Neurodegenerative diseases are a group of diseases that share common features, such as the generation of misfolded protein deposits and increased oxidative stress. Among them, amyotrophic lateral sclerosis (ALS), whose pathogenesis is still not entirely clear, is a complex neurodegenerative disease linked both to gene mutations affecting different proteins, such as superoxide dismutase 1, Tar DNA binding protein 43, Chromosome 9 open frame 72, and Fused in Sarcoma, and to altered iron homeostasis, mitochondrial dysfunction, oxidative stress, and impaired glutamate metabolism. The purpose of this review is to highlight the molecular targets common to ALS and ferroptosis. Indeed, many pathways implicated in the disease are hallmarks of ferroptosis, a recently discovered type of iron-dependent programmed cell death characterized by increased reactive oxygen species (ROS) and lipid peroxidation. Iron accumulation results in mitochondrial dysfunction and increased levels of ROS, lipid peroxidation, and ferroptosis triggers; in addition, the inhibition of the Xc⁻ system results in reduced cystine levels and glutamate accumulation, leading to excitotoxicity and the inhibition of GPx4 synthesis. These results highlight the potential involvement of ferroptosis in ALS, providing new molecular and biochemical targets that could be exploited in the treatment of the disease using polyphenols.

Sickle cell disease (SCD) is an inherited hemoglobin disorder that is widespread across the globe. It is characterized by a very complex pathogenesis, but at the basis of the disease is the mutation of the HBB gene, which determines the production of a mutated hemoglobin: sickle cell hemoglobin (HbS). The polymerization of HbS, which occurs when the protein is in a deoxygenated state, and the greater fragility of sickle cell red blood cells (sRBCs) determine the release of iron, free heme, and HbS in the blood, favoring oxidative stress and the production of reactive oxygen species (ROS). These features are common to the features of a new model of cell death known as ferroptosis, which is characterized by the increase of iron and ROS concentrations and by the inhibition of glutathione peroxidase 4 (GPx4) and the System Xc⁻. In this context, this review aims to discuss the potential molecular and biochemical pathways of ferroptosis involved in SCD, aiming to highlight possible tags involved in treating the disease and inhibiting ferroptosis.

Red blood cells (RBCs) are the main cells of the blood, perform numerous functions within the body and are in continuous contact with endogenous and exogenous molecules. In this context, the study aims to investigate the effect of epicatechin (EC) (flavan-3-ols) on the erythrocytes, analyzing the protective effect of the molecule and the action exerted on metabolism and RBC membrane. The effect of EC on RBC viability has been evaluated through the change in hemolysis and methemoglobin, assessing caspase 3 activity and performing a cytofluorometric analysis. Next, the impact of the molecule on RBC metabolism was assessed by measuring anion flux kinetics, ATP production, and phosphatase activity. Finally, an evaluation of the potential protection against different stressors was performed. Our results show no detrimental effects of EC on RBCs (no change in hemolysis or methemoglobin and no caspase 3 activation recorded); rather, a protective effect was recorded given the reduction in hemolysis induced by hydrogen peroxide treatment and temperature increase. The increase in anion exchange and intracellular ATP values, with the inhibition of phosphatase PTP1B activity, highlights several biochemical alterations induced by EC. The present results contribute to clarifying the influence of EC on RBCs, confirming the beneficial effects of catechins.

Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs.

This paper aims to investigate the dielectric properties of blood for tumor detection and staging. The application of complex thermodynamic models and the study of the trend over time of some thermodynamic functions have allowed us to highlight the generation of displacement currents caused by changes in charge, i.e., by the activation and consequent accumulation of platelets on migrating tumor cells. Although few studies exist to date in this regard, the technique used has provided promising results, especially in terms of building a database. In this context, the evaluation of the dielectric parameters of healthy and cancerous blood can be exploited for the staging of cancer. The main advantages of this method include easy application, non-invasiveness, low cost, and online monitoring.

Catechins are characterized by a basic structure consisting of two benzene rings and a hydropyran heterocyclic ring. In (-)-epicatechin (ECT), the substituents in C2 and C3 of the dihydropyran ring are in cis conformation, whereas in (+)-catechin (CT), they are in trans conformation. Catechins tend to interact with membrane proteins, affecting their activity and/or function and metabolic processes. In this study, the impact of CT and ECT on erythrocyte membrane and cell functions was analyzed. Surprisingly, although the two compounds have a very similar structure that differs only in the orientation of the hydroxyl group in C3, they promote different effects on anion exchange through the phospholipid bilayer and on the release of ATP from cells. Anion transport mediated by Band 3 protein is reduced in the presence of CT compared with ECT which conversely increases it, and this observation aligns with the mechanisms of action we hypothesized in silico for the two compounds. Finally, ECT causes an increase in intracellular ATP levels unlike CT, and both molecules cause a decrease in ATP released from the erythrocyte. These findings could pave the way for further studies aimed at better understanding of the potential properties and structure–activity relationships of these molecules.