Navegando por Palavras-chave "Cytotoxicity"

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    Análise da citotoxicidade e da atividade antioxidante de Baccharis trimera (Less.) DC. (Asteraceae) em queratinócitos
    (Universidade Federal de São Paulo, 2022-12-01) Barsalobra, Karine Pires [UNIFESP]; Lopes, Patricia Santos [UNIFESP]; Andreo, Marcio Adriano [UNIFESP]; http://lattes.cnpq.br/4495354534371511; http://lattes.cnpq.br/7939687315116927; http://lattes.cnpq.br/6376936575357091
    Radicais livres produzidos em excesso podem causar danos à pele, tais como a perda de elasticidade e aceleração do envelhecimento. Os antioxidantes são capazes minimizar ou prevenir esses danos, reduzindo a formação de radicais livres. A Baccharis trimera (Less.) DC. (Asteraceae), conhecida popularmente como “carqueja”, possui substâncias com grande potencial antioxidante, tornando a sua investigação importante para identificar compostos naturais que possam retardar o envelhecimento cutâneo. Diante disso, este estudo teve por objetivo realizar testes in vitro em uma linhagem de queratinócitos humanos imortalizados (HaCaT) para identificar a citotoxicidade e a atividade antioxidante de extratos de B. trimera (Less.) DC. A citotoxicidade foi determinada pelo método de coloração com a solução de MTS/PMS. No ensaio de atividade antioxidante, a fluorescência foi obtida utilizando o 2’,7’–dicloroflurosceína diacetato (DCFH-DA). As substâncias isoladas e identificadas foram os flavonoides quercetina, luteolina e apigenina. Os resultados também determinaram o IC50 de 1961 μg/ml para o extrato aquoso, 460 μg/ml para o extrato hidroalcoólico, 50 μg/ml para a luteolina, 240 μg/ml para a apigenina e 241,3 μg/ml para a quercetina. As amostras testadas mostraram ótimos resultados, evidenciando um potencial antioxidante de 80,5% para o extrato aquoso, 86,0% para o extrato hidroalcoólico; 78,0% para a luteolina; 83,0% para a apigenina e 86,8% para a quercetina, indicando resultados promissores para seu uso em cosméticos, principalmente relacionados ao extrato hidroalcoólico.
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    Análise do potencial anticâncer de extratos obtidos de esponjas marinhas de Fernando de Noronha
    (Universidade Federal de São Paulo, 2021-03-29) Santos, Letícia Schmitz Saraiva [UNIFESP]; Jimenez, Paula Christine [UNIFESP]; http://lattes.cnpq.br/4248251483705135; http://lattes.cnpq.br/4552158300334014; Universidade Federal de São Paulo (UNIFESP)
    A natureza vem contribuindo há tempos com recursos e inspirações para busca de compostos com funções terapêuticas. Sobretudo, o oceano tem demonstrado ser um ambiente de grande significância nestas descobertas devido à biodiversidade extremamente rica presente. As esponjas marinhas figuram entre os grupos de organismos mais estudados por seu potencial farmacológico, sendo inclusive representadas por dois dos oito medicamentos aprovados para tratamento de câncer (Ara-C e Mesilato de eribulina). Com a rica biodiversidade brasileira e a grande necessidade mundial por tratamentos anticâncer mais eficazes e com menos efeitos colaterais, o objetivo deste estudo foi investigar o potencial de extratos obtidos de esponjas marinhas coletadas no Arquipélago de Fernando de Noronha, através da avaliação da atividade citotóxica dos extratos obtidos em células tumorais em cultura. No capítulo I realizou-se um estudo bioprospectivo. Para tanto, exemplares de 47 esponjas foram coletadas no ano de 1998 em diversos locais do Arquipélago, classificadas taxonomicamente e extraídas em solvente orgânico, dando origem aos respectivos extratos brutos. Destes, 39 extratos brutos foram submetidos à avaliação qualitativa de sua citotoxicidade em duas linhagens de células tumorais humanas em cultura: HCT116 (carcinoma colorretal) e MCF-7 (adenocarcinoma mamário) pelo ensaio de MTT. Os resultados obtidos através desta triagem selecionaram, para abordagem quantitativa, as amostras com porcentagem de ao menos 75% de inibição do crescimento celular na presença de concentrações de 5 e 50 μg/mL dos extratos. Dos 39 testados contra as células HCT-116, aproximadamente 46% mostraram-se ativos, enquanto por volta de 29% dos 34 testados demonstraram resultados promissores contra MCF-7. Entre os extratos ativos, o FN98-017 obtido da espécie Ectyoplasia ferox foi considerado promissor e selecionado para prosseguir em investigação, realizado no capítulo II deste estudo. Para tanto, foi realizado o fracionamento bioguiado deste extrato, identificando a partição But P e a fração F16 como as amostras mais citotóxicas. Estas amostras ainda se apresentaram citotóxicas contra linhagens tumorais de diversas origens histológicas. Mais além, foram submetidas à verificação dos respectivos efeitos sobre a viabilidade celular e quanto à indução de alterações morfológicas, buscando gerar evidências para aprofundar o conhecimento do modo de ação destas amostras. A partir destas análises, é possível sugerir que But P e F16 são capazes de disparar o processo de apoptose celular, logo, mostram-se promissoras para estudos mais aprofundados sobre os seus efeitos anticâncer.
