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      Nuclear factor-kB and nitric oxide synthases in red blood cells: Good or bad in obesity? A preliminary study

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          Abstract

          Emerging evidence suggests that red blood cells (RBCs) are involved in many functions essential for life. Nuclear factor-kB (NF-kB), nitric oxide synthases (inducible nitric oxide synthase -iNOS-, endothelial nitric oxide synthase -eNOS-) and interleukin-1β (-IL-1β-) are all proteins that have been identified in RBCs. In nucleated cells, such as white blood cells (WBCs), these proteins have well investigated roles, linked to stress and inflammation. It is not the same in erythrocytes. For this reason, we considered obese patients for studying the morphology of RBCs. We studied a possible correlation between their morphological changes and several protein expressions. Moreover, we compared the results about the aforementioned proteins and antioxidant markers with those obtained in WBCs from healthy and obese patients before and after omega-3 polyunsaturated fatty acid supplementation. This latter scientific point is important in order to determine whether there are differences in the expression of nucleated and anucleated cells. The morphology of RBCs changed in obese patients, but it is significantly restored after six weeks of supplementation. The expression of antioxidant enzymes changed in RBCs and WBCs in obesity but all proteins restore their positivity after supplementation. We found that: the presence of NF-kB, antioxidant enzymes and eNOS in healthy RBCs could indicate a role of these proteins as regulators of cellular metabolism; obese WBCs showed a higher NF-kB, iNOS and IL-1β positivity, whereas eNOS presence did not significantly change in these cells. We tried to explain the different positivity of NF-kB, proposing a dual role for this protein, as prolifespan and as proinflammatory processes, depending on examined cells. In conclusion, we have considered the literature that focuses on the omega- 6/omega-3 ratio. The ratio changed from the past, especially in people whose diet is strongly westernized worsening the state of health of the patient and leading to an higher incidence of obesity. Our study hypothesizes that the supplementation could help to restore the correct ratio.

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          iNOS-mediated nitric oxide production and its regulation.

          This review focuses on the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and its regulation under physiological and pathophysiological conditions. NO is an important biological mediator in the living organism that is synthesized from L-arginine using NADPH and molecular oxygen. However, the overproduction of NO which is catalyzed by iNOS, a soluble enzyme and active in its dimeric form, is cytotoxic. Immunostimulating cytokines or bacterial pathogens activate iNOS and generate high concentrations of NO through the activation of inducible nuclear factors, including NFkB. iNOS activation is regulated mainly at the transcriptional level, but also at posttranscriptional, translational and postranslational levels through effects on protein stability, dimerization, phosphorylation, cofactor binding and availability of oxygen and L-arginine as substrates. The prevention of the overproduction of NO in the living organism through control of regulatory pathways may assist in the treatment of high NO-mediated disorders without changing physiological levels of NO. Copyright 2004 Elsevier Inc.
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            Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue – a review

            Background Immunohistochemistry (IHC) is a well-established, widely accepted method in both clinical and experimental parts of medical science. It allows receiving valuable information about any process in any tissue, and especially in bone. Each year the amount of data, received by IHC, grows in geometric progression. But the lack of standardization, especially on the post-analytical stage (interpreting and reporting of results), makes the comparison of the results of different studies impossible. Methods Comprehensive PubMED literature search with a combination of search words “immunohistochemistry” and “scoring system” was performed and 773 articles describing IHC results were identified. After further manual analysis 120 articles were selected for detailed evaluation of used approaches. Results Six major approaches to the interpretation and presentation of IHC analysis results were identified, analyzed and described. Conclusions The overview of the existing approaches in evaluation and interpretation of IHC data, which are provided in the article, can be used in bone tissue research and for either better understanding of existing scoring systems or developing a new one. Standard multiparametric, semiquantitative IHC scoring systems should simplify and clarify the process of interpretation and reporting of received data. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_221
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              Interleukin-1 Beta—A Friend or Foe in Malignancies?

              Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.
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                Author and article information

                Journal
                Eur J Histochem
                IJA
                European Journal of Histochemistry : EJH
                PAGEPress Publications, Pavia, Italy
                1121-760X
                2038-8306
                21 January 2020
                10 January 2020
                : 64
                : 1
                : 3081
                Affiliations
                [1 ]Department of Medical and Clinical Biochemistry, Faculty of Medicine, P.J. Šafárik University , Košice, Slovak Republic
                [2 ]Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia , Italy
                [3 ]Department of Experimental Medicine, Faculty of Medicine, P.J. Šafarik University , Košice, Slovak Republic
                [4 ]Interdipartimental University Center of Research "Adaption and Regeneration of Tissues and Organs-(ARTO)", University of Brescia , Italy
                Author notes
                Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Piazza del Mercato 15, 25121 Brescia, Italy. Tel. +39.030.3717483 - +39.030.3717486. rita.rezzani@ 123456unibs.it

                Contributions: ZH, realized and wrote the project; ZG, MS, ZH, conceived and planned the clinical trials; CF, ZG, MS carried on the experiments and contributed to the interpretation of the results; ZH, VT, LFR, RR supervised the project; RR wrote the manuscript with input from all Authors. All Authors discussed the results and contributed drafting the final manuscript. MS and CF contributed equally to this work.

                Conflict of interest: The authors declare no conflict of interest.

                Ethical approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki; the Ethical Committee of Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Slovakia, approved it (N. 7N/2016). All the participants provided written consent to participate in the study.

                Patient consent for publication: obtained.

                Article
                10.4081/ejh.2020.3081
                7003140
                31988533
                31fdd448-4309-4cca-b279-2cdcb39a31e1
                ©Copyright: the Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

                History
                : 10 November 2019
                : 07 January 2020
                Page count
                Figures: 8, Tables: 4, Equations: 0, References: 97, Pages: 14
                Funding
                Funding: This work was supported by 60% grant (University of Brescia, Italy) and by VEGA and APVV grant (VEGA 1/0584/16; APVV-16-0176) of the Ministry for Education, Science, Research and Sport of the Slovak Republic. Moreover, this publication has been produced thanks to the support of the Operational Program Research and Innovation for the project: Bioactive substances to promote health and prevent chronic diseases (PROBIO-3: NFP313010T651), financed by the European Regional Development Fund.
                Categories
                Article

                Clinical chemistry
                metabolic syndrome,erythrocytes,inflammation,oxidative stress,therapeutic strategies

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