RESUMO
In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.
Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Idoso , Humanos , Disbiose , Envelhecimento , ComunicaçãoRESUMO
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.
Assuntos
Adipogenia , Microbioma Gastrointestinal , Humanos , Cafeína/farmacologia , Cafeína/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Dieta HiperlipídicaRESUMO
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals with potential adverse health effects. Information concerning PFAS concentrations in relation to pregnancy is scarce in South America and non-existent in Argentina. AIM: We aimed to investigate an extended maternal PFAS profile herein serum concentrations in a regional and global view, source appointment, and determinants in Argentinean women. METHODS: A cross-sectional study with a sampling period from 2011 to 2012 included 689 women from Ushuaia and Salta in Argentina. Serum samples collected two days postpartum were analyzed by ultra-high pressure liquid chromatography coupled to electrospray negative ionisation tandem-quadrupole mass-spectrometry. Principal Component Analysis (PCA) following absolute principal component score-multiple linear regression (APCS-MLR) was used for PFAS source appointments. Determinants of PFAS were explored through a MLR approach. A review of previous studies within the same period was conducted to compare with present levels. RESULTS: Argentinean PFAS concentrations were the lowest worldwide, with PFOS (0.74 ng/mL) and PFOA (0.11 ng/mL) as the dominant substances. Detection frequencies largely aligned with the compared studies, indicating the worldwide PFAS distribution considering the restrictions. The PCA revealed region-specific loading patterns of two component groups of PFAS, a mixture of replaced and legacy substances in Ushuaia and long-chain in Salta. This might relate to a mix of non-diet and diet exposure in Ushuaia and diet in Salta. Region, age, lactation, parity, household members, migration, bottled water, and freshwater fish were among the determinants of various PFAS. CONCLUSION: This is the first study to monitor human PFAS exposure in Argentina. Maternal PFAS concentrations were the lowest observed worldwide in the same period. Exposure contributions are suggested to be affected by restrictions and substitutions. Given the limited population-based studies and the emergence of PFAS, it is essential to conduct further monitoring of PFAS in Argentina and South America.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Gravidez , Animais , Humanos , Feminino , Estudos Transversais , Dieta , Lactação , Fluorocarbonos/análise , Ácidos Alcanossulfônicos/análiseRESUMO
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.
RESUMO
Pregnant women's levels of toxic and essential minerals have been linked to birth outcomes yet have not been adequately investigated in South America. In Argentina, n = 696 maternal whole blood samples from Ushuaia (n = 198) and Salta (n = 498) were collected in 2011-2012 among singleton women at 36 ± 12 h postpartum and analyzed for blood concentrations of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), copper (Cu), manganese (Mn), selenium (Se) and zinc (Zn). This study examined the associations between maternal elements levels and birth outcomes, and sociodemographic factors contributing to elements levels. Maternal age, parity, body mass index, smoking, and education were linked to concentrations of some but not all elements. In adjusted models, one ln-unit increase in Pb levels was associated with increased gestational age (0.2 weeks, 95% CI = 0.01-0.48) and decreased birth weight (-88.90 g, 95% CI = -173.69 to -4.11) and birth length (-0.46 cm, 95% CI = -0.85 to -0.08) in the Salta sample. Toxic elements concentrations were not associated with birth outcomes in Ushuaia participants. Birth outcomes are multifactorial problems, and these findings provide a foundation for understanding how the body burden of toxic and essential elements, within the socioeconomic context, may influence birth outcomes.
Assuntos
Arsênio , Mercúrio , Selênio , Oligoelementos , Argentina/epidemiologia , Cádmio , Feminino , Humanos , Recém-Nascido , Chumbo , Gravidez , Oligoelementos/análise , ZincoRESUMO
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.
Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Quercetina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicas/metabolismo , Quercetina/química , Quercetina/farmacologia , Espécies Reativas de OxigênioAssuntos
Doença de Chagas/prevenção & controle , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Sífilis/prevenção & controle , Adulto , Argentina , Bolívia , Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Criança , Pré-Escolar , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite B/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Masculino , Paraguai , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , População Rural/estatística & dados numéricos , Sífilis/epidemiologia , Sífilis/transmissão , Adulto JovemRESUMO
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.
Assuntos
Células Dendríticas/metabolismo , Exossomos/metabolismo , Neoplasias/imunologia , Células Dendríticas/fisiologia , Exossomos/fisiologia , Humanos , Imunidade/imunologia , Fatores Imunológicos/imunologia , Imunoterapia/métodos , Neoplasias/patologia , Evasão Tumoral/imunologiaRESUMO
The role of tumour microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stromal cell (BMMSC) contribution to disease progression remains poorly explored. We previously reported that the expression of serine protease inhibitor kunitz-type2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, is significantly lower in BMMSC from myelodysplastic syndromes (MDS) patients compared to healthy donors (HD). Thus, to investigate whether this loss of expression was due to SPINT2/HAI-2 methylation, BMMSC from MDS and de novo acute myeloid leukaemia (de novo AML) patients were treated with 5-Azacitidine (Aza), a DNA methyltransferase inhibitor. In MDS- and de novo AML-BMMSC, Aza treatment resulted in a pronounced SPINT2/HAI-2 levels up-regulation. Moreover, Aza treatment of HD-BMMSC did not improve SPINT2/HAI-2 levels. To understand the role of SPINT2/HAI-2 down-regulation in BMMSC physiology, SPINT2/HAI-2 expression was inhibited by lentivirus. SPINT2 underexpression resulted in an increased production of HGF by HS-5 stromal cells and improved survival of CD34+ de novo AML cells. We also observed an increased adhesion of de novo AML hematopoietic cells to SPINT2/HAI-2 silenced cells. Interestingly, BMMSC isolated from MDS and de novo AML patients had increased expression of the integrins CD49b, CD49d, and CD49e. Thus, SPINT2/HAI-2 may contribute to functional and morphological abnormalities of the microenvironment niche and to stem/progenitor cancer cell progression. Hence, down-regulation in SPINT2/HAI-2 gene expression, due to methylation in MDS-BMMSC and de novo AML-BMMSC, provides novel insights into the pathogenic role of the leukemic bone marrow microenvironment.
Assuntos
Azacitidina/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Glicoproteínas de Membrana/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Integrina alfa2/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: 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. RESULTS: 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). CONCLUSIONS: 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.