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    Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins
    (Elsevier B.V., 2014-09-01) Figueiredo, Carlos R. [UNIFESP]; Matsuo, Alisson L. [UNIFESP]; Massaoka, Mariana H. [UNIFESP]; Polonelli, Luciano; Travassos, Luiz R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Parma; Recepta Biopharma
    Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light-and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, theyalso exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. in this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. the present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs. (C) 2014 Elsevier Inc. All rights reserved.
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    Atividade inflamatória, oxidante e proliferativa em fígado e rim de ratos expostos ao crack
    (Universidade Federal de São Paulo, 2021-09-29) Souza, Daniel Vitor de [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Peres, Rogerio Correa [UNIFESP]; http://lattes.cnpq.br/9555994793258800; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/7955161915979529; Universidade Federal de São Paulo (UNIFESP)
    O crack é uma das drogas ilícitas mais utilizadas ao redor do mundo, sendo o consumo e a disseminação desenfreada representam grande problema de saúde pública. O objetivo do presente estudo foi investigar os efeitos da exposição subaguda de crack no contexto inflamatório, oxidativo e proliferativo em fígado e rim de ratos Wistar. Para tanto, o trabalho foi dividido em 4 capítulos a citar: o Capítulo I foi dedicado a estabelecer uma revisão de literatura acerca do assunto; o Capítulo II apresentamos uma revisão de literatura intitulada “Genotoxicity, oxidative stress and inflammatory response induced by crack cocaine: relevance to carcingoenesis” publicada na Revista Environmental Science and Pollution Research; o Capítulo III apresentamos o artigo intitulado “Histopathological and inflammatory response in multiple organs of rats exposed to crack“, que foi aceito para a publicação na Revista International Journal of Environmental Health Research e finalmente o Capítulo IV apresentamos o artigo intitulado “Genomic instability suppresses toll like signaling pathway in rat liver exposed to crack cocaine, que foi aceito para publicação na revista In Vivo.
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    Avaliação da citotoxicidade, genotoxicidade e mutagenicidade em ratos wistar expostos ao efluente lançado no emissário submarino da cidade de Santos/SP
    (Universidade Federal de São Paulo (UNIFESP), 2016-04-07) Silva, Victor Hugo Pereira da [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Nowadays, it has been demonstrated that wastewater released in continental or even marine coast is one of the most causes of pollution in the environment. Urban sewage is generated from residual water treatment process from domestic, medical, industrial, and rural anthropogenic activities. Due to chemical?physical process involved in this treatment, the sewage tends to concentrate compounds such as nitrates, ammonia and phosphate, heavy metals and organic trace compounds poorly degradable including PAH (polycyclic aromatic hydrocarbons) as well as pathogenic and non-pathogenic organisms. Nevertheless, the presence of persistent organic pollutants, nanocompouds, pharmaceutical compounds and personal care and disinfection by products know as emergent pollutants are expected as well. The interaction between these chemicals compounds is able to cause environmental effects such as reproductive, metabolic and genetic. The aim of this present study was to evaluate cytotoxicity, genotoxicity and mutagenicity in multiple organs of Wistar rats exposed to municipal effluents discharged by municipal outfall in Santos city. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. The analysis for characterization of organic compounds was performed by high resolution liquid chromatography (UPLC) in negative mode. For analysis of histopathological changes, liver and kidney were analyzed, the comet assay was used to evaluate the genotoxic damage in blood, liver and kidney, and the challenge test was used for DNA repair evaluation in liver cells under exposure to 4-NQO and H2O2. To analyze micronuclei frequency histological slide stained with Feulgen and bone marrow smears stained with Giemsa were used to evaluate the mutagenicity. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100% concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was also detected in liver cells. Significant statistical differences (p<0,05) for micronucleated cells from liver were noticed at 50% concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats.
