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Neonatal undernutrition in rats results in short- and long-term behavioral and hormonal alterations in the offspring. It is not clear, however, whether these effects are present since the original insult or if they develop at some specific age later in life. Here, we assessed the ontogenetic profile of behavioral parameters associated with anxiety, exploration and memory/learning of Wistar rat offspring that were subjected to protein malnutrition during lactation. Dams and respective litters were separated into two groups: (1) protein-restricted (PR), which received a hypoproteic chow (8% protein) from birth to weaning [postnatal day (PN) 21]; (2) control (C), which received normoproteic chow. Offspring’s behaviors, corticosterone, catecholamines, T3 and T4 levels were assessed at PN21 (weaning), PN45 (adolescence), PN90 (young adulthood) or PN180 (adulthood). PR offspring showed an age-independent reduction in the levels of anxiety-like behaviors in the Elevated Plus Maze and better memory performance in the Radial Arm Water Maze. PR offspring showed peak exploratory activity in the Open Field earlier in life, at PN45, than C, which showed theirs at PN90. Corticosterone was reduced in PR offspring, particularly at young adulthood, while catecholamines were increased at weaning and adulthood. The current study shows that considerable age-dependent variations in the expression of the observed behaviors and hormonal levels exist from weaning to adulthood in rats, and that protein restriction during lactation has complex variable-dependent effects on the ontogenesis of the assessed parameters.

Summary Meloidogyne enterolobii is a species capable of overcoming plant resistance moderated by the Mi-1 gene, which is effective against most species of root-knot nematode. This study evaluated the effect of induced resistance in tomato plants (Solanum lycopersicum ‘H-9553’) with the Mi-1 gene against the development and reproduction of M. enterolobii. Seedlings of tomato ‘H-9553’ were transplanted into pots, inoculated with 2000 eggs and second-stage juveniles (J2) of M. enterolobii and treated with Acibenzolar-S-Methyl, Bacillus subtilis, B. subtilis + B. licheniformis + Trichoderma longibrachiatum and extract of Reynoutria sachalinensis. The plants were collected at 5, 10, 15, 20, 25 and 30 days after inoculation (DAI) for the analyses of nematode penetration and development, and at 30 DAI for nematode reproduction. The use of B. subtilis increased fresh root weight when compared to the other treatments (20 DAI). There was a reduction in penetration of J2 in the roots of plants subjected to different resistance inducers. The population density of M. enterolobii was significantly reduced only when plants were treated with R. sachalinensis, indicating it as a potential resistance-inducing agent in tomato plants.

The biodistribution of radiotracer peptide KETO[

In this study, phosphate-buffered saline solution (PBS) was successfully radiolabeled with technetium-99m. The biodistribution profile and bone accumulation of the [99mTc]Tc-PBS system were evaluated in healthy swiss mice. The radiolabeling of the system was successfully obtained, yielding around 90 % of radiochemical purity. The system stability was tested in the presence of saline medium at 25 oC and mouse plasma at 37 oC, and results revealed that [99mTc]Tc-PBS showed excellent stability over time, in both media. It was observed a biphasic clearance profile, with fast elimination from the bloodstream by renal filtration. The radiolabeled system revealed a high specificity bone accumulation was observed, demonstrating an uptake behavior from 20 to 50 times higher than muscle, used as control. From all results obtained, the system constituted by [99mTc]Tc-PBS can be considered a potential selective agent for bone imaging.

