Synthesis, Biological Evaluation and Docking Studies of Chalcone and Flavone Analogs as Antioxidants and Acetylcholinesterase Inhibitors

Several oxidative processes are related to a wide range of human chronic and degenerative diseases, like Alzheimer’s disease, which also has been related to cholinergic processes. Therefore, search for new or improved antioxidant molecules with acetylcholinesterase activity is essential to offer alternative chemotherapeutic agents to support current drug therapies. A series of chalcone (2a–2k) and flavone (3a–3k) analogs were synthesized, characterized, and evaluated as acetylcholinesterase (AChE) inhibitors, and antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2-20-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS•), and β-carotene/linoleic acid bleaching assay. Compounds more active were 3j and 2k in DPPH with EC50 of 1 × 10−8 and 5.4 × 10−3 µg/mL, respectively; 2g and 3i in ABTS (1.14 × 10−2 and 1.9 × 10−3 µg/mL); 2e, 2f, 3f, 2j, and 3j exceeded the α-tocopherol control in the β-carotene assay (98–99% of antioxidant activity). At acetylcholinesterase inhibition assay, flavones were more active than chalcones; the best results were compounds 2d and 3d (IC50 21.5 and 26.8 µg/mL, respectively), suggesting that the presence of the nitro group enhances the inhibitory activity. The docking of these two structures were made to understand their interactions with the AChE receptor. Although further in vivo testing must be performed, our results represent an important step towards the identification of improved antioxidants and acetylcholinesterase inhibitors

Synthesis, characterization and biological evaluation of octyltrimethylammonium tetrathiotungstate

Octyltrimethylammonium tetrathiotungstate salt (ATT-C8) was synthesized and its ability to chelate copper was evaluated. The biological and toxic aspects were evaluated by in vitro and in vivo assays, using bovine aorta endothelial cells (BAEC) and zebrafish (Danio rerio) embryos. The obtained results suggest that ATT-C8 has better biocompatibility, showing a significantly lower lethal concentration 50 (LC50) value in comparison to ammonium tetrathiotungstate (ATT). Zebrafish embryos assay results indicate that both tetrathiotungstate salts at the studied concentrations increase the hatching time. Even more, an in vivo assay showed that synthesized materials behave as copper antagonists and have the ability to inhibit its toxicological effects. Also, both materials were found to be active for the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The characterization of the materials was carried out using the following spectroscopic techniques: Ultraviolet–Visible (UV–Vis), Fourier Transform Infrared (FTIR) and proton nuclear magnetic resonance (1H-NRM).The authors gratefully acknowledge the financial support provided by the UABC-UNAM SENERCONACYT 117373 project. Authors thank David Navas Fernandez for excellent technical support in these experiments, as well as Dr. Raúl Romero Rivera for his valuable comments. The scientific work developed by MAM’s group is supported by grants PID2019-105010RB-I00 (Spanish Ministry of Science, Innovation and Universities), and UMA18- FEDERJA-220 (Andalusian Government and FEDER) and funds from group BIO 267 (Andalusian Government), as well as funds from ‘‘Plan Propio de Investigación y Transferencia’’ (U. Málaga)

Impact of treatment and clinical characteristics on the survival of children with medulloblastoma in Mexico

IntroductionData on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico’s healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting.MethodsA retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico.ResultsHigh-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01)

