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      Effects of Dietary n–3 and n–6 Polyunsaturated Fatty Acids in Inflammation and Cancerogenesis

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          Abstract

          The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.

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          The basics of epithelial-mesenchymal transition.

          The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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            Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications

            Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment components. Tumor-associated macrophages (TAMs) are the key cells that create an immunosuppressive tumor microenvironment (TME) by producing cytokines, chemokines, growth factors, and triggering the inhibitory immune checkpoint proteins release in T cells. In doing so, TAMs exhibit important functions in facilitating a metastatic cascade of cancer cells and, meanwhile, provide multiple targets of certain checkpoint blockade immunotherapies for opposing tumor progression. In this article, we summarize the regulating networks of TAM polarization and the mechanisms underlying TAM-facilitated metastasis. Based on the overview of current experimental evidence dissecting the critical roles of TAMs in tumor metastasis, we discuss and prospect the potential applications of TAM-focused therapeutic strategies in clinical cancer treatment at present and in the future.
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              Hypoxia--a key regulatory factor in tumour growth.

              Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                28 June 2021
                July 2021
                : 22
                : 13
                : 6965
                Affiliations
                [1 ]Department of Genomics and Biodiversity, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, ul. Postepu 36A, Jastrzebiec, 05-552 Magdalenka, Poland; k.liput@ 123456igbzpan.pl (K.P.L.); m.ogluszka@ 123456igbzpan.pl (M.O.); a.nawrocka@ 123456igbzpan.pl (A.N.); e.polawska@ 123456igbzpan.pl (E.P.)
                [2 ]Department of Molecular Biology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, ul. Postepu 36A, Jastrzebiec, 05-552 Magdalenka, Poland
                [3 ]Department of Physiology, Cytobiology and Proteomics, West Pomeranian University of Technology, ul. K. Janickiego 29, 71-270 Szczecin, Poland; adam.lepczynski@ 123456zut.edu.pl (A.L.); agata.grzesiak@ 123456zut.edu.pl (A.G.)
                [4 ]Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, ul. Postepu 36A, Jastrzebiec, 05-552 Magdalenka, Poland
                [5 ]Institute of Biological Bases of Animal Production, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland; brygida.slaska@ 123456up.lublin.pl
                [6 ]Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, ul. J. Gagarina 7, 87-100 Toruń, Poland; pareekcs@ 123456umk.pl
                [7 ]Division of Functional Genomics in Biological and Biomedical Research, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, ul. Wilenska 4, 87-100 Torun, Poland
                [8 ]Department of Pig Breeding, Faculty of Animal Bio-Engineering, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn, Poland; czar@ 123456uwm.edu.pl
                Author notes
                [* ]Correspondence: m.pierzchala@ 123456igbzpan.pl ;
                Author information
                https://orcid.org/0000-0003-2139-8241
                https://orcid.org/0000-0003-2806-6194
                https://orcid.org/0000-0003-3933-2400
                https://orcid.org/0000-0002-0329-787X
                Article
                ijms-22-06965
                10.3390/ijms22136965
                8268933
                34203461
                fdd88eed-8988-4c4b-ac32-6d408fff796a
                © 2021 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 01 June 2021
                : 24 June 2021
                Categories
                Review

                Molecular biology
                pufa,omega-3 fatty acids,omega-6 fatty acids,oxylipins,inflammation,cancerogenesis
                Molecular biology
                pufa, omega-3 fatty acids, omega-6 fatty acids, oxylipins, inflammation, cancerogenesis

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