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Vaccinium ashei Reade, popularly known as Rabbiteye blueberry, has several therapeutic properties attributed to the phenolic compounds present in its leaves and fruits. Here, we sought to evaluate the effects of the hydroalcoholic extract from V. ashei leaves (Bluegem cultivar, VAB) in T-cell Acute lymphoblastic leukemia (T-ALL). The VAB extract was toxic to T-ALL cells at the ∼60 µg/ml concentration. T-ALL cell death occurred through apoptosis. VAB extract was found to induce micronuclei formation, p53 pathway activation, and cell cycle arrest. Those mutagenic effects were evidenced through microscopy analysis and molecular p53 pathway activation. A series of phenolic compounds were identified in VAB extract by mass spectrometry, such as vanillic acid, catechin, caffeic acid, chlorogenic acid, rutin, coumaric acid, taxifolin, quercetin and naringenin, some of which are presumed to induce DNA damage. In conclusion, the V. ashei leaves extract may have important secondary metabolites with antileukemic properties.

Regulatory B cells (Bregs) are cells that modulate the immune response through secretion of interleukins such as IL-10, IL-35 and TGF-β. Different subsets of Breg cells vary not only in their phenotype, but also in their action mechanism. Studies have identified the presence of Breg cells during the development of some types of tumors. The aim of this paper is to survey the literature on some of the Bregs cell’s phenotypes, their origin and their immune response modulation mechanisms, as well as their role in some types of tumors. Regarding methodology, the SciELO and PubMed databases and theirs descriptors “regulatory B cells”, associated with “IL-10” and “tumor immunity” were used in order to survey both original and review articles. We found 108 articles referring to the subject from which 74 articles were selected taking into consideration the objectives proposed for this review. We conclude that there are several phenotypes of Breg cells and that these cells act mostly through immunosuppression mechanisms, thus enabling the development and progression of some diseases, such as cancer. Understanding the mechanisms by which Breg cells influence the immune response profile in certain diseases is important for designing safe and effective immunotherapies targeted at these cells.

Alteracoes cromossomicas e mutacoes pro-oncogenicas podem afetar o processo normal de diferenciacao e proliferacao celular ocasionando o câncer. A mutacao estudada do gene IL7R ativa a via JAK-STAT, que esta relacionada com o processo de diferenciacao e proliferacao celular. O projeto analisou o possivel papel oncogenico de gene IL7R em tumores solidos utilizando camundongos knockin do IL7R mutante obtidos por nosso grupo. Os animais portadores do alelo knockin foram cruzados com a linhagem parental C57Bl6 a fim de obter animais com o IL7R mutante em todas as celulas do corpo afim de estudar o possivel desenvolvimento de tumores solidos.

Despite the success achieved in the treatment of acute lymphoblastic leukemia (ALL), the search for new drugs featuring selectivity against leukemia cells and effectiveness to prevent relapsed ALL is still highly desirable. Here, we described the synthesis of several novel 3-substituted and 3,6-disubstituted-2-carboalkoxy indoles followed by the elucidation of their mechanism of action and in vivo anti-leukemia efficacy. The synthesis of 3-substituted-2-carboalkoxy indoles relied on two Heck arylations of methyl acrylate and methyl cinnamates respectively, to generate β,β-disubstituted acrylates followed by an efficient Cadogan-Sundberg reaction of these latter intermediates. The method developed led to the synthesis of twenty-one novel functionalized indoles. Of these, indole 20 showed selective cytotoxicity against leukemia cells at the nanomolar scale, and, therefore, it was selected for the investigation of its mechanism of action. Indole 20 was found to target tubulin leading to G2/M cell cycle arrest, DNA damage and apoptosis. Indole 20 decreased β-tubulin protein in leukemia cells in a time-dependent manner and induced depolymerization of the microtubule network in Hela cells, thus fully characterizing its microtubule destabilizer activity. The connectivity map analysis of HL60 promyelocytic leukemia cells treated with indole 20 revealed a transcriptional profile similar to that of cells treated with prostaglandins, apparently due to the induction of cellular differentiation as addressed by the expression of CD11 and CD14 markers. Finally, indole 20 given intraperitoneally, at 10 mg/kg, 5x/week significantly prolonged the overall survival of NOD/SCID mice transplanted with RS4; 11 B-ALL cells.

As células B regulatórias (Bregs) são células que modulam a resposta imunológica através da secreção de interleucinas como a IL-10, IL-35 e TGF-. Diferentes subconjuntos de células Bregs variam não apenas em seu fenótipo, mas também em seu mecanismo de ação. Alguns estudos identificaram a presença de células Bregs durante o desenvolvimento de alguns tipos de tumores. O objetivo deste artigo foi realizar um levantamento da literatura sobre alguns dos fenótipos de células Bregs, sua origem, seus mecanismos de modulação de resposta imunológica, bem como sua atuação em alguns tipos de tumores. Como metodologia, foram utilizadas as bases de dados SciELO e PubMed e os descritores “células B regulatórias”, associada com “IL-10” e “imunidade tumoral” para levantamento de artigos originais e de revisão. Foram encontrados 108 artigos referentes ao tema e foram selecionados 74 artigos levando em consideração os objetivos propostos para esta revisão. Conclui-se que diversos são os fenótipos das células Bregs e que estas células atuam na maioria das vezes através de mecanismos de imunossupessão favorecendo desta forma o desenvolvimento e progresão de algumas doenças, a exemplo do câncer. A compreensão dos mecanismos pelos quais as células Bregs influenciam o perfil de resposta imunológica em determinadas doenças é importante para projetar imunoterapias seguras e eficazes direcionadas a estas células.

As hortaliças possuem um potencial risco à saúde, uma vez que podem conter cistos de protozoários, ovos e larvas de helmintos servindo como via de transmissão viável para parasitos intestinais, especialmente consumidas cruas. Dentre as consequências marcantes desencadeantes das enteroparasitoses estão à diarreia, anemia, hemorragia, desequilíbrios nutricionais e em alguns casos raros levando ao óbito. Estudos revelam que houve aumento de infecções alimentares difundidas por hortaliças, sendo um dos principais veículos disseminadores de estruturas infectantes. No que se referem às técnicas parasitológicas, estas são bastante antigas e ainda não conseguem ser tão eficazes, entretanto são consideradas de baixo custo, simples de realizar e enfatizam os estudos de difusão de enteroparasitos. Com base nestes aspectos e considerando, sobretudo a carência de informações no município de Dourados-MS, buscou-se através do presente trabalho analisar qualitativa e quantitativamente a presença de ovos de parasitos em alfaces vendidas nas gôndolas do supermercado da cidade. Avaliaram-se 80 amostras de alfaces, os quais foram divididos ao meio, com o mesmo peso para ambos e então utilizou-se duas técnicas metodológicas (centrífugo-flutuação e sedimentação espontânea), para comparação de diagnóstico. Foram encontrados ovos dos gêneros: Ancylostomídeos (21,87%), Ascaris sp. (53,32%), Balantidium sp. (2,34%), Diphyllobothirum sp. (3,23%), Enterobius sp. (0,90%), Hymenolepis sp. (0,81%), Paragonymus sp.(0,30%), Shistosoma sp. (14,56%), Taenia sp. (0,88%) e Trichuris sp. (1,63%). A técnica da sedimentação espontânea apresentou maior capacidade de obtenção de ovos de parasitos do que o método da centrifugo-flutuação.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL. Full transformation associates with transcriptional upregulation of oncogenes such as Myc or Bcl2, downregulation of tumor suppressors such as Ikzf1 or Arid2, and major IL-7R signaling upregulation (involving JAK/STAT5 and PI3K/mTOR), required for leukemia cell viability. Accordingly, maximal signaling drives full penetrance and early leukemia onset in homozygous IL7R mutant animals. Notably, we identify 2 transcriptional subgroups in mouse and human Ph-like ALL, and show that dactolisib and sphingosine-kinase inhibitors are potential treatment avenues for IL-7R-related cases. Our model, a resource to explore the pathophysiology and therapeutic vulnerabilities of B-ALL, demonstrates that IL7R can initiate this malignancy., This work was supported by the ERC CoG-648455 consolidator and the ERC PoC-862545 proof-of-concept grants from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme, and the FAPESP/20015/2014 grant from FCT, to J.T.B.; by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grants 2012/12802-1 and 2014/20015-5 to J.A.Y.; and by an NCI Outstanding Investigator Award R35 R35CA197695 and the American Lebanese Syrian Associated Charities of St Jude Children’s Research Hospital, to C.G.M. A.R.G. is the recipient of an FCT Investigator Grant (CEECIND/02699/2017). A.C. (SFRH/BD/147411/2019), M.B.F. (SFRH/BD/135508/2018), and M.L.O. (SFRH/BD/114102/2015) were recipients of FCT fellowships. M.E. (2016/07724-2, 2017/10653-2), J.R.C. (2017/02400-7) and P.P.Z. (2012/03660-9) were recipients of FAPESP fellowships. J.A.Y. received a productivity fellowship from the National Counsel of Technological and Scientific Development (CNPq 301596/2017-4).