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      Antioxidant and Anti-Inflammatory Properties of Cherry Extract: Nanosystems-Based Strategies to Improve Endothelial Function and Intestinal Absorption

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          Abstract

          Cherry fruit has a high content in flavonoids. These are important diet components protecting against oxidative stress, inflammation, and endothelial dysfunction, which are all involved in the pathogenesis of atherosclerosis, which is the major cause of cardiovascular diseases (CVD). Since the seasonal availability of fresh fruit is limited, research has been focused on cherry extract (CE), which also possesses a high nutraceutical potential. Many clinical studies have demonstrated the nutraceutical efficacy of fresh cherries, but only a few studies on CE antioxidant and anti-inflammatory activities have been carried out. Here, the results concerning the antioxidant and anti-inflammatory activities of CE are reviewed. These were obtained by an in vitro model based on Human Umbilical Vein Endothelial Cells (HUVEC). To clarify the CE mechanism of action, cells were stressed to induce inflammation and endothelial dysfunction. Considering that antioxidants’ polyphenol compounds are easily degraded in the gastrointestinal tract, recent strategies to reduce the degradation and improve the bioavailability of CE are also presented and discussed. In particular, we report on results obtained with nanoparticles (NP) based on chitosan derivatives (Ch-der), which improved the mucoadhesive properties of the chitosan polymers, as well as their positive charge, to favor high cellular interaction and polyphenols intestinal absorption, compared with a non-mucoadhesive negative surface charged poly(lactic-co-glycolic) acid NP. The advantages and safety of different nanosystems loaded with natural CE or other nutraceuticals are also discussed.

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          To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?

          F Danhier (2016)
          Tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents and to provide clinicians the ability to overcome shortcomings of current cancer treatment. The major underlying mechanism of the design of nanomedicines was the Enhanced Permeability and Retention (EPR) effect, considered as the "royal gate" in the drug delivery field. However, after the publication of thousands of research papers, the verdict has been handed down: the EPR effect works in rodents but not in humans! Thus the basic rationale of the design and development of nanomedicines in cancer therapy is failing making it necessary to stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be proved in the clinic. It is probably time to dethrone the EPR effect and to ask the question: what is the future of nanomedicines without the EPR effect? The aim of this review is to provide a general overview on (i) the current state of the EPR effect, (ii) the future of nanomedicine and (iii) the strategies of modulation of the tumor microenvironment to improve the delivery of nanomedicine.
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            Cytokines in atherosclerosis: pathogenic and regulatory pathways.

            Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
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              Encapsulation of polyphenols – a review

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                Author and article information

                Journal
                Foods
                Foods
                foods
                Foods
                MDPI
                2304-8158
                17 February 2020
                February 2020
                : 9
                : 2
                : 207
                Affiliations
                [1 ]Department of Life Sciences, University of Siena, via Aldo Moro 2, 53100 Siena, Italy
                [2 ]Cardiovascular Research Laboratory, Department of Surgery, Medical, Molecular, and Critical Area Pathology, University of Pisa, via Paradisa 2, 56100 Pisa, Italy; francesca.felice@ 123456for.unipi.it
                [3 ]Department of Pharmacy, University of Pisa, via Bonanno 33, 56100 Pisa, Italy; angela.fabiano@ 123456unipi.it (A.F.); ylenia.zambito@ 123456unipi.it (Y.Z.)
                [4 ]i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-153 Porto, Portugal; bruno.sarmento@ 123456ineb.up.pt
                [5 ]INEB—Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
                [6 ]CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
                [7 ]Interdepartmental Research Center Nutraceuticals and Food for Health, University of Pisa, via Borghetto 80, 56100 Pisa, Italy
                Author notes
                Author information
                https://orcid.org/0000-0003-0587-3313
                https://orcid.org/0000-0001-8968-2228
                https://orcid.org/0000-0001-5763-7553
                https://orcid.org/0000-0003-0064-233X
                Article
                foods-09-00207
                10.3390/foods9020207
                7074069
                32079234
                ba404679-4143-41d9-9ae0-f9c7124ede5a
                © 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
                : 31 December 2019
                : 14 February 2020
                Categories
                Review

                cherry,nutraceuticals,polyphenols,antioxidant,anti-inflammatory,intestinal absorption,nanoparticles,nanosystems,huvec

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