IGFBP7 as a new therapeutic target in acute lymphoblastic leukemia

Orientador: José Andrés YunesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: A Leucemia Linfoide Aguda (LLA) é o tipo de câncer mais comum na infância, representando cerca de 30% de todos os casos de cânceres e 80% de todas as leucemias que ocorrem até a faixa etária de 15 anos. Apesar da melhora da terapia para LLA, essa doença ainda é a causa mais comum de morte relacionada a câncer em crianças em todo o mundo. Na última década, alguns trabalhos demostraram que a maior expressão de IGFBP7 estaria relacionada a um pior prognóstico dos pacientes com LLA. Mostramos anteriormente que as células de LLA são a principal fonte de IGFBP7 no microambiente da leucemia, a qual exerce um efeito parácrino sobre as células estromais da medula óssea, refletindo na resistência a terapia primária pelos pacientes. Aqui, demostramos que IGFBP7 exerce também um efeito autócrino sobre as células de LLA (linhas celulares e células primárias). Observamos que os efeitos positivos de proliferação mediados por Insulina/IGFs nas linhagens celulares de LLA são significativamente aumentados pela adição de IGFBP7 recombinante, promovendo a maior ativação da via PI3k/Akt/mTOR. Todavia, o silenciamento de IGFBP7 prejudica este efeito, impulsionando a ativação da via p53 nas células silenciadas. Ainda, ilustramos que o knockdown de IGFBP7 sensibiliza as células de LLA diante das ações citostáticas mediadas pelo fármaco Dexametasona e confirmamos que IGFBP7 promove resistência quimioterápica aos glicocorticoides na LLA. Nossos dados demostram ainda que a neutralização de IGFBP7 com anticorpo monoclonal é prejudicial para a viabilidade in vitro e in vivo da leucemia. Por fim, relatamos também que a associação do anticorpo anti-IGFBP7 com Dexametasona reduz drasticamente a viabilidade celular da LLA, confirmando a importância da IGFBP7 na progressão desta neoplasiaAbstract: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, corresponding to about 30% of all cases of cancer and 80% of all leukemia in patients of less than 15 years old. Despite the improvement on the therapy of ALL, this disease is still the most common cause of cancer-related death in young people around the world. In the last decade, some studies have shown that high expression of IGFBP7 would be related to a worse prognosis in ALL patients. We have previously shown that ALL cells are the main source of IGFBP7 in the leukemia microenvironment, where it exerts a paracrine effect on bone marrow stromal cells, reflecting resistance to primary therapy by patients. Here we show that IGFBP7 exerts also an autocrine effect on ALL cells (cell lines and primary cells). We observed that the positive effects of INS/IGF on ALL cell lines viability were significantly enhanced by recombinant IGFBP7, promoting PI3k/Akt/mTOR pathway activation. However, IGFBP7 silencing impairs this effect, boosting the p53 pathway activation in the silenced cells. Furthermore, we illustrate that IGFBP7 knockdown sensitizes ALL cells to cytostatic actions mediated by Dexamethasone and confirmed that IGFBP7 promotes chemo-therapeutic resistance to glucocorticoids in ALL. Our data further demonstrates that IGFBP7 neutralization with monoclonal antibody is detrimental to the in vitro and in vivo leukemia viability. Finally, we have shown that association of anti-IGFBP7 antibody plus Dexamethasone dramatically reduces the ALL cellular viability, revealing the importance of IGFBP7 in leukemia progressionMestradoGenetica Animal e EvoluçãoMestre em Genética e Biologia Molecular2017/03239-5FAPES

Integrated use of sewage sludge and basalt mine waste as soil substitute for environmental restoration

If not managed properly, mining waste can be detrimental to the environment. In addition, sewage treatment plants produce sludge, a biowaste rich in organic matter which is often sent to landfills. The present study evaluated the use of sewage sludge as an amendment for mine waste from a basalt quarry as an alternative to the use of soil from borrow areas during environmental restoration. An ex situ experiment was developed at the Federal University of Rio Grande do Sul – UFRGS. The experimental delineation compared the addition of two sources of organic matter (sewage sludge – SS and cover soil from that same region - CS) to basalt waste rock (BWR) against the sole use of cover soil, which a current restoration technique. The graminoid Avena strigosa (black oats) and soil fertility tests were used as indicators of soil conditions. Amending BWR with SS led to the best physical and chemical conditions and the highest production of dry matter in comparison to the use of CS as amendment or its single use as cover soil. These results show that mixing SS to BWR can be used as a substitute for cover soil during the environmental restoration of basalt quarries, further contributing to the final disposal of these materials

Integrated use of sewage sludge and basalt mine waste as soil substitute for environmental restoration

If not managed properly, mining waste can be detrimental to the environment. In addition, sewage treatment plants produce sludge, a biowaste rich in organic matter which is often sent to landfills. The present study evaluated the use of sewage sludge as an amendment for mine waste from a basalt quarry as an alternative to the use of soil from borrow areas during environmental restoration. An ex situ experiment was developed at the Federal University of Rio Grande do Sul – UFRGS. The experimental delineation compared the addition of two sources of organic matter (sewage sludge – SS and cover soil from that same region - CS) to basalt waste rock (BWR) against the sole use of cover soil, which a current restoration technique. The graminoid Avena strigosa (black oats) and soil fertility tests were used as indicators of soil conditions. Amending BWR with SS led to the best physical and chemical conditions and the highest production of dry matter in comparison to the use of CS as amendment or its single use as cover soil. These results show that mixing SS to BWR can be used as a substitute for cover soil during the environmental restoration of basalt quarries, further contributing to the final disposal of these materials

Cytotoxic, genotoxic, mutagenic, and phytotoxic effects of the extracts from eragrostis plana nees, 1841 (poaceae), grown in a coal-contaminated region'

Coal and its byproducts and mineral waste constitute complex mixtures, which contain a variety of chemical compounds that impact the ecosystems. For this reason, procedures are required to monitor coal-degraded areas, including the use of biomonitoring organisms. In this light, the aim of the present study was to evaluate the cytotoxicity, genotoxicity, mutagenicity, and phytotoxicity of the aerial part and root extracts from Eragrostis plana Nees collected in the surroundings of the Thermoelectric Power Plant President Médici-UTPM (Candiota, Brazil), through Allium cepa bioassay. Cytotoxicity, genotoxicity, and mutagenicity in the A. cepa meristematic cells were verified through the mitotic index (MI), chromosomal alterations, and micronucleus formation, respectively. In addition, the germination rate, vigor index, and morphological abnormalities were verified in A. cepa seedlings. Treatment with root extracts from E. plana (ACR) specimens collected in a coal-contaminated region resulted in the lowest MI values (8.9%, 12.7%, and 16.0%), representing the most cytotoxic effect when compared with the negative control—NC (dH2O) (MI = 35.8%). ACR extract also was the most genotoxic and mutagenic sample compared with NC and other treatments. Phytotoxicity analyses corroborated the toxic action of ACR, presenting abnormal seedlings and change in vigor index. The high concentration of dissolved total chlorides and electrical conductivity presented in the root extracts of E. plana, which were grown in the carboniferous region, indicates an increase in the absorption of metallic ions and organic compound and supports the hypothesis that this species has bioaccumulator potential, being a new biomonitor model of coal-contaminated region23

UTILIZAÇÃO DE PLANTAS MEDICINAIS EM UM MUNICÍPIO INSERIDO NO BIOMA PAMPA BRASILEIRODOI: http://dx.doi.org/10.5892/ruvrd.v14i2.2672

Este estudo objetivou verificar o perfil de utilização de plantas medicinais por moradores do município de Hulha Negra, com população predominantemente de origem alemã e que está inserido no Bioma Pampa (RS), Brasil. O cálculo amostral compreendeu a população residente da zona urbana (2.909 mil habitantes). e resultou em valor de N= 344 indivíduos. Visitas domiciliares foram realizadas em dias úteis da semana entre agosto a novembro de 2011. Aplicou-se um questionário com abordagem sócio-demográfica e utilização de plantas medicinais, com base em condição de saúde. A categorização dos problemas de saúde à partir do motivo de uso das plantas foi realizada por sistemas orgânicos. As plantas foram classificads como nativas do Bioma Pampa e exóticas ao bioma. Foi possível acessar 137 moradores, sendo 128 usuários de plantas medicinais. Destes, 69,5% representados por mulheres, 39,8% com idades superior a 50 anos e 46,8% com nove anos de estudo ou mais. As famílias botânicas mais prevalentes foram Asteraceae (21%) e Laminaceae (16%), sendo a Macela a planta mais citada (55). Os principais motivos de uso de plantas medicinais foram os sintomas associados ao sistema digestivo (29%), as condições de dor e inflamação (24%) e ligadas ao sistema cardiovascular (14%). Do total de espécies identificadas (67) 38,8% corresponderam a plantas nativas do Bioma Pampa

Utilização de plantas medicinais em um município Inserido no bioma Pampa brasileiro

Este estudo objetivou verificar o perfil de utilização de plantas medicinais por moradores do município de Hulha Negra, com população predominantemente de origem alemã e que está inserido no Bioma Pampa (RS), Brasil. O cálculo amostral compreendeu a população residente da zona urbana (2.909 mil habitantes). e resultou em valor de N= 344 indivíduos. Visitas domiciliares foram realizadas em dias úteis da semana entre agosto a novembro de 2011. Aplicou-se um questionário com abordagem sócio-demográfica e utilização de plantas medicinais, com base em condição de saúde. A categorização dos problemas de saúde à partir do motivo de uso das plantas foi realizada por sistemas orgânicos. As plantas foram classificads como nativas do Bioma Pampa e exóticas ao bioma. Foi possível acessar 137 moradores, sendo 128 usuários de plantas medicinais. Destes, 69,5% representados por mulheres, 39,8% com idades superior a 50 anos e 46,8% com nove anos de estudo ou mais. As famílias botânicas mais prevalentes foram Asteraceae (21%) e Laminaceae (16%), sendo a Macela a planta mais citada (55). Os principais motivos de uso de plantas medicinais foram os sintomas associados ao sistema digestivo (29%), as condições de dor e inflamação (24%) e ligadas ao sistema cardiovascular (14%). Do total de espécies identificadas (67) 38,8% corresponderam a plantas nativas do Bioma Pampa

Karyotype characterization and comparison of three hexaploid species of Bromus Linnaeus, 1753 (Poaceae)

Chromosome morphometry and nuclear DNA content are useful data for cytotaxonomy and to under- stand the evolutionary history of different taxa. For the genus Bromus Linnaeus, 1753, distinct ploidy levels have been reported, occurring from diploid to duodecaploid species. The geographic distribution of Bromus species has been correlated with chromosome number and ploidy level. In this study, the aims were to determine the nuclear genome size and characterize the karyotype of the South American Bromus species: Bromus auleticus Trinius ex Nees, 1829, Bromus brachyanthera Döll, 1878 and Bromus catharticus Vahl, 1791. The mean nuclear 2C value ranged from 2C = 12.64 pg for B. catharticus to 2C = 17.92 pg for B. auleticus, meaning a maximum variation of 2C = 5.28 pg, equivalent to 41.70%. Despite this significant difference in 2C value, the three species exhibit the same chromosome number, 2n = 6x = 42, which confirms their hexaploid origin. Corroborating the genome size, the chromosome morphometry (total, short- and long-arm length) and, consequently, the class differed among the karyotypes of the species. Based on the first karyograms for these Bromus species, some morphologically similar and several distinct chromosome pairs were found. Therefore, the karyotype characterization confirmed the hexaploid origin of the studied Bromus species, which differ in relation to the karyogram and the nuclear 2C value. Considering this, cytogenetics and flow cytometry can be used to discriminate Bromus species, contributing to taxonomy and systematic studies and providing information on the evolutionary history of this taxa

Oncogenic basic amino acid insertions at the extracellular juxtamembrane region of IL7Rα cause receptor hypersensitivity

sem informação1331112591263CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP305896/2013-0; 301596/2017-4sem informação12/12802-1; 14/20015-5; 10/16947-9; 13/08293-7Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/12802-1, 14/20015-5, 10/16947-9, 13/08293-7]; National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [APP1084797]; Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCAPES; Brazilian National Counsel of Technological and Scientific Development (CNPq)National Council for Scientific and Technological Development (CNPq) [305896/2013-0, 301596/2017-4