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      Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment

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          Abstract

          In this work, new nanohybrids based on superparamagnetic iron oxide nanoparticles (SPIONs) were elaborated and discussed for the first time as nanovectors of a derivative molecule of trans-resveratrol (RSV), a natural antioxidant molecule, which can be useful for brain disease treatment. The derivative molecule was chemically synthesized (4’-hydroxy-4-(3-aminopropoxy) trans-stilbene: HAPtS) and then grafted onto SPIONs surface using an organosilane coupling agent, which is 3-chloropropyltriethoxysilane (CPTES) and based on nucleophilic substitution reactions. The amount of HAPtS loaded onto SPIONs surface was estimated by thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) analyses at 116 µmol·g −1 SPIONs. The synthesized HAPtS molecule, as well as the associated nanohybrids, were fully characterized by transmission electron microscopy (TEM), XPS, TGA, infrared (IR) and UV-visible spectroscopies, dynamic light scattering (DLS), and zeta potential measurements. The in vitro biological assessment of the synthesized nanohybrid’s efficiency was carried out on C6 glioma cells and showed that the nanovector SPIONs-CPTES-HAPtS do not affect the mitochondrial metabolism (MTT test), but damage the plasma membrane (FDA test), which could contribute to limiting the proliferation of cancerous cells (clonogenic test) at a HAPtS concentration of 50 µM. These nanoparticles have a potential cytotoxic effect that could be used to eliminate cancer cells.

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          The free radical theory of aging matures.

          The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it has attracted an increasing number of scientists from an expanding circle of fields. During the past decade, several lines of evidence have convinced a number of scientists that oxidants play an important role in aging. (For the sake of simplicity, we use the term oxidant to refer to all "reactive oxygen species," including O2-., H2O2, and .OH, even though the former often acts as a reductant and produces oxidants indirectly.) The pace and scope of research in the last few years have been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the literature. Therefore, we have systematically reviewed the status of the free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, the manipulation of metabolic activity and oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro senescence, classical and population genetics, molecular genetics, transgenic organisms, the study of human diseases of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.
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            Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

            The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.
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              SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

              A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                18 February 2019
                February 2019
                : 9
                : 2
                : 287
                Affiliations
                [1 ]Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS/Université Bourgogne Franche-Comté, 21000 Dijon, France; fadouasallem@ 123456gmail.com (F.S.); lionelmaurizi@ 123456gmail.com (L.M.); julien.boudon@ 123456u-bourgogne.fr (J.B.)
                [2 ]Institut de Chimie Moléculaire de l’Université de Bourgogne (ICMUB), UMR 6302 CNRS/Université Bourgogne Franche-Comté, 21000 Dijon, France; hajirihab22@ 123456yahoo.com (R.H.); dominique.vervandier-fasseur@ 123456u-bourgogne.fr (D.V.-F.)
                [3 ]Laboratoire Bio-PeroxIL, EA7270, Université de Bourgogne Franche-Comté/Inserm, 21000 Dijon, France; thomas.nury@ 123456u-bourgogne.fr (T.N.); gerard.lizard@ 123456u-bourgogne.fr (G.L.)
                Author notes
                Author information
                https://orcid.org/0000-0002-2998-5873
                https://orcid.org/0000-0002-6346-7623
                https://orcid.org/0000-0002-2500-5030
                https://orcid.org/0000-0001-6330-0172
                https://orcid.org/0000-0002-0127-3858
                Article
                nanomaterials-09-00287
                10.3390/nano9020287
                6409721
                30781702
                d391de72-285d-4f74-b895-fc60afc8617e
                © 2019 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
                : 09 January 2019
                : 15 February 2019
                Categories
                Article

                iron oxide superparamagnetic nanoparticles,trans-resveratrol derivative,drug delivery,glioma

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