Browsing by Author "Pino Sans, Javier del"
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Publication APRENDIZAJE GLOBAL, FLEXIBLE Y PERSONALIZADO PARA ATENDER LA DIVERSIDAD Y FAVORECER LA INSERCION LABORAL DE LOS ESTUDIANTES, MEDIANTE EL USO DEL FLIPPED LEARNING (MICRO-LEARING/TEACHING), A TRAVÉS DEL USO DE INFOGRAFIAS Y HERRAMIENTAS TACs DIGITALES(2023-07-12) Moyano-Cires Ivanoff, Paula Viviana; Abascal Camacho, Mª Luisa; Anadón Baselga, Mª José; Bellón López, Miguel Angel; Capo Marti, Miguel Andres; Frias Gonzalez, Mariano de; Frejo Moya, Maria Teresa; Flores Calle, Andrea; García Lobo, Jimena; García Sánchez, Jose Manuel; Guerra Menendez, Lucia; Lobo Alonso, Margarita; Naval Lopez, Maria Victoria; Pelayo Alarcon, Adela; Pino Sans, Javier del; Pinzón Bayón, Alba; Ruiz Fernández, Matilde; Sanjuán López, Javier; Sola Vendrell, EmmaPublication Aprendizaje global, flexible y personalizado para atender la diversidad y la inserción laboral, usando el flipped learning, integrando mundos y sistemas virtuales de respuesta en el aula, y otras herramientas TACs digitales(2022) Moyano-Cires Ivanoff, Paula; Anadón Baselga, María José; Pino Sans, Javier del; Frejo Moya, María Teresa; Pelayo Alarcon, Adela; Sola Vendrell, Emma; Naval López, María Victoria; Capo Marti, Miguel Andrés; Guerra Menéndez, Lucia; Flores Calle, Andrea; Ruiz Fernandez, Matilde; García Sánchez, José Manuel; Garcia Lobo, Jimena; Lobo Alonso, Margarita; De Frías González, Mariano; Sanjuán López, Javier; Vílchez Romero, Carmen; Sanz Rey, Laura; Manzano Reyes, Ana María; Bellón López, Miguel AngelPublication Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption(Elsevier, 2021-12-28) Sola Vendrell, Emma; Moyano-Cires Ivanoff, Paula Viviana; Flores, Andrea; Garcia Lobo, Jimena; García Sánchez, José Manuel; Anadón Baselga, María José; Frejo Moya, María Teresa; Pelayo Alarcon, Adela; Fernández Fernández, María de la Cabeza; Pino Sans, Javier delCadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neurons (BFCN) regulate cognitive functions. BFCN loss or cholinergic neurotransmission dysfunction leads to cognitive disabilities. Thyroid hormones (THs) maintain BFCN viability and functions, and Cd disrupts their levels. However, Cd-induced BFCN damages and THs disruption involvement was not studied. To research this we treated male Wistar rats intraperitoneally with Cd once (1 mg/kg) or repetitively for 28 days (0.1 mg/kg) with/without triiodothyronine (T3, 40 µg/kg/day). Cd increased thyroid-stimulating-hormone (TSH) and decreased T3 and tetraiodothyronine (T4). Cd altered cholinergic transmission and induced a more pronounced neurodegeneration on BFCN, mediated partially by THs reduction. Additionally, Cd antagonized muscarinic 1 receptor (M1R), overexpressed acetylcholinesterase S variant (AChE-S), downregulated AChE-R, M2R, M3R and M4R, and reduced AChE and choline acetyltransferase activities through THs disruption. These results may assist to discover cadmium mechanisms that induce cognitive disabilities, revealing a new possible therapeutic tool.Publication Efectos del amitraz sobre neurotransmisores monoaminérgicos en el sistema nervioso central de rata(Universidad Complutense de Madrid, Servicio de Publicaciones, 2010-02-11) Pino Sans, Javier del; Martínez-Larrañaga, María Rosa; Anadón Navarro, ArturoPor todo ello, el presente trabajo de investigación tiene dos objetivos: (1) el estudio de las posibles alteraciones en los sistemas serotoninérgico, noradrenérgico y dopaminérgico en regiones del SNC de ratas de edad 30 y 60 días expuestas a dosis múltiples de amitraz, y (2) el estudio de las posibles alteraciones permanentes heredadas en ratas a la edad de 60 días, procedentes de madres a las que se les administró amitraz durante el periodo de la preñez y la lactancia. La elección de la rata como modelo animal experimental se justifica, en general, en que los roedores poseen una serie de ventajas para los estudios toxicológicos, como son su pequeño tamaño, fácil manejo, resistencia a infecciones, corto ciclo de vida y de gestación, y grandes camadas (en número). Además, es un modelo animal aceptado para proporcionar datos que pueden ser incorporados a la evaluación del riesgo para el hombre de pesticidas. En los estudios de niveles de neurotransmisores en el SNC, la rata tiene la ventaja añadida de que por el tamaño de su encéfalo permite una buena localización de las distintas regiones encefálicas. Además, a fecha de hoy existen distintos atlas que detallan la anatomía de su sistema nervioso y la distribución de las sustancias neuroactivas (PAROXINOS y WATSON, 1998; TOHYAMA y TAKATSUJI, 1998).Publication Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ1–42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells(ACS Publications, 2022-11-17) Abascal, Maria Luisa; Sanjuan, Javier; Moyano-Cires Ivanoff, Paula Viviana; Sola Vendrell, Emma; Flores, Andrea; García Sánchez, José Manuel; García Lobo, Jimena; Frejo Moya, María Teresa; Pino Sans, Javier delAcute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aβ1–42 and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3β (p-GSK3β; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction.Publication Neuroprotective Action of Multitarget 7-Aminophenanthridin-6(5H)-one Derivatives against Metal-Induced Cell Death and Oxidative Stress in SN56 Cells(ACS Publications, 2021-08-30) Moyano-Cires Ivanoff, Paula Viviana; Vicente Zurdo, David; Blázquez-Barbadillo, Cristina; Menéndez Ramos, José Carlos; González Matilla, Juan Francisco; Rosales Conrado, Noelia; Pino Sans, Javier delNeurodegenerative diseases have been associated with