1,567 research outputs found

    Piplartine eliminates CD34+ AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling

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    Data availability: Data will be made available on request.Supplementary information is available online at: https://www.nature.com/articles/s41420-024-01909-4#Sec20 .Author notes: These authors contributed equally: Cristina Pina, Daniel P. Bezerra.Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.This work received financial support and fellowships from the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB, Brazil). Work in the Pina lab was funded by a British Society for Haematology Early-stage Research Grant (33932) and a BRIEF award by Brunel University London (2020–2022)

    Factors affecting post-fire crown regeneration in cork oak (Quercus suber L.) trees

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    Cork oak (Quercus suber) forests are acknowledged for their biodiversity and economic (mainly cork production) values. WildWres are one of the main threats contributing to cork oak decline in the Mediterranean Basin, and one major question that managers face after Wre in cork oak stands is whether the burned trees should be coppiced or not. This decision can be based on the degree of expected crown regeneration assessed immediately after Wre. In this study we carried out a post-Wre assessment of the degree of crown recovery in 858 trees being exploited for cork production in southern Portugal, 1.5 years after a wildWre. Using logistic regression, we modelled good or poor crown recovery probability as a function of tree and stand variables. The main variables inXuencing the likelihood of good or poor crown regeneration were bark thickness, charring height, aspect and tree diameter. We also developed management models, including simpler but easier to measure variables, which had a lower predictive power but can be used to help managers to identify, immediately after Wre, trees that will likely show good crown regeneration, and trees that will likely die or show poor regeneration (and thus, potential candidates for trunk coppicin

    Produção orgânica de rabanete em plantio direto sobre cobertura morta e viva.

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    O objetivo deste trabalho foi avaliar o uso de plantas espontâneas e cobertura viva de amendoim forrageiro(Arachis pintoi), associado à aplicação de composto orgânico na produção orgânica do rabanete em plantio direto. O experimento foi instalado na Universidade Federal do Acre, em Rio Branco-AC, de 15/06 a 14/07/2007. O delineamento experimental utilizado foi em blocos casualizados com parcelas subdivididas 4x3, em quatro repetições. As parcelas corresponderam ao sistema de plantio direto com cobertura viva de amendoim forrageiro, cobertura viva de planta espontânea, cobertura morta de planta espontânea e sistema de plantio em canteiro com solo descoberto. As subparcelas foram compostas pelas doses de composto orgânico de 5, 10 e 15 t ha-1 (base seca). O plantio direto na palha de plantas espontâneas teve desempenho semelhante ao preparo convencional do solo, ambos superiores ao plantio sobre as coberturas vivas. A produtividade do rabanete cv. Cometo, não foi afetada pelas doses crescentes de composto orgânico, podendo aplicar-se apenas 5 t ha-1, enquanto em preparo convencional do solo, o aumento da produtividade ultrapassa o plantio direto na palha apenas na dose maior de composto (15 t ha-1)
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