Until the early 1990s, cyst nematodes were abundant pathogens in fields where hosts of Heterodera spp. were frequent members of crop rotations along California’s Central Coast. To mitigate damage caused by Heterodera schachtii and H. cruciferae, the soil fumigant 1,3-dichloropropene (1,3-D) was used by more than 43% of surveyed broccoli growers. Over the last few decades, use of 1,3-D and other nematicides has dramatically diminished, suggesting a decline in nematode disease pressure. The goal of this study was to examine the hypothesis that increased population densities of nematophagous fungi contribute to the low populations of Heterodera spp. in fields frequently cropped to their hosts. In 2016, soil samples were collected from 152 Brassica fields with a broad geographical distribution, from Santa Barbara County to Santa Cruz County. The average number of Heterodera cysts per 250 cm3 of soil ranged from 0.5 to 27.5, with 62% of the soils harboring no detectable cyst nematodes and only a few samples reaching a potentially damaging threshold level. A baiting experiment with H. schachtii and cabbage was performed in a greenhouse to detect nematophagous fungi associated with nematode females as their posterior end emerged and became exposed to the soil’s rhizosphere. An Illumina-based sequence analysis of these H. schachtii females identified several known nematophagous fungi, including members of the Hyalorbilia oviparasitica clade, Pochonia chlamydosporia, certain Fusarium spp., and others. These soils clearly harbor a diverse population of hyperparasitic fungi that could be biologically suppressing cyst nematodes below a damaging threshold. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Objective: the objective of this study was to analyze the scientific evidence of violence against the elderly, highlighting the role of nursing in the description of these violent acts. Methodology: This is an integrative review of the literature with a quantitative and qualitative approach, based on the guiding question: “What is the state of the art, in the scientific literature published from 2015 to 2020, about violence and abuse in the elderly?” Keywords were used to search for articles: Aging, Violence against the Elderly, Elder Abuse and Nursing Assessment. The bibliographic survey was conducted over the Internet, in the databases LILACS (Latin American Literature in Health Sciences), SciELO (Scientific Electronic Library Online), BDENF (Bibliographic Database Specialized in the Area of Nursing in Brazil), Medline (Medical Literature Analysis and Retrieval System Online) and PubMed. Results and Discussion: Twenty articles were part of the results. As for the qualitative analysis, three thematic categories emerged: “Contextualizing violence and abuse against the elderly,” “Impacts of violence on the elderly population,” “Nursing versus Violence.” Final Considerations: This review pointed out that it is essential to train professionals for the reception of elderly victims of violence, as care is based on knowledge of the aging process, early detection of the risk of violence, through anamnesis and physical examination. Suitable. Thus, there is a need to increase discussions and reflections on the subject, through educational actions, strengthening the professional's knowledge, to contribute to the improvement of the quality of life of elderly patients. Objetivo: el objetivo de este estudio fue analizar las evidencias científicas de la violencia contra los ancianos, destacando el papel de la enfermería en la descripción de estos actos violentos. Metodología: Se trata de una revisión integradora de la literatura con enfoque cuantitativo y cualitativo, a partir de la pregunta orientadora: “¿Cuál es el estado del arte, en la literatura científica publicada de 2015 a 2020, sobre la violencia y el maltrato en el anciano?” Se utilizaron palabras clave para la búsqueda de artículos: Envejecimiento, Violencia contra el Anciano, maltrato al Anciano y Evaluación de Enfermería. El levantamiento bibliográfico se realizó por Internet, en las bases de datos LILACS (Literatura Latinoamericana en Ciencias de la Salud), SciELO (Biblioteca Científica Electrónica en Línea), BDENF (Base de Datos Bibliográfica Especializada en el Área de Enfermería en Brasil), Medline Sistema de recuperación y análisis de literatura en línea), PubMed y CAPES Periódicos. Resultados y Discusión: Veinte artículos formaron parte de los resultados. En cuanto al análisis cualitativo, surgieron tres categorías temáticas: “Contextualizando la violencia y el maltrato al anciano”, “Impactos de la violencia en la población anciana”, “Enfermería versus Violencia”. Consideraciones Finales: Esta revisión señaló que es fundamental la formación de profesionales para la acogida de ancianos víctimas de violencia, una vez que la atención se basa en el conocimiento del proceso de envejecimiento, detección precoz del riesgo de violencia, a través de la anamnesis y el examen físico apropiado. Por lo tanto, existe la necesidad de aumentar las discusiones y reflexiones sobre el tema, a través de acciones educativas, fortaleciendo el conocimiento del profesional, para contribuir a la mejora de la calidad de vida de los ancianos. Objetivo: o objetivo deste estudo foi analisar as evidências científicas da violência praticada contra a pessoa idosa, destacando a atuação da enfermagem, na descrição desses atos violentos. Metodologia: Trata-se de uma revisão integrativa da literatura de abordagem quantitativa e qualitativa, baseado na questão norteadora: “Qual o estado da arte, na literatura científica publicada no período de 2015 a 2020, acerca da violência e maus-tratos em idosos?” Para a busca dos artigos foram utilizadas palavras-chaves: Envelhecimento, Violência contra o Idoso, Abuso de Idosos e Avaliação em Enfermagem. O levantamento bibliográfico foi realizado pela Internet, nas bases de dados LILACS (Literatura Latino-Americana em Ciências de Saúde), SciELO (Scientific Electronic Library Online), BDENF (Base de Dados Bibliográficos Especializada na Área de Enfermagem do Brasil), Medline (Medical Literature Analysis and Retrieval System Online), PubMed e CAPES Periódicos. Resultados e Discussão: Fizeram parte dos resultados 20 artigos. Quanto à análise qualitativa emergiram três categorias temáticas: “Contextualizando a violência e o abuso contra a pessoa idosa”, “Impactos da violência na população idosa”, “Enfermagem versus Violência”. Considerações Finais: Esta revisão apontou que é fundamental a capacitação do profissional para o acolhimento da pessoa idosa vítima de violência, pois o cuidado baseia-se no conhecimento do processo do envelhecimento, a detecção precoce do risco de violência, através de anamnese e exame físico adequados. Desta forma, aponta-se necessidade de aumentar as discussões e reflexões sobre o tema, através de ações educativas, fortalecendo o conhecimento do profissional, de forma a contribuir na melhora da qualidade de vida dos pacientes idosos.