brain metal accumulation, which produces oxidative stress (OS), matrix metalloproteinases (MMPs) induction, and neuronal cell death. Several metals have been reported to downregulate both the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the antioxidant enzymes regulated by it, mediating OS induction and neurodegeneration. Among a recently discovered family of multitarget 7-amino-phenanthridin-6-one derivatives (APH) the most promising compounds were tested against metal-induced cell death and OS in SN56 cells. These compounds, designed to have chelating activity, are known to inhibit some MMPs and to present antioxidant and neuroprotective effects against hydrogen peroxide treatment to SN56 neuronal cells. However, the mechanisms that mediate this protective effect are not fully understood. The obtained results show that compounds APH1, APH2, APH3, APH4, and APH5 were only able to chelate iron and copper ions among all metals studied and that APH3, APH4, and APH5 were also able to chelate mercury ion. However, none of them was able to chelate zinc, cadmium, and aluminum, thus exhibiting selective chelating activity that can be partly responsible for their neuroprotective action. Otherwise, our results indicate that their antioxidant effect is mediated through induction of the Nrf2 pathway that leads to overexpression of antioxidant enzymes. Finally, these compounds exhibited neuroprotective effects, reversing partially or completely the cytotoxic effects induced by the metals studied depending on the compound used. APH4 was the most effective and safe compound.Publication Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6(5H)-one derivatives against metal-induced amyloid proteins generation and aggregation(Elsevier, 2022-07-02) Moyano-Cires Ivanoff, Paula Viviana; Vicente Zurdo, David; Blázquez Barbadillo, Cristina; Menéndez, J. Carlos; González Matilla, Juan Francisco; Rosales Conrado, Noelia; Pino Sans, Javier delBrain’s metals accumulation is associated with toxic proteins, like amyloid-proteins (Aβ), formation, accumulation, and aggregation, leading to neurodegeneration. Metals downregulate the correct folding, disaggregation, or degradation mechanisms of toxic proteins, as heat shock proteins (HSPs) and proteasome. The 7-amino-phenanthridin-6(5H)-one derivatives (APH) showed neuroprotective effects against metal-induced cell death through their antioxidant effect, independently of their chelating activity. However, additional neuroprotective mechanisms seem to be involved. We tested the most promising APH compounds (APH1-5, 10–100 μM) chemical ability to prevent metal-induced Aβ proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on Aβ formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against Aβ proteins (1 μM) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced Aβ proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced Aβ proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against Aβ proteins-induced neuronal cell death, reversing partially or completely this effect. These data may help to provide a new therapeutic approach against the neurotoxic effect induced by metals and other environmental pollutants, especially when mediated by toxic proteins.Publication Toxicological and pharmacological evaluation, antioxidant, ADMET and molecular modeling of selected racemic chromenotacrines {11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ols} for the potential prevention and treatment of Alzheimer’s disease(Elsevier, 2014-01-08) Oset Gasque, María Jesús; González Prieto, María Pilar; Pérez Peña, Javier; García Font, Nuria; Romero Martínez, Alejandro; Pino Sans, Javier del; Ramos, Eva; Hadjipavlou-Litina, Dimitra; Soriano, Elena; Chioua, Mourad; Samadi, Abdelouahid; Raghuvanshi, Dushyant S.; Singh, Krishna N.; Marco Contelles, JoséThe pharmacological analysis of racemic chromenotacrines (CT) 1e7, bearing the 11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol ring skeleton, in a series of experiments targeted to explore their potential use for the treatment of Alzheimer’s disease (AD), is reported. The toxicological evaluation showed that among all these chromenotacrines, CT6 is much less hepatotoxic than tacrine in a range of concentrations from 1 to 300 mM, measured as cell viability in HepG2 cells. Moreover, CT6 did not significantly increase lactate dehydrogenase, aspartate transaminase, and alanine transaminase release in HepG2 cells. Besides,CT6treatment exerts a high protective effect against thelipid peroxidationinduced after H2O2-treated SHSY5Y cells, in a concentration-dependent manner. CT6 showed an excellent antioxidant profile in the AAPH test, and protects against the decrease in cell viability induced by respiratory chain inhibitors (Oligomicyn A/Rotenone)and NO donors in neuronal cultures. This effect could be due to a mixed antiapoptotic and antinecrotic neuroprotective effect at low and intermediate CT6 concentrations, respectively. CT1-7 are potent and selective inhibitors of EeAChE in the submicromolar range. CT3 [IC50 (EeAChE) ¼ 0.007 0.003 mM], and CT6 [IC50 (EeAChE) ¼ 0.041 0.001 mM] are the most potent AChE inhibitors. Kinetic studies on the non-toxic chromenotacrine CT6 showed that this compound behaves as a non-competitive inhibitor (Ki ¼ 0.047 0.003 mM),indicating that CT6 binds at the peripheral anionic site, a fact confirmed by molecular modeling analysis. In silico ADMET analysis showed also that CT6 should have a moderate BBB permeability. Consequently, non-toxic chromenotacrine CT6can be considered as an ttractivemultipotent molecule for the potential treatment of AD.