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Metabolic pathways

M Mezzelani, S Gorbi, D Fattorini, G d'Errico, M Benedetti, M Milan, L Bargelloni, F Regoli
The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses...
October 11, 2016: Aquatic Toxicology
Christina Cimenti, Axel Schlagenhauf, Bettina Leschnik, Elke Fröhlich-Reiterer, Hildegard Jasser-Nitsche, Harald Haidl, Elisabeth Suppan, Gudrun Weinhandl, Maximilian Leberl, Martin Borkenstein, Wolfgang E Muntean
BACKGROUND: Micro- and macrovascular diseases are frequent complications in patients with diabetes. Hypercoagulability may contribute to microvascular alterations. OBJECTIVE: In this study, we investigated whether type 1 diabetes in children is associated with a hypercoagulable state by performing a global function test of coagulation - the thrombin generation assay. SUBJECTS: 75 patients with type 1 diabetes aged between 2 and 19years were compared to an age-matched healthy control group...
October 17, 2016: Thrombosis Research
A M Cardoso, M G Alves, P P Mathur, P F Oliveira, J E Cavaco, L Rato
In the last decades, several studies evidenced a decrease in male fertility in developed countries. Although the aetiology of this trend in male reproductive health remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as contributors because of their action as endocrine disruptors. Obesogens favour adipogenesis by an imbalance of metabolic processes and can be found virtually everywhere. These compounds easily accumulate in tissues with high lipid content...
October 24, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Jari E Kaikkonen, Peter Würtz, Emmi Suomela, Miia Lehtovirta, Antti J Kangas, Antti Jula, Vera Mikkilä, Jorma S A Viikari, Markus Juonala, Tapani Rönnemaa, Nina Hutri-Kähönen, Mika Kähönen, Terho Lehtimäki, Pasi Soininen, Mika Ala-Korpela, Olli T Raitakari
: Non-alcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n=1,575), 2007 (n=1,509) and 2011 (n=2,002)...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Pavel Sumazin, Yidong Chen, Lisa R Treviño, Stephen F Sarabia, Oliver A Hampton, Kayuri Patel, Toni-Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J Finegold, Gail Tomlinson, D Williams Parsons, Dolores López-Terrada
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pre-treatment tumors have been molecularly profiled and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pre-treatment HBs at diagnosis. Our analysis of 88 clinically-annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression, and high coordinated expression of oncofetal proteins and stem cell markers; while low-risk tumors had low LIN28B and let-7 expression, and high HNF1A activity...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Toshiyuki Yamaji, Aya Horie, Yuriko Tachida, Chisato Sakuma, Yusuke Suzuki, Yasunori Kushi, Kentaro Hanada
Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20-26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments...
October 21, 2016: International Journal of Molecular Sciences
Hongtao Guo, Xuyan Niu, Yan Gu, Cheng Lu, Cheng Xiao, Kevin Yue, Ge Zhang, Xiaohua Pan, Miao Jiang, Yong Tan, Hongwei Kong, Zhenli Liu, Guowang Xu, Aiping Lu
Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software...
October 21, 2016: International Journal of Molecular Sciences
Kaiyu Qian, Gang Wang, Rui Cao, Tao Liu, Guofeng Qian, Xinyuan Guan, Zhongqiang Guo, Yu Xiao, Xinghuan Wang
Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa...
October 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marta Spodenkiewicz, Carmen Diez-Fernandez, Véronique Rüfenacht, Corinne Gemperle-Britschgi, Johannes Häberle
Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism-congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy...
October 19, 2016: Biology
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
M Kvandová, M Majzúnová, I Dovinová
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways...
October 24, 2016: Physiological Research
Karthik Anantharaman, Christopher T Brown, Laura A Hug, Itai Sharon, Cindy J Castelle, Alexander J Probst, Brian C Thomas, Andrea Singh, Michael J Wilkins, Ulas Karaoz, Eoin L Brodie, Kenneth H Williams, Susan S Hubbard, Jillian F Banfield
The subterranean world hosts up to one-fifth of all biomass, including microbial communities that drive transformations central to Earth's biogeochemical cycles. However, little is known about how complex microbial communities in such environments are structured, and how inter-organism interactions shape ecosystem function. Here we apply terabase-scale cultivation-independent metagenomics to aquifer sediments and groundwater, and reconstruct 2,540 draft-quality, near-complete and complete strain-resolved genomes that represent the majority of known bacterial phyla as well as 47 newly discovered phylum-level lineages...
October 24, 2016: Nature Communications
Pedro Casado, Maruan Hijazi, David Britton, Pedro R Cutillas
Signalling pathways driven by protein and lipid kinases are altered in most human diseases. Therefore, pharmacological inhibitors of cell signalling are one of the most intensively pursued therapeutic approaches for the treatment of diseases such as cancer, neurodegeneration and metabolic syndromes. Phosphoproteomics is a technique that measures the products of kinase activities and, with the appropriate bioinformatics techniques, the methodology can also provide measures of kinase pathway activation and network circuitry...
October 24, 2016: Proteomics
Hongli Hu, Wenwei Zhu, Jun Qin, Min Chen, Liyan Gong, Long Li, Xiangyuan Liu, Yongzhen Tao, Huiyong Yin, Hu Zhou, Lisha Zhou, Dan Ye, Qinghai Ye, Daming Gao
: Phosphoglycerate kinase 1(PGK1) is an important enzyme in metabolic glycolysis pathway. In this study, we observed a significant over-expression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patients survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified the acetylation at K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Elisete P Rodrigues, Cleiton de Paula Soares, Patrícia G Galvão, Eddie L Imada, Jean L Simões-Araújo, Luc F M Rouws, André L M de Oliveira, Márcia S Vidal, José I Baldani
Gluconacetobacter diazotrophicus is a beneficial nitrogen-fixing endophyte found in association with sugarcane plants and other important crops. Beneficial effects of G. diazotrophicus on sugarcane growth and productivity have been attributed to biological nitrogen fixation process and production of phytohormones especially indole-3-acetic acid (IAA); however, information about the biosynthesis and function of IAA in G. diazotrophicus is still scarce. Therefore, the aim of this work was to identify genes and pathways involved in IAA biosynthesis in this bacterium...
2016: Frontiers in Microbiology
Matteo Mori, Miguel Ponce-de-León, Juli Peretó, Francisco Montero
Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway...
2016: Frontiers in Microbiology
Hui-Li Tan, Kok-Gan Chan, Priyia Pusparajah, Acharaporn Duangjai, Surasak Saokaew, Tahir Mehmood Khan, Learn-Han Lee, Bey-Hing Goh
Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism...
2016: Frontiers in Pharmacology
Jorge L Gutierrez-Pajares, Céline Ben Hassen, Stéphan Chevalier, Philippe G Frank
Studies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI), which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol...
2016: Frontiers in Pharmacology
Jean-Pierre Routy, Bertrand Routy, Gina M Graziani, Vikram Mehraj
The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege...
2016: International Journal of Tryptophan Research: IJTR
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