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Acetylcholinesterase (AChE) enzymes play an essential role in the development of Alzheimer’s disease (AD). Its excessive activity causes several neuronal problems, particularly psychopathies and neuronal cell death. A bioactive pose on the hAChE B site of the human acetylcholinesterase (hAChE) enzyme employed in this investigation, which was obtained from the Protein Data Bank (PDB ID 4EY6), allowed for the prediction of the binding affinity and free binding energy between the protein and the ligand. Virtual screening was performed to obtain structures similar to Galantamine (GNT) with potential hAChE activity. The top 200 hit compounds were prioritized through the use of filters in ZincPharmer, with special features related to the pharmacophore. Critical analyses were carried out, such as hierarchical clustering analysis (HCA), ADME/Tox predictions, molecular docking, molecular simulation studies, synthetic accessibility (SA), lipophilicity, water solubility, and hot spots to confirm the stable binding of the two promising molecules (ZINC16951574-LMQC2, and ZINC08342556-LMQC5). The metabolism prediction, with metabolites M3-2, which is formed by Glutathionation reaction (Phase II), M1-2, and M2-2 formed from the reaction of S-oxidation and Aliphatic hydroxylation (Phase I), were both reactive but with no side effects. Theoretical synthetic routes and prediction of synthetic accessibility for the most promising compounds are also proposed. In conclusion, this study shows that in silico modeling can be used to create new drug candidate inhibitors for hAChE. The compounds ZINC16951574-LMQC2, and ZINC08342556-LMQC5 are particularly promising for oral administration because they have a favorable drug-likeness profile, excellent lipid solubility, high bioavailability, and adequate pharmacokinetics.

Inflammation is a complex reaction involving cellular and molecular components and an unspecific response to a specific aggression. The use of scientific and technological innovations as a research tool combining multidisciplinary knowledge in informatics, biotechnology, chemistry and biology are essential for optimizing time and reducing costs in the drug design. Thus, the integration of these in silico techniques makes it possible to search for new anti-inflammatory drugs with better pharmacokinetic and toxicological profiles compared to commercially used drugs. This in silico study evaluated the anti-inflammatory potential of two benzoylpropionic acid derivatives (MBPA and DHBPA) using molecular docking and their thermodynamic profiles by molecular dynamics, in addition to predicting oral bioavailability, bioactivity and toxicity. In accordance to our predictions the derivatives proposed here had the potential capacity for COX-2 inhibition in the human and mice enzyme, due to containing similar interactions with the control compound (ibuprofen). Ibuprofen showed toxic predictions of hepatotoxicity (in human, mouse and rat; toxicophoric group 2-arylacetic or 3-arylpropionic acid) and irritation of the gastrointestinal tract (in human, mouse and rat; toxicophoric group alpha-substituted propionic acid or ester) confirming the literature data, as well as the efficiency of the DEREK 10.0.2 program. Moreover, the proposed compounds are predicted to have a good oral bioavailability profile and low toxicity (LD50 < 700 mg/kg) and safety when compared to the commercial compound. Therefore, future studies are necessary to confirm the anti-inflammatory potential of these compounds.

The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using 1H NMR and 13C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.

The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones.

Based on ethnopharmacological studies, a lot of plants, as well as its compounds, have been investigated for the potential use as wound healing agents. In Brazil, Curatella americana is traditionally used by local people to treat wounds, ulcers and inflammations. However, to the best of our knowledge, its traditional use in the treatment of wounds has not been validated by a scientific study. Here, some compounds, many of them flavonoids, were identified in the hydroethanolic extract from the leaves of C. americana (HECA) by LC-HRMS and LC-MS/MS. Besides that, solutions containing different concentrations of HECA and a gel produced with this extract were evaluated for its antimicrobial, coagulant and wound healing activities on an excision mouse wound model as well as its acute dermal safety. A total of thirteen compounds were identified in HECA, mainly quercetin, kaempferol and glucoside derivatives of both, besides catechin and epicatechin known as wound healing agents. The group treated with 1% of HECA exhibited highest wound healing activity and best rate of wound contraction confirmed by histopathology results. The present study provides scientific evidence of, this extract (HECA) possess remarkable wound healing activity, thereby, supporting the traditional use.

The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11) = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (PSkin), plasma protein binding (PPB) and penetration of the blood-brain barrier (CBrain/Blood), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

Background Worldwide, primary care is for most people the gateway into many health systems. Offering solutions to the demands of the communities served requires the constant preparation of professionals, especially doctors and medical undergraduate students. We analyze and propose ways to improve the teaching and learning processes facilitated by the Basic Family Health Units (BFHUs) based on the use of electronic portals with evidence-based medicine criteria. Method First phase: The authors conducted a qualitative-quantitative study on students and instructors of primary care (PC) medicine by administering a survey of open- and closed-ended questions at medical schools. The closed-ended questions were studied with descriptive statistics, and open-ended questions were analyzed via the creation of categories. Perceptions of major teaching and learning problems were then identified. Second phase: Meetings were held with students and their instructors for 6 months and involved the use of electronic portals and the application of new questionnaires using a Likert scale for pre- and postevaluation. Results In the first phase, 40% of the students considered local instructor training levels a problem. A similar result was found regarding teachers’ lectures, revealing a lack of adequate PC training and performance. Building on our results, we focused on BFHUs to apply new strategies for teaching and learning, such as the use of the Evidence-Based Health (SBE) Portal, which includes several databases with clinical evidence criteria. In the second phase, the authors identified an improvement in the quality of learning among instructors and students. This outcome improved safety in daily clinical practice in PC, possibly with better results for its users. Conclusions The use of electronic portals can facilitate BFHU teaching and learning and promote the health of users.

