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Microglial cells play a key role in protecting the central nervous system from pathogens and toxic compounds and are involved in the pathogenesis of different neurodegenerative diseases. Cadmium is a widespread toxic heavy metal, released into the environment at a rate of 30,000 tons/year by anthropogenic activities; it is easily uptaken by the human body through diet and cigarette smoke, as well as by occupational exposure. Once inside the body, cadmium enters the cells and substitutes to zinc and other divalent cations altering many biological functions. Its extremely long half-life makes it a serious health threat. Recent data suggest a role for heavy metals in many neurodegenerative diseases; however, the role of cadmium is still to be elucidated. In this work we report the investigation of cadmium toxicity towards murine BV2 microglial cells, a widely used model for the study of neurodegeneration. Results show that increasing cadmium concentrations increase oxidative stress, a proposed mechanism of neurodegeneration, but also that BV2 cells can keep oxidative stress under control by increasing glutathione reduction. Moreover, cadmium induces alterations of cell morphology and metabolism leading to mitochondrial impairment, without switching the cells to Warburg effect. Finally cadmium induces the release of proinflammatory cytokines, but does not markedly switch BV2 cells to M1 phenotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The literature is currently lacking effect-based monitoring studies targeted at evaluating the performance of full-scale membrane bioreactor plants. In this research, a monitoring campaign was performed at a full-scale wastewater treatment facility with two parallel lines (traditional activated sludge and membrane bioreactor). Beside the standard parameters (COD, nitrogen, phosphorus, and metals), 6 polynuclear aromatic hydrocarbons, 29 insecticides, 2 herbicides, and 3 endocrine disrupting compounds were measured. A multi-tiered battery of bioassays complemented the investigation, targeting different toxic modes of action and employing various biological systems (uni/multicellular, prokaryotes/eukaryotes, trophic level occupation). A traffic light scoring approach was proposed to quickly visualize the impact of treatment on overall toxicity that occurred after the exposure to raw and concentrated wastewater. Analysis of the effluents of the CAS and MBR lines show very good performance of the two systems for removal of organic micropollutants and metals. The most noticeable differences between CAS and MBR occurred in the concentration of suspended solids; chemical analyses did not show major differences. On the other hand, bioassays demonstrated better performance for the MBR. Both treatment lines complied with the Italian law's "ecotoxicity standard for effluent discharge in surface water". Yet, residual biological activity was still detected, demonstrating the adequacy and sensitivity of the toxicological tools, which, by their inherent nature, allow the overall effects of complex mixtures to be taken into account., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The inhalation of zinc oxide nanoparticles (nZnO) may induce systemic diseases, damages to the alveolar epithelium and inflammatory response to endothelial cells. In this work the use of an in vitro air-blood barrier (ABB) model provided a tool to elucidate the biological mechanisms underlying the potential effects of inhaled nanoparticles (NPs). The ABB model used is composed of a Transwell co-culture of a lung epithelial cell line (NCI-H441) and an immortalized pulmonary microvascular endothelial cell line (HPMEC-ST1.6R). In addition, a tri-culture model was developed by adding monocytes (THP-1) on the basal compartment of the inserts. These models have been set up to analyse the importance of the interplay among the different cell types on various responses after nZnO exposure: inflammation, endothelial damage and modulation of the immune system. The barrier integrity was assessed by measuring the transepithelial electrical resistance (TEER); the pro-inflammatory and immune cells responses were analysed by ELISA. The results have evidenced that nZnO do not affect the barrier integrity, since no TEER reduction was measured after 24h of exposure, but an activation of endothelial cells, which released pro-inflammatory mediators (IL-6, IL-8), and endothelial dysfunction markers (sICAM-1 and sVCAM-1) were induced. These results confirm that apical exposure to NPs promote endothelium activation. The in vitro-ABB model here used is thus a useful tool able to evidence the interaction between lung epithelium and endothelium in inducing biological response, and the role of endothelium dysfunction following NPs inhalation., (Copyright © 2017 Elsevier B.V. All rights reserved.)