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In recent years, micro- and nanoplastics (MNPs) have represented an emerging threat for the aquatic environment due to their persistence and widespread distribution. Indeed, their small size and increased surface area lead to a high biological reactivity, which can be crucial for the health status of biota. To date, several studies have investigated lethal and sublethal endpoints of MNPs, while one of the main challenges is to understand their mechanisms of toxicity in a comprehensive manner. With this aim, the field of aquatic ecotoxicology can now benefit from the -omics approaches. This review focuses on the recent advances related to the use of transcriptomics, proteomics, and metabolomics to deeply investigate the molecular and biochemical responses of aquatic organisms, both fishes and aquatic invertebrates, to pristine polystyrene (PS) MNPs. The literature reviewed revealed that transcriptomics and metabolomics are the most frequently used -omic approaches. Overall, the studies taken into consideration shed light on the events triggered by PS MNPs at molecular and cellular levels, identifying as mechanisms of toxicity the pathways involved in oxidative stress, energy metabolism, immune response, and the nervous system. Future studies should therefore focus on the use and integration of multi-omics approaches for a more comprehensive understanding of the mechanisms involved in MNPs toxicity.

Mercury (Hg) is a dangerous and persistent trace element. Its organic and highly toxic form, methylmercury (MeHg), easily crosses biological membranes and accumulates in biota. Nevertheless, understanding the mechanisms of dietary MeHg toxicity in fish remains a challenge. A time-course experiment was conducted with juvenile white seabreams, Diplodus sargus (Linnaeus, 1758), exposed to realistic levels of MeHg in feed (8.7 μg g−1, dry weight), comprising exposure (E; 7 and 14 days) and post-exposure (PE; 28 days) periods. Total Hg levels increased with time in gills and liver during E and decreased significantly in PE (though levels of control fish were reached only for gills), with liver exhibiting higher levels (2.7 times) than gills. Nuclear magnetic resonance (NMR)-based metabolomics revealed multiple and often differential metabolic changes between fish organs. Gills exhibited protein catabolism, disturbances in cholinergic neurotransmission, and changes in osmoregulation and lipid and energy metabolism. However, dietary MeHg exposure provoked altered protein metabolism in the liver with decreased amino acids, likely for activation of defensive strategies. PE allowed for the partial recovery of both organs, even if with occurrence of oxidative stress and changes of energy metabolism. Overall, these findings support organ-specific responses according to their sensitivity to Hg exposure, pointing out that indications obtained in biomonitoring studies may depend also on the selected organ.

Interleukin (IL)-12 is a pro-inflammatory cytokine that mediates T-helper type 1 responses and cytotoxic T-cell activation, contributing to its utility as anti-cancer agent. Systemic administration of IL-12 often results in unacceptable toxicity; therefore, strategies to direct delivery of IL-12 to tumors are under investigation. The objective of this study was to assist the preclinical development of NHS-IL12, an immunocytokine consisting of an antibody, which targets necrotic tumor regions, linked to IL-12. Specifically this study sought to evaluate the safety, serum pharmacokinetics, anti-tumor activity, and immune modulation of NHS-IL12 in dogs with naturally occurring cancers.A rapid dose-escalation study of NHS-IL12 administered subcutaneously to dogs with melanoma was conducted through the Comparative Oncology Trials Consortium (COTC). Eleven dogs were enrolled in four dose-escalation cohorts; thereafter, an additional seven dogs were treated at the defined tolerable dose of 0.8 mg/m2. The expanded cohort at this fixed dose (ten dogs in total) was accrued for further pharmacokinetics and pharmacodynamics assessment. NHS-IL12 levels, serum cytokine concentrations, and peripheral blood mononuclear cell characterization (post-treatment) and draining lymph node immune profiling, and tumor biopsies (pre- and post-treatment) were collected. Adverse events included thrombocytopenia, liver enzymopathies, fever, and vasculitis. Correlation between interferon (IFN)-γ induction, adverse events, and NHS-IL12 exposure (maximum concentration and area under the concentration-time curve) were dose-dependent. Serum IL-10 levels and intratumoral CD8+ populations increased after treatment. Partial responses, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, were observed in two dogs treated with NHS-IL12 0.8 mg/m2 and 1.6 mg/m2.NHS-IL12 was administered safely to dogs with melanoma and both immunologic and clinical activity was observed. This study successfully defined a narrow therapeutic window for systemic delivery of NHS-IL12 via the subcutaneous route. Results will inform the design and implementation of first-in-human clinical trials of NHS-IL12 in cancer patients.