RESENHA “GEOMETRIAS DA MEMÓRIA: CONFIGURAÇÕES PÓS-COLONIAIS” DE ANTÓNIO SOUSA RIBEIRO E MARGARIDA CALAFATE RIBEIRO

BOOK REVIEWRESENH

Le langage tropical de Sony Labou Tansi

L’écriture de Sony Labou Tansi engage une réflexion historique, politico-sociale et idéologique par l’emploi d’un mode de langage qui bouleverse les normes. Par l’analyse de deux de ses romans, La vie et demie et Les sept solitudes de Lorsa Lopez nous voulons montrer comment il s’approprie de la langue française pour faire de l’hybridation un troisième espace habité et habitable par la différence, une différence créatrice de nouvelles possibilités de comprendre le divers.A escrita de Sony Labou Tansi mobiliza uma reflexão histórica, política, social e ideológica a partir do uso de um modo de linguagem que perturba as normas. Pela análise de dois romances, La vie et demie e Les sept solitudes de Lorsa Lopez, nós queremos mostrar como ele se apropria da língua francesa para fazer da hibridação um terceiro espaço habitável pela diferença, diferença essa criadora de novas possibilidades de compreender o diverso

Tiam1 as a Signaling Mediator of Nerve Growth Factor-Dependent Neurite Outgrowth

Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras-GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF

Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks

Alzheimer disease (AD) is the most common neurodegenerative disease featuring progressive and degenerative neurological impairments resulting in memory loss and cognitive decline. The specific mechanisms underlying AD are still poorly understood, but it is suggested that a deficiency in the brain neurotransmitter acetylcholine, the deposition of insoluble aggregates of fibrillar β-amyloid 1–42 (Aβ42), and iron and glutamate accumulation play an important role in the disease progress. Despite the existence of approved cholinergic drugs, none of them demonstrated effectiveness in modifying disease progression. Accordingly, the development of new chemical entities acting on more than one target is attracting progressively more attention as they can tackle intricate network targets and modulate their effects. Within this endeavor, a series of mitochondriotropic antioxidants inspired on hydroxycinnamic (HCA’s) scaffold were synthesized, screened toward cholinesterases and evaluated as neuroprotectors in a differentiated human SH-SY5Y cell line. From the series, compounds 7 and 11 with a 10-carbon chain can be viewed as multi-target leads for the treatment of AD, as they act as dual and bifunctional cholinesterase inhibitors and prevent the neuronal damage caused by diverse aggressors related to protein misfolding and aggregation, iron accumulation and excitotoxicityThis work was funded by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and national funds by FCT-Foundation for Science and Technology under research grants (UID/QUI/00081, NORTE-01-0145-FEDER-000028, PTDC/DTP-FTO/2433/2014, PTDC/BIA-MOL/28607/2017, POCI-01-0145-FEDER-028607). S. Benfeito and C. Fernandes grants are supported by FCT, POPH and QREN. The authors also thank the COST action CA15135 for supportS

Solid Lipid Nanoparticles: Multitasking Nano-Carriers for Cancer Treatment

Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment

Limitaciones para la implementación de la lactancia materna exclusiva y su efecto en el estado nutricional de los niños menores de 1 año

La mayoría de las madres pueden y deberían amamantar a sus hijos, la implementación de una lactancia materna adecuada podría prevenir la muerte de 820 000 menores de 5 años en todo el mundo (Organización Mundial de la Salud [OMS], 2018). En Nicaragua se ha abordado muy poco esta temática a pesar de su relevancia en la salud infantil por tanto el presente estudio tuvo como objetivo determinar las limitaciones para la implementación de la lactancia materna exclusiva y su efecto en el estado nutricional de los niños menores de 1 año atendidos en la consulta externa de pediatría del Hospital Alemán Nicaragüense en el mes de mayo de 2019. Se realizó un estudio descriptivo de corte transversal, la muestra fueron 120 madres y niños menores de 1 año, la cual se obtuvo mediante un muestreo por conveniencia utilizando como instrumento una encuesta y ficha de recolección de información, obteniendo los siguientes resultados: el 35.8% de las madres encuestadas tenía entre 16 a 20 años de las cuales el 18.3% brindó lactancia materna, el 65.8% refirió estar en unión libre y tener escolaridad secundaria, ser amas de casa que provenían de la ciudad de Managua y reportaron 1 parto previo además de depresión postparto. Al interrogar a las pacientes sobre cómo consideraban la lactancia materna el 4.2% considera que es una práctica indecente por lo que no brinda lactancia materna, El 59.25% mencionó falta de apoyo familiar y el 40.8%de las mujeres encuestadas tuvieron un conocimiento regular sobre la lactancia materna. El 66.7% refirió haber recibido consejería sobre lactancia y no reportaron enfermedades de la mama, infecciones o enfermedades graves, ni uso de drogas ni fármacos que dificultaran la lactancia, el 45.8 % no reporto factores del niño que impidieran la lactancia, el 35.8% de los niños tenía subnutrición grave y el 36.7% tenían entre 1 a 3 meses de edad. Concluimos que el principal factor psicosocial que influye en la negación de la lactancia materna es la falta de apoyo familiar y no la edad de la madre, la negación de lactancia materna repercute en el estado nutricional del niño por lo que recomendamos el fortalecimiento sobre la concientización de sus beneficios

Computational Drug Target Screening through Protein Interaction Profiles

The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50 values of 25 and 65μM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3′-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50 in hCOX-1 of 24 and 25μM respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin3′-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25μM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safetyThis study was supported by grant R01 LM006910 (GH) “Discovering and Applying Knowledge in Clinical Databases” from the U.S. National Library of Medicine, “Angeles Alvariño, Plan Galego de Investigación, Innovación e Crecemento 2011–2015 (I2C)” and European Social Fund (ESF)S

Autogestão da doença crónica: dos modelos aos programas de intervenção

info:eu-repo/semantics/publishedVersio

Structural Modifications on Natural-based Products: Synthetic Strategies and Biological Applications

Coumarins are a class of heterocyclic compounds present in a significant quantity in several plants. The simplest coumarin, a benzene ring fused with a pyran-2-one heterocycle, was first discovered in the 19th century and since then, due to the synthetic accessibility and the biological properties of its derivatives, has been playing an important role in the Medicinal Chemistry field. In fact, coumarins have been previously described as anticancer, antiviral, anti-inflammatory, antimicrobial, enzymatic inhibitory and antioxidant agents.Another two interesting compounds found widely in nature are resveratrol derivatives and chalcones. Both families of compounds are known for having remarkable antioxidant activity, cardio- and neuroprotective effects, among other relevant biological properties. Therefore, we devised several synthetic strategies to incorporate these natural products in one compound, combining their potential as promising agents for the treatment of several illnesses. In our group, we have already synthesised multiple novel compounds incorporating into the coumarin scaffold the resveratrol or chalcones moieties with remarkable activities towards different pharmacological targets. In this work, we continue exploiting this strategy by incorporating different linkers at coumarin position 3, thus giving us a wide range of possibilities for new compound