The use of Maytenus ilicifolia to prevent cisplatin-induced ototoxicity

Maytenus ilicifolia é uma planta sul americana apresenta várias propriedades medicinais, entre elas, a ação antioxidante. OBJETIVO: Por meio de um modelo original de ototoxicidade induzida pela cisplatina, verificar uma possível ação otoprotetora do extrato aquoso desta planta. MATERIAL E MÉTODO: Estudo clínico e experimental com cobaias fêmeas, albinas divididas em 5 grupos: 9 animais recebendo somente 3 doses de 7,5mg/kg/d do protocolo de cisplatina, 4 animais somente com o extrato, 10 animais com cisplatina e 1g/kg/d de extrato por 8 dias, 5 animais com cisplatina e 3g/kg/d do extrato por 8 dias e 5 animais recebendo extrato por 3 semanas e cisplatina na última semana. Os exames foram emissões otoacústica por produtos de distorção, potencial de tronco encefálico pré e após administração de cisplatina e, microscopia eletrônica de varredura. RESULTADOS: Os animais que receberam a cisplatina com o extrato, independente da dose, obtiveram alterações em todos os testes, com lesões na região basal na microscopia eletrônica. CONCLUSÃO: Apesar do efeito antioxidante da Maytenus ilicifolia, ela não foi suficiente para bloquear o efeito ototóxico da cisplatina.Maytenus ilicifolia is a native plant from South America, with several medicinal properties including antioxidant effects. AIM: using an original cisplatin induced ototoxicity model, we evaluated a possible otoprotection caused by Maytenus ilicifolia extract. MATERIALS AND METHODS: clinical and experimental study design with female albino guinea pigs divided in groups as follows: 9 animals receiving cisplatin only (three doses of 7.5mg/kg/day), 4 animals receiving the plant extract only, 10 animals receiving the cisplatin protocol and 1g/kg/day of extract for 8 days, 5 animals with cisplatin and 3g/kg/day of extract for 8 days, and 5 animals receiving extract for 3 weeks and cisplatin in the last week. The tests were distortion product otoacoustic emissions, brainstem auditory response, before and after medication and scanning electron microscopy. RESULTS: the animals receiving cisplatin plus plant extract, had alterations in all the tests, showing lesions on the basal cochlear region under electron microscopy. CONCLUSIONS: Despite of the plant extract's antioxidant effect, it was not sufficient to protect the cochlea against cisplatin ototoxicity

Antiproliferative activity of extracts of Euphorbia tirucalli L (Euphorbiaceae) from three regions of Brazil

Purpose: To investigate Euphorbia tirucalli extract for probable geographic variations in its antiproliferative activity.Methods: The aerial parts of E. tirucalli were collected in the Brazilian states of Mato Grosso, Rio de Janeiro, Pará, Minas Gerais and Santa Catarina. The 70 % ethanol extract was obtained according to the procedure described in Brazilian Homeopathic Pharmacopeia. The antiproliferative activity of extracts, in concentrations of 62, 125, 250, and 500 μg mL-1, was tested against leukemia (HL-60), lymphoma (Daudi) and melanoma (B16F10) cell lines using methyl thiazol tetrazolium assay (MTT). Phytochemical analysis were carried out using High-performance liquid chromatography-diode array (HPLC-UV-DAD) and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(-) FT-ICR MS) assays.Results: There was significant regional variability in the cytotoxicity of E. tirucalli extracts in a dosedependent manner. The extracts had similar activity towards leukemia cell line HL-60, decreasing cell viability to about 60 – 70 %. The extract showed the presence of ellagitannins, flavonoids, veracylglucan, and acid triterpenes as the major compounds.Conclusion: While the results support the ethnopharmacological use of E. tirucalli throughout Brazil, regional quantitative differences found in some classes of secondary metabolites may explain the variations observed in antitumor activity.Keywords: Aveloz, Cancer, Cytotoxicity, Antiproliferative, Ethnopharmacological, Traditional medicin

High molecular weight polystyrene particles by cationic miniemulsion polymerization catalyzed by an iron-containing imidazolium-based ionic liquid

Cationic styrene polymerizations in aqueous media were conducted using the miniemulsion polymerization technique with the ionic liquid 1-N-butyl-3-N-methylimidazolium heptachloro diferrate (BMI.Fe2Cl7) as catalyst, hexadecyltrimethylammonium bromide (CTAB) as surfactant and hexadecane as costabilizer. The ionic liquid was effective to initiate styrene miniemulsion polymerization at a BMI.Fe2Cl7:styrene molar ratios as low as 1:1000. Increasing the reaction temperature from 70 °C to 90 °C led to an increase in both, conversion and molecular weight. And polystyrene with much higher molecular weight (viscosity average molecular weights of up to 2231 kDa) than those usually obtained in cationic polymerizations was produced. Furthermore, while particle sizes remained almost constant around 150 nm during polymerizations, an almost linear increase of conversion with reaction time was observed. In addition, molecular weight increased steadily with conversion approaching the behavior of living cationic polymerization. Please click Additional Files below to see the full abstrac

Perillyl alcohol in Solid Lipid Nanoparticles (SLN-PA): Cytotoxicity and antitumor potential in sarcoma 180 mice model

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Flow cytometry immunophenotyping for diagnostic orientation and classification of pediatric cancer based on the euroflow solid tumor orientation tube (Stot)