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

1er. Coloquio de educación para el diseño en la sociedad 5.0

Las memorias del 1er. Coloquio de Educación para el Diseño en la Sociedad 5.0 debenser entendidas como un esfuerzo colectivo de la comunidad de académicos de la División de Ciencias y Artes para el Diseño, que pone de manifiesto los retos y oportunidades que enfrenta la educación en diseño en un contexto de cambio acelerado y rompimiento de paradigmas.El evento se realizó el pasado mes de mayo de 2018 y se recibieron más de 50 ponencias por parte de las profesoras y profesores de la División.Las experiencias y/o propuestas innovadoras en cuanto a procesos de enseñanza y aprendizaje que presentan los autores en cada uno de sus textos son una invitación a reflexionar sobre nuestra situación actual en la materia, y emprender acciones en la División para continuar brindando una educación de calidad en diseño a nuestras alumnas, alumnos y la sociedad.Adicionalmente, se organizaron tres conferencias magistrales sobre la situación actual de la educación en Diseño y de las Instituciones de Educación Superior, impartidas por el Mtro. Luis Sarale, profesor de la Universidad Nacional de Cuyo en Mendoza (Argentina), y Presidente en su momento, de la Red de Carreras de Diseño en Universidades Públicas Latinoamericanas (DISUR), el Dr. Romualdo López Zárate, Rector de la Unidad Azcapotzalco, así como del Mtro. Luis Antonio Rivera Díaz, Jefe de Departamento de Teoría y Procesos del Diseño de la División de la Ciencias de la Comunicación y Diseño, en la Unidad Cuajimalpa de nuestra institución.La publicación de estas memorias son un esfuerzo divisional, organizado desde la Coordinación de Docencia Divisional y la Coordinación de Tecnologías del Aprendizaje, del Conocimiento y la Comunicación, para contribuir a los objetivos planteados en el documento ACCIONES:Agenda CyAD2021, en particular al eje de Innovación Educativa. Es necesario impulsar a todos los niveles de la División espacios de discusión orientados a reflexionar sobre el presente y futuro en la educación del diseñador, que contribuya a mejorar la calidad de la docencia y favorezca al fortalecimiento de los procesos de enseñanza y aprendizaje.Finalmente, extiendo un amplio reconocimiento a todos los miembros de la División que hicieron posible este evento, así como a todos los ponentes y participantes por compartir su conocimiento para que la División sea cada día mejor

Mononuclear and Tetranuclear Copper(II) Complexes Bearing Amino Acid Schiff Base Ligands: Structural Characterization and Catalytic Applications

Two new glycine-Schiff base copper(II) complexes were synthesized. Single crystal X-ray diffraction (SCXRD) allowed us to establish the structure of both complexes in the solid state. The glycine-Schiff base copper(II) complex derived from 2′-hydroxy-5′-nitroacetophenone showed a mononuclear hydrated structure, in which the Schiff base acted as a tridentate ligand, and the glycine-Schiff base copper(II) complex derived from 2′-hydroxy-5′-methylacetophenone showed a less common tetranuclear anhydrous metallocyclic structure, in which the Schiff base acted as a tetradentate ligand. In both compounds, copper(II) had a tetracoordinated square planar geometry. The results of vibrational, electronic, and paramagnetic spectroscopies, as well as thermal analysis, were consistent with the crystal structures. Both complexes were evaluated as catalysts in the olefin cyclopropanation by carbene transference, and both led to very high diastereoselectivity (greater than 98%)

Chemical Tools of <i>Octopus maya</i> during Crab Predation Are Also Active on Conspecifics

<div><p><i>Octopus maya</i> is a major socio-economic resource from the Yucatán Peninsula in Mexico. In this study we report for the first time the chemical composition of the saliva of <i>O</i>. <i>maya</i> and its effect on natural prey, i.e. the blue crab (<i>Callinectes sapidus</i>), the crown conch snail (<i>Melongena corona bispinosa</i>), as well as conspecifics. Salivary posterior glands were collected from octopus caught by local fishers and extracted with water; this extract paralyzed and predigested crabs when it was injected into the third pereiopod. The water extract was fractionated by membrane ultrafiltration with a molecular weight cut-off of 3kDa leading to a metabolic phase (>3kDa) and a neurotoxic fraction (<3kDa). The neurotoxic fraction injected in the crabs caused paralysis and postural changes. Crabs recovered to their initial condition within two hours, which suggests that the effects of the neurotoxic fraction were reversible. The neurotoxic fraction was also active on <i>O</i>. <i>maya</i> conspecifics, partly paralyzing and sedating them; this suggests that octopus saliva might be used among conspecifics for defense and for reduction of competition. Bioguided separation of the neurotoxic fraction by chromatography led to a paralysis fraction and a relaxing fraction. The paralyzing activity of the saliva was exerted by amino acids, while the relaxing activity was due to the presence of serotonin. Prey-handling studies revealed that <i>O</i>. <i>maya</i> punctures the eye or arthrodial membrane when predating blue crabs and uses the radula to bore through crown conch shells; these differing strategies may help <i>O</i>. <i>maya</i> to reduce the time needed to handle its prey.</p></div

Injury to the eye of <i>Callinectes sapidus</i> after an attack by <i>Octopus maya</i>.

<p>A) Normal physiognomy of the peduncle eye (stereoscopic microscope 3X). B) Injury to the rostrum of a crab attacked by <i>O</i>. <i>maya</i> (stereoscopic microscope 3X).</p