Antileishmanial activity and evaluation of the mechanism of action of strychnobiflavone flavonoid isolated from Strychnos pseudoquina against Leishmania infantum

© 2015, Springer-Verlag Berlin Heidelberg. The present study aimed to investigate the in vitro antileishmanial activity of strychnobiflavone flavonoid against Leishmania infantum, as well as its mechanism of action, and evaluate the ex vivo biodistribution profile of the flavonoid in naive BALB/c mice. The antileishmanial activity (IC50 value) of strychnobiflavone against stationary promastigote and amastigote-like stages of the parasites was of 5.4 and 18.9 μM, respectively; with a 50% cytotoxic concentration (CC50) value of 125.0 μM on murine macrophages, resulting in selectivity index (SI) of 23.2 and 6.6, respectively. Amphotericin B, used as a positive control, presented SI values of 7.6 and 3.3 for promastigote and amastigote-like stages of L. infantum, respectively. The strychnobiflavone was also effective in reducing in significant levels the percentage of infected macrophages, as well as the number of amastigotes per macrophage, after the treatment of infected macrophages using the flavonoid. By using different fluorescent probes, we investigated the bioenergetics metabolism of L. infantum promastigotes and demonstrated that the flavonoid caused the depolarization of the mitochondrial membrane potential, without affecting the production of reactive oxygen species. In addition, using SYTOX® green as a fluorescent probe, the strychnobiflavone demonstrated no interference in plasma membrane permeability. For the ex vivo biodistribution assays, the flavonoid was labeled with technetium-99m and studied in a mouse model by intraperitoneal route. After a single dose administration, the scintigraphic images demonstrated a highest uptake by the liver and spleen of the animals within 60 min, resulting in low concentrations after 24 h. The present study therefore demonstrated, for the first time, the antileishmanial activity of the strychnobiflavone against L. infantum, and suggests that the mitochondria of the parasites may be the possible target organelle. The preferential distribution of this compound into the liver and spleen of the animals could warrant its employ in the treatment of visceral leishmaniasis.This work was supported by grants from Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00819-12), CNPq (APQ-472090/2011-9, APQ- 482976/2012-8, and APQ-488237/2013-0) and São Paulo State Research Fundation (FAPESP 2012/18756-1). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC and AGT are grant recipient of CNPqPeer Reviewe

Algae as a source of bioactive compounds to prevent the development of type 2 diabetes mellitus

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. It is considered a new pandemic and its control involves numerous challenges. Although many of the measures are based on improving life habits, diet is also of vital importance due to bioactive compounds present in food. In this regard, several raw materials have been investigated whose bioactivities seem to slow the progression of this disease. Within these matrices, there are algae of importance, such as brown algae, showing to have beneficial effects on glycemic control. These pieces of evidence are increasing every day due to the development of cell or animal models, which lead to the conclusion that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion and preventing the formation of amyloid plaques.Serbian co-authors thank the Ministry of Education, Science, and Technological Development of the Republic of Serbia for the support within the contracts for the realization and financing of scientific research work in 2021 ; financial support from Programa de Cooperación Interreg V-A España—Portugal (POCTEP) 2014–2020; MICINN supporting the Ramón&Cajal grant for M.A. Prieto; to Xunta de Galicia and University of Vigo supporting the pre-doctoral grants for A.G. Pereira, and P. García-Oliveira; to Ibero-American Program on Science and Technology for financial support. This project has received funding from the Bio Based Industries Joint Undertaking (JU); the JU receives support from the European Union’s Horizon 2020 research and innovation program and the Bio Based Industries Consortium.info:eu-repo/semantics/publishedVersio

Sensitive and specific serodiagnosis of Leishmania infantum infection in dogs by using peptides selected from hypothetical proteins identified by an immunoproteomic approach

In Brazil, the percentage of infected dogs living in areas where canine visceral leishmaniasis (CVL) is endemic ranges from 10 to 62%; however, the prevalence of infection in dogs is probably higher than figures reported from serological studies. In addition, problems with the occurrence of false-positive or false-negative results in the serodiagnosis of CVL have been reported. The present work analyzed the potential of synthetic peptides mapped from hypothetical proteins for improvement of the serodiagnosis of Leishmania infantum infection in dogs. From 26 identified leishmanial proteins, eight were selected, considering that no homologies between these proteins and others from trypanosomatide sequence databases were encountered. The sequences of these proteins were mapped to identify linear B-cell epitopes, and 17 peptides were synthesized and tested in enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of L. infantum infection in dogs. Of these, three exhibited sensitivity and specificity values higher than 75% and 90%, respectively, to differentiate L. infantum-infected animals from Trypanosoma cruziinfected animals and healthy animals. Soluble Leishmania antigen (SLA) showed poor sensitivity (4%) and specificity (36%) to differentiate L. infantum-infected dogs from healthy and T. cruzi-infected dogs. Lastly, the three selected peptides were combined in different mixtures and higher sensitivity and specificity values were obtained, even when sera from T. cruzi-infected dogs were used. The study’s findings suggest that these three peptides can constitute a potential tool for more sensitive and specific serodiagnosis of L. infantum infection in dogsThis work was supported by grants from the Pró-Reitoria de Pesquisa from UFMG (Edital 07/2012), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-NANOBIOFAR, Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (CBB-APQ-02364-08, CBB-APQ-00356-10, CBB-APQ-00496-11, and CBB-APQ-00819-12), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (APQ-472090/2011-9), and the Instituto Nacional de Ciência e Tecnologia em Vacinas (INCT-V). E.A.F.C. and A.P.F. are CNPq grant recipients. M.A.C.-F. is a FAPEMIG/CAPES grant recipient. This study was supported in Spain, in part, by grants from the Ministerio de Ciencia e Innovación (FIS/PI1100095)

Seafood processing, preservation, and analytical techniques in the age of industry 4.0

Fish and other seafood products are essential dietary components that are highly appreciated and consumed worldwide. However, the high perishability of these products has driven the development of a wide range of processing, preservation, and analytical techniques. This development has been accelerated in recent years with the advent of the fourth industrial revolution (Industry 4.0) technologies, digitally transforming almost every industry, including the food and seafood industry. The purpose of this review paper is to provide an updated overview of recent thermal and nonthermal processing and preservation technologies, as well as advanced analytical techniques used in the seafood industry. A special focus will be given to the role of different Industry 4.0 technologies to achieve smart seafood manufacturing, with high automation and digitalization. The literature discussed in this work showed that emerging technologies (e.g., ohmic heating, pulsed electric field, high pressure processing, nanotechnology, advanced mass spectrometry and spectroscopic techniques, and hyperspectral imaging sensors) are key elements in industrial revolutions not only in the seafood industry but also in all food industry sectors. More research is still needed to explore how to harness the Industry 4.0 innovations in order to achieve a green transition toward more profitable and sustainable food production systems.José S. Câmara and Rosa Perestrelo acknowledge FCT-Fundação para a Ciência e a Tecnologia through the CQM Base Fund—UIDB/00674/2020, and Programmatic Fund—UIDP/00674/2020, Madeira 14–20 Program, project PROEQUIPRAM—Reforço do Investimento em Equipamentos e Infraestruturas Científicas na RAM (M1420-01-0145-FEDER-000008), and ARDITI—Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação, through M1420-01-0145- FEDER-000005—Centro de Química da Madeira—CQM+ (Madeira 14–20 Program) for their support. The research leading to these results was supported by MICINN supporting the Ramón y Cajal grant for M.A. Prieto (RYC-2017-22891); by Xunta de Galicia for supporting the program EXCELENCIAED431F 2020/12; and the pre-doctoral grant of P. Garcia-Oliveira (ED481A-2019/295); and by the program BENEFICIOS DO CONSUMO DAS ESPECIES TINTORERA-(CO-0019-2021).info:eu-repo/semantics/publishedVersio

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasisThis work was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 01/2014), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00496-11 and CBB-APQ-00819-12), and CNPq (APQ-472090/2011-9 and APQ-482976/2012-8). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC, and AAGF are grant recipients of CNPq. Eduardo AF Coelho and André AG Faraco are co-senior authors of this stud

Validación del Nursing Activities Score en unidades de cuidados intensivos portuguesas

Objective: to describe the process of adaptation and validation of the Nursing Activities Score to the Portuguese context. Method: this was a pilot study of adaptation and validation of the Nursing Activities Score with a sample consisting of 67 patients hospitalized in the intensive care units of three Portuguese hospitals. The construct validity was assessed through factor analysis procedures and the internal consistency of the items was measured through the Cronbach’s alpha coeffi cient. Results: a mean workload value of 63.04% (SD = 14.25; Median = 61.30) was obtained. Psychometric data revealed a Cronbach’s alpha of 0.71 in the total scale, indicating an acceptable accuracy. Confi rmatory factor analysis suggested an appropriate adjustment between the model and the data (χ2 (199) = 214.5, p = 0.214; CFI = 0.95; RMSA = 0.035). Conclusion: in the present study, the Portuguese version of the Nursing Activities Score was found to be a valid instrument, enabling a safe assessment of the workload of nurses.Objetivo: descrever o processo de adaptação e validação do Nursing Activities Score para o contexto português. Método: trata-se de um estudo-piloto de adaptação e validação do Nursing Activities Score, com amostra de 67 doentes internados em unidades de cuidados intensivos de três hospitais portugueses. A validade de constructo avaliou-se mediante procedimentos de análise fatorial e a consistência interna dos itens através do coefi ciente Alpha de Cronbach. Resultados: obteve-se um valor médio da carga de trabalho de 63,04% (DP = 14,25; Mediana = 61,30). Os dados psicométricos revelaram um Alpha de Cronbach de 0,71, na escala total, indicando uma fi delidade aceitável. A análise fatorial confi rmatória sugeriu um ajustamento adequado entre o modelo e os dados (χ2(199) = 214,5, p = 0,214; CFI = 0,95; RMSA = 0,035). Conclusão: neste estudo, a versão portuguesa do Nursing Activities Score revelou-se um instrumento válido, permitindo avaliar a carga de trabalho dos enfermeiros com segurançaObjetivo: describir el proceso de adaptación y validación del Nursing Activities Score al contexto portugués. Método: estudio piloto de adaptación y validación del Nursing Activities Score, con muestra de 67 pacientes internados en unidades de cuidados intensivos de tres hospitales portugueses. La validez del constructo se evaluó mediante análisis factorial y por consistencia interna de los ítems evaluados a través del coefi ciente Alpha de Cronbach. Resultados: se obtuvo un valor medio de carga de trabajo de 63,04% (SD=14,25; Mediana=61,30). Los datos psicométricos expresaron un Alpha de Cronbach de 0,71 en la escala total, indicando fi delidad aceptable. El análisis factorial confi rmatorio sugirió un ajuste adecuado entre el modelo y os datos (χ2 (199)=214,5; p=0,214; CFI=0,95; RMSA=0,035). Conclusión: en este estudio, la versión portuguesa del Nursing Activities Score demostró ser un instrumento válido, permitiendo evaluar la carga de trabajo de los enfermeros con precisión

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity