Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.

Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resistance to oxidants, serves as one of the key defensive factors against a range of pathological processes such as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals. An increase in human exposure to toxic metals via air, food, and water has been recently observed, which is mainly due to anthropogenic activities. The relationship between environmental exposure to heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well as metaloid arsenic (As), and transition metal chromium (Cr), and the development of various human diseases has been extensively investigated. Their ability to induce reactive oxygen species (ROS) production through direct and indirect actions and cause oxidative stress has been documented in various organs. Taking into account that Nrf2 signaling represents an important pathway in maintaining antioxidant balance, recent research indicates that it can play a dual role depending on the specific biological context. On one side, Nrf2 represents a potential crucial protective mechanism in metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogenesis under conditions of prolonged exposure and continuous activation. Thus, this review aims to summarize the state-of-the-art knowledge regarding the functional interrelation between the toxic metals and Nrf2 signaling.

Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA)) with the effects of their mixture through different biochemical, hormonal, and hematological parameters. Rats were divided into five experimental groups: Control (corn oil), DEHP (50 mg/kg b.w./day), DBP (50 mg/kg b.w./day), BPA (25 mg/kg b.w./day), and MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral treatment and blood was collected for further analysis. The results demonstrated that the mixture produced significant changes in lipid profile, liver-related biochemical parameters, and glucose level. Furthermore, the opposite effects of single substances on the thyroxine level have been shown in comparison with the mixture, as well as a more pronounced effect of the mixture on testosterone level. This study contributes to the body of knowledge on the toxicology of mixtures and gives one more evidence of the paramount importance of mixture toxicity studies, especially in assessing the endocrine disruptive effects of chemicals.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.