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      Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

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          Abstract

          Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies. In this review, we focus on the most important protein carbonylation and lipid peroxidation biomarkers in hematological malignancies, their role in disease development, and potential treatment implications.

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          Most cited references237

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          Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress☆

          Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H2O2 in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of H2O2 and on the role of H2O2 in redox signaling under physiological conditions (1–10 nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB. Supraphysiological concentrations of H2O2 (>100 nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can H2O2 be assayed in the biological setting? What are the metabolic sources and sinks of H2O2? What is the role of H2O2 in redox signaling and oxidative stress?
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            Acute Lymphoblastic Leukemia in Children.

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              The Essential Medicinal Chemistry of Curcumin

              Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                01 December 2020
                December 2020
                : 9
                : 12
                : 1212
                Affiliations
                [1 ]Department of Translational Hematology, Instituto de Investigación Hospital 12 de Octubre (i+12), Hematological Malignancies Clinical Research Unit H120-CNIO, CIBERONC, ES 28041 Madrid, Spain; albrod04@ 123456ucm.es (A.R.-G.); roberg09@ 123456ucm.es (R.G.-V.); marimo13@ 123456ucm.es (M.L.M.); mortiz06@ 123456ucm.es (A.O.-R.); jmarti01@ 123456med.ucm.es (J.M.-L.)
                [2 ]Department of Medicine, Medicine School, Universidad Complutense de Madrid, ES 28040 Madrid, Spain
                [3 ]Department of Biochemistry and Molecular Biology, Pharmacy School, Universidad Complutense de Madrid, ES 28040 Madrid, Spain
                Author notes
                [* ]Correspondence: mlinares@ 123456ucm.es ; Tel.: +34-917-792-611
                Author information
                https://orcid.org/0000-0002-6786-2006
                https://orcid.org/0000-0002-4796-9391
                https://orcid.org/0000-0002-0685-8441
                https://orcid.org/0000-0003-4059-8839
                https://orcid.org/0000-0001-7908-0063
                https://orcid.org/0000-0003-3180-6560
                Article
                antioxidants-09-01212
                10.3390/antiox9121212
                7761105
                33271863
                c7b63e44-cadd-4fcd-b9d8-ebed898f3fa2
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 October 2020
                : 28 November 2020
                Categories
                Review

                oxidative stress,protein carbonylation,lipid peroxidation,hematological malignancies

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