O presente artigo objetiva analisar o desenvolvimento socioeconômico e educacional de egressos escolarizados na Casa Escola da Pesca (CEPE), uma escola pública municipal do campo, em regime de tempo integral na modalidade EJA, com habilitação profissional técnica na área da pesca, correspondente aos níveis de ensino fundamental e médio. Tomou-se como referência empírica a atual realidade vivida por ex-alunos moradores da ilha de Cotijuba, Belém, Pará que concluíram a formação básica no ano de 2015. Metodologicamente, o trabalho baseia-se em pesquisa qualitativa de campo, com recolhimento de documentos, aplicação de questionários, realização de entrevistas e observações in loco. Conclui-se que as condições materiais objetivas dos sujeitos da pesquisa, associada à ausência de ralações cotidianas em contextos organizativos condicionam negativamente o desenvolvimento socioeconômico e educacional dos egressos da CEPE o que pressuporia que a escola tivesse o associativismo como princípio educativo. The objective of this article is to analyze the socioeconomic and educational development of students enrolled in the House School of Fisheries (CEPE), a full-time municipal public rural school in the EJA modality, with professional qualification in the fishing area, corresponding to Elementary School and High School levels. The current reality of ex-students living on the island of Cotijuba, Belem, Para, who completed basic training in the year 2015, was taken as an empirical reference. Methodologically, this work is based on qualitative field research, with collection of documents, application of questionnaires, interviews and local observations. It’s concluded that the material conditions of the interviewees, coupled with the absence of day by day relations in organizational contexts, negatively affect the socioeconomic and educational development of the CEPE graduates, which would imply that the school had the associativism as an educational principle. El presente artículo tiene como objetivo analizar el desarrollo socioeconómico y educativo de egresados escolarizados en la Casa Escuela de la Pesca (CEPE), una escuela pública municipal del campo, en régimen de tiempo completo en la modalidad Educación de Jóvenes y Adultos, con habilitación profesional técnica en el área de la pesca, correspondiente a los niveles de enseñanza fundamental y media. Se tomó como referencia empírica la actual realidad vivida por ex alumnos de la isla de Cotijuba, Belém, Pará que concluyeran la formación básica en el año 2015. Metodológicamente, el trabajo está embasado en investigación cualitativa de campo, con investigación documental, aplicación de cuestionarios, realización de entrevistas y observaciones in situ. Se concluye que las condiciones materiales objetivas de los sujetos de la investigación, asociada a la ausencia de relaciones cotidianas en contextos organizativos condicionan negativamente el desarrollo socioeconómico y educativo de los egresados de la CEPE, es esta eduque con base en el asociativismo como principio educativo.

Este artigo analisa o Projeto de Educação Ambiental Saneamento e Cidadania desenvolvido no Parque Estadual do Utinga pela Companhia de Saneamento do Pará. Resultante de informações bibliográficas, documentais e pesquisa de campo com viés etnográfico, o texto ressalta as características preservacionistas do Projeto, o qual ratifica a hegemonia ideológico-conceitual das análises conservadoras que dominam a EA no estado do Pará.

Este artigo analisa o voto do relator do Habeas Corpus 143.641-São Paulo, que foi o ministro do STF Ricardo Lewandowski. Este remédio constitucional tinha o intuito de evitar que mulheres grávidas ou com filhos até doze anos de idade permanecessem encarceradas em prisão preventiva, muitas vezes em condições indignas que afetavam a elas e à sua prole. Um dos principais eixos da justificativa de Lewandowski foi o combate à cultura do encarceramento. Esta mentalidade punitiva tem suas bases na história das sociedades disciplinares, estudadas por Foucault. Percebe-se a importância da prisão para a Modernidade, especialmente a partir do século XX e início do século XXI, quando essa instituição foi desenvolvida de diferentes maneiras, concretizando abusos e centralizando o controle social e a repressão que ultrapassam seus limites e prejudicam os direitos humanos. Palavras-chave: Prisão preventiva. Direitos humanos. Cultura do encarceramento. Disciplina. História. This article analyzes the rapporteur's vote of the Habeas Corpus 143,641-São Paulo, who was the minister of the Supreme Court (STF) Ricardo Lewandowski. This constitutional remedy was intended to avoid the preventive detention of pregnant women or mothers of children with age until twelve years old, often in unworthy conditions that affected them and their offspring. One of the main axes of Lewandowski's justification was the fight against the culture of incarceration. This punitive mentality is based on the history of disciplinary societies, studied by Foucault. One perceives the importance of prison for Modernity, especially from the 20th century and the beginning of the 21st century, when this institution was developed in different ways, concretizing abuses and centralizing social control and repression that go beyond its limits and hurt rights humans. Keywords: Preventive detention. Human rights. Incarceration culture. Discipline. History.