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  1. Article ; Online: Assessing Changes in Human Natural Killer Cell Metabolism Using the Seahorse Extracellular Flux Analyzer.

    Traba, Javier / Antón, Olga M

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2463, Page(s) 165–180

    Abstract: Natural killer (NK) cells are cytotoxic cells that mediate anti-tumor and anti-viral immunity. The response of NK cells to different cytokines and stimuli may involve cell survival, proliferation, and changes in their cytotoxic function. These responses ... ...

    Abstract Natural killer (NK) cells are cytotoxic cells that mediate anti-tumor and anti-viral immunity. The response of NK cells to different cytokines and stimuli may involve cell survival, proliferation, and changes in their cytotoxic function. These responses will be supported by changes in cellular metabolism. Therefore, changes in NK metabolic parameters could somehow predict changes in NK cell function and cytotoxicity. In this chapter, we describe a protocol to measure NK cell metabolism in primary human NK cells by using an extracellular flux analyzer. This machine measures pH and oxygen changes in the medium and allows the study of NK cell glycolysis and mitochondrial respiration in real time with a small number of cells.
    MeSH term(s) Animals ; Energy Metabolism ; Glycolysis ; Humans ; Killer Cells, Natural ; Oxidative Phosphorylation ; Smegmamorpha
    Language English
    Publishing date 2022-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2160-8_12
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  2. Article ; Online: Measurement of Cytosolic Mitochondrial DNA After NLRP3 Inflammasome Activation.

    Antón, Olga M / Traba, Javier

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2459, Page(s) 117–129

    Abstract: The NLRP3 inflammasome, a key component of the innate immune system that mediates caspase-1 activation, which in turn induces cleavage of the pyroptosis executioner gasdermin D and the proinflammatory cytokines IL-1β and IL-18, requires two signals to be ...

    Abstract The NLRP3 inflammasome, a key component of the innate immune system that mediates caspase-1 activation, which in turn induces cleavage of the pyroptosis executioner gasdermin D and the proinflammatory cytokines IL-1β and IL-18, requires two signals to be activated. First, inflammasome priming is achieved after activation of Toll-like receptors, which leads to NF-κB signaling and transcriptional activation of the genes for NLRP3 and IL-1β. Next, the inflammasome complex is activated by a second signal that induces extrusion of mitochondrial DNA to the cytosol of the cell, which leads to its oligomerization by a not fully understood mechanism. Here we describe a simple method that employs quantitative polymerase chain reaction (qPCR) using SYBR green to measure the presence of mitochondrial DNA (mtDNA) in the cytosol, which can be used to measure cytosolic mtDNA levels after inflammasome activation.
    MeSH term(s) Caspase 1 ; Cytosol ; DNA, Mitochondrial/genetics ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Pyroptosis
    Chemical Substances DNA, Mitochondrial ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1 (EC 3.4.22.36)
    Language English
    Publishing date 2022-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2144-8_12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Acute pancreatitis in children with covid-19 associated multisistem inflammatory syndrome.

    Traba Zubiaurre, Marta / Eizaguirre Arocena, Francisco Javier / Urrutikoetxea Aiartza, Marta / Izquierdo Iribarren, Ainhoa

    Anales de pediatria

    2022  Volume 96, Issue 3, Page(s) 270–272

    MeSH term(s) Acute Disease ; COVID-19/complications ; Child ; Humans ; Pancreatitis/complications ; Pancreatitis/diagnosis ; SARS-CoV-2 ; Syndrome
    Language English
    Publishing date 2022-02-07
    Publishing country Spain
    Document type Case Reports
    ZDB-ID 2830901-7
    ISSN 2341-2879 ; 2341-2879
    ISSN (online) 2341-2879
    ISSN 2341-2879
    DOI 10.1016/j.anpede.2021.01.007
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  4. Article ; Online: Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance.

    Traba, Javier / Sack, Michael N / Waldmann, Thomas A / Anton, Olga M

    Frontiers in immunology

    2021  Volume 12, Page(s) 657293

    Abstract: Constitutive activity of the immune surveillance system detects and kills cancerous cells, although many cancers have developed strategies to avoid detection and to resist their destruction. Cancer immunotherapy entails the manipulation of components of ... ...

    Abstract Constitutive activity of the immune surveillance system detects and kills cancerous cells, although many cancers have developed strategies to avoid detection and to resist their destruction. Cancer immunotherapy entails the manipulation of components of the endogenous immune system as targeted approaches to control and destroy cancer cells. Since one of the major limitations for the antitumor activity of immune cells is the immunosuppressive tumor microenvironment (TME), boosting the immune system to overcome the inhibition provided by the TME is a critical component of oncotherapeutics. In this article, we discuss the main effects of the TME on the metabolism and function of immune cells, and review emerging strategies to potentiate immune cell metabolism to promote antitumor effects either as monotherapeutics or in combination with conventional chemotherapy to optimize cancer management.
    MeSH term(s) Adaptive Immunity ; Animals ; Cell Communication/immunology ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/metabolism ; Cytokines/metabolism ; Disease Management ; Disease Susceptibility/immunology ; Disease Susceptibility/metabolism ; Energy Metabolism ; Humans ; Immunity, Innate ; Immunomodulation ; Immunotherapy ; Molecular Targeted Therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Tumor Escape/genetics ; Tumor Escape/immunology ; Tumor Microenvironment/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2021-05-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.657293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Analysis of Human Natural Killer Cell Metabolism.

    Traba, Javier / Waldmann, Thomas A / Anton, Olga M

    Journal of visualized experiments : JoVE

    2020  , Issue 160

    Abstract: Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses and respond to a variety of cytokines and other stimuli to promote survival, cellular proliferation, production of cytokines such as interferon gamma (IFNγ) and/or ...

    Abstract Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses and respond to a variety of cytokines and other stimuli to promote survival, cellular proliferation, production of cytokines such as interferon gamma (IFNγ) and/or cytotoxicity programs. NK cell activation by cytokine stimulation requires a substantial remodeling of metabolic pathways to support their bioenergetic and biosynthetic requirements. There is a large body of evidence that suggests that impaired NK cell metabolism is associated with a number of chronic diseases including obesity and cancer, which highlights the clinical importance of the availability of a method to determine NK cell metabolism. Here we describe the use of an extracellular flux analyzer, a platform that allows real-time measurements of glycolysis and mitochondrial oxygen consumption, as a tool to monitor changes in the energy metabolism of human NK cells. The method described here also allows for the monitoring of metabolic changes after stimulation of NK cells with cytokines such as IL-15, a system that is currently being investigated in a wide range of clinical trials.
    MeSH term(s) Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Humans ; Interferon-gamma/biosynthesis ; Interleukin-15/metabolism ; Killer Cells, Natural/cytology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/physiology ; Lymphocyte Activation/immunology
    Chemical Substances Cytokines ; IL15 protein, human ; Interleukin-15 ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2020-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/61466
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Analysis of human natural killer cell metabolism

    Traba, Javier / Waldmann, Thomas A / Anton, Olga M

    Journal of visualized experiments. 2020 June 22, , no. 160

    2020  

    Abstract: Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses and respond to a variety of cytokines and other stimuli to promote survival, cellular proliferation, production of cytokines such as interferon gamma (IFNγ) and/or ...

    Abstract Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses and respond to a variety of cytokines and other stimuli to promote survival, cellular proliferation, production of cytokines such as interferon gamma (IFNγ) and/or cytotoxicity programs. NK cell activation by cytokine stimulation requires a substantial remodeling of metabolic pathways to support their bioenergetic and biosynthetic requirements. There is a large body of evidence that suggests that impaired NK cell metabolism is associated with a number of chronic diseases including obesity and cancer, which highlights the clinical importance of the availability of a method to determine NK cell metabolism. Here we describe the use of an extracellular flux analyzer, a platform that allows real-time measurements of glycolysis and mitochondrial oxygen consumption, as a tool to monitor changes in the energy metabolism of human NK cells. The method described here also allows for the monitoring of metabolic changes after stimulation of NK cells with cytokines such as IL-15, a system that is currently being investigated in a wide range of clinical trials.
    Keywords biosynthesis ; cell proliferation ; cytotoxicity ; energy metabolism ; glycolysis ; humans ; interferon-gamma ; interleukin-15 ; mitochondria ; natural killer cells ; obesity ; oxygen consumption
    Language English
    Dates of publication 2020-0622
    Size p. e61466.
    Publishing place Journal of Visualized Experiments
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/61466
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  7. Article ; Online: Pancreatitis aguda en paciente pediátrico afecto de síndrome inflamatorio multisistémico atribuido a COVID-19.

    Traba Zubiaurre, Marta / Eizaguirre Arocena, Francisco Javier / Urrutikoetxea Aiartza, Markel / Izquierdo Iribarren, Ainhoa

    Anales de pediatria

    2021  

    Title translation Acute pancreatitis in children with COVID-19-associated multisystem inflammatory syndrome.
    Language Spanish
    Publishing date 2021-02-26
    Publishing country Spain
    Document type Case Reports
    ZDB-ID 2830901-7
    ISSN 2341-2879 ; 2341-2879
    ISSN (online) 2341-2879
    ISSN 2341-2879
    DOI 10.1016/j.anpedi.2021.01.013
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  8. Article ; Online: Pretarsal blepharospasm: Clinical and electromyographic characteristics.

    Grandas, Francisco / Traba, Alfredo / Perez-Sanchez, Javier Ricardo / Esteban, Angel

    Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

    2020  Volume 131, Issue 7, Page(s) 1678–1685

    Abstract: Objective: To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle.: Methods: Clinical assessment and simultaneous electromyographic ... ...

    Abstract Objective: To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle.
    Methods: Clinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin.
    Results: We found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections.
    Conclusions: Pretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings.
    Significance: Recognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle.
    MeSH term(s) Adult ; Aged ; Blepharospasm/diagnosis ; Blepharospasm/physiopathology ; Botulinum Toxins/pharmacology ; Electromyography/methods ; Eyelids/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Oculomotor Muscles/drug effects ; Oculomotor Muscles/physiopathology
    Chemical Substances Botulinum Toxins (EC 3.4.24.69)
    Language English
    Publishing date 2020-04-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1463630-x
    ISSN 1872-8952 ; 0921-884X ; 1388-2457
    ISSN (online) 1872-8952
    ISSN 0921-884X ; 1388-2457
    DOI 10.1016/j.clinph.2020.03.016
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  9. Article: The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

    Traba, Javier / Michael N. Sack

    Cellular and molecular life sciences. 2017 May, v. 74, no. 10

    2017  

    Abstract: Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, ... ...

    Abstract Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.
    Keywords diabetes ; homeostasis ; inflammasomes ; inflammation ; low calorie diet ; mitochondria ; obesity
    Language English
    Dates of publication 2017-05
    Size p. 1777-1791.
    Publishing place Springer International Publishing
    Document type Article
    Note Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-016-2431-7
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    In stock of ZB MED Bonn / Germany

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  10. Article ; Online: The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome.

    Traba, Javier / Sack, Michael N

    Cellular and molecular life sciences : CMLS

    2016  Volume 74, Issue 10, Page(s) 1777–1791

    Abstract: Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, ... ...

    Abstract Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/pathology ; Energy Intake ; Humans ; Inflammasomes/immunology ; Inflammation/immunology ; Inflammation/pathology ; Mitochondria/immunology ; Mitochondria/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; Obesity/immunology ; Sirtuins/immunology
    Chemical Substances Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Sirtuins (EC 3.5.1.-)
    Language English
    Publishing date 2016-12-10
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-016-2431-7
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    In stock of ZB MED Cologne/Königswinter

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