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  1. Article: Protoporphyrin IX Binds to Iron(II)-Loaded and to Zinc-Loaded Human Frataxin.

    Bernardo-Seisdedos, Ganeko / Schedlbauer, Andreas / Pereira-Ortuzar, Tania / Mato, José M / Millet, Oscar

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 1

    Abstract: 1) Background: Human frataxin is an iron binding protein that participates in the biogenesis of iron sulfur clusters and enhances ferrochelatase activity. While frataxin association to other proteins has been extensively characterized up to the ... ...

    Abstract (1) Background: Human frataxin is an iron binding protein that participates in the biogenesis of iron sulfur clusters and enhances ferrochelatase activity. While frataxin association to other proteins has been extensively characterized up to the structural level, much less is known about the putative capacity of frataxin to interact with functionally related metabolites. In turn, current knowledge about frataxin's capacity to coordinate metal ions is limited to iron (II and III); (2) Methods: here, we used NMR spectroscopy, Molecular Dynamics, and Docking approaches to demonstrate new roles of frataxin; (3) Results: We demonstrate that frataxin also binds Zn
    Language English
    Publishing date 2023-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13010222
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  2. Article: Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19.

    Bruzzone, Chiara / Conde, Ricardo / Embade, Nieves / Mato, José M / Millet, Oscar

    Frontiers in molecular biosciences

    2023  Volume 10, Page(s) 1111482

    Abstract: COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately ... ...

    Abstract COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.
    Language English
    Publishing date 2023-02-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2023.1111482
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  3. Article ; Online: Impaired Hepatic Very Low-Density Lipoprotein Secretion Promotes Tumorigenesis and Is Accelerated with Fabp1 Deletion.

    Newberry, Elizabeth P / Molitor, Elizabeth A / Liu, Allen / Chong, Kamyar / Liu, Xiuli / Alonso, Cristina / Mato, Jose M / Davidson, Nicholas O

    The American journal of pathology

    2024  

    Abstract: Genetic polymorphisms that impair very low-density lipoprotein (VLDL) secretion are linked to hepatic steatosis, fibrosis, and hepatocellular cancer. Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, ... ...

    Abstract Genetic polymorphisms that impair very low-density lipoprotein (VLDL) secretion are linked to hepatic steatosis, fibrosis, and hepatocellular cancer. Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1-null [Fabp1/Mttp double knockout (DKO)] mice. Here, we examine the impact of impaired VLDL secretion in Mttp-LKO mice on hepatocellular cancer incidence and progression in comparison to Fabp1/Mttp DKO mice. Diethylnitrosamine-treated Mttp-LKO mice exhibited steatosis with increased tumor burden compared with flox controls, whereas diethylnitrosamine-treated Fabp1/Mttp DKO mice exhibited a paradoxical increase in tumor burden and >50% mortality by 50 weeks. Serum high-density lipoprotein cholesterol was elevated in both Mttp-LKO and Fabp1/Mttp DKO mice, with increased intratumoral expression of apolipoprotein A1 and apolipoprotein E. Lipidomic surveys revealed progressive enrichment in distinct triglyceride species in livers from Mttp-LKO mice with further enrichment in Fabp1/Mttp DKO mice. RNA sequencing revealed mRNA changes suggesting altered monocarboxylic acid use and increased aerobic glycolysis, whereas hepatocytes from Fabp1/Mttp DKO mice exhibited increased capacity to use glucose and glutamine. These metabolic shifts were accompanied by reduced expression of HNF1a, which correlated with tumor burden. Taken together, these findings demonstrate that hepatic tumorigenesis is increased in mice with impaired VLDL secretion and further accelerated via pathways including altered fatty acid compartmentalization and shifts in hepatic energy use.
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2024.02.005
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    In stock of ZB MED Cologne/Königswinter

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  4. Article ; Online: Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

    Chiara Bruzzone / Ricardo Conde / Nieves Embade / José M. Mato / Oscar Millet

    Frontiers in Molecular Biosciences, Vol

    2023  Volume 10

    Abstract: COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately ... ...

    Abstract COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.
    Keywords COVID-19 ; SARS-CoV-2 infection ; metabolomics ; lipidomics ; NMR ; LC/GC-MS ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review.

    Noureddin, Mazen / Sander-Struckmeier, Suntje / Mato, José M

    World journal of hepatology

    2020  Volume 12, Issue 2, Page(s) 46–63

    Abstract: Background: S-adenosylmethionine (AdoMet) is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis (IHC) and chronic liver diseases. While the efficacy of AdoMet has been demonstrated previously, it has not been systematically ... ...

    Abstract Background: S-adenosylmethionine (AdoMet) is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis (IHC) and chronic liver diseases. While the efficacy of AdoMet has been demonstrated previously, it has not been systematically investigated within the early weeks of treatment.
    Aim: To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.
    Methods: Studies reporting the efficacy of intravenous, intramuscular, or oral forms of AdoMet within 8 wk of treatment initiation were considered; three randomized and six non-randomized studies were eligible for inclusion (PROSPERO registration number CRD42018090936). Of the three randomized studies, two were double-blind and placebo-controlled, and one was comparator-controlled with unclear blinding and a relatively high risk of bias. Mean serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) following AdoMet treatment
    Results: Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet
    Conclusion: Data from both randomized and non-randomized studies suggest that AdoMet improves some biochemical liver parameters and symptoms of cholestasis within 2 wk, with further improvements observed in some studies after 4 and 8 wk of treatment.
    Language English
    Publishing date 2020-02-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573703-X
    ISSN 1948-5182
    ISSN 1948-5182
    DOI 10.4254/wjh.v12.i2.46
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  6. Article ; Online: Shape-Shifting Molecules: Unveiling the Valence Tautomerism Phenomena in Bare Barbaralones.

    Sanz-Novo, Miguel / Mato, Mauro / León, Íker / Echavarren, Antonio M / Alonso, José L

    Angewandte Chemie (International ed. in English)

    2022  Volume 61, Issue 18, Page(s) e202117045

    Abstract: We report a state-of-the-art spectroscopic study of an archetypical barbaralone, conclusively revealing the valence tautomerism phenomena for this bistable molecular system. The two distinct 1- and 5-substituted valence tautomers have been isolated in a ... ...

    Abstract We report a state-of-the-art spectroscopic study of an archetypical barbaralone, conclusively revealing the valence tautomerism phenomena for this bistable molecular system. The two distinct 1- and 5-substituted valence tautomers have been isolated in a supersonic expansion for the first time and successfully characterized by high-resolution rotational spectroscopy. This work provides irrefutable experimental evidence of the [3,3]-rearrangement in barbaralones and highlights the use of rotational spectroscopy to analyze shape-shifting mixtures. Moreover, this observation opens the window toward the characterization of new fluxional systems in the isolation conditions of the gas phase and should serve as a reference point in the general understanding of valence tautomerism.
    Language English
    Publishing date 2022-03-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202117045
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  7. Article ; Online: The use of pharmacological chaperones in rare diseases caused by reduced protein stability.

    Gil-Martínez, Jon / Bernardo-Seisdedos, Ganeko / Mato, José M / Millet, Oscar

    Proteomics

    2022  Volume 22, Issue 23-24, Page(s) e2200222

    Abstract: Rare diseases are most often caused by inherited genetic disorders that, after translation, will result in a protein with altered function. Decreased protein stability is the most frequent mechanism associated with a congenital pathogenic missense ... ...

    Abstract Rare diseases are most often caused by inherited genetic disorders that, after translation, will result in a protein with altered function. Decreased protein stability is the most frequent mechanism associated with a congenital pathogenic missense mutation and it implies the destabilization of the folded conformation in favour of unfolded or misfolded states. In the cellular context and when experimental data is available, a mutant protein with altered thermodynamic stability often also results in impaired homeostasis, with the deleterious accumulation of protein aggregates, metabolites and/or metabolic by-products. In the last decades, a significant effort has enabled the characterization of rare diseases associated to protein stability defects and triggered the development of innovative therapeutic intervention lines, say, the use of pharmacological chaperones to correct the intracellular impaired homeostasis. Here, we review the current knowledge on rare diseases caused by reduced protein stability, paying special attention to the thermodynamic aspects of the protein destabilization, also focusing on some examples where pharmacological chaperones are being tested.
    MeSH term(s) Humans ; Protein Folding ; Molecular Chaperones ; Rare Diseases/drug therapy ; Protein Stability ; Protein Aggregates
    Chemical Substances Molecular Chaperones ; Protein Aggregates
    Language English
    Publishing date 2022-10-19
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2032093-0
    ISSN 1615-9861 ; 1615-9853
    ISSN (online) 1615-9861
    ISSN 1615-9853
    DOI 10.1002/pmic.202200222
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5386: Show issues Location:
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  8. Article ; Online: S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver.

    Barbier-Torres, Lucía / Chhimwal, Jyoti / Kim, So Yeon / Ramani, Komal / Robinson, Aaron / Yang, Heping / Van Eyk, Jenny / Liangpunsakul, Suthat / Seki, Ekihiro / Mato, José M / Lu, Shelly C

    International journal of biological sciences

    2024  Volume 20, Issue 4, Page(s) 1218–1237

    Abstract: MCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is ... ...

    Abstract MCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is frequently depleted in chronic liver diseases. Here, we show that SAMe negatively regulates MCJ in the liver. While deficiency in methionine adenosyltransferase alpha 1 (MATα1), enzyme that catalyzes SAMe biosynthesis, leads to hepatic MCJ upregulation, MAT1A overexpression and SAMe treatment reduced MCJ expression. We found that MCJ is methylated at lysine residues and that it interacts with MATα1 in liver mitochondria, likely to facilitate its methylation. Lastly, we observed that MCJ is upregulated in alcohol-associated liver disease, a condition characterized by reduced
    MeSH term(s) Humans ; S-Adenosylmethionine/metabolism ; Electron Transport ; Liver/metabolism ; Mitochondria/metabolism ; Liver Diseases, Alcoholic/metabolism
    Chemical Substances S-Adenosylmethionine (7LP2MPO46S)
    Language English
    Publishing date 2024-01-27
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2179208-2
    ISSN 1449-2288 ; 1449-2288
    ISSN (online) 1449-2288
    ISSN 1449-2288
    DOI 10.7150/ijbs.90104
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  9. Article ; Online: High-resolution X-Ray imaging of small animal samples based on Commercial-Off-The-Shelf CMOS image sensors.

    Pérez, MartÍn / Lado, Gerardo M / Mato, Germán / Franco, Diego G / Vinciguerra, Ignacio Artola / Berisso, Mariano Gómez / Pomiro, Federico J / Lipovetzky, José / Marpegan, Luciano

    Journal of X-ray science and technology

    2024  Volume 32, Issue 2, Page(s) 355–367

    Abstract: An automated system for acquiring microscopic-resolution radiographic images of biological samples was developed. Mass-produced, low-cost, and easily automated components were used, such as Commercial-Off-The-Self CMOS image sensors (CIS), stepper motors, ...

    Abstract An automated system for acquiring microscopic-resolution radiographic images of biological samples was developed. Mass-produced, low-cost, and easily automated components were used, such as Commercial-Off-The-Self CMOS image sensors (CIS), stepper motors, and control boards based on Arduino and RaspberryPi. System configuration, imaging protocols, and Image processing (filtering and stitching) were defined to obtain high-resolution images and for successful computational image reconstruction. Radiographic images were obtained for animal samples including the widely used animal models zebrafish (Danio rerio) and the fruit-fly (Drosophila melanogaster), as well as other small animal samples. The use of phosphotungstic acid (PTA) as a contrast agent was also studied. Radiographic images with resolutions of up to (7±0.6)μm were obtained, making this system comparable to commercial ones. This work constitutes a starting point for the development of more complex systems such as X-ray attenuation micro-tomography systems based on low-cost off-the-shelf technology. It will also bring the possibility to expand the studies that can be carried out with small animal models at many institutions (mostly those working on tight budgets), particularly those on the effects of ionizing radiation and absorption of heavy metal contaminants in animal tissues.
    MeSH term(s) Animals ; X-Rays ; Drosophila melanogaster ; Zebrafish ; Radiography ; Image Processing, Computer-Assisted/methods
    Language English
    Publishing date 2024-02-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2012019-9
    ISSN 1095-9114 ; 0895-3996
    ISSN (online) 1095-9114
    ISSN 0895-3996
    DOI 10.3233/XST-230232
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  10. Article ; Online: Liver receptor homolog 1 and transmethylation fluxes in nonalcoholic steatohepatitis.

    Mato, José M / Lu, Shelly C

    Hepatology (Baltimore, Md.)

    2016  Volume 63, Issue 1, Page(s) 17–19

    MeSH term(s) Animals ; Liver/metabolism ; Male ; Methylation ; Receptors, Cytoplasmic and Nuclear/physiology
    Chemical Substances Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2016-01
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.28146
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    In stock of ZB MED Cologne/Königswinter

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