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  • The Limitations of our data include the

    2023-11-20

    The Limitations of our data include the absence of functional/behavioral assessments and lack of direct comparison with females which would require additional studies and conceivably support sex-specific interventions for stroke [50].
    Competing interests
    Acknowledgements This study was supported by a grant from Korea Institute of Science and Technology (DWC) and National Natural Science Foundation of China (Grant No. 81371260).
    Introduction During the last decades various human activities have contributed to increase the number of chemicals introduced in air, water and soil, with a consequent increase of harmful compounds present in the environment. A lot of concern is about the so-called “emerging pollutants”, a series of compounds such as pesticides, cosmetics, personal and household care products, pharmaceuticals that have been recently detected for example in urban rivers and that are potentially toxic for human health and environment [1]. However, their toxicity, together with their concentrations and persistence in the environment, still need to be assessed through a combination of chemical and biological assays. In general, the toxicity of new chemical entities should be checked before their introduction in the environment. Thus, research and innovation should aim at the development of methods that allow to verify the toxicity of such compounds that are used in everyday life. Such methods should include high throughput assays that allow the screening of several chemicals on key molecular targets in order to quickly identify the ones that are potentially harmful. Among others, the pexidartinib is a well-known target for chemicals that are toxic for human health. The so-called endocrine disrupting chemicals (EDCs) are a series of compounds able to interact with the hormone system by influencing hormone metabolism [2]. They can disrupt the synthesis, secretion, transport, binding, action or elimination of hormones, including the ones that are responsible for behaviour and fertility, resulting always in severe consequences for the reproductive and endocrine systems [3]. EDCs include a huge variety of different molecules, from pesticides to plasticizers, pharmaceuticals, personal care products and dietary components, which have caught the attention of scientists in the last twenty years because of their widespread diffusion and incidence on human health. They are widely used for several daily applications, like medical devices, children toys as well as food and beverage packaging [4]. They are raising much concern because of their possible solubilisation and thus contamination for example of food products due to the non-covalent interactions between plastic materials and plasticizers [5]. The molecular targets of such compounds are different proteins, including enzymes involved in hormones biosynthesis and hormone receptors. Among them, different cytochromes P450 are involved in steroidogenesis, including human aromatase that catalyses the conversion of androgens into estrogens, a step that can be crucial for the development of estrogen-dependent pathologies such as breast cancer [6], [7], [8], [9]. The enzyme is also expressed in several regions of the brain, where estrogens are responsible for neurite growth and migration [10], and protection against neurodegenerative pathologies like Alzheimer's and Parkinson's diseases [11], [12], [13]. Thus, considering the central role human aromatase plays at the endocrine and neuroendocrine levels, a method for the fast and reliable screening of aromatase potential inhibitors can represent a step forward for the identification of EDCs. Up to now the most widely used aromatase activity assay in cell lines as well as on the purified protein is based on radiolabelled androstenedione [14], [15], [16], [17]. Such a methodology implies the use of a radiolabelled substrate that is an expensive molecule that needs adequately equipped laboratories to be handled. Moreover, this method cannot be adapted to a high throughput format for the rapid screening of different molecules. Another possibility is the use of ELISA that quantifies estrogens, but again these commercially available kits are quite expensive.