Chitosan-Gold Nanoparticle Composites for Biomedical Application

The aim of this work is to synthesize chitosan-gold nanoparticles films by direct chemical reduction of HAuCl4 in a chitosan solution and to investigate the influence of gold nanoparticles concentration on the structure of films, conductivity and healing effect on mice skin after surgery. Results obtained have shown that new chitosan-gold nanoparticle-collagen bionananocomposites demonstrated better healing effect on the mice skin after surgery than control performed on commercial TheraFormTM material. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3540

Period Change Rates of Large Magellanic Cloud Cepheids using MESA

Pulsating stars, such as Cepheids and RR Lyrae, offer us a window to measure and study changes due to stellar evolution. In this work, we study the former by calculating a set of evolutionary tracks of stars with an initial mass of 4 to 7 $M_\odot$, varying the initial rotation rate and metallicity, using the stellar evolution code Modules for Experiments in Stellar Astrophysics (MESA). Using Radial Stellar Pulsations (RSP), a recently added functionality of MESA, we obtained theoretical instability strip (IS) edges and linear periods for the radial fundamental mode. Period-age, period-age-temperature, period-luminosity, and period-luminosity-temperature relationships were derived for three rotation rates and metallicities, showing a dependence on crossing number, position in the IS, rotation, and metallicity. We calculated period change rates (PCRs) based on the linear periods from RSP. We compared our models with literature results using the Geneva code, and found large differences, as expected due to the different implementations of rotation between codes. In addition, we compared our theoretical PCRs with those measured in our recent work for Large Magellanic Cloud Cepheids. We found good overall agreement, even though our models do not reach the short-period regime exhibited by the empirical data. Implementations of physical processes not yet included in our models, such as pulsation-driven mass loss, an improved treatment of convection that may lead to a better description of the instability strip edges, as well as consideration of a wider initial mass range, could all help improve the agreement with the observed PCRs.Comment: 19 pages, 17 figures. Accepted by MNRA

Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment?

[Background]: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO2peak)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. [Methods]: We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO2peak in patients (both sexes, N = 145) and healthy controls (N = 133). [Results]: Besides corroborating very poor VO2peak values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. [Conclusions]: In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses.The present study was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, PI17/02052, PI18/00139, PI19/01313, and PI20/00645) and cofunded by ‘Fondos FEDER’. Gisela Nogales-Gadea and Carmen Fiuza-Luces are supported by the Miguel Servet research contracts (ISCIII CD14/00032 and CP18/00034, respectively and cofounded by Fondos FEDER′). Research by Pedro L. Valenzuela is funded by a postdoctoral contract granted by Instituto de Salud Carlos III (Sara Borrell, CD21/00138). Monica Villarreal Salazar is supported by the Mexican National Council for Science and Technology (CONACYT)

New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati

Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future

New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati

Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future

IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain

Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics. Here, we evaluated the mechanical antinociceptive effect of IQM-PC332, a novel ligand of the multifunctional protein downstream regulatory element antagonist modulator (DREAM) in rats subjected to chronic constriction injury of the sciatic nerve as a model of neuropathic pain. IQM-PC332 administered by intraplantar (0.01–10 µg) or intraperitoneal (0.02–1 µg/kg) injection reduced mechanical sensitivity by ≈100% of the maximum possible effect, with ED50 of 0.27 ± 0.05 µg and 0.09 ± 0.01 µg/kg, respectively. Perforated-patch whole-cell recordings in isolated dorsal root ganglion (DRG) neurons showed that IQM-PC332 (1 and 10 µM) reduced ionic currents through voltage-gated K+ channels responsible for A-type potassium currents, low, T-type, and high voltage-activated Ca2+ channels, and transient receptor potential vanilloid-1 (TRPV1) channels. Furthermore, IQM-PC332 (1 µM) reduced electrically evoked action potentials in DRG neurons from neuropathic animals. It is suggested that by modulating multiple DREAM–ion channel signaling complexes, IQM-PC332 may serve a lead compound of novel multimodal analgesics

Proyecto COSINES: abordando el reto de relacionar fenómenos meteorológicos costeros y retroceso de acantilados en Asturias

Ponencia presentada en: XXXV Jornadas Científicas de la AME y el XIX Encuentro Hispano Luso de Meteorología celebrado en León, del 5 al 7 de marzo de 2018.La costa es un entorno muy sensible a los cambios ambientales y climáticos, respondiendo rápidamente a ellos. El escenario actual de calentamiento global predice un ascenso del nivel del mar y un incremento en la intensidad y frecuencia de los temporales, por lo que es esperable una intensificación del oleaje y de la actividad geomorfológica costera. Por ello, en las costas acantiladas se prevé un incremento de las inestabilidades de ladera, considerados el proceso más importante de retroceso costero. Asturias es una región con 660 km de línea de costa, de los que, más de la mitad corresponden a acantilados donde son frecuentes las inestabilidades de ladera. Por otra parte, los municipios costeros presentan además de la exposición al riesgo, una gran vulnerabilidad social y económica debido a su elevada densidad de población, numerosas infraestructuras, actividad industrial y patrimonio cultural. Teniendo en cuenta lo anterior, se ha puesto en marcha el proyecto de investigación “INEStabilidad de laderas como indicador del retroceso de la COSta cantábrica: caracterización multidisciplinar, COSINES”, financiado en la Convocatoria 2017 de Proyectos RETOS de Investigación de la Agencia Estatal de Investigación. El proyecto pretende caracterizar cualitativa y cuantitativamente el retroceso de la costa asturiana utilizando como indicador las inestabilidades en acantilados. Sus objetivos específicos son: 1) establecer la distribución espacial de movimientos de ladera en los acantilados; 2) determinar su tipología; 3) establecer el papel de sus factores condicionantes (litología y estructura geológica) y desencadenantes (fenómenos meteorológicos); 4) elaborar modelos conceptuales de su funcionamiento; 5) establecer su evolución en términos espaciales y temporales; y 6) cuantificar su contribución al retroceso de la línea costera.Esta investigación forma parte del Proyecto “COSINES” (CGL2017-83909-R), de la Convocatoria 2017 de Proyectos RETOS financiada por el Ministerio de Economía, Industria y Competitividad (MINECO), la Agencia Estatal de Investigación (AEI) y el Fondo Europeo de Desarrollo Regional (FEDER)