Polystyrene is a thermoplastic polymer widely used in commercial products. Like all plastics, polystyrene can be degraded into microplastic and nanoplastic particles and ingested via food chain contamination. Although the ecological impact due to plastic contamination is well known, there are no studies indicating a carcinogenic potential of polystyrene microplastics (MPs) and nanoplastics (NPs). Here, we evaluated the effects of the MPs and NPs on normal human intestinal CCD-18Co cells. Our results show that internalization of NPs and MPs induces metabolic changes under both acute and chronic exposure by inducing oxidative stress, increasing glycolysis via lactate to sustain energy metabolism and glutamine metabolism to sustain anabolic processes. We also show that this decoupling of nutrients mirrors the effect of the potent carcinogenic agent azoxymethane and HCT15 colon cancer cells, carrying out the typical strategy of cancer cells to optimize nutrients utilization and allowing metabolic adaptation to environmental stress conditions. Taken together our data provide new evidence that chronic NPs and MPs exposure could act as cancer risk factor for human health.

Cell metabolism is the biochemical machinery that provides energy and building blocks to sustain life. Understanding its fine regulation is of pivotal relevance in several fields, from metabolic engineering applications to the treatment of metabolic disorders and cancer. Sophisticated computational approaches are needed to unravel the complexity of metabolism. To this aim, a plethora of methods have been developed, yet it is generally hard to identify which computational strategy is most suited for the investigation of a specific aspect of metabolism. This review provides an up-to-date description of the computational methods available for the analysis of metabolic pathways, discussing their main advantages and drawbacks. In particular, attention is devoted to the identification of the appropriate scale and level of accuracy in the reconstruction of metabolic networks, and to the inference of model structure and parameters, especially when dealing with a shortage of experimental measurements. The choice of the proper computational methods to derive in silico data is then addressed, including topological analyses, constraint-based modeling and simulation of the system dynamics. A description of some computational approaches to gain new biological knowledge or to formulate hypotheses is finally provided.

Microplastics are now polluting all seas and, while studies have found numerous negative interactions between plastic pollution and marine animals, the effects on embryonic development are poorly understood. A potentially important source of developmental ecotoxicity comes from chemicals leached from plastic particles to the marine environment. Here we investigate the effects of leachates from new and beach-collected pellets on the embryonic and larval development of the sea urchin Strongylocentrotus purpuratus and demonstrate that exposure of developing embryos to these leachates elicits severe, consistent and treatment-specific developmental abnormalities including radialisation of the embryo and malformation of the skeleton, neural and immune cells. Using a multi-omics approach we define the developmental pathways disturbed upon exposure to PVC leachates and provide a mechanistic view that pinpoints cellular redox stress and energy production as drivers of phenotypic abnormalities following exposure to PVC leachates. Analysis of leachates identified high concentrations of zinc that are the likely cause of these observed defects. Our findings point to clear and specific detrimental effects of marine plastic pollution on the development of echinoderms, demonstrating that chemicals leached from plastic particles into sea water can produce strong developmental abnormalities via specific pathways, and therefore have the potential to impact on a wide range of organisms.

Sunscreens are emulsions of water and oil that contain filters capable of protecting against the detrimental effects of ultraviolet radiation (UV). The widespread use of cosmetic products based on nanoparticulate UV filters has increased concerns regarding their safety and compatibility with both the environment and human health. In the present work, we evaluated the effects of titanium dioxide nanoparticle (TiO₂ NP)-based UV filters with three different surface coatings on the development and immunity of the sea urchin, Paracentrotus lividus. A wide range of NP concentrations was analyzed, corresponding to different levels of dilution starting from the original cosmetic dispersion. Variations in surface coating, concentration, particle shape, and pre-dispersant medium (i.e., water or oil) influenced the embryonic development without producing a relevant developmental impairment. The most common embryonic abnormalities were related to the skeletal growth and the presence of a few cells, which were presumably involved in the particle uptake. Adult P. lividus immune cells exposed to silica-coated TiO₂ NP-based filters showed a broad metabolic plasticity based on the biosynthesis of metabolites that mediate inflammation, phagocytosis, and antioxidant response. The results presented here highlight the biosafety of the TiO₂ NP-based UV filters toward sea urchin, and the importance of developing safer-by-design sunscreens.

During tumor progression, hypoxia, nutrient deprivation or changes in the extracellular environment (i.e., induced by anti-cancer drugs) elicit adaptive responses in cancer cells. Cellular plasticity increases the chance that tumor cells may survive in a challenging microenvironment, acquire new mechanisms of resistance to conventional drugs, and spread to distant sites. Re-activation of stem pathways appears as a significant cause of cellular plasticity because it promotes the acquisition of stem-like properties through a profound phenotypic reprogramming of cancer cells. In addition, it is a major contributor to tumor heterogeneity, depending on the coexistence of phenotypically distinct subpopulations in the same tumor bulk. Several cellular mechanisms may drive this fundamental change, in particular, high-throughput sequencing technologies revealed a key role for alternative splicing (AS). Effectively, AS is one of the most important pre-mRNA processes that increases the diversity of transcriptome and proteome in a tissue- and development-dependent manner. Moreover, defective AS has been associated with several human diseases. However, its role in cancer cell plasticity and tumor heterogeneity remains unclear. Therefore, unravelling the intricate relationship between AS and the maintenance of a stem-like phenotype may explain molecular mechanisms underlying cancer cell plasticity and improve cancer diagnosis and treatment.

Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.