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      Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome

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          Abstract

          Wound-healing is a dynamic skin reparative process that results in a sequence of events, including inflammation, proliferation, and migration of different cell types as fibroblasts. Fibroblasts play a crucial role in repairing processes, from the late inflammatory phase until the fully final epithelization of the injured tissue. Within this context, identifying tools able to implement cell proliferation and migration could improve tissue regeneration. Recently, plants species from all over the world are coming out as novel tools for therapeutic applications thanks to their phytochemicals, which have antioxidant properties and can promote wound healing. In this paper, we aimed at investigating antioxidant activity of waste extracts from different medicinal plants, endemic of the Mediterranean area, on fibroblast proliferation and wound healing. We determined the amount of total phenols and anti-oxidant activity by ABTS assay. We then evaluated the cytotoxicity of the compounds and the proliferative capabilities of fibroblasts by scratch assay. Our results showed that waste extracts retain antioxidant and regenerative properties, inducing tissue re-establishment after environmental stress exposure. Taken together, our findings suggest that waste material could be used in the future also in combinations to stimulate wound healing processes and antioxidant responses in damaged skin.

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          Keratinocyte-fibroblast interactions in wound healing.

          Cutaneous tissue repair aims at restoring the barrier function of the skin. To achieve this, defects need to be replaced by granulation tissue to form new connective tissue, and epithelial wound closure is required to restore the physical barrier. Different wound-healing phases are recognized, starting with an inflammation-dominated early phase giving way to granulation tissue build-up and scar remodeling after epithelial wound closure has been achieved. In the granulation tissue, mesenchymal cells are maximally activated, cells proliferate, and synthesize huge amounts of extracellular matrix. Epithelial cells also proliferate and migrate over the provisional matrix of the underlying granulation tissue, eventually closing the defect. This review focuses on the role of keratinocyte-fibroblast interactions in the wound-healing process. There is ample evidence that keratinocytes stimulate fibroblasts to synthesize growth factors, which in turn will stimulate keratinocyte proliferation in a double paracrine manner. Moreover, fibroblasts can acquire a myofibroblast phenotype under the control of keratinocytes. This depends on a finely tuned balance between a proinflammatory or a transforming growth factor (TGF)-beta-dominated environment. As the phenotype of fibroblasts from different tissues or body sites becomes better defined, we may understand their individual contribution in wound healing in more detail and possibly explain different clinical outcomes.
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            The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

            Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices.
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              Extraction, isolation and characterization of bioactive compounds from plants' extracts.

              Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. Due to an increasing demand for chemical diversity in screening programs, seeking therapeutic drugs from natural products, interest particularly in edible plants has grown throughout the world. Botanicals and herbal preparations for medicinal usage contain various types of bioactive compounds. The focus of this paper is on the analytical methodologies, which include the extraction, isolation and characterization of active ingredients in botanicals and herbal preparations. The common problems and key challenges in the extraction, isolation and characterization of active ingredients in botanicals and herbal preparations are discussed. As extraction is the most important step in the analysis of constituents present in botanicals and herbal preparations, the strengths and weaknesses of different extraction techniques are discussed. The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays, chromatographic techniques such as HPLC and, TLC as well as non-chromatographic techniques such as immunoassay and Fourier Transform Infra Red (FTIR) are discussed.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2020
                7 April 2020
                : 17
                : 8
                : 1030-1042
                Affiliations
                [1 ]Department of Chemistry and Pharmacy, University of Sassari, Via F. Muroni 23/b, 07100, Sassari, Italy;
                [2 ]Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy;
                [3 ]Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy;
                [4 ]Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems - Eldor Lab, Innovation Accelerator, Consiglio Nazionale delle Ricerche, Bologna, Italy.
                [5 ]Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
                [6 ]Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy
                Author notes
                ✉ Corresponding author: mmaioli@ 123456uniss.it ; tel +39-079228277

                *Equal contributors

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv17p1030
                10.7150/ijms.43986
                7211158
                32410832
                ba2d0b51-fa3f-43dc-baed-e8cc3e43bb62
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 15 January 2020
                : 18 March 2020
                Categories
                Research Paper

                Medicine
                cellular mechanisms,cell proliferation,tissue regeneration,antioxidants,natural molecules,oxidative stress

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