Metabolic alterations are recognized as one of the hallmarks of cancer. Among these, alterations in mitochondrial function have been associated with an enhanced production of Reactive Oxygen Species (ROS), which activate ROS-regulated cancer cell signaling pathways. Breast cancer is the main cancer-related cause of death for women globally. It is a heterogeneous disease with subtypes characterized by specific molecular features and patient outcomes. With the purpose of identifying differences in energy metabolism and the oxidative stress management system in non-tumorigenic, estrogen receptor positive (ER+) and triple negative (TN) breast cancer cells, we evaluated ROS production, protein enzyme levels and activities and profiled energy metabolism. We found differences in energetic metabolism and ROS management systems between non-tumorigenic and cancer cells and between ER+ and TN breast cancer cells. Our results indicate a dependence on glycolysis despite different glycolytic ATP levels in all cancer cell lines tested. In addition, our data show that high levels of ROS in TN cells are a result of limited antioxidant capacity in the NADPH producing and GSH systems, mitochondrial dysfunction and non-mitochondrial ROS production, making them more sensitive to GSH synthesis inhibitors. Our data suggest that metabolic and antioxidant profiling of breast cancer will provide important targets for metabolic inhibitors or antioxidant treatments for breast cancer therapy.

Pseudomonas aeruginosa is the main bacterial model to study cooperative behaviors, since it yields exoproducts such as exoproteases and siderophores that act as public goods and can be exploited by selfish non-producers that behave as social cheaters. Non-producers of the siderophore pyoverdine are typically isolated in media with low free iron, mainly casamino acids medium supplemented with transferrin. Nevertheless, using a protein as the iron chelator could additionally select mutants unable to produce exoproteases that degrade the transferrin to facilitate iron release. Here, we investigated the dynamics of pyoverdine and exoprotease production in media in which iron was limited by using either transferrin or a cation chelating resin. Our experiments show that concomitant loss of pyoverdine and exoprotease production readily develops in media with transferrin whereas only lack of pyoverdine emerges in medium treated with the resin. Genomic characterization of the exoprotease- and pyoverdine-less mutants revealed large deletions (13 to 33 Kb) including Quorum Sensing ( lasR, rsal and lasl ) and flagellar genes. Complementation experiments, PCR and motility tests confirmed the deletions. Our work shows that using transferrin as an iron chelator imposes simultaneous selective pressure for the loss of pyoverdine and exoprotease production. The unintended effect of transferrin observed in our experiment settings can help revisiting or informing the design of similar studies.

Background: Hyperuricemia and gout are closely associated with alterations in gut microbiota function. Short-chain fatty acids (SCFAs) produced by intestinal microorganisms may modulate immune responses and inflammation relevant to gout pathophysiology. This study evaluated fecal SCFA concentrations, their associations with dietary purine intake, and the relationship between Akkermansia spp. and Prevotella spp. abundance and fecal SCFA profiles across the clinical spectrum of hyperuricemia. Methods: This cross-sectional study included 380 Mexican adults: normouricemic controls (n = 141), individuals with asymptomatic hyperuricemia (AH; n = 98), and patients with gout (n = 141). Fecal SCFAs were quantified by GC-FID and bacterial abundance by qPCR. Dietary intake was assessed by semi-quantitative food frequency questionnaire and classified by purine content. Between-group differences were evaluated by the Kruskal–Wallis test (Benjamini–Hochberg correction); multivariable linear regression adjusted for age, sex, and BMI was used to assess associations, including a pre-specified dietary purine intake per clinical group interaction term. Results: Fecal acetate and propionate were significantly higher in gout patients than controls, whereas AH individuals had significantly higher butyrate. Moderate-purine food intake showed opposing associations with fecal acetate in controls (β = +3.61, p = 0.019) and gout patients (β = −4.59, p = 0.036), with a significant interaction (p = 0.004). Exploratory analyses revealed a positive association between Prevotella spp. abundance and fecal acetate exclusively in the gout group (β = 0.085, p = 0.020). Conclusion: These findings suggest distinct fecal SCFA profiles across stages of urate-related disease, with a disease-specific gut metabolic response to dietary purine intake potentially contributing to the inflammatory environment of established gout. Longitudinal studies with whole-microbiome profiling are needed to establish causality.