In the present study, we investigated the molecular mechanisms underlying the pro-apoptotic effects of quercetin (Qu) by evaluating the effect of Qu treatment on DNA methylation and posttranslational histone modifications of genes related to the apoptosis pathway. This study was performed in vivo in two human xenograft acute myeloid leukemia (AML) models and in vitro using HL60 and U937 cell lines. Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent. The treatment also downregulated class I HDACs. Furthermore, treatment of the cell lines with the proteasome inhibitor, MG132, together with Qu prevented degradation of class I HDACs compared to cells treated with Qu alone, indicating increased proteasome degradation of class I HDACS by Qu. Qu induced demethylation of the pro-apoptotic BCL2L11, DAPK1 genes, in a dose- and time-dependent manner. Moreover, Qu (50 μmol/L) treatment of cell lines for 48 h caused accumulation of acetylated histone 3 and histone 4, resulting in three- to ten fold increases in the promoter region of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L. In addition, Qu treatment significantly increased the mRNA levels of all these genes, when compared to cells treated with vehicle only (control cells) (*p < 0.05). In summary, our results showed that enhanced apoptosis, induced by Qu, might be caused in part by its DNA demethylating activity, by HDAC inhibition, and by the enrichment of H3ac and H4ac in the promoter regions of genes involved in the apoptosis pathway, leading to their transcription activation.

La Argentina ha implementado medidas de aislamiento social obligatorio inicialmente previsto para un período de quince días y luego prorrogado, recién iniciado el año escolar. Este artículo brinda una aproximación a las estrategias de gestión que se desarrollaron ante el contexto de aislamiento obligatorio, un análisis de los primeros instrumentos normativos, su relación con el desarrollo curricular, y sus efectos en términos de segregación educativa. Se trata de un estudio exploratorio y descriptivo, utilizando un método cualitativo, a partir de análisis documental y entrevistas a protagonistas del sistema educativo que debieron implementar las políticas en dicho contexto. La preexistencia de brechas en el acceso a recursos digitales, la invisibilización de las condiciones reales de la población, las decisiones vertiginosas de los niveles de gobierno centrales combinado con la heterogeneidad de las resoluciones a nivel institucional y a nivel de grupo escolar evidencian aspectos de profundización de la segmentación educativa

Flavonoids are ubiquitous groups of polyphenolic compounds present in most natural products and plants. These substances have been shown to have promising chemopreventive and chemotherapeutic properties with multiple target interactions and multiple pathway regulations against various human cancers. Polyphenolic flavonoid compounds can block the initiation or reverse the promotion stage of multistep carcinogenesis. Quercetin is one of the most abundant flavonoids found in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) therapy remains a challenge for hematologists worldwide, and the outcomes for patients with both disorders continue to be poor. This scenario indicates the increasing demand for innovative drugs and rational combinative therapies. Herein, we discuss the multitarget effects of the flavonoid quercetin, a naturally occurring flavonol, on AML and MDS.

Dendritic cells play a fundamental role in the antitumor immunity cycle, and the loss of their antigen-presenting function is a recognized mechanism of tumor evasion. We have recently demonstrated the effect of exosomes extracted from serum of patients with acute myeloid leukemia as important inducers of dendritic cell immunotolerance, and several other works have recently demonstrated the effects of these nanoparticles on immunity to other tumor types as well. The aim of this review was to highlight the recent findings on the effects of tumor exosomes on dendritic cell functions, the mechanisms by which they can lead to tumor evasion, and their manipulation as a possible strategy in cancer treatment.

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota’s substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine’s anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine’s influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

Green tea catechins are bioactive polyphenol compounds which have attracted significant attention for their diverse biological activities and potential health benefits. Notably, epigallocatechin-3-gallate (EGCG) has emerged as a potent apoptosis inducer through mechanisms involving caspase activation, modulation of Bcl-2 family proteins, disruption of survival signaling pathways and by regulating the redox balance, inducing oxidative stress. Furthermore, emerging evidence suggests that green tea catechins can modulate epigenetic alterations, including DNA methylation and histone modifications. In addition to their apoptotic actions, ROS signaling effects and reversal of epigenetic alterations, green tea catechins have shown promising results in promoting the differentiation of leukemia cells. This review highlights the comprehensive actions of green tea catechins and provides valuable insights from clinical trials investigating the therapeutic potential of green tea catechins in leukemia treatment. Understanding these multifaceted mechanisms and the outcomes of clinical trials may pave the way for the development of innovative strategies and the integration of green tea catechins into clinical practice for improving leukemia patient outcomes.