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Our recent data show the valuable potential of TnP for the development of a new and safe anti-inflammatory drug due to its ability to control the traffic and activation of leukocytes in response to inflammation. Although there is considerable knowledge surrounding the cellular mechanisms of TnP, less is known about the mechanistic molecular role of TnP underlying its immunomodulatory functions. Here, we conducted investigations to identify whether miRNAs could be one of the molecular bases of the therapeutic effect of TnP. Using a zebrafish model of neutrophilic inflammation with a combination of genetic gain- and loss-of-function approaches, we showed that TnP treatment was followed by up-regulation of only four known miRNAs, and mature dre-miR-26a-1, herein referred just as miR-26a was the first most highly expressed. The knockdown of miR-26a ubiquitously resulted in a significant reduction of miR-26a in embryos, accompanied by impaired TnP immunomodulatory function observed by the loss of the control of the removal of neutrophils in response to inflammation, while the overexpression increased the inhibition of neutrophilic inflammation promoted by TnP. The striking importance of miR-26a was confirmed when rescue strategies were used (morpholino and mimic combination). Our results identified miR-26a as an essential molecular regulator of the therapeutic action of TnP, and suggest that miR-26a or its targets could be used as promising therapeutic candidates for enhancing the resolution of inflammation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The aquatic environment is the major recipient of wastes containing nanoparticles and other contaminants. Titanium dioxide nanoparticles (NPTiO 2 ) are one of the most produced and used nanoparticle worldwide. This study investigated the toxicity of NPTiO 2 , as well as the toxicity interaction between NPTiO 2 and lead (Pb), in response to genetic and biochemical biomarkers using freshwater fish Rhamdia quelen, as an animal model. The results showed genotoxicity in blood and kidney tissues. No effect of NPTiO 2 alone or in co-exposure with Pb on liver genotoxicity were observed. Alterations in the antioxidant hepatic enzymes activities, as well as alterations in glutathione levels indicated that NPTiO 2 alone or in co-exposure with Pb can cause antioxidant imbalance. The lipid peroxidation was also raised after exposure to NPTiO 2 . In general, the results of this study indicated that both NPTiO 2 alone and their co-exposure with Pb are capable of producing significant toxic effects in short-term exposure., (Copyright © 2020. Published by Elsevier B.V.)