Plant-parasitic nematodes are significant pests for many crops with considerable economic impact worldwide. Alternatives to highly toxic soil fumigants and nematicides are urgently sought after. Fluazaindolizine is a fluorinated nematicide with a novel, unknown mode-of-action and very low mammalian toxicity. The current research investigated the early responses of several plant-parasitic nematode species to the compound by in vitro mortality and parasitism trials with nematode-susceptible host plants. After a 72-h in vitro exposure time, fluazaindolizine exhibited the most potent toxic activity against the second-stage juveniles (J2) of Meloidogyne incognita and Tylenchulus semipenetrans with LC50 values of 177.14 and 355.2 mg L−1, respectively. Pratylenchus brachyurus, J2 of the Heterodera schachtii, and eggs of M. incognita were considerably less sensitive to the nematicide. The fitness of M. incognita J2 was strongly affected when exposed to various concentrations of fluazaindolizine for 12 h before inoculation of cucumber seedlings in soilless seed pouches. The lowest level of 5 mg L−1 reduced root galling, egg mass production, and the number of eggs to about 25% compared to the water control. In another bioassay, H. schachtii J2 were exposed to fluazaindolizine at 100 and 200 mg L−1 for 72 h before used to infest soil with 3-day-old radish seedlings. About 39.8% and 59.6%, respectively, fewer J2 invaded the roots compared to the control. In conclusion, the tested nematode species varied considerably in their in vitro mortality following fluazaindolizine exposure. However, the bioassays demonstrated that parasitism was already severely impacted at non-lethal concentrations and short-term exposure to the nematicide.

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.

Colorectal cancer has been considered a worldwide public health problem since current treatments are often ineffective. Irinotecan is a frontline chemotherapeutic agent that has dose-limiting side effects that compromise its therapeutic potential. Therefore, it is necessary to develop a novel, targeted drug delivery system with high therapeutic efficacy and an improved safety profile. Here, micellar formulations composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2k) containing irinotecan were proposed as a strategy for colorectal cancer therapy. Firstly, the irinotecan-loaded micelles were prepared using the solvent evaporation method. Then, micelles were characterized in terms of size, polydispersity, zeta potential, entrapment efficiency, and release kinetics. Cytotoxicity and in vivo antitumor activity were evaluated. The micelles showed size around 13 nm, zeta potential near neutral (−0.5 mV), and encapsulation efficiency around 68.5% (irinotecan 3 mg/mL) with a sustained drug release within the first 8 h. The micelles were evaluated in a CT26 tumor animal model showing inhibition of tumor growth (89%) higher than free drug (68.7%). Body weight variation, hemolytic activity, hematological, and biochemical data showed that, at the dose of 7.5 mg/kg, the irinotecan-loaded micelles have low toxicity. In summary, our findings provide evidence that DSPE-mPEG2k micelles could be considered potential carriers for future irinotecan delivery and their possible therapeutic application against colorectal cancer.

Made available in DSpace on 2022-04-28T19:45:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This study aims to demonstrate the applicability and importance of zebrafish (Danio rerio) model to study acute and chronic inflammatory responses induced by different stimuli: carrageenan phlogogen (nonimmune); acute infection by bacteria (immune); foreign body reaction (chronic inflammation by round glass coverslip implantation); reaction induced by xenotransplantation. In addition to the advantages of presenting low breeding cost, high prolificity, transparent embryos, high number of individuals belonging to the same spawning and high genetic similarity that favor translational responses to vertebrate organisms like humans, zebrafish proved to be an excellent tool, allowing the evaluation of edema formation, accumulation of inflammatory cells in the exudate, mediators, signaling pathways, gene expression and production of specific proteins. Our studies demonstrated the versatility of fish models to investigate the inflammatory response and its pathophysiology, essential for the successful development of studies to discover innovative pharmacological strategies. Laboratory of Animal Pharmacology and Toxicology Brazil University (UB) Department of Preventive Veterinary Medicine São Paulo State University (UNESP) Department of Morphology Federal University of Minas Gerais (UFMG) Department of Physiology and Pharmacology Federal University of Minas Gerais (UFMG) Department of Biochemistry and Immunology Federal University of Minas Gerais (UFMG) Department of zootechnics at the Veterinary School Federal University of Minas Gerais (UFMG) Postgraduate Program in Health Sciences - PROCISA Federal University of Roraima Immunochemistry Laboratory Butantan Institute Department of Clinical and Toxicological Analyses Federal University of Minas Gerais (UFMG) Department of Pharmacology University of São Paulo (ICB-USP) Department of Preventive Veterinary Medicine São Paulo State University (UNESP) FAPESP: 2013/25971-9 FAPESP: 2018/07098-0 FAPESP: 2019/19939-1 CNPq: 301473 / 2016-1 CNPq: 307526/2018-6 CNPq: 477816/2013-4

