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      Agaricus brasiliensis Mushroom Protects Against Sepsis by Alleviating Oxidative and Inflammatory Response

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          Abstract

          Sepsis is characterized by the host's dysregulated immune response to an infection followed by a potentially fatal organ dysfunction. Although there have been some advances in the treatment of sepsis, mainly focused on broad-spectrum antibiotics, mortality rates remain high, urging for the search of new therapies. Oxidative stress is one of the main features of septic patients, so antioxidants can be a good alternative treatment. Agaricus brasiliensis is a nutraceutical rich in bioactive compounds such as polyphenols and polysaccharides, exhibiting antioxidant, antitumor, and immunomodulatory activities. Here, we investigated the immunomodulatory and antioxidant effects of A. brasilensis aqueous extract in the cecal ligation and puncture (CLP) sepsis model. Our data showed that aqueous extract of A. brasiliensis reduced systemic inflammatory response and improved bacteria clearance and mice survival. In addition, A brasiliensis decreased the oxidative stress markers in serum, peritoneal cavity, heart and liver of septic animals, as well as ROS production ( in vitro and in vivo) and tert-Butyl hydroperoxide-induced DNA damage in peripheral blood mononuclear cells from healthy donors in vitro. In conclusion, the aqueous extract of A. brasiliensis was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.

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          Most cited references50

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          Antioxidant activity applying an improved ABTS radical cation decolorization assay.

          A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
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            A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates.

            1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS.+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
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              Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis

              Background Septic shock is the most severe form of sepsis, in which profound underlying abnormalities in circulatory and cellular/metabolic parameters lead to substantially increased mortality. A clear understanding and up-to-date assessment of the burden and epidemiology of septic shock are needed to help guide resource allocation and thus ultimately improve patient care. The aim of this systematic review and meta-analysis was therefore to provide a recent evaluation of the frequency of septic shock in intensive care units (ICUs) and associated ICU and hospital mortality. Methods We searched MEDLINE, Embase, and the Cochrane Library from 1 January 2005 to 20 February 2018 for observational studies that reported on the frequency and mortality of septic shock. Four reviewers independently selected studies and extracted data. Disagreements were resolved via consensus. Random effects meta-analyses were performed to estimate pooled frequency of septic shock diagnosed at admission and during the ICU stay and to estimate septic shock mortality in the ICU, hospital, and at 28 or 30 days. Results The literature search identified 6291 records of which 71 articles met the inclusion criteria. The frequency of septic shock was estimated at 10.4% (95% CI 5.9 to 16.1%) in studies reporting values for patients diagnosed at ICU admission and at 8.3% (95% CI 6.1 to 10.7%) in studies reporting values for patients diagnosed at any time during the ICU stay. ICU mortality was 37.3% (95% CI 31.5 to 43.5%), hospital mortality 39.0% (95% CI 34.4 to 43.9%), and 28-/30-day mortality 36.7% (95% CI 32.8 to 40.8%). Significant between-study heterogeneity was observed. Conclusions Our literature review reaffirms the continued common occurrence of septic shock and estimates a high mortality of around 38%. The high level of heterogeneity observed in this review may be driven by variability in defining and applying the diagnostic criteria, as well as differences in treatment and care across settings and countries. Electronic supplementary material The online version of this article (10.1186/s13054-019-2478-6) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                01 July 2020
                2020
                : 11
                : 1238
                Affiliations
                [1] 1Neuroscience and Cellular Biology Post Graduation Program, Institute of Biological Sciences, Federal University of Pará , Pará, Brazil
                [2] 2Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo , São Paulo, Brazil
                [3] 3Graduate Program in Basic and Applied Immunology, Ribeirao Preto Medical School, University of São Paulo , São Paulo, Brazil
                [4] 4School of Pharmacy, Health Science Institute, Federal University of Pará , Pará, Brazil
                [5] 5Pharmaceutical Science Post-Graduation Program, Faculty of Pharmacy, Federal University of Pará , Pará, Brazil
                [6] 6Department of Food Engineering, Midwest State University-UNICENTRO , Guarapuava, Brazil
                [7] 7Department of Biochemistry, Federal University of Rio Grande de Sul , Porto Alegre, Brazil
                [8] 8Laboratory of Cellular and Molecular Immunology, Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre , Porto Alegre, Brazil
                Author notes

                Edited by: Thomas Griffith, University of Minnesota Twin Cities, United States

                Reviewed by: Lucinéia Gainski Danielski, Universidade de Sul de Santa Catarina, Brazil; Thais Martins De Lima, University of São Paulo, Brazil

                *Correspondence: Marta Chagas Monteiro martachagas2@ 123456yahoo.com.br

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.01238
                7342083
                32714320
                eab1a451-ae0e-4aee-81d6-42c2dd8ca21f
                Copyright © 2020 Navegantes-Lima, Monteiro, de França Gaspar, de Brito Oliveira, de Oliveira, Reis, de Souza Gomes, Rodrigues, Stutz, Sovrani, Peres, Romão and Monteiro.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 March 2020
                : 18 May 2020
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 53, Pages: 14, Words: 7784
                Categories
                Immunology
                Original Research

                Immunology
                polymicrobial sepsis,clp,agaricus brasiliensis,sun mushroom,antioxidant,immunomodulator,protection

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