Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

The aim of this study was to provide information on the levels of toxic (Cd and Pb) and essential (Cu, Fe and Zn) elements in cow’s milk produced in the State of Pernambuco (Brazil). A total of 142 samples of raw milk were collected, and the concentrations of essential and toxic elements were determined by inductively coupled plasma-optical emission spectrometry. In almost 30 % of the samples analyzed, the Pb content exceeded the maximum level established in the Brazilian legislation (0.05 mg/l). By contrast, in all samples the Cd content was below the maximum allowable level (0.02 mg/L). The essential trace elements Cu, Fe and Zn were generally present at lower concentrations than reported in other studies and can be considered within the deficient range for cow’s milk. Statistical and chemometric procedures were used to evaluate the main factors influencing the metal concentrations (proximity to major roads, presence of effluents, and milking method). The study findings demonstrate that the proximity of the farms to major roads influences the concentrations of Cd, Pb and Cu and that this is the main factor explaining the Pb content of milk. In addition, the presence of effluents influenced the concentrations of Cu, while no relationship between the metal content and the milking method was observed. Thus, in accordance with the study findings, consumption of cow’s milk produced in the region can be considered a risk to public health due to the high concentrations of Pb and the low concentrations of other essential minerals such as Cu, Zn and Fe in some of the milk samples.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drug, food, water treatment and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity and (epi)genotoxicity. Also, new technologies, such as organ-on-chip and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of how from the production to final disposition chain of nanomaterials is evaluated under Life Cycle Assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review we give an overview of all these elements of nanosafety.