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior To associate paclitaxel (PTX) with doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Despite the high response rates for this combination, it presents a cardiotoxic synergism, attributed to pharmacokinetic interactions between PTX and both DXR and its metabolite, doxorubicinol. One of the main strategies to minimize the cardiotoxicity of the combination is to extend the interval of time between DXR and PTX administration. However, it has been previously suggested that their co-administration leads to better efficacy compared to their sequential administration. In the present study, we investigated different molar ratio combinations of PTX:DXR (10:1; 1:1, and 1:10) against the 4T1 murine breast cancer cell line and concluded that there is no benefit of enhancing PTX concentration above that of DXR on the combination. Therefore, we obtained a long-circulating and fusogenic liposomal formulation co-encapsulating PTX and DXR (LCFL-PTX/DXR) at a molar ratio of 1:10, respectively, which maintained the in vitro biological activity of the combination. This formulation was investigated for its antitumor activity and toxicity in Balb/c mice bearing 4T1 breast tumor, and compared to treatments with free PTX, free DXR, and the mixture of free PTX:DXR at 1:10 molar ratio. The higher tumor inhibition ratios were observed for the treatments with free and co-encapsulated PTX:DXR in liposomes (66.87 and 66.52%, respectively, P>0.05) as compared to the control. The great advantage of the treatment with LCFL-PTX/DXR was its improved cardiac toxicity profile. While degeneration was observed in the hearts of all animals treated with the free PTX:DXR combination, no signs of cardiac toxicity were observed for animals treated with the LCFL-PTX/DXR. Thus, LCFL-PTX/DXR enables the co-administration of PTX and DXR, and might be considered valuable for breast cancer management. Associar paclitaxel (PTX) à doxorrubicina (DXR) é uma das principais estratégias de quimioterapia para o manejo do câncer de mama (CM). Apesar das altas taxas de resposta para esta combinação, ela apresenta um sinergismo cardiotóxico, atribuído às interações farmacocinéticas entre PTX e DXR e seu metabólito, doxorrubicinol. Uma das principais estratégias para minimizar a cardiotoxicidade da combinação é prolongar o intervalo de tempo entre a administração de DXR e PTX. No entanto, foi previamente sugerido que a sua co-administração conduz a uma melhor eficácia em comparação com a sua administração sequencial. No presente estudo, investigamos diferentes combinações de razões molares de PTX:DXR (10:1; 1:1 e 1:10) contra a linhagem celular de câncer de mama murino 4T1 e concluímos que não há benefício de aumentar a concentração de PTX acima dessa de DXR na combinação. Portanto, obtivemos uma formulação lipossômica fusogênica de longa circulação e co-encapsulamento de PTX e DXR (LCFL-PTX/DXR) em uma razão molar de 1:10, respectivamente, que manteve a atividade biológica in vitro da combinação. Esta formulação foi investigada quanto à sua atividade antitumoral e toxicidade em camundongos Balb/c com tumor de mama 4T1, e comparada aos tratamentos com PTX livre, DXR livre e a mistura de PTX livre:DXR na razão molar de 1:10. As maiores razões de inibição tumoral foram observadas para os tratamentos com PTX:DXR livre e co-encapsulado em lipossomas (66,87 e 66,52%, respectivamente, P>0,05) em relação ao controle. A grande vantagem do tratamento com LCFL-PTX/DXR foi a melhora do perfil de toxicidade cardíaca. Enquanto a degeneração foi observada nos corações de todos os animais tratados com a combinação PTX:DXR livre, nenhum sinal de toxicidade cardíaca foi observado para os animais tratados com o LCFL-PTX/DXR. Assim, LCFL-PTX/DXR permite a coadministração de PTX e DXR e pode ser considerado valioso para o tratamento do câncer de mama.

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people. RT-PCR remains the gold standard for diagnosing COVID-19. However, new methods, such as other molecular techniques and immunoassays emerged. Also, the need for accessible tests with quick results boosted the development of point of care tests (POCT) that are fast, and automated, with high precision and accuracy. This assay reduces the dependence on laboratory conditions and mass testing of the population, dispersing the pressure regarding screening and detection. This review summarizes the advances in the diagnostic field since the pandemic started, emphasizing various laboratory techniques for detecting COVID-19. We reviewed the main existing diagnostic methods, as well as POCT under development, starting with RT-PCR detection, but also exploring other nucleic acid techniques, such as digital PCR, loop-mediated isothermal amplification-based assay (RT-LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS), and immunoassay tests, and nanoparticle-based biosensors, developed as portable instruments for the rapid standard diagnosis of COVID-19.

Lapachol (LAP) is a natural compound with various biological properties, including anticancer activity. However, its clinical application is limited due to the low aqueous solubility and potential adverse side effects. Nanoemulsions are drug delivery systems that can assist in the administration of hydrophobic drugs, increasing their bioavailability and protecting from degradation. Thus, this study aimed to prepare a LAP-loaded nanoemulsion (NE-LAP), and evaluate its antitumor activity. For this purpose, the nanoemulsion was prepared using a hot homogenization method and characterized morphologically by cryogenic transmission electron microscopy (cryo-TEM). Mean diameter, polydispersity index, and zeta potential was evaluated by DLS, encapsulation efficiency was measured by HPLC. Moreover, the short-term storage stability, the drug release and hemolysis in vitro was determined. Additionally, pharmacokinetic, toxicology and toxicity properties of99mTc-NE-LAP were evaluated in a breast cancer (4T1) tumor model. The cryo-TEM showed spherical globules, and the physicochemical characterization of NE-LAP showed a homogeneous stable nanoemulsion with a mean diameter of ∼170 nm, zeta potential of around −20 mV, and encapsulation greater than 85 %. In vitro studies validated that encapsulation did not impair the cytotoxicity activity of LAP. The nanoemulsion was successfully radiolabeled and 99mTc-NE-LAP showed prolonged blood circulation and tumor affinity was confirmed by tumor-to-muscle ratio. Moreover, NE-LAP showed higher antitumor activity than the free drug and the treatment did not result in any signs of toxicity. Therefore, these findings suggest that NE-LAP can be considered an effective strategy for cancer treatment.

Objetivo: o objetivo deste estudo foi analisar as evidências científicas da violência praticada contra a pessoa idosa, destacando a atuação da enfermagem, na descrição desses atos violentos. Metodologia: Trata-se de uma revisão integrativa da literatura de abordagem quantitativa e qualitativa, baseado na questão norteadora: “Qual o estado da arte, na literatura científica publicada no período de 2015 a 2020, acerca da violência e maus-tratos em idosos?” Para a busca dos artigos foram utilizadas palavras-chaves: Envelhecimento, Violência contra o Idoso, Abuso de Idosos e Avaliação em Enfermagem. O levantamento bibliográfico foi realizado pela Internet, nas bases de dados LILACS (Literatura Latino-Americana em Ciências de Saúde), SciELO (Scientific Electronic Library Online), BDENF (Base de Dados Bibliográficos Especializada na Área de Enfermagem do Brasil), Medline (Medical Literature Analysis and Retrieval System Online), PubMed e CAPES Periódicos. Resultados e Discussão: Fizeram parte dos resultados 20 artigos. Quanto à análise qualitativa emergiram três categorias temáticas: “Contextualizando a violência e o abuso contra a pessoa idosa”, “Impactos da violência na população idosa”, “Enfermagem versus Violência”. Considerações Finais: Esta revisão apontou que é fundamental a capacitação do profissional para o acolhimento da pessoa idosa vítima de violência, pois o cuidado baseia-se no conhecimento do processo do envelhecimento, a detecção precoce do risco de violência, através de anamnese e exame físico adequados. Desta forma, aponta-se necessidade de aumentar as discussões e reflexões sobre o tema, através de ações educativas, fortalecendo o conhecimento do profissional, de forma a contribuir na melhora da qualidade de vida dos pacientes idosos.

Doxorubicin (DOX) is widely used in cancer treatment, however, its use is often limited due to its side effects. To avoid these shortcomings, the encapsulation of DOX into nanocarriers has been suggested. Herein, we proposed a novel nanostructured lipid carrier (NLC) formulation loading DOX, docosahexaenoic acid (DHA), and α-tocopherol succinate (TS) for cancer treatment. DHA is an omega-3 fatty acid and TS is a vitamin E derivative. It has been proposed that these compounds can enhance the antitumor activity of chemotherapeutics. Thus, we hypothesized that the combination of DOX, DHA, and TS in NLC (NLC-DHA-DOX-TS) could increase antitumor efficacy and also reduce toxicity. NLC-DHA-DOX-TS was prepared using emulsification-ultrasound. DOX was incorporated after preparing the NLC, which prevented its degradation during manufacture. High DOX encapsulation efficiency was obtained due to the ion-pairing with TS. This ion-pairing increases lipophilicity of DOX and reduces its crystallinity, contributing to its encapsulation in the lipid matrix. Controlled DOX release from the NLC was observed in vitro, with increased drug release at the acidic environment. In vitro cell studies indicated that DOX, DHA, and TS have synergistic effects against 4T1 tumor cells. The in vivo study showed that NLC-DHA-DOX-TS exhibited the greatest antitumor efficacy by reducing tumor growth in 4T1 tumor-bearing mice. In addition, this formulation reduced mice mortality, prevented lung metastasis, and decreased DOX-induced toxicity to the heart and liver, which was demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that NLC-DHA-DOX-TS may be a promising carrier for breast cancer treatment.

