Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.

Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (ΔΨ), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance.

With the aim of characterising the hypo‐lipidemic function of the Brumex™ ingredient obtained from the whole fruit of Citrus bergamia, a combined pre‐clinical and clinical study was conducted. In the HepG2 experimental model, we first demonstrated that Brumex™ does not trigger any significant alteration in cell viability over the tested concentration range of 1–2000 μg/mL (4 and 24 h). By stimulating the phosphorylation of AMP‐activated protein kinase (AMPK) at threonine 172, Brumex™ significantly reduces both cholesterol and triglyceride (TG) intracellular content of HepG2 cells and impairs the expression levels of lipid synthesis‐related genes (namely, SREBF1c, SREBF2, ACACA, SCD1, HMGCR and FASN). In vitro data have been validated in a dedicated double‐blind, placebo‐controlled, randomised clinical trial performed in 50 healthy moderately hyper‐cholesterolemic subjects, undergoing supplementation with either Brumex™ (400 mg) or placebo for 12 weeks. Clinical and blood laboratory data were evaluated at the baseline and at the end of the trial. Brumex™ positively impacted on both plasma lipid pattern and liver enzymes compared with the placebo, mainly in terms of significant reduction of total cholesterol (TC), TG, low‐density lipoprotein‐cholesterol (LDL‐C), non‐high‐density lipoprotein‐cholesterol (non‐HDL‐C), apolipoprotein B100 (ApoB), fasting plasma glucose (FPG), glutamic‐oxaloacetic transaminase (GOT), glutamate pyruvate transaminase (GPT) and gamma‐glutamyl‐transferase (gGT).