Ferroptosis is a recently recognized form of regulated cell death involving lipid peroxidation. Glutathione peroxidase 4 (GPX4) plays a central role in the regulation of ferroptosis through the suppression of lipid peroxidation generation. Connections have been reported between ferroptosis, lipid metabolism, cancer onset, and drug resistance. Recently, interest has grown in ferroptosis induction as a potential strategy to overcome drug resistance in hematological malignancies. GATA-1 is a key transcriptional factor controlling hematopoiesis-related gene expression. Two GATA-1 isoforms, the full-length protein (GATA-1_FL) and a shorter isoform (GATA-1_S), are described. A balanced GATA-1_FL/GATA-1_S ratio helps to control hematopoiesis, with GATA-1_S overexpression being associated with hematological malignancies by promoting proliferation and survival pathways in hematopoietic precursors. Recently, optical techniques allowed us to highlight different lipid profiles associated with the expression of GATA-1 isoforms, thus raising the hypothesis that ferroptosis-regulated processes could be involved. Lipidomic and functional analysis were conducted to elucidate these mechanisms. Studies on lipid peroxidation production, cell viability, cell death, and gene expression were used to evaluate the impact of GPX4 inhibition. Here, we provide the first evidence that over-expressed GATA-1_S prevents K562 myeloid leukemia cells from lipid peroxidation-induced ferroptosis. Targeting ferroptosis is a promising strategy to overcome chemoresistance. Therefore, our results could provide novel potential therapeutic approaches and targets to overcome drug resistance in hematological malignancies.

To fight neurodegenerative diseases, several therapeutic strategies have been proposed that, to date, are either ineffective or at the early preclinical stages. Intracellular protein aggregates represent the cause of about 70% of neurodegenerative disorders, such as Alzheimer’s disease. Thus, autophagy, i.e., lysosomal degradation of macromolecules, could be employed in this context as a therapeutic strategy. Searching for a compound that stimulates this process led us to the identification of a 37/67kDa laminin receptor inhibitor, NSC48478. We have analysed the effects of this small molecule on the autophagic process in mouse neuronal cells and found that NSC48478 induces the conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) into the LC3-phosphatidylethanolamine conjugate (LC3-II). Interestingly, upon NSC48478 treatment, the contribution of membranes to the autophagic process derived mainly from the non-canonical m-TOR-independent endocytic pathway, involving the Rab proteins that control endocytosis and vesicle recycling. Finally, qRT-PCR analysis suggests that, while the expression of key genes linked to canonical autophagy was unchanged, the main genes related to the positive regulation of endocytosis (pinocytosis and receptor mediated), along with genes regulating vesicle fusion and autolysosomal maturation, were upregulated under NSC48478 conditions. These results strongly suggest that 37/67 kDa inhibitor could be a useful tool for future studies in pathological conditions.

Wastewater monitoring has been recognized as a valid tool for monitoring coronavirus disease 2019 (COVID-19) diffusion. In this paper we analyse a dataset composed by the measurements of SARS-CoV-2 RNA load in 605 raw wastewater samples collected from nine wastewater treatment plants (WWTPs) in the Campania region from October 2021 to May 2025. We analyse the correlation structure of the dataset using multivariate statistical techniques with the aim of identifying the most representative sentinel WWTPs and thus optimizing the number of samples. Results of spatial analysis showed that there are two isolated elements, SA3 and NA1, with the highest and lowest SARS-CoV-2 load values, respectively, and other two clusters (Cl1 and Cl2) from the other WWTPs. Temporal analysis showed that NA3 WWTP had a statistically significant difference in SARS-CoV-2 load from 2022 to 2023. Our method suggests limiting samplings to three sites, as follows: SA3 (which can act as a sentinel site because it is the first site that records variation in viral load) and two with the higher variation coefficients (CV%) belonging to the two clusters, as follows: CE1 for Cl1 and NA4 for Cl2. This data analysis procedure could allow to focus only on certain WWTPs for SARS-CoV-2 monitoring, to promptly identify outbreaks.