is one of the key steps in the development of allergic contact dermatitis (ACD). Recent evidence suggests that metabolic reprogramming is a prerequisite for the activation of DCs, macrophages and monocytes. Therefore, we used an integrated approach by combining proteomics and metabolomics to investigate the metabolism of human THP-1 cells in response to the strong contact allergen, 2,4-dinitrochlorobenzene (DNCB). Cells were treated with 5, 10 and 20μM DNCB for 4, 8, and 24h, respectively...
December 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29287419/bioaccessibility-of-phenolic-compounds-following-in-vitro-large-intestine-fermentation-of-nuts-for-human-consumption
#16
Gabriele Rocchetti, Giulia Chiodelli, Gianluca Giuberti, Luigi Lucini
A bioaccessibility study of polyphenols after in vitro simulated large intestine fermentation was carried out on edible nuts. Raw nuts were also analysed for total phenolic content and antioxidant potential, considering both bound and free phenolics. The highest phenolic content was found in walnuts, followed by pistachios extracts (596.9 and 410.1 mg gallic acid equivalents 100 g-1, respectively). Consistently, the total antioxidant capacity was highest in walnuts (3689.7 μM trolox equivalents 100 g-1) followed by peanuts and pistachios (3169...
April 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29285820/maldi-imaging-detects-endogenous-digoxin-in-glioblastoma-cells-infected-by-zika-virus-would-it-be-the-oncolytic-key
#17
Estela de O Lima, Tatiane M Guerreiro, Carlos Fernando O R Melo, Diogo N de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R Catharino
Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate Zika virus' tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course...
December 28, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29282673/the-microbiome-gut-behavior-axis-crosstalk-between-the-gut-microbiome-and-oligodendrocytes-modulates-behavioral-responses
#18
REVIEW
Achilles Ntranos, Patrizia Casaccia
Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis...
December 27, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29279329/purine-nucleotide-metabolism-regulates-expression-of-the-human-immune-ligand-mica
#19
Michael T McCarthy, Gerald Moncayo, Thomas K Hiron, Niels A Jakobsen, Alessandro Vali, Tomoyoshi Soga, Julie Adam, Christopher A O'Callaghan
Expression of the cell surface glycoprotein MHC class I polypeptide-related sequence A (MICA) is induced in dangerous, abnormal or 'stressed' cells, including cancer cells, virus-infected cells and rapidly proliferating cells. MICA is recognized by the activating immune cell receptor NKG2D, providing a mechanism by which immune cells can identify and potentially eliminate pathological cells. Immune recognition through NKG2D is implicated in cancer, atherosclerosis, transplant rejection and inflammatory diseases such as rheumatoid arthritis...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29278751/correlation-between-gut-microbiota-and-personality-in-adults-a-cross-sectional-study
#20
Han-Na Kim, Yeojun Yun, Seungho Ryu, Yoosoo Chang, Min-Jung Kwon, Juhee Cho, Hocheol Shin, Hyung-Lae Kim
Personality affects fundamental behavior patterns and has been related with health outcomes and mental disorders. Recent evidence has emerged supporting a relationship between the microbiota and behavior, referred to as brain-gut relationships. Here, we first report correlations between personality traits and gut microbiota. This research was performed using the Revised NEO Personality Inventory and the sequencing data of the 16S rRNA gene in 672 adults. The diversity and the composition of the human gut microbiota exhibited significant difference when stratified by personality traits...
December 23, 2017: Brain, Behavior, and Immunity
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