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

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)

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio

Stellar mass as a galaxy cluster mass proxy: application to the Dark Energy Survey redMaPPer clusters

We introduce a galaxy cluster mass observable, μ⋆, based on the stellar masses of cluster members, and we present results for the Dark Energy Survey (DES) Year 1 (Y1) observations. Stellar masses are computed using a Bayesian model averaging method, and are validated for DES data using simulations and COSMOS data. We show that μ⋆ works as a promising mass proxy by comparing our predictions to X-ray measurements. We measure the X-ray temperature–μ_{⋆} relation for a total of 129 clusters matched between the wide-field DES Y1 redMaPPer catalogue and Chandra and XMM archival observations, spanning the redshift range 0.1 < z < 0.7. For a scaling relation that is linear in logarithmic space, we find a slope of α = 0.488 ± 0.043 and a scatter in the X-ray temperature at fixed μ_{*} of σ1nT_{x}|μ_{*} = 0.266_{-0.020}^{+0.019} for the joint sample. By using the halo mass scaling relations of the X-ray temperature from the Weighing the Giants program, we further derive the μ⋆-conditioned scatter in mass, finding σ1nM|μ_{*} = 0.26_{-0.10}^{+0.15}. These results are competitive with well-established cluster mass proxies used for cosmological analyses, showing that μ_{⋆} can be used as a reliable and physically motivated mass proxy to derive cosmological constraints

Análise crítica dos resumos de teses de um Programa de Pós-Graduação Análisis crítico de los resúmenes de tesis de un Programa de Postgrado Critical analysis of doctoral dissertation abstracts of a Graduate Program in Nursing

OBJETIVO: Analisar os resumos de teses de um Programa de Pós-Graduação em Enfermagem. MÉTODOS: Estudo exploratório, cuja coleta de dados ocorreu em dezembro/2005. Os resumos foram avaliados baseados na NBR 6028/1990 da Associação Brasileira de Normas Técnicas utilizando uma escala de 12 itens. A análise foi feita por meio do software GraphPad Prism. RESULTADOS: Identificou-se 65 teses defendidas entre fevereiro de 2001 e dezembro de 2005. A análise revelou que 38,98% das teses foram produzidas na área da saúde pública. Os resumos de 2005 apresentaram freqüência maior do escore máximo (c²=6,84, p=0,008). Os escores da escala foram transformados em notas o que resultou em 61% de aprovação. CONCLUSÕES: Os resultados mostram a importância deste estudo e contribuem para a reflexão dos docentes e discentes dos cursos de pós-graduação no sentido de melhorar a elaboração dos resumos de teses, dentro dos critérios exigidos.<br>OBJETIVO: Analizar los resúmenes de tesis de un Programa de Post-Grado en Enfermería. MÉTODOS: Se trata de un estudio exploratorio, cuya recolección de datos se llevó a cabo en diciembre/2005. Los resúmenes fueron evaluados basados en la NBR 6028/1990 de la Associación Brasileña de las Normas Técnicas utilizando una escala de 12 items. El análisis fue realizado por medio del software GraphPad Prism. RESULTADOS: Se identificó 65 tesis sustentadas entre febrero de 2001 y diciembre de 2005. El análisis reveló que el 38,98% de las tesis fueron producidas en el área de la salud pública. Los resúmenes del 2005 presentaron frecuencia mayor del escore máximo (c²=6,84, p=0,008). Los escores de la escala fueron transformados en notas lo que resultó en el 61% de aprobación. CONCLUSIONES: Los resultados muestran la importancia de este estudio y contribuyen para la reflexión de los docentes y discentes de los cursos de post-grado en el sentido de mejorar la elaboración de los resúmenes de tesis, dentro de los criterios exigidos.<br>OBJECTIVE: To analyze doctoral dissertation abstracts of a graduate program in nursing. METHODS: This exploratory study was conducted in December, 2005. The doctoral dissertation abstracts were evaluated using criteria set by the NBR 6028/1990 of the Brazilian Association of Technical Norms on a 12-item scale. The analysis was conducted with the GraphPad Prism software. RESULTS: Sixty five doctoral dissertations were defended between February 2001 and December 2005. Among these dissertations, 38.98% consisted of topics in public health. Abstracts published in 2005 had higher score in the ABNT scale (c²=6.84, p=0.008). Scores were transformed into grades, which led to 61% of approval. CONCLUSIONS: The findings of this study might contribute to faculty and student's reflections on the quality of doctoral dissertation abstracts, which must meet established NBR/ABNT criteria