Tuning the Biological Activity of Camphorimine Complexes through Metal Selection

This research was funded by FCT—Fundação para a Ciência e a Tecnologia, through projects CQE (UIDB/00100/2020 and UIDP/00100/2020) and C2TN (UID/MULTI/04349/2019), the projects of the Research Unit Institute for Bioengineering and Biosciences—iBB (UIDB/04565/2020 and UIDP/04565/2020), the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB, and a PhD grant to J.P.C. (UI/BD/152244/2021).The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex 5 using the nematode Caenorhabditis elegans was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).publishersversionpublishe

Genomic variations in patients with myelodysplastic syndrome and karyotypes without numerical or structural changes

Myelodysplastic syndrome (MDS) is an onco-hematologic disease with distinct levels of peripheral blood cytopenias, dysplasias in cell differentiation and various forms of chromosomal and cytogenomic alterations. In this study, the Chromosomal Microarray Analysis (CMA) was performed in patients with primary MDS without numerical and/or structural chromosomal alterations in karyotypes. A total of 17 patients was evaluated by GTG banding and eight patients showed no numerical and/or structural alterations. Then, the CMA was carried out and identified gains and losses CNVs and long continuous stretches of homozygosity (LCSHs). They were mapped on chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 14, 16, 17, 18, 19, 20, 21, X, and Y. Ninety-one genes that have already been implicated in molecular pathways important for cell viability were selected and in-silico expression analyses demonstrated 28 genes differentially expressed in mesenchymal stromal cells of patients. Alterations in these genes may be related to the inactivation of suppressor genes or the activation of oncogenes contributing to the evolution and malignization of MDS. CMA provided additional information in patients without visible changes in the karyotype and our findings could contribute with additional information to improve the prognostic and personalized stratification for patients

Preparation of a Nanoemulsion with Carapa guianensis

Andiroba (Carapa guianensis) seeds are the source of an oil with a wide range of biological activities and ethnopharmacological uses. However, few studies have devoted attention to innovative formulations, including nanoemulsions. The present study aimed to obtain a colloidal system with the andiroba oil using a low-energy and organic-solvent-free method. Moreover, the preliminary residual larvicidal activity of the nanoemulsion against Aedes aegypti was evaluated. Oleic and palmitic acids were the major fatty acids, in addition to the phytosterol β-sitosterol and limonoids (tetranortriterpenoids). The required hydrophile-lipophile was around 11.0 and the optimal nanoemulsion was obtained using polysorbate 85. The particle size distribution suggested the presence of small droplets (mean diameter around 150 nm) and low polydispersity index (around 0.150). The effect of temperature on particle size distribution revealed that no major droplet size increase occurred. The preliminary residual larvicidal assay suggested that the mortality increased as a function of time. The present study allowed achievement of a potential bioactive oil in water nanoemulsion that may be a promising controlled release system. Moreover, the ecofriendly approach involved in the preparation associated with the great bioactive potential of C. guianensis makes this nanoemulsion very promising for valorization of this Amazon raw material

R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome

Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the IKr inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of IKr on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.Fil: Mesquita, Fernanda C. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Arantes, Paulo C.. Universidade Federal do Rio de Janeiro; BrasilFil: Kasai Brunswick, Tais H.. Universidade Federal do Rio de Janeiro; BrasilFil: Araujo, Dayana S.. Universidade Federal do Rio de Janeiro; BrasilFil: Gubert, Fernanda. Universidade Federal do Rio de Janeiro; BrasilFil: Monnerat, Gustavo. Universidade Federal do Rio de Janeiro; BrasilFil: Silva dos Santos, Danúbia. Universidade Federal do Rio de Janeiro; BrasilFil: Neiman, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Leitão, Isabela C.. Universidade Federal do Rio de Janeiro; BrasilFil: Barbosa, Raiana A. Q.. Universidade Federal do Rio de Janeiro; BrasilFil: Coutinho, Jorge L.. National Institute Of Cardiology; BrasilFil: Vaz, Isadora M.. Pontificia Universidad Catolica de Parana; BrasilFil: dos Santos, Marcus N.. Universidade Federal do Rio de Janeiro; BrasilFil: Borgonovo, Tamara. Pontificia Universidad Catolica de Parana; BrasilFil: Cruz, Fernando E. S.. National Institute of Cardiology; BrasilFil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Medei, Emiliano H.. Universidade Federal do Rio de Janeiro; BrasilFil: Campos de Carvalho, Antonio C.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Cardiology; Brasil. National Institute for Science and Technology in Regenerative Medicine; BrasilFil: Carvalho, Adriana B.. Universidade Federal do Rio de Janeiro; Brasil. National Institute for Science and Technology in Regenerative Medicine; Brasi