Paclitaxel (PTX) has a great clinical significance as an antitumor drug, although several side effects are strongly dose-limiting. In this way, we prepared a PTX-loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] polymeric micelles (PM/PTX) in an attempt to improve safety and effectiveness of conventional PTX formulation (CrEL/EtOH/PTX). In this study, we evaluated from both formulations: stability after dilution, hemocompatibility, cellular uptake, acute toxicity in healthy mice, antitumor activity, and toxicity after multiple-dose treatment. PM/PTX appeared to be more stable than CrEL/EtOH/PTX after dilution. PM/PTX did not exhibit hemolytic activity (values

Cancer is one of the main causes of death in the world and thus a global public health problem. Among the treatments available for cancer are surgery, radiotherapy, and chemotherapy. Currently, there is increased interest in the combination of two or more antitumor agents to achieve a synergistic effect in cancer therapy. Doxorubicin (DOX), a chemotherapeutic which has a potent antineoplastic action, has been used in the treatment of various tumors. However, the use of DOX is limited, mainly due to the cardiotoxicity. Therefore, nanostructured systems, such as liposomes, have been developed to carry this drug and target the tumor region, since tumor tissues present enhanced permeability and retention for nanosystems. Cardiac glycosides, such as digitoxin, have recently shown great antitumor potential despite the low therapeutic index which may limit their use. Furthermore, some compounds of this class have low water solubility, which makes their in vivo administration difficult. In this context, liposomes represent a valid strategy to carry simultaneously antitumor drugs allowing their intravenous administration. In this study, liposomes loaded with glucoevatromonoside containing peracetylated glucose hydroxyl groups (GEVPG) and DOX at molar ratio of 1:1 (SpHL-GEVPG:DOX 1:1) were developed, and their chemical and physicochemical properties were evaluated. This formulation presented a combination index (CI) lower than 1 at inhibitory concentration of 90 % growth (IC90) for three human breast tumor lines evaluated (0.52 ± 0.39 for MDA-MB-231, 0.19 ± 0.13 for MCF-7, and 0.99 ± 0.09 for SKBR-3). These results indicate a synergistic cytotoxic effect of the GEVPG and DOX combination encapsulated in liposomes. In addition, SpHL-GEVPG:DOX 1:1 presented selectivity towards these cancer cells. Long-term in vitro cytotoxicity studies demonstrated that MDA-MB-231 surviving cells after treatment with SpHL-GEVPG:DOX 1:1 did not recover proliferation capacity after 21 d. From the studies of cell cycle and death pathway evaluation, it was observed that SpHL-GEVPG:DOX 1:1 arrested the cell cycle in the G2/M phase and similarly induced apoptosis and necrosis. However, SpHL-GEVPG:DOX at molar ratio of 1:1 showed lower induction of both apoptotic and necrotic pathways compared to free DOX and SpHL-DOX, suggesting that the mechanism of death involved may not be related to necrosis or apoptosis. Lastly, SpHL-GEVPG:DOX 1:1 showed a good storage stability for 90 d at 4 °C. Therefore, the results of the present work indicate the potential use of SpHL-GEVPG:DOX 1:1 as a new anticancer formulation.

Made available in DSpace on 2021-06-25T11:04:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish. Department of Pharmacology University of São Paulo-ICB/USP Laboratório Integrado de Biociências Translacionais (LIBT) Instituto de Biodiversidade e Sustentabilidade (NUPEM) Universidade Federal do Rio de Janeiro (UFRJ) Department of Morphology ICB-UFMG Aquiculture Laboratory (Laqua) UFMG Department of Preventive Veterinary Medicine São Paulo State University Department of Postgraduate in Health Sciences PROCISA Federal University of Roraima (UFRR) Institute of Chemistry São Paulo State University (Unesp) Laboratory of Animal Pharmacology and Toxicology Brasil University Department of Clinical and Toxicological Analyses Faculty of Pharmacy-UFMG Laboratory of Applied Immunology Federal University of São Carlos School of Veterinary Medicine Department of Clinic and Veterinary Surgery UFMG Faculty of Medicine São Leopoldo Mandic Institute of Science and Technology of Sorocaba São Paulo State University Department of Preventive Veterinary Medicine São Paulo State University Institute of Chemistry São Paulo State University (Unesp) Institute of Science and Technology of Sorocaba São Paulo State University

The relationships between co-occurrence patterns of plant-parasitic nematodes and arbuscular mycorrhizal fungus (AMFs) are not fully understood. Few field studies assess co-occurrence patterns, evidencing the lack of information on soil-limiting conditions for favorable management of AMFs. The aim was therefore to evaluate co-occurrence patterns between plant-parasitic nematodes and AMFs and the probable environmental conditions that were associated to these patterns. We sampled three sites in each of ten fields and collected an abundance of nematodes and AMF spores and physical-chemical soil data. We evaluated co-occurrence patterns using combinations between nematodes and AMFs in both samplings (soil and roots) through probabilistic models. We also performed a redundancy analysis to evaluate which environmental variables were correlated to negative and positive patterns found between both groups. Plant-parasitic nematodes and AMFs showed negative co-occurrence patterns on the root-rhizospheric soil interface as a result of the competition. In the soil, the groups showed an apparent differentiation of niche, and the competition occurs within each group. Soil variation, mainly on alterations of potassium, phosphorus and moisture are the main characteristics that are associated to changes in the assemblages of these groups. Co-occurrence patterns indicated in the present study show an important pathway to conservative management of the soil and improvement of the crop growth in agricultural landscapes.

Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL-DOX (14.6 ± 5.2%) compared to animals receiving free DOX (35.7 ± 4.0%) or non-pH-sensitive liposomes (nSpHL-DOX) (47.0 ± 9.8%). These results corroborate with SpHL-DOX biodistribution studies published by our group. In conclusion, the SpHL-DOX showed less toxic effects on mice compared to free DOX or nSpHL-DOX indicating that SpHL-DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX.

Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.

Objetivo: O presente artigo buscou discutir a relação existente entre a psoríase e a depressão, pretendendo apresentar informações que correlacionam de que forma a piora da psoríase pode intensificar os sintomas depressivos, bem como o aumento dos sintomas depressivos pode levar à progressão da psicodermatose. Revisão bibliográfica: Foi demonstrado que o tratamento antidepressivo contribui para o manejo da patologia dermatológica, assim como inibidores de Fator de Necrose Tumoral (TNF), usados no tratamento da psoríase, colaboram com a melhora dos sintomas depressivos, uma vez que ambas têm relação com a liberação elevada de citocinas pró-inflamatórias. Entretanto, o mecanismo exato de como a inflamação intervém nas duas patologias ainda não está elucidado por completo. Considerações finais: Assim, é necessário um tratamento multidimensional e que leve em consideração o aspecto psicológico, social e de bem-estar físico, visto que a psoríase não apresenta cura e o tratamento da depressão minimizaria os efeitos adversos dessa dermatose.

Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of cancer, however, it is associated with the occurrence of adverse reactions that limits its clinical use. In this context, the encapsulation of DOX in micelles responsive to pH variations has shown to be a strategy for tumor delivery of the drug, with the potential to increase therapeutic efficacy and to reduce the toxic effects. In addition, radiolabeling nanoparticles with a radioactive isotope is of great use in preclinical studies, since it allows the in vivo monitoring of the nanostructure through the acquisition of quantitative images. Therefore, this study aimed to develop, characterize, and evaluate the antitumor activity of a pH-sensitive micelle composed of DSPE-PEG2000, oleic acid, and DOX. The micelles had a diameter of 13 nm, zeta potential near to neutrality, and high encapsulation percentage. The critical micellar concentration (CMC) was 1.4 × 10−5 mol L-1. The pH-sensitivity was confirmed in vitro through a drug release assay. Cytotoxicity studies confirmed that the encapsulation of DOX into the micelles did not impair the drug cytotoxic activity. Moreover, the incorporation of DSPE-PEG2000-DTPA into the micelles allowed it radiolabeling with the technetium-99 m in high yield and stability, permitting its use to monitor antitumor therapy. In this sense, the pH-sensitive micelles were able to inhibit tumor growth significantly when compared to non-pH-sensitive micelles and the free drug. in vivo toxicity evaluation in the zebrafish model revealed significantly lower toxicity of pH-sensitive micelles compared to the free drug. These results indicate that the developed formulation presents itself as a promising alternative to potentiate the treatment of tumors.

pH-sensitive liposomes are interesting carriers for drug-delivery, undertaking rapid bilayer destabilization in response to pH changes, allied to tumor accumulation, a desirable behavior in the treatment of cancer cells. Previously, we have shown that pH-sensitive liposomes accumulate in tumor tissues of mice, in which an acidic environment accelerates drug delivery. Ultimately, these formulations can be internalized by tumor cells and take the endosome-lysosomal route. However, the mechanism of doxorubicin release and intracellular traffic of pH-sensitive liposomes remains unclear. To investigate the molecular mechanisms underlying the intracellular release of doxorubicin from pH-sensitive liposomes, we followed HeLa cells viability, internalization, intracellular trafficking, and doxorubicin's intracellular delivery mechanisms from pH-sensitive (SpHL-DOX) and non-pH-sensitive (nSpHL-DOX) formulations. We found that SpHL-DOX has faster internalization kinetics and intracellular release of doxorubicin, followed by strong nuclear accumulation compared to nSpHL-DOX. The increased nuclear accumulation led to the activation of cleaved caspase-3, which efficiently induced apoptosis. Remarkably, we found that chloroquine and E64d enhanced the cytotoxicity of SpHL-DOX. This knowledge is paramount to improve the efficiency of pH-sensitive liposomes or to be used as a rational strategy for developing new formulations to be applied in vivo.