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    Avaliação da segurança e eficácia "in vitro" da Cuscuta racemosa Martius
    (Universidade Federal de São Paulo, 2017-07-04) Bertoluci, Raquel Silveira [UNIFESP]; Lopes, Patricia Santos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Cuscuta racemosa, Mart is a parasitic plant belonging to the family Convolvulaceae, known in Brazil for the popular synonymy of "cipó chumbo" and "yarn of eggs". It is popularly used for its anti-inflammatory and healing actions, applied to diuretic and digestive disorders and presents itself as an alternative of biodiversity for use in medicines and cosmetics. The present study verified the in vitro evaluation of the safety and efficacy of the Cuscuta racemosa extract for possible cosmetic and drug applications. Assays were carried out from crude extract and alkaloids fraction from Cuscuta racemosa to evaluate cytotoxicity, and phototoxicity, as well as determination of antimicrobial and antitumor activity. Cytotoxicity and phototoxicity assays were performed according to the standards recommended by the Organization for Economic Co-operation and Development (OECD) using 3T3 BALB cells. Microbiological analyzes were conducted with Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The evaluation of antimicrobial activity was performed in liquid and solid media. Antitumor activity assays were performed with the HeLa, MDA-DB and Sk-Mel lines. Cytotoxicity tests revealed a cytotoxic effect of the crude extract at concentrations of 34.01 and 50 mg / mL, but at lower concentrations did not present significant action, indicating its safety for possible cosmetic and medicinal applications. Both samples tested showed no phototoxicity. The lethal dose estimated at 50% of the cells calculated for the crude extract was 352.25mg / kg. With respect to the antimicrobial activity, the samples did not present zone of inhibition in solid culture medium in the concentrations tested for none of the tested microorganisms. The crude extract was cytotoxic in all its concentrations in tumor lines. The results indicate the possibility of using the samples in cosmetics, since the alkaloid fraction showed absence of phototoxicity and absence of cytotoxicity, although the samples did not present significant antimicrobial in the concentrations tested. With respect to antitumor activity, complementary studies are necessary directing the active only to the place of action, minimizing the risks of performance of the extract in normal cells.
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    Avaliação ecotoxicológica de sedimentos contaminados com poluentes emergentes empregando o organismo Callinectes SP
    (Universidade Federal de São Paulo, 2018-09-28) Moreno, Beatriz Barbosa [UNIFESP]; Cesar, Augusto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Population Growth In Coastal Zones Has Generated Environmental Impacts Of Various Natures, Among Which Can Be Highlight The Inadequate Disposal Of Industrial And Domestic Effluents In Marine And Estuarine Waters. Domestic Effluents Carry A Wide Variety Of Contaminants Such As Pharmaceuticals And Personal Care (Ppcps), Which Can Be Classified As Emerging Pollutants. With This, The European And North American Environmental Agencies Began To Regulate The Approval, Commercialization And Disposal Of These Pollutants Through Directives. It Has Been Shown That Changes In Biological Responses Are An Important Tool In Assessing The Risks Associated With The Introduction Of These Substances In The Environment, Since The Responses Observed Are Sensitive To The Exposure And Effect Of These Xenobiotics, Providing Relevant Information On Their Bioavailability And Toxicity. The Aim Of The Present Study Was To Determine The Environmental Concentrations Of Triclosan (Tcs) And Ibuprofen (Ibu) In Marine Sediments Around The San
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    Biochemical characterization of a Kunitz type inhibitor similar to dendrotoxins produced by Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) hemocytes
    (Elsevier B.V., 2010-02-10) Lima, Cassia A. [UNIFESP]; Torquato, Ricardo J. S. [UNIFESP]; Sasaki, Sergio D. [UNIFESP]; Justo, Giselle Z. [UNIFESP]; Tanaka, Aparecida S. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)
    A novel chymotrypsin inhibitor identified in fat body and hemocyte cDNA libraries of Boophilus microplus was named BmCI (B. microplus Chymotrypsin Inhibitor) (Genbank EU636772). the putative BmCI amino acid sequence presented a 22-residue-signal peptide and 58-residue-mature protein. BmCI amino acid sequence analysis allowed its classification as a Kunitz-BPTI inhibitor with six cysteine residues, a theoretical pI of 7.8, and the presence of Tyr at P1 position in the putative reactive site, suggesting inhibitory activity toward chymotrypsin. in this work, we reported the biochemical characterization of BmCI. the recombinant BmCI expressed in yeast Pichia pastoris was purified by size exclusion and reverse phase chromatographies. rBmCI expression yield was of I mg L-1 of culture. Purified rBmCI confirmed its chymotrypsin inhibitory activity with a low K-i (6.2 pM). the BmCI gene expression analysis by semi-quantitative RT-PCR indicated its transcription in the hemocytes, salivary gland and ovary. the cytotoxic activity of purified rBmCI was demonstrated in BALB/c 3T3 mouse fibroblasts. As assessed by the MTT reduction assay, rBMCI induced a dose-dependent decrease in 3T3 fibroblasts viability (IC50 = 8 mu M). Moreover, flow cytometry analysis revealed that rBmCI is able to induce apoptosis, whereas no effect was observed on cell cycle progression. in conclusion, we demonstrated that rBmCI is cytotoxic against mammalian cells and obtained evidence that this growth inhibition is caused by an apoptosis-inducing activity. (C) 2009 Published by Elsevier B.V.
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    Biocompatibilidade in vitro da hidroxiapatita extraída de resíduo de peixe (Micropogonias furnieri)
    (Universidade Federal de São Paulo, 2022-01-24) Pires, Larissa Mariano [UNIFESP]; Granito, Renata Neves [UNIFESP]; Prado, João Paulo dos Santos [UNIFESP]; http://lattes.cnpq.br/1803025633941465; http://lattes.cnpq.br/1941145984734628; http://lattes.cnpq.br/3609399669096247; Universidade Federal de São Paulo (UNIFESP)
    O osso é um tecido conjuntivo especializado no qual a matriz orgânica colagênica é mineralizada, uma vez que é permeada por cristais de hidroxiapatita (HAP), um mineral que contribui para as suas propriedades mecânicas. Em casos de fraturas ósseas, a HAP, de diferentes origens, pode ser usada como um biomaterial implantável. Quando extraída de resíduo de peixe, pode constituir uma alternativa econômica e ecologicamente mais viável do que a HAP sintética, visto que este biomaterial natural seria descartado e poderia constituir um problema ambiental. Com base neste cenário, este trabalho teve como objetivo avaliar a citotoxicidade da hidroxiapatita (HAP) extraída de resíduos de peixes (Micropogonias furnieri), bem como a proliferação in vitro e a expressão gênica de células pré-osteoblásticas MC3T3-E1 expostas a um meio condicionado com esse biomaterial natural. A HAP foi extraída de resíduo de peixe e as células pré-osteoblásticas MC3T3-E1 foram cultivadas em meio enriquecido com o biomaterial (HAP) ou em meio de cultura padrão (controle). Após 1, 3 e 6 dias de cultura, foram realizados os teste de alamarBlue, quantificação de DNA (PicoGreen) e RT-PCR, para quantificar a expressão dos genes osteogênicos BPM4 e Runx2. Na avaliação, os estudos de viabilidade celular alamarBlue não indicaram diferenças estatísticas entre os grupos. Por outro lado, após 3 e 6 dias de exposição, a taxa de redução do alamarBlue foi maior nas amostras de HAP indicando maior viabilidade celular. O resultado da quantificação de DNA sugeriu uma menor quantidade de células nos poços contendo meio enriquecido com HAP quando comparadas ao grupo controle. No entanto, como houve maior redução da resazurina em resorufin no teste de alarme Blue, sugerindo maior atividade metabólica das células cultivadas em meio enriquecido com HAP. Não houve diferença significativa na expressão dos genes BPM4 e Runx2. Os resultados indicam que a HAP extraída de carcaça de peixe, um material reaproveitado de resíduos, não apresenta citotoxicidade e pode ter um efeito positivo no metabolismo celular, indicando seu potencial para sua aplicação como biomaterial na engenharia de tecidos.
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    Biocompatibility of glass-ionomer cements using mouse lymphoma cells in vitro
    (Blackwell Publishing, 2006-12-01) Ribeiro, Daniel Araki [UNIFESP]; Marques, Mariangela Esther Alencar; Salvadori, Daisy Maria Favero; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Glass-ionomer cements are widely used in dentistry as restorative materials and adhesives for composite restorations. A number of genotoxicity studies have been conducted using these materials with results conflicting so far. Thus, the approach was aimed to look at the genotoxic and cytotoxic potential of three different glass-ionomer cements available commercially (Ketac Cem, Ketac Molar and Vitrebond) by the single cell gel (comet) assay and trypan blue exclusion test, respectively. for this, such materials were exposed to mouse lymphoma cells in vitro for 1 h at 37 degrees C. Data were assessed by Kruskall-Wallis non-parametric test. the results showed that all powders assayed did not show genotoxic effects. On the other hand, the liquid from Vitrebond at 0.1% dilution caused an increase of DNA injury. Significant statistically differences (P < 0.05) in cytotoxicity provoked by all powders tested were observed for exposure at 1000 mu g mL(-1) concentration and 100 mu g mL(-1) for Ketac Molar. With respect to liquids of glass-ionomer cements evaluated, the major toxic effect on cell viability was produced at 1%, beginning at the dilution of 0.5% for Vitrebond. Taken together, these results support the notion that some components of glass-ionomer cements show both genotoxic and cytotoxic effects in higher concentrations.
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    Biomonitoramento citogenético em células da mucosa bucal e sangue periférico em pintores de automóveis
    (Universidade Federal de São Paulo, 2012-04-10) Silva, Victor Hugo Pereira da [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/4534973277501184; Universidade Federal de São Paulo (UNIFESP)
    Os pintores de automóveis estão ocupacionalmente expostos a uma gama de substâncias danosas provenientes não somente das tintas automotivas, mas também de solventes orgânicos, hidrocarbonetos aromáticos policíclicos, resinas plásticas e metais. Essa exposição prolongada pode estar relacionada ao aumento da incidência de doenças crônico-degenerativas inclusive o câncer. O objetivo do presente estudo foi avaliar a citotoxicidade e mutagenicidade por meio do teste do micronúcleo em células da mucosa jugal e genotoxicidade a partir do teste do cometa em leucócitos de sangue periférico em pintores de automóveis. Para o teste do micronúcleo, foi utilizado um total de 24 indivíduos expostos e 21 voluntários controle (indivíduos não-expostos). Para o ensaio do cometa, um total de 24 voluntários expostos e 19 voluntários controle foram avaliados. A análise de células bucais revelou que a frequência de micronúcleos em indivíduos expostos foi significativamente maior uma vez comparada ao controle (p<0,05). Porém, a citotoxicidade não foi diferente entre os grupos. O teste do cometa revelou um aumento estatisticamente significativo no momento da cauda dos cometas dos pintores de automóveis quando comparado ao grupo controle (p<0,05). Em suma, tais resultados sugerem que indivíduos ocupacionalmente expostos a tintas automotivas apresentam genotoxicidade e mutagenicidade em células de sangue periférico e mucosa bucal, respectivamente, sendo necessárias ações profiláticas que diminuam a exposição desses profissionais a esses produtos de risco.
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    Bionanomining of copper-based nanoparticles using pre-processed mine tailings as the precursor
    (Elsevier, 2023-03-28) Brandão, Igor Yannick Vasconcellos; Macedo, Erenilda Ferreira de; Silva, Pedro Henrique Barboza de Souza; Batista, Aline Fontana; Petroni, Sérgio Luis Graciano; Gonçalves, Maraisa [UNIFESP]; Conceição, Katia [UNIFESP]; Trichês, Eliandra de Sousa [UNIFESP]; Tada, Dayane Batista [UNIFESP]; Maass, Danielle [UNIFESP]; http://lattes.cnpq.br/3431482044015696
    The bacterial synthesis of copper nanoparticles emerges as an eco-friendly alternative to conventional techniques since it comprises a single-step and bottom-up approach, which leads to stable metal nanoparticles. In this paper, we studied the biosynthesis of Cu-based nanoparticles by Rhodococcus erythropolis ATCC4277 using a preprocessed mining tailing as a precursor. The influence of pulp density and stirring rate on particle size was evaluated using a factor-at-time experimental design. The experiments were carried out in a stirred tank bioreactor for 24 h at 25 ◦C, wherein 5% (v/v) of bacterial inoculum was employed. The O2 flow rate was maintained at 1.0 L min-1 and the pH at 7.0. Copper nanoparticles (CuNPs), with an average hydrodynamic diameter of 21 ± 1 nm, were synthesized using 25 g.L-1 of mining tailing and a stirring rate of 250 rpm. Aiming to visualize some possible biomedical applications of the as-synthesized CuNPs, their antibacterial activity was evaluated against Escherichia coli and their cytotoxicity was evaluated against Murine Embryonic Fibroblast (MEF) cells. The 7-day extract of CuNPs at 0.1 mg mL-1 resulted in 75% of MEF cell viability. In the direct method, the suspension of CuNPs at 0.1 mg mL-1 resulted in 70% of MEF cell viability. Moreover, the CuNPs at 0.1 mg mL-1 inhibited 60% of E. coli growth. Furthermore, the NPs were evaluated regarding their photocatalytic activity by monitoring the oxidation of methylene blue (MB) dye. The CuNPs synthesized showed rapid oxidation of MB dye, with the degradation of approximately 65% of dye content in 4 h. These results show that the biosynthesis of CuNPs by R. erythropolis using pre-processed mine tailing can be a suitable method to obtain CuNPs from environmental and economical perspectives, resulting in NPs useful for biomedical and photocatalytic applications.
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    Bioprospecção de actinobactérias recuperadas de sedimento marinho na ilha de Queimada Grande com potencial anticâncer
    (Universidade Federal de São Paulo, 2022-07-25) Farias, Evelyn da Cruz [UNIFESP]; Jimenez, Paula Christine [UNIFESP]; http://lattes.cnpq.br/4248251483705135; http://lattes.cnpq.br/7936986715655214; Universidade Federal de São Paulo (UNIFESP)
    O uso de substâncias naturais como forma de tratamento de diversas doenças está em vigor até os dias atuais. E embora o meio marinho seja conhecido pela vasta biodiversidade de microrganismos, somente no século passado houve um enfoque maior em pesquisas relacionadas a bioprospecção de microrganismos com potencial farmacológico, principalmente potencial anticâncer, por ser uma das doenças que mais assolam a humanidade. Nesse aspecto, as actinobactérias são conhecidas como uma fonte quase que inesgotável de recursos biotecnológicos, pois possuem metabólitos secundários que podem ser utilizados como agentes antitumorais, o que nos mostra a importância de estudos nessa temática. O Brasil, em particular, é dotado de uma rica flora e fauna, especialmente em áreas insulares, pois o processo de especiação é mais acentuado nessas regiões, e apesar da abundante riqueza de espécies, esse ambiente carece de exploração. Neste contexto, o objetivo do presente trabalho é prospectar o potencial anticâncer de actinobactérias recuperadas de sedimento marinho coletado no entorno da Ilha da Queimada Grande, no litoral de São Paulo. Foram recuperadas, isoladas e purificadas 12 cepas de actinobactérias, das quais foram obtidos os extratos em meio sólido e líquido que, posteriormente, foram testados quanto à citotoxicidade contra células da linhagem tumoral humana HCT-116 pelo ensaio do MTT. Dentre os 20 extratos obtidos e testados, dois se mostraram mais ativos, sendo aqueles obtidos em meio líquido das cepas BRB 537 e BRB 558, inibindo pelo menos 75% do crescimento das células após 72h de exposição a 50 μg/mL. Por fim, estes extratos foram submetidos a uma análise quantitativa de citotoxicidade, visando determinar o valor respectivo de IC50 contra HCT-116, que foi calculado em 7,04 μg/mL e 27,59 μg/mL, respectivamente. Esses resultados evidenciam o potencial anticâncer de actinobactérias recuperadas do sedimento marinho da ilha de Queimada Grande.
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    Biosilicate/PLGA osteogenic effects modulated by laser therapy: In vitro and in vivo studies
    (Elsevier Science Sa, 2017) Fernandes, Kelly Rossetti [UNIFESP]; Magri, Angela Maria Paiva [UNIFESP]; Kido, Hueliton Wilian [UNIFESP]; Parisi, Julia Risso; Assis, Livia [UNIFESP]; Fernandes, Kristianne Porta Santos; Mesquita Ferrari, Raquel Agnelli; Martins, V. C.; Plepis, Ana M.; Zanotto, Edgar Dutra; Peitl Filho, Oscar; Renno, Ana Claudia Muniz [UNIFESP]
    The main purpose of the present work was to evaluate if low laser level therapy (LLLT) can improve the effects of Biosilicate®/PLGA (BS/PLGA) composites on cell viability and bone consolidation using a tibial defects of rats. The composites were characterized by scanning electron microscope (SEM) and reflection Fourier transform infrared spectrometer (FTIR). For the in vitro study, fibroblast and osteoblast cells were seeded in the extract of the composites irradiated or not with LLLT (Ga-Al-As, 808 nm, 10 J/cm2) to assess cell viability after 24, 48 and 72 h. For the in vivo study, 80 Wistar rats with tibial bone defects were distributed into 4 groups (BS; BS + LLLT; BS/PLGA and BS/PLGA + LLLT) and euthanized after 2 and 6 weeks. Laser irradiation Ga-Al-As (808 nm, 30 J/cm2) in the rats was performed 3 times a week. The SEM and FTIR results revealed that PLGA were successfully inserted into BS and the microparticles degraded over time. The in vitro findings demonstrated higher fibroblast viability in both BS/PLGA groups after 24 h and higher osteoblast viability in BS/PLGA + LLLT in all periods. As a conclusion, animals treated with BS/PLGA + LLLT demonstrated an improved material degradation and an increased amount of granulation tissue and newly formed bone.
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    Cafestol, a diterpene molecule found in coffee, induces leukemia cell death
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Limaa, Caue S. [UNIFESP]; Spindola, Daniel G. [UNIFESP]; Bechara, Alexandre [UNIFESP]; Garcia, Daniel M. [UNIFESP]; Palmeira-dos-Santos, Caroline [UNIFESP]; Peixoto-da-Silva, Janaina [UNIFESP]; Erustes, Adolfo G. [UNIFESP]; Michelin, Luis F. G. [UNIFESP]; Pereira, Gustavo J. S. [UNIFESP]; Smaili, Soraya S. [UNIFESP]; Paredes-Gamero, Edgar [UNIFESP]; Calgarotto, Andrana K. [UNIFESP]; Oliveira, Carlos R. [UNIFESP]; Bincoletto, Claudia [UNIFESP]
    To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit-granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol. (C) 2017 Elsevier Masson SAS. All rights reserved.
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    Characterization and biocompatibility of a fibrous glassy scaffold
    (Wiley, 2017) Gabbai-Armelin, Paulo Roberto; Souza, M. T.; Kido, Hueliton Wilian; Tim, Carla Roberta; Bossini, Paulo Sergio [UNIFESP]; Fernandes, Kelly Rossetti [UNIFESP]; Magri, Angela Maria Paiva [UNIFESP]; Parizotto, Nivaldo Antonio; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Ribeiro, Daniel Araki [UNIFESP]; Zanotto, Edgar Dutra; Peitl Filho, Oscar [UNIFESP]; Renno, Ana Claudia Muniz [UNIFESP]
    Bioactive glasses (BGs) are known for their ability to bond to living bone and cartilage. In general, they are readily available in powder and monolithic forms, which are not ideal for the optimal filling of bone defects with irregular shapes. In this context, the development of BG-based scaffolds containing flexible fibres is a relevant approach to improve the performance of BGs. This study is aimed at characterizing a new, highly porous, fibrous glassy scaffold and evaluating its in vitro and in vivo biocompatibility. The developed scaffolds were characterized in terms of porosity, mineralization and morphological features. Additionally, fibroblast and osteoblast cells were seeded in contact with extracts of the scaffolds to assess cell proliferation and genotoxicity after 24, 72 and 144 h. Finally, scaffolds were placed subcutaneously in rats for 15, 30 and 60 days. The scaffolds presented interconnected porous structures, and the precursor bioglass could mineralize a hydroxyapatite (HCA) layer in simulated body fluid (SBF) after only 12 h. The biomaterial elicited increased fibroblast and osteoblast cell proliferation, and no DNA damage was observed. The in vivo experiment showed degradation of the biomaterial over time, with soft tissue ingrowth into the degraded area and the presence of multinucleated giant cells around the implant. At day 60, the scaffolds were almost completely degraded and an organized granulation tissue filled the area. The results highlight the potential of this fibrous, glassy material for bone regeneration, due to its bioactive properties, non-cytotoxicity and biocompatibility. Future investigations should focus on translating these findings to orthotopic applications. Copyright (c) 2015 John Wiley & Sons, Ltd.
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    Characterization and biological evaluation of the introduction of PLGA into biosilicate
    (Wiley, 2017) Fernandes, Kelly Rossetti [UNIFESP]; Magri, Angela Maria Paiva [UNIFESP]; Kido, Hueliton Wilian [UNIFESP]; Ueno, Fabio Roberto [UNIFESP]; Assis, Livia [UNIFESP]; Fernandes, Kristianne Porta Santos; Mesquita Ferrari, Raquel Agnelli; Martins, V. C.; Plepis, Ana M.; Zanotto, Edgar Dutra; Peitl Filho, Oscar; Ribeiro, Daniel Araki [UNIFESP]; Van den Beucken, Jeroen J.; Renno, Ana Claudia Muniz [UNIFESP]
    The aims of this study were to characterize different BS/PLGA composites for their physicochemical and morphological characteristics and evaluate the in vitro and in vivo biological performance. The physicochemical and morphological modifications were analyzed by pH, mass loss, XRD, setting time, and SEM. For in vitro analysis, the osteoblast and fibroblast viability was evaluated. For in vivo evaluations, histopathology and immunohistochemistry were performed in a tibial defect in rats. After incubation, all composites presented lower values in pH and mass loss over time. Moreover, XRD and SEM analysis confirmed that the composites degraded over time. Additionally, pore formation was observed by SEM analysis after incubation mainly in BS/PLGA groups. BS/PLGA showed significantly increased in osteoblast viability 24 h. Moreover, BS/PLGA composites demonstrated an increase in fibroblast viability in all periods analyzed when compared to BS. In the in vivo study, after 2 and 6 weeks of implantation of biomaterials, histopathological findings revealed that the BS/PLGA composites degrades over time, mainly at periphery. Moreover, can be observed the presence of granulation tissue, bone formation, Runx-2, and RANKL immunoexpression in all groups. In conclusion, BS/PLGA composites present appropriate physicochemical characteristics, stimulate the cellular viability, and enhance the bone repair in vivo. (C) 2016 Wiley Periodicals, Inc.
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    Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin
    (Elsevier B.V., 2012-05-01) Ridolfi, Daniela M.; Marcato, Priscyla D.; Justo, Giselle Z. [UNIFESP]; Cordi, Livia; Machado, Daisy; Duran, Nelson; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Universidade Federal do ABC (UFABC)
    Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. the aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. the hydrodynamic mean diameter and zeta potential were 162.7 +/- 1.4 nm and -31.9 +/- 2.0 mV for SLN-TRE, and 284.8 +/- 15.0 nm and 55.9 +/- 3.1 mV for SLN-chitosan-TRE. the SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. (C) 2011 Elsevier B.V. All rights reserved.
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    Chromomycin A2 Induces Autophagy in Melanoma Cells
    (Mdpi Ag, 2014-12-01) Guimaraes, Larissa Alves; Jimenez, Paula Christine [UNIFESP]; Sousa, Thiciana da Silva; Freitas, Hozana Patricia Silva de; Rocha, Danilo Damasceno; Wilke, Diego Veras; Martin, Jesus; Reyes, Fernando; Pessoa, Otilia Deusdenia Loiola; Costa-Lotufo, Leticia Veras; Univ Fed Ceara; Universidade Federal de São Paulo (UNIFESP); Fdn MEDINA
    The present study highlights the biological effects of chromomycin A2 toward metastatic melanoma cells in culture. Besides chromomycin A2, chromomycin A3 and demethylchromomycin A2 were also identified from the extract derived from Streptomyces sp., recovered from Paracuru Beach, located in the northeast region of Brazil. the cytotoxic activity of chromomycin A2 was evaluated across a panel of human tumor cell lines, which found IC50 values in the nM-range for exposures of 48 and 72 h. MALME-3M, a metastatic melanoma cell line, showed the highest sensitivity to chromomycin A2 after 48h incubation, and was chosen as a model to investigate this potent cytotoxic effect. Treatment with chromomycin A2 at 30 nM reduced cell proliferation, but had no significant effect upon cell viability. Additionally, chromomycin A2 induced accumulation of cells in G(0)/G(1) phase of the cell cycle, with consequent reduction of S and G(2)/M and unbalanced expression of cyclins. Chromomycin A2 treated cells depicted several cellular fragments resembling autophagosomes and increased expression of proteins LC3-A and LC3-B. Moreover, exposure to chromomycin A2 also induced the appearance of acidic vacuolar organelles in treated cells. These features combined are suggestive of the induction of autophagy promoted by chromomycin A2, a feature not previously described for chromomycins.
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    Citogenotoxicidade e mutagenicidade da água do Sistema Estuarino de Santos-São Vicente
    (Universidade Federal de São Paulo (UNIFESP), 2019-11-25) Cardoso, Caroline Margonato [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/4298143669596994; Universidade Federal de São Paulo (UNIFESP)
    The Santos-São Vicente Estuarine System (SESS) is one of the most degraded estuaries in Brazil. The disorderly urbanization of the Baixada Santista Metropolitan Region (RMBS) added with the inefficiency of regulatory mechanisms and basic sanitation, poverty, poor housing conditions, and environmental pollution make this region suitable for environmental monitoring studies. Thus, the aim of this study was to evaluate the water-induced cytogenotoxicity and mutagenicity of SSES collected at the points described as most contaminated (São Vicente and Piaçaguera Channels) using Wistar rats as an experimental model and Centropomus undecimalis fish. For this purpose, surface water was collected São Vicente Channel (SVC) and Piaçaguera Channel (PIC) of SESS and non-essential metals and metalloids (Cd, Pb, Hg and As) were quantified. Adult male Wistar rats were divided into four groups (n = 5) and exposed for 5 days: a) negative control received filtered water, b) saline control received saline water, c) experimental group received estuarine water from PIC and d) experimental group received estuarine water from SVC. Blood and liver were used for comet assay; bone marrow was used to perform the micronucleus test; histopathological, immunohistochemical analyzes (TNF-α, ki67 and 8-OHdG) and realtime PCR of caspase-3 were performed in the liver. The results revealed that rats exposed to water from SESS showed biological responses associated with genotoxicity, mutagenicity and cytotoxicity. Juvenile fish (n = 6) from C. undecimalis were collected from the SVC and compared to fish (n = 10) obtained from a pisciculture laboratory (control group). Micronucleus tests and nuclear abnormalities were performed with blood, and quantification of lipid peroxidation and DNA damage were performed with gills and livers of fish. Erythrocyte nuclear abnormalities in blood and lipid peroxidation in gills were higher in fish from SESS. In conclusion, SESS is capable of both mutagenic and cytotoxic activities in murine and fish, both having similar responses to environmental contaminants.