Nursing knowledge on skin ulcer healing: a living scoping review protocol

Objective: This review aims to continuously map the nursing knowledge on skin ulcer healing in any context of care. Introduction: Chronic wounds are an increasing concern for society and health care providers. Pressure ulcers and venous ulcers, among others, have devastating effects on morbidity and quality of life and require a systematic approach. The nursing process is an important method that allows a better organization and overall care quality for a systematic and continuous professional approach to nursing management of skin ulcers. The integration of this nursing knowledge in informatics systems creates an opportunity to embed decision-support models in clinical activity, promoting evidence-based practice. Inclusion criteria: This scoping review will consider articles on nursing data, diagnosis, interventions, and outcomes focused on people with skin ulcers in all contexts of care. This review will include quantitative, qualitative, and mixed methods study designs as well as systematic reviews and dissertations. Methods: JBI’s scoping review guidance, as well as the Cochrane Collaboration’s guidance on living reviews, will be followed to meet the review’s objective. Screening of new literature will be performed regularly, with the review updated according to new findings. The search strategy will map published and unpublished studies. The databases to be searched include MEDLINE, CINAHL, Scopus, JBI Evidence Synthesis, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and PEDro. Searches for unpublished studies will include OpenGrey and Reposito´ rios Cientı´ficos de Acesso Aberto de Portugal. Studies published in English and Portuguese since 2010 will be considered for inclusion.info:eu-repo/semantics/publishedVersio

Nursing knowledge of people with paresis of voluntary muscles: a living scoping review protocol

Objective: This review aims to continuously map the nursing knowledge about people with paresis of voluntary muscles in any context of care. Introduction: Muscle paresis is a condition that significantly impacts quality of life. Nurses have a crucial role in managing this condition, particularly paresis of voluntary movement muscles. However, nursing knowledge about patients with paresis of voluntary muscles is dispersed, hampering the integration of evidence within the structure of information systems. Mapping how the nursing process components are identified is the first step in creating a Nursing Clinical Information Model for this condition, capable of integrating evidence into information systems. Inclusion criteria: This scoping review will consider studies focusing on the nursing process regarding people with paresis of voluntary muscles in all care contexts. The review will include quantitative, qualitative, and mixed-methods study designs, systematic reviews, clinical guidelines, dissertations, and theses. Methods: The review process will follow JBI's scoping review guidance, as well as the Cochrane Collaboration's guidance on living reviews. Screening of new literature will be performed regularly, with the review being updated according to new findings. The search strategy will map published and unpublished studies. The databases to be searched will include MEDLINE, CINAHL, Scopus, JBI Evidence Synthesis, and the Cochrane Central Register of Controlled Trials. Searches for unpublished studies will include OpenGrey and Repositorios Cientificos de Acesso Aberto de Portugal. Studies published in English and Portuguese from 1975 will be considered for inclusion.info:eu-repo/semantics/publishedVersio

Relationship among medical student resilience, educational environment and quality of life

Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students. We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young's resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire - short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score >= 14 and STAI state or anxiety scores >= 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (beta=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (beta=-0.85; 95% CI=-1.25 to -0.45) QoL scores, environment (beta=-6.48; 95% CI=-10.01 to -2.95), psychological (beta=-22.89; 95% CI=-25.70 to -20.07), social relationships (beta=-14.28; 95% CI=-19.07 to -9.49), and physical health (beta=-10.74; 95% CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (beta=-31.42; 95% CI=-37.86 to -24.98), learning (beta=-7.32; 95% CI=-9.23 to -5.41), teachers (beta=-5.37; 95% CI=-7.16 to -3.58), academic self-perception (beta=-7.33; 95% CI=-8.53 to -6.12), atmosphere (beta=-8.29; 95% CI=-10.13 to -6.44) and social self-perception (beta=-3.12; 95% CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements. Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training106CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPE