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This toxicology study was conducted to assess the impact of formaldehyde, a common air pollutant found in Chinese gymnasiums, on the brain function of athletes. In this research, a total of 24 Balb/c male mice of SPF-grade were divided into four groups, each consisting of six mice. The mice were exposed to formaldehyde at different concentrations, including 0 mg/m3, 0.5 mg/m3, 3.0 mg/m3, and 3.0 mg/m3 in combination with an injection of L-NMMA (NG-monomethyl-L-arginine), which is a nitric oxide synthase antagonist. Following a one-week test period (8 h per day, over 7 days), measurements of biomarkers related to the nitric oxide (NO)/cGMP-cAMP signaling pathway were carried out on the experimental animals post-treatment. The study found that: (1) Exposure to formaldehyde can lead to brain cell apoptosis and neurotoxicity; (2) Additionally, formaldehyde exposure was found to alter the biomarkers of the NO/cGMP-cAMP signaling pathway, with some changes being statistically significant (p < 0.05 or p < 0.01); (3) The use of L-NMMA, an antagonist of the NO/cGMP-cAMP signaling pathway, was found to prevent these biomarker changes and had a protective effect on brain cells. The study suggests that the negative impact of formaldehyde on the brain function of mice is linked to the regulation of the NO/cGMP-cAMP signaling pathway. [ABSTRACT FROM AUTHOR]

In this study, a novel mouse model of hepatocellular carcinoma (HCC) was established by simultaneously knocking out Pten and p53 suppressor genes and overexpressing c-Met and △90-β-catenin proto-oncogenes in the livers of mice via hydrodynamic injection (HDI). The mutations were introduced using the CRISPR/Cas9 and Sleeping Beauty transposon systems. In this way, a primary liver cancer model was established within six weeks. In addition, macrophages expressing arginase-1(Arg1) promoter coupled with firefly luciferase were engineered for bioluminescence imaging (BLI) of the tumor microenvironment. This novel, rapidly-generated model of primary hepatocellular carcinoma can be monitored noninvasively, which can facilitate not only applications of the model, but also the development of new drugs and treatment strategies of HCC. [ABSTRACT FROM AUTHOR]

Dibutyl phthalate (DBP), used as a plasticizer, is of wide concern as an environmental pollutant since it has certain immunotoxicity. Although there is growing evidence supporting a link between DBP exposure and allergic airway inflammation, there is less information concerned with whether the ferroptosis pathway is involved in DBP-aggravated allergic asthma in ovalbumin (OVA)-sensitized mice. This study aimed to investigate the role and underlying mechanisms of ferroptosis in DBP-exposed allergic asthmatic mice. Balb/c mice were orally exposed to 40 mg/kg−1 DBP for 28 days, followed by sensitization with OVA and seven consecutive challenges with nebulized OVA. We analyzed airway hyperresponsiveness (AHR), immunoglobulins, inflammation and pulmonary histopathology, to investigate whether DBP exacerbates allergic asthma in OVA-induced mice. We also measured the biomarkers of ferroptosis (Fe2+, GPX4, PTGS2), proteins related to the ferroptosis pathway (VEGF, IL-33, HMGB1, SLC7A11, ALOX15, PEBP1), and indices of lipid peroxidation (ROS, Lipid ROS, GSH, MDA, 4-HNE), to explore the role of ferroptosis in DBP+OVA mice. Finally, we used ferrostatin-1 (Fer-1) as an antagonist against the harmful effects of DBP. The results showed that, DBP+OVA mice had a significant increase in AHR, airway wall remodeling and airway inflammation. Further, we showed that DBP aggravated allergic asthma via ferroptosis and lipid peroxidation, and that Fer-1 inhibited ferroptosis and alleviated the pulmonary toxicity of DBP. These results suggest that ferroptosis participates in the exacerbation of allergic asthma resulting from oral exposure to DBP, highlighting a novel pathway for the connection between DBP and allergic asthma. [Display omitted] • Oral exposure to DBP exacerbates allergic asthma in OVA- sensitized mice. • Ferroptosis participates in DBP-aggravated allergic asthma via lipid peroxidation. • Ferrostatin-1 inhibits ferroptosis and alleviates the pulmonary toxicity of DBP. [ABSTRACT FROM AUTHOR]

Epidemiological evidence indicates a significant relationship between exposure to diisononyl phthalate and allergic asthma. Despite this, the mechanism underlying this association remains unclear. Previous toxicological researches have suggested that the development of allergic asthma may involve the activation of endoplasmic reticulum stress (ERS) and the nuclear factor κ-B (NF-κB) pathways. Nevertheless, it is currently unknown whether these specific signaling pathways are implicated in diisononyl phthalate (DINP)-induced allergic asthma. The objective of this research was to understand how DINP exacerbates allergic asthma in Balb/c mice through ERS and NF-κB pathways. To systematically examine the aggravated effects of DINP in Balb/c mice, we measured airway hyperresponsiveness (AHR), lung tissue pathology, cytokines, and ERS and NF-κB pathway biomarkers. Additionally, we applied the ERS antagonist phenylbutyric acid (4-PBA) or the NF-κB antagonist pyrrolidine dithiocarbamate (PDTC) to verify the mediating effects of ERS and NF-κB on DINP-exacerbated allergic asthma. The results of our experiment show that oral DINP exposure may exacerbate airway hyperresponsiveness and airway remodeling. This deterioration is accompanied by an imbalance in immunoglobulin levels, Th17/Treg cells, ERS, and NF-κB biomarkers, leading to the activation of pro-inflammatory pathways. Furthermore, our study found that the blocking effect of 4-PBA or PDTC can inhibit the Th17/Treg imbalance and effectively alleviate symptoms resembling allergic asthma. In conclusion, ERS and NF-κB signaling pathways play an important role in regulating DINP-induced allergic asthma exacerbations. [Display omitted] • Exposure to diisononyl phthalate aggravates allergic asthma in Balb/c mice. • Endoplasmic reticulum stress and NF-κB pathway is involved in allergic asthma exacerbated by diisononyl phthalate. • Exposure to diisononyl phthalate triggers Th17/Treg immune imbalance in Balb/c mice. • 4-PBA or PDTC treatment can alleviate allergic asthma caused by combined exposure to ovalbumin and diisononyl phthalate. [ABSTRACT FROM AUTHOR]