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Fumonisin B1 (FB1) is a mycotoxin that poses a great threat to agricultural production and the health of humans and animals. Pterostilbene (PTE) is a natural plant polyphenolic compound with good anti-inflammatory, antioxidant and cell regeneration effects, yet its effectiveness in treating FB1-induced cytotoxicity remains to be explored. In this study, we used porcine alveolar macrophages (3D4/21) as a model to characterize the cytotoxicity induced by FB1, and to investigate the potential alleviating effect of PTE on FB1-induced cytotoxicity. We demonstrate that FB1 induces cytotoxicity, apoptosis, pro-inflammatory cytokine production and mitochondrial damage, which can be largely recovered by PTE treatment, suggesting the promising application of PTE to treat FB1-induced damage. Mechanistically, FB1 activates the JAK/STAT signaling pathway, while PTE attenuates FB1-induced cytotoxicity through the inhibition of key JAK/STAT genes such as JAK2 and STAT3. Overall, our study characterized the molecular mechanism for FB1-induced cytotoxicity and found PTE to be a promising component which can alleviate FB1-induced cytotoxicity by interfering in the activation of JAK/STAT pathway. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is a burdensome coronavirus for the global pig industry. Although its fecal-oral route has been well-recognized, increasing evidence suggests that PEDV can also spread through airborne routes, indicating that the infection may also occur in the respiratory tract. N6-methyladenosine (m6A) has been known to regