Immune system cells, including neutrophils, are recruited by the tumor microenvironment as a site of chronic inflammation and begin to favor tumor growth. Neutrophils present in the tumor site are called tumor-associated neutrophils (TAN) and can present two phenotypes: N1 (antitumor) or N2 (pro-tumor). Evidence shows the high capacity of immune system cells to interact with extracellular vesicles (Evs) released by tumor cells. Evs can modulate the phenotype of cells within the immune system, contributing to tumor development. Here, we investigated the role of MDA-MB-231-derived Evs upon the polarization of neutrophils towards an N2 phenotype and the underlying mechanisms. We observed that neutrophils treated with Evs released by MDA cells (MDA-Evs) had their half-life increased, increased their chemotactic capacity, and released higher levels of NETs and ROS than neutrophils treated with non-tumoral Evs. We also observed that neutrophils treated with MDA-Evs released increased IL-8, VEGF, MMP9, and increased expression of CD184, an N2-neutrophil marker. Finally, neutrophils treated with MDA-Evs increased tumor cell viability. Our results show that MDA-Evs induce an N2-like phenotype, and the blockage of phosphatidylserine by annexin-V may be an essential agent counter-regulating this effect.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary inflammation and the destruction of the pulmonary parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. This study evaluated the effects of DMF and its metabolite, monomethyl fumarate (MMF), on pulmonary inflammation induced by cigarette smoke (in vitro) and porcine pancreatic elastase (PPE) in mice (in vivo). In vitro, human pulmonary epithelial cells (PC-9) were treated with MMF at concentrations of 10, 30, and 100 µM and exposed to cigarette smoke extract (CSE) to assess cell viability, oxidative stress (ROS), lipid peroxidation, and nitrite production. In vivo, C57BL/6 mice were treated with DMF (30 and 100 mg/kg) during and after the induction of emphysema by PPE. ROS levels, total cell count in bronchoalveolar lavage fluid (BALF), lung histology, and the expression of oxidative stress proteins (SOD1 and HO-1) were analyzed. MMF reduced oxidative stress and lipid peroxidation under in vitro conditions. In vivo, DMF reduced ROS levels, inflammation, and prevented lung damage, such as alveolar enlargement. The expression of SOD1 and HO-1 was modulated by DMF treatment. The results suggest that DMF could be an effective therapeutic alternative for COPD, reducing oxidative stress and inflammation.

Obesity is increasingly recognized as a complex metabolic disorder characterized by persistent redox imbalance, rather than merely excess body weight. Its pathophysiology extends beyond energy imbalance to encompass chronic redox disruption. Expansion of adipose tissue, particularly in visceral depots, exceeds mitochondrial capacity, impairs antioxidant defenses such as superoxide dismutase, catalase, and glutathione peroxidase, and perpetuates chronic low-grade inflammation via nuclear factor kappa B (NF-kB) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways. This review synthesizes preclinical evidence for diverse interventions, including vitamins A, B, C, E, and D; minerals such as zinc and selenium; amino acids such as N-acetylcysteine (NAC), L-carnitine, and taurine; various antioxidant compounds; and approved drugs including metformin, exenatide, fenofibrate, and orlistat. Despite differing structures and mechanisms, these interventions converge on restoring redox balance by activating nuclear factor erythroid 2–related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK), increasing glutathione, and stabilizing mitochondria. However, translation of these preclinical findings into clinical practice requires further clarification of dosing, delivery methods, and long-term safety.