Nowadays cancer is one of the most common causes of deaths worldwide. Conventional antitumor agents still present various problems related to specificity for tumor cells often leading to therapeutic failure. Nanoscale particles are considered potential alternative to direct access of drugs into tumor cells, therefore increasing the drug accumulation and performance. The aim of this study was to evaluate the antitumor activity of doxorubicin (DOX)-loaded nanostructured lipid carriers (NLC) versus liposomes against a breast cancer animal experimental model. NLC-DOX and liposomes-DOX were successfully prepared and characterized. Tumor-bearing mice were divided into five groups (blank-NLC, blank-liposome, DOX, NLC-DOX, liposome-DOX). Each animal received by the tail vein four doses of antitumoral drugs (total dose, 16mg/kg), every 3 days. Antitumor efficacy was assessed by measuring 1) tumor volume, calculating the inhibitory ratio (TV-IR, see after) and 2) acquiring scintigraphic images of the tumor using doxorubicin radiolabeled with technetium-99m as an imaging tumor probe. Liposome-DOX and free DOX did not showed differences in the tumor mean volume, whereas NLC-DOX proved to be the best treatments in controlling the tumor growth. NLC-DOX showed an inhibition ration (TV-IR) of 73.5% while free DOX and liposome-DOX decreased TV-RI of 48.8% and 68.0%, respectively. Tumor was clearly visualized in controls, DOX, and liposome-DOX groups. Yet, regarding the NLC-DOX group, tumor was barely identified by the image, indicating antitumor efficacy. Moreover, both NLC and liposomes proved to be able to delay the occurrence of lung metastasis. In conclusion, results of this study indicated that NLC-DOX might be an alternative strategy to achieve an efficient antitumor activity.

Objective Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice. Materials and methods Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection. Results The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a β half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios. Conclusion DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.

New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck-Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a-l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck-Matsuda desymmetrization of 3-cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4-arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons.

PURPOSE: Nanotheranostic platforms, i.e., the combination of both therapeutic and diagnostic agents on a single platform, are emerging as an interesting tool for the personalized cancer medicine. Therefore, the aim of this work was to evaluate the in vivo properties of a Tc-99m-labeled nanostructured lipid carrier (NLC) formulation, co-loaded with doxorubicin (DOX) and docosahexaenoic acid (DHA), for theranostic applications. PROCEDURES: NLC-DHA-DOX were prepared busing the hot melting homogenization method using an emulsification-ultrasound and were radiolabeled with Tc-99m. Biodistribution studies, scintigraphic images, and antitumor activity were performed in 4T1 tumor-bearing mice. RESULTS: NCL was successfully radiolabeled with Tc-99m. Blood clearance showed a relatively long half-life, with blood levels decaying in a biphasic manner (T(1/2)α = 38.7 min; T(1/2)β = 516.5 min). The biodistribution profile and scintigraphic images showed higher tumor uptake compared to contralateral muscle in all time-points investigated. Antitumor activity studies showed a substantial tumor growth inhibition ratio for NLC-DHA-DOX formulation. In addition, the formulation showed more favorable toxicity profiles when compared to equivalent doses of free administered drugs, being able to reduce heart and liver damage. CONCLUSIONS: Therefore, NLC-DHA-DOX formulation demonstrated feasibility in breast cancer treatment and diagnosis/monitoring, leading to a new possibility of a theranostic platform.

Para o manejo de fitonematoides, nematicidas químicos podem ser aplicados em sulco de plantio, utilizados para tratamento de sementes e recentemente tem sido observado em campo a aplicação em pós-emergência, sobre as plantas. O modo de aplicação de produtos fitossanitários pode determinar a sua eficiência no controle desses organismos. O objetivo deste estudo foi avaliar a eficiência de diferentes modos de aplicação de dois nematicidas químicos sobre o nematoide Meloidogyne javanica em soja. Os tratamentos foram compostos por dois produtos químicos [(abamectin (Avicta® 500 FS) e imidacloprid+thiodicarb (Cropstar®)], aplicados em três diferentes sistemas (tratamento de sementes, aplicação no solo e aplicação foliar), e a testemunha sem aplicação. O delineamento utilizado foi inteiramente casualizado, com sete tratamentos e oito repetições. Avaliou-se a massa fresca de raiz, o número de ovos e J2/10g de raiz, fator de reprodução, índice de massa de ovos e índice de galhas de M. javanica, aos 45 dias após a inoculação. O número de ovos e J2 de M. javanica e o fator de reprodução foram menores para os tratamentos com abamectin e imidacloprid+thiodicarb aplicados em tratamento de sementes e sobre o solo em comparação às aplicações foliares e à testemunha. Não houve efeito significativo dos tratamentos sobre a massa fresca de raiz, índice de massa de ovos e índice de galhas. A aplicação de abamectin e imidacloprid+thiodicarb sobre as folhas das plantas de soja não favorecem a redução da população de M. javanica.