Di (2-ethylhexyl) phthalate and polystyrene microplastics co-exposure caused oxidative stress to activate NF-κB/NLRP3 pathway aggravated pyroptosis and inflammation in mouse kidney.

Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.

MiR-129-3p regulates ferroptosis in the liver of Selenium-deficient broilers by targeting SLC7A11.

Selenium (Se) has been proven to be an essential trace element for organism. Se deficiency in poultry can cause widespread damage, such as exudative diathesis. The liver is not only the main organ of metabolism, but also one of the organs with high Se content in organism. Recent studies have shown that solute carrier family 7 member 11 (SLC7A11) plays a key role in the negative regulation of ferroptosis. In order to explore the mechanism of Se deficiency induces liver ferroptosis in broilers, and the role of microRNAs (miRNAs) in this process, we divided broilers into 2 groups: control group (0.2 mg/kg Se) and Se deficiency group (0.03 mg/kg Se). Hematoxylin-Eosin staining detected liver tissue damage in broilers. Predicted and verified the targeting relationship between miR-129-3p and SLC7A11 through miRDB and dual luciferase report experiments. The genes related to ferroptosis were detected by qRT-PCR and Western Blot. The results showed that the expression level of miR-129-3p mRNA in Se-deficient liver was significantly increased. To understand whether the miR-129-3p/SLC7A11 axis could involve in the process of ferroptosis, our further research showed that overexpression of miR-129-3p could reduce the expression of SLC7A11 and its downstream GCL, GSS, and GPX4, thereby inducing ferroptosis. These data indicates that miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage.

MiR-1656 targets GPX4 to trigger pyroptosis in broilers kidney tissues by activating NLRP3 inflammasome under Se deficiency.

Selenium (Se) is a vital minor element for the organism. Se deficiency caused inflammation in kidney tissue and regulate the expression of selenoproteins and microRNAs (miRNAs). Pyroptosis involved in the inflammatory response, however, whether microRNA targets GPX4 to regulate Se-deficient kidney tissue pyroptosis is unclear. In this study, broilers were divided into two groups, Control group with 0.3mg/kg Se diet and Se-deficient group with 0.03mg/kg Se diet. The dual luciferase reporter assay system and quantitative real-time PCR (qRT-PCR) were used to screen the specificity of miR-1656 and its target protein in Se-deficient broilers. We tested the pyroptosis-related genes of Se-deficient broilers kidney and miR-1656-transfected primary broilers kidney by qRT-PCR, Western blot (WB) and immunofluorescence staining. Our research indicated that the GPX4 is one of the target genes of miR-1656, and Se deficiency leaded to the overexpression of miR-1656 and the increased expression of pyroptosis-related genes. The overexpression of miR-1656 can induce increased expression of pyroptosis-related genes including NLRP3, Caspase-1, IL-18, and IL-1ß by inhibiting the release of GPX4. This study showed that miR-1656 could increase the release of ROS by targeting GPX4, activated the NLRP3 inflammasome, and release the inflammatory factors IL-1ß and IL-18 to trigger pyroptosis in the kidney tissue of Se-deficient broilers. This finding may provide new research ideas for kidney injury and cell death due to Se deficiency.