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      Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications

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          Graphic abstract

          Over the past few years, there has been a growing potential use of graphene and its derivatives in several biomedical areas, such as drug delivery systems, biosensors, and imaging systems, especially for having excellent optical, electronic, thermal, and mechanical properties. Therefore, nanomaterials in the graphene family have shown promising results in several areas of science. The different physicochemical properties of graphene and its derivatives guide its biocompatibility and toxicity. Hence, further studies to explain the interactions of these nanomaterials with biological systems are fundamental. This review has shown the applicability of the graphene family in several biomedical modalities, with particular attention for cancer therapy and diagnosis, as a potent theranostic. This ability is derivative from the considerable number of forms that the graphene family can assume. The graphene-based materials biodistribution profile, clearance, toxicity, and cytotoxicity, interacting with biological systems, are discussed here, focusing on its synthesis methodology, physicochemical properties, and production quality. Despite the growing increase in the bioavailability and toxicity studies of graphene and its derivatives, there is still much to be unveiled to develop safe and effective formulations.

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          Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

          Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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            Re-epithelialization and immune cell behaviour in an ex vivo human skin model

            A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.
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              Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease

              Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.
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                Author and article information

                Contributors
                presidenciaradiofarmacia@gmail.com , roliveira@ien.gov.br
                Journal
                J Nanostructure Chem
                J Nanostructure Chem
                Journal of Nanostructure in Chemistry
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2008-9244
                2193-8865
                6 September 2021
                : 1-35
                Affiliations
                [1 ]GRID grid.457037.2, ISNI 0000 0001 0287 6514, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, ; Rio de Janeiro, 21941906 Brazil
                [2 ]GRID grid.411204.2, ISNI 0000 0001 2165 7632, Biophysics and Nanosystems Laboratory, Department of Physics, , Federal University of Maranhão, ; São Luis, Maranhão 65080805 Brazil
                [3 ]Department of Natural Sciences, Mathematics and Statistics, Federal Rural University of the Semi-Arid, Mossoró, RN 59625-900 Brazil
                [4 ]GRID grid.442019.a, ISNI 0000 0000 9679 970X, Laboratory of Advanced Science, , Universidade Unigranrio, ; Duque de Caxias, RJ 25071-202 Brazil
                [5 ]GRID grid.8395.7, ISNI 0000 0001 2160 0329, Group of Chemistry of Advanced Materials (GQMat)-Department of Analytical Chemistry and Physic-Chemistry, , Federal University of Ceará-Campus do Pici, ; Fortaleza, Ceará 60451-970 Brazil
                [6 ]GRID grid.441837.d, ISNI 0000 0001 0765 9762, Institute of Applied Chemical Sciences, , Universidad Autónoma de Chile, ; 8910060 Santiago, Chile
                [7 ]GRID grid.440624.0, ISNI 0000 0004 0637 7917, Education and Scientific Center of Nanotechnology, School of Engineering, , Far Eastern Federal University, ; Vladivostok, Russia
                [8 ]GRID grid.465429.8, ISNI 0000 0001 1012 0610, N.I. Vavilov All-Russian Institute of Plant Genetic Resources, ; Saint-Petersburg, Russia
                [9 ]GRID grid.4643.5, ISNI 0000 0004 1937 0327, Laboratory of Supramolecular and Bio-Nanomaterials, Department of Chemistry, , Materials, and Chemical Engineering “Giulio Natta” Politecnico Di Milano, ; Via L. Mancinelli 7, 20131 Milano, Italy
                [10 ]GRID grid.412211.5, Laboratory of Nanoradiopharmacy and Synthesis of Radiopharmaceuticals, , Zona Oeste State University, ; Av Manuel Caldeira de Alvarenga, 200, Campo Grande, Rio de Janeiro, 2100000 Brazil
                Author information
                http://orcid.org/0000-0002-7221-6404
                Article
                444
                10.1007/s40097-021-00444-3
                8419677
                34512930
                6bb1e537-d63c-4ed0-beda-e4729950d7d0
                © Islamic Azad University 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 25 June 2021
                : 30 August 2021
                Funding
                Funded by: cnpq
                Award ID: Bolsa Produtividade 1B
                Award Recipient :
                Categories
                Review

                graphene,nanomaterials,carbon,nanoparticles,nanomedicine
                graphene, nanomaterials, carbon, nanoparticles, nanomedicine

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