Environmental Toxicology最新文献

Sepsis remains the leading cause of multiple-organ injury due to endotoxemia. Astaxanthin (ASTA), widely used in marine aquaculture, has an extraordinary potential for antioxidant and anti-inflammatory activity. Purinergic receptor (e.g., P2X7R) activation is a powerful signaling in the modulation of inflammation. The effect of ASTA was investigated on the regulation of oxidative stress, inflammatory response, apoptotic mediators, and P2X7R expression in the lung injury during lipopolysaccharide (LPS)-induced endotoxemia. Twenty-four rats were blocked into four groups as Control, LPS, ASTA, and LPS + ASTA. LPS was administered by intraperitoneal injection and ASTA by gavage. Blood and lung samples were taken 6 h after the administrations. The methods were ELISA, western blotting, histopathology, and immunohistochemistry. Sepsis was confirmed by the elevations of IL-1β, IL-6, IL-10, and TNF-α levels in bloodstream. Lung injury was determined by histopathological changes. There were increased P2X7R expression, malondialdehyde (MDA), IL-1β, TNF-α, nuclear factor kappa B (NF-κB), and Caspase-3 and decreased B-cell lymphoma 2 (Bcl-2) and glutathione (GSH) in the septic lung tissue (p < 0.05). ASTA treatment improved MDA, GSH, IL-1β, TNF-α, P2X7R, NF-κB, Caspase-3, and Bcl-2 levels and reduced P2X7R immunoreactivity and histological abnormalities in the lung (p < 0.05). The production of pro-inflammatory cytokines, oxidative stress, P2X7R expression, and apoptotic mediators in the lung is associated with LPS-induced endotoxemia. The ASTA administration appears to regulate the expressions of P2X7R, NF-κB, Bcl-2, and Caspase-3 improving the antioxidative and anti-inflammatory response of the lung tissue in sepsis, in vivo.

The cardiovascular risks linked to PM_2.5 include calcification in both vasculature and myocardial tissues, leading to structural changes and functional decline. Through the selection of a clinically proven endogenous agent, sodium thiosulfate (STS), capable of addressing PM_2.5 related cardiac abnormalities, we not only address the absence of effective solutions to mitigate PM_2.5 toxicity, but also provide evidence for the repurposing potential of STS in ameliorating PM_2.5 induced cardiac damage. Female Wistar rats were exposed to PM_2.5 (250 μg/m³) for 3 h daily for 21 days. STS was administered thrice weekly for 3 weeks during exposure after which the hearts were excised and mounted on a Langendorff apparatus for induction of ischemia-reperfusion injury (IR). STS administration improved cardiac function in PM_2.5 exposed rat hearts, accompanied by increased expression of the master regulator gene PGC1-α and increased mitochondrial mass. Moreover, STS restored bioenergetic function and balanced mitochondrial fission-fusion dynamics. The beneficial effects of STS were further evidenced by its ability to scavenge metals, thereby reducing heavy metal deposition in mitochondria and alleviating oxidative stress and inflammation. Furthermore, STS facilitated the clearance of damaged mitochondria through mitophagy. Additionally, STS activated the PI3K/AKT/GSK3ß signaling pathway, providing cardio protection against IR injury in PM_2.5-exposed hearts by preserving mitochondrial function. These results underscore the potential therapeutic benefits of STS in mitigating the adverse cardiac effects induced by PM_2.5 exposure. The translation of these findings to clinical practice holds promise for the development of targeted interventions aimed at reducing the cardiovascular toxicity associated with PM_2.5 exposure.

The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (-)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bioconstituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear. Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells. EGCG inhibited β-catenin expression and its nuclear localization caused by TGF-β1, suggesting that EGCG blocks the crosstalk between the PI3K/Akt/GSK-3β route and β-catenin. Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.

Retraction: J. Zhang, S. He, and H. Ying, "Refining Molecular Subtypes and Risk Stratification of Ovarian Cancer Through Multi-Omics Consensus Portfolio and Machine Learning," Environmental Toxicology (EarlyView): https://doi.org/10.1002/tox.24222. The above article, published online on 13 March 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.