Meng Yu

This study investigates the early oncogenic transformation of gastric epithelial cells (GES-1) and adenocarcinoma cells (AGS) following long-term exposure to N-nitroso compounds (NOCs), using N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as a model carcinogen. Prolonged MNNG treatment enhanced proliferation, migration, invasion, and anchorage-independent growth. These effects were accompanied by persistent activation of endoplasmic reticulum stress (ERS) and autophagy, characterized by elevated PERK, eIF2α, ATF4, CHOP, Beclin-1, and LC3-II, and reduced p62. Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) was markedly upregulated and acted as a competing endogenous RNA, sponging microRNA-329-3p (miR-329-3p) to derepress ATF4. Silencing NEAT1 or restoring miR-329-3p expression suppressed ERS, autophagy, and malignant traits. These findings establish a NEAT1/miR-329-3p/ATF4 signaling axis that links stress response to early gastric epithelial transformation, offering a potential target for intervention.

The contamination of food and feed by mycotoxins, particularly zearalenone (ZEA) and deoxynivalenol (DON), is a global issue. Prenatal exposure to ZEA and DON can result in congenital cardiac malformations in fetuses. Addressing the prevention and mitigation of embryonic cardiotoxicity caused by these toxins is crucial. Citrus limonoid nomilin (NOM) is an extract known for its pathological properties in various diseases. This study investigated the potential mechanism of NOM in mitigating cardiotoxicity caused by ZEA and DON co-exposure in a zebrafish model. The findings indicated that NOM pretreatment alleviated cardiac developmental toxicity induced by ZEA and DON and normalized the expression of key genes involved in heart development, including gata4, vmhc, nkx2.5, and sox9b. Co-exposure to NOM, ZEA, and DON enhanced SOD and catalase activity, increased glutathione levels, and reduced ROS and malondialdehyde production. Furthermore, NOM reduced cardiac oxidative damage by activating the Keap1/Nrf2 signaling pathway. In summary, this study offers new insights for preventive interventions against congenital heart disease caused by mycotoxin exposure.