Angiotensin Receptors Heterodimerization and Trafficking: How Much Do They Influence Their Biological Function?

G-protein–coupled receptors (GPCRs) are targets for around one third of currently approved and clinical prescribed drugs and represent the largest and most structurally diverse family of transmembrane signaling proteins, with almost 1000 members identified in the human genome. Upon agonist stimulation, GPCRs are internalized and trafficked inside the cell: they may be targeted to different organelles, recycled back to the plasma membrane or be degraded. Once inside the cell, the receptors may initiate other signaling pathways leading to different biological responses. GPCRs’ biological function may also be influenced by interaction with other receptors. Thus, the ultimate cellular response may depend not only on the activation of the receptor from the cell membrane, but also from receptor trafficking and/or the interaction with other receptors. This review is focused on angiotensin receptors and how their biological function is influenced by trafficking and interaction with others receptors.Fil: Rukavina Mikusic, Natalia Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Silva, Mauro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Pineda, Angélica M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Widespread cortical thinning, excessive glutamate and impaired linguistic functioning in schizophrenia: A cluster analytic approach

Introduction: Symptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structure, is suspected in schizophrenia, we aimed to first seek patient subgroups with different neurobiological signatures and then quantify linguistic indices that capture the symptoms of “negative formal thought disorder” (i.e., fluency, cohesion, and complexity of language production). Methods: Atlas-based cortical thickness values (obtained with a 7T MRI scanner) of 66 patients with first-episode psychosis and 36 healthy controls were analyzed with hierarchical clustering algorithms to produce neuroanatomical subtypes. We then examined the generated subtypes and investigated the quantitative differences in MRS-based glutamate levels [in the dorsal anterior cingulate cortex (dACC)] as well as in three aspects of language production features: fluency, syntactic complexity, and lexical cohesion. Results: Two neuroanatomical subtypes among patients were observed, one with near-normal cortical thickness patterns while the other with widespread cortical thinning. Compared to the subgroup of patients with relatively normal cortical thickness patterns, the subgroup with widespread cortical thinning was older, with higher glutamate concentration in dACC and produced speech with reduced mean length of T-units (complexity) and lower repeats of content words (lexical cohesion), despite being equally fluent (number of words). Conclusion: We characterized a patient subgroup with thinner cortex in first-episode psychosis. This subgroup, identifiable through macroscopic changes, is also distinguishable in terms of neurochemistry (frontal glutamate) and language behavior (complexity and cohesion of speech). This study supports the hypothesis that glutamate-mediated cortical thinning may contribute to a phenotype that is detectable using the tools of computational linguistics in schizophrenia

Programa de Intervenção e Educação em Saúde Antibullying (PIESA): validação através do método DELPHI

Para a construção de um modelo prático de intervenção antibullying é necessário dotar as escolas com instrumentos institucionais, pedagógicos e disciplinares, para que possam concretizar sua função formativa e socializadora. Para tanto é fundamental envolver a gestão escolar, estabelecer espaços de discussão a partir do seu projeto educativo e contemplar experiências lúdicas, como um dos eixos do trabalho educativo, e a articulação com a rede social básica, a exemplo da área da saúde. Assim objetiva-se apresentar a proposta de um programa de intervenção antibullying na escola, os resultados da validação e sua pertinência para atuação do enfermeiro no contexto escolar. O programa foi denominado de Programa de Intervenção e Educação em Saúde Antibullying – PIESA e é composto por 6 domínios e 25 recomendações. O método Delphi foi utilizado para a obtenção do consenso entre 11 especialistas. Cada domínio e recomendação foram considerados adequados ao programa de intervenção quando obteve entre os especialistas o valor igual ou superior a 80% de consenso. Após a primeira rodada de avaliação do programa, observou-se que a maioria dos domínios apresentou concordância total, ou seja, 100% de consenso quanto a sua relevância. Os domínios que apresentaram concordância parcial ainda apresentaram um alto grau de consenso, ou seja, acima de 80% quanto a sua relevância. Na segunda rodada a recomendação que insere a participação do enfermeiro no planejamento escolar obteve 90,9% de consenso entre os especialistas, afirmando que o programa delineado atende às prerrogativas da atuação do enfermeiro no contexto escolar. A atuação do enfermeiro na escola e a promoção da educação dialógica, crítica e reflexiva fundamentada particularmente em metodologias ativas e participativas poderão possibilitar uma postura proativa, crítica e emancipatória dos alunos para o enfrentamento das situações do bullying entre pares.CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT

Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction

Although metastasis is the primary cause of death in patients with malignant solid tumors, efficient anti-metastatic therapies are not clinically available currently. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting on different steps of the metastatic process. Oversulfated dermatan sulfates from ascidians are effective in preventing metastasis by inhibition of P-selectin, a platelet surface protein involved in the platelet-tumor cell emboli formation. We report in this work that the heparan sulfate isolated from the viscera of the ascidian Phallusia nigra drastically attenuates metastases of colon carcinoma cells in mice. Our in vitro and in vivo assessments demonstrate that the P. nigra glycan has very low anticoagulant and antithrombotic activities and a reduced hypotension potential, although it efficiently prevented metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug

Antioxidant, photoprotective and inhibitory activity of tyrosinase in extracts of Dalbergia ecastaphyllum

Dalbergia ecastaphyllum is a native Brazil plant with importance for beekeeping, and widely used in folk medicine. For the first time, the extracts of this plant were assessed for the presence of hydrophilic and lipophilic antioxidants, as well as inhibition of tyrosinase, free radicals scavenging and sunscreen protection. The antioxidant activity was evaluated by free radical scavenging (DPPH) andβ-carotene bleaching assay. The tyrosinase inhibitory activity was evaluated and calculated the EC50. The photoprotective activity was measured using different concentrations of D. ecastaphyllum extracts. The Sun Protection Factor (SPF) of the samples was higher than 6, and the sample from Ilhe ´us showed the most pronounced photoprotective effect. Sample from Canavieiras presented the highest antioxidant activity by free radical scavenging DPPH andβ-carotene bleaching method, with 92.41% and 48.34%, respectively. All samples inhibited the tyrosinase, especially the sample from Prado that was most effective (124.62μg.mL-1). Significant negative correlation was found between flavonoid contents and inhibition of tyrosinase. The overall results provide relevant information about the Dalbergia ecastaphyllum species, indicating as potential material to cosmetic and pharmaceutical industry.We thank MSc Vandira Pereira da Mata for the support during the sample collectioninfo:eu-repo/semantics/publishedVersio

Antioxidant and antimicrobial films based on brewers spent grain arabinoxylans, nanocellulose and feruloylated compounds for active packaging

In this study, brewers spent grain (BSG) arabinoxylans-based nanocomposite films were prepared by solvent casting of arabinoxylans (AX) suspensions containing different amounts of nanofibrillated cellulose (NFC, 5, 10, 25, 50 and 75% mass fraction). The obtained nanocomposite films were homogeneous and presented thermal stability up to 230 °C and good mechanical properties (Young's modulus up to 7.5 GPa). Additionally, the films with 50% NFC were loaded with ferulic acid or feruloylated arabinoxylo-oligosaccharides enriched fraction from BSG (75 mg per g of film). This combination enhanced the UV–Vis barrier properties and imparted additional functionalities to the films, namely (i) antioxidant activity up to 90% (DPPH scavenging activity), (ii) antibacterial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, and (iii) antifungal activity towards the polymorphic fungus Candida albicans. Therefore, these fully biobased nanocomposite films show potential for application as active food packaging systems.publishe

Chemical composition and biological activities of mono- and heterofloral bee pollen of different geographical origins

Recent research shows variations in pollen chemical constituents and, consequently, in their therapeutic properties. Mono and multifloral bee pollen extracts were investigated for antioxidant and enzyme inhibitory activity properties, phenolic compounds and fatty acid composition. Generally, Eucalyptus spp. and multifloral extracts exhibited potent inhibitory activity against -amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic activity. Cocos nucifera and Miconia spp. extracts exhibited important antioxidant properties in the different assays (ABTS, DPPH, -carotene/linoleic acid and reducing power). Moreover, these extracts had greater amounts of total phenols and flavonoids in comparison to others. The increase in antioxidant activity (decrease in EC50 values) was accompanied by an increase in the amount of total phenols in the extracts. The pollen extracts contained linoleic acid and -linolenic acid as major fatty acids, followed by palmitic acid, and oleic acid. In this study, differences were observed in both chemical constituents and biological activities of the samples related to the geographical and botanical origin of bee pollen.We thank the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES) and National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq) for a scholarship granted to Jucilene Silva Araújo (CAPES), for a research scholarship granted to Carlos Alfredo Lopes de Carvalho (CNPq), financial support for the project and scholarship (CAPES) granted to Emerson Dechechi Chambó, Leticia M. Estevinho and Samira Maria Peixoto Cavalcante da Silva. We thank beekeeper Márcio Brazil for the pollen samples. This work was supported by the strategic programmer UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the Fundação para a Ciência e a Tecnologia (FCT), Portugal and by the European Regional Development Fund (ERDF) through the COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI).info:eu-repo/semantics/publishedVersio

Phytochemical study and antioxidant activity of Dalbergia ecastaphyllum

The chemical profile of Dalbergia ecastaphyllum has been indicated as the botanical origin of Brazilian red propolis, an apicultural product with proven therapeutic properties. However, few studies have investigated this plant species. This study evaluated and compared microbiological quality, chemical composition, and antioxidant activity of stem and leaf samples of D. ecastaphyllum. The samples were collected in February 2015, in the southern region of the state of Bahia, Brazil. We performed the microbiological analyses, determined the contents of fatty acid, total phenol and flavonoid, and identified the chemical profile and antioxidant activit. Escherichia coli, Salmonella spp. and sulfite reducing clostridial spores were not detected in the samples. Acids of the family ω3 were recorded in the stems and ω6 in the leaves. The leaves presented better nutritional quality of the fraction, better antioxidant capacity in the tests by the DPPH method and β-carotene bleaching. There were 49 chemical compounds, of which 38 belonged to the class of flavonoids. The results indicate that stems and leaves of D. ecastaphyllum have biological properties. Leaves particularly are better for functional food formulation and as natural antioxidant.info:eu-repo/semantics/publishedVersio