© 2021 by the authors.Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination—solid tumor orientation tube, STOT—for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design–test–evaluate–redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/numyogenin/CD4-EpCAM/CD56/GD2/smCD3-CD19/cyCD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained. In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45− CD56++ non-hematopoietic solid tumors: 13/13 (GD2++ numyogenin− CD271−/+ nuMyoD1− CD99− EpCAM−) neuroblastoma samples, 5/5 (GD2− numyogenin++ CD271++ nuMyoD1++ CD99−/+ EpCAM−) rhabdomyosarcomas, 2/2 (GD2−/+ numyogenin− CD271+ nuMyoD1− CD99+ EpCAM−) Ewing sarcoma family of tumors, and 7/7 (GD2− numyogenin− CD271+ nuMyoD1− CD99− EpCAM+) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.This research was funded by the EuroFlow Consortium; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil (FAPERJ), numbers: E26/110.105/2014, E-26/010.101259/2018, and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, Brazil (CNPQ), Brasília, Brazil, numbers: 303765/2018-6, 409440/2016-7, and 400194/2014-7; and Instituto Desiderata/Chevron, Rio de Janeiro, Brazil, grant “Actions to improve pediatric cancer assistance in RJ”; the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15

FITOQUÍMICA E ATIVIDADE FARMACOLÓGICA PRELIMINAR DO EXTRATO AQUOSO DE Tynanthus micranthus Corr. Méllo ex K. Schum: UM EXEMPLO DA CAPACIDADE PREDITIVA E DOS CUSTOS NO DESENVOLVIMENTO DE NOVOS PRODUTOS FARMACÊUTICOS

Os produtos naturais têm servido de inspiração para o desenvolvimento de vários produtos pela indústria farmacêutica local e mundial. O objetivo do presente trabalho foi avaliar a atividade farmacológica preliminar do extrato aquoso das folhas secas de Tynanthus micranthus, usando o teste hipocrático em camundongos, como uma ferramenta para direcionar estudos farmacológicos futuros, bem como avaliar os custos envolvidos na execução deste estudo. AT. micranthus Corr. Méllo ex K. Schum, conhecida popularmente como cipó-cravo, é facilmente encontrada na região Noroeste do Estado do Paraná, Brasil, sendo utilizada pela população como calmante e analgésica. No entanto, existem poucos trabalhos científicos com esta espécie vegetal. O cálculo do custo contábil foi realizado para simular o valor gasto por uma empresa privada na realização destas atividades de Pesquisa e Desenvolvimento. Nossos resultados mostram que além do baixo custo, o teste hipocrático proporciona resultados importantes para a decisão da via de administração, toxicidade aguda, efeitos com altas doses e por diferentes vias, além de fornecer informações sobre a latência para os efeitos observados. Com essas informações e uma análise fitoquímica mais aprofundada, isolando e identificando os compostos majoritários, é possível avaliar na literatura a relação composto x atividade farmacológica direcionando de forma mais assertiva as pesquisas a serem realizadas. De maneira geral, apresentamos dados inéditos da espécie estudada (T. micranthus), mostrando uma estratégia de triagem farmacológica simples e de baixo custo para a pesquisa de plantas medicinais nativas que apresentem informações restritas na literatura e que possam servir para o desenvolvimento de novos produtos farmacêuticos

Expanding the knowledge on lignocellulolytic and redox enzymes of worker and soldier castes from the lower termite coptotermes gestroi

Termites are considered one of the most efficient decomposers of lignocelluloses on Earth due to their ability to produce, along with its microbial symbionts, a repertoire of carbohydrate-active enzymes (CAZymes). Recently, a set of Pro-oxidant, Antioxidant, and Detoxification enzymes (PAD) were also correlated with the metabolism of carbohydrates and lignin in termites. The lower termite Coptotermes gestroi is considered the main urban pest in Brazil, causing damage to wood constructions. Recently, analysis of the enzymatic repertoire of C. gestroi unveiled the presence of different CAZymes. Because the gene profile of CAZy/PAD enzymes endogenously synthesized by C. gestroi and also by their symbiotic protists remains unclear, the aim of this study was to explore the eukaryotic repertoire of these enzymes in worker and soldier castes of C. gestroi. Our findings showed that worker and soldier castes present similar repertoires of CAZy/PAD enzymes, and also confirmed that endo-glucanases (GH9) and beta-glucosidases (GH1) were the most important glycoside hydrolase families related to lignocellulose degradation in both castes. Classical cellulases such as exo-glucanases (GH7) and endo-glucanases (GH5 and GH45), as well as classical xylanases (GH10 and GH11), were found in both castes only taxonomically related to protists, highlighting the importance of symbiosis in C. gestroi. Moreover, our analysis revealed the presence of Auxiliary Activity enzyme families (AAs), which could be related to lignin modifications in termite digestomes. In conclusion, this report expanded the knowledge on genes and proteins related to CAZy/PAD enzymes from worker and soldier castes of lower termites, revealing new potential enzyme candidates for second-generation biofuel processes7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140796/2013-4; 310186/2014-5; 442333/2014-511/20977-3; 15/06971-3; 12/19040-0; 14/10351-8; 06/59086-8; 14/20576- 7; 13/03061-0; 10/11469-1; 08/58037-9; 14/50371-8; 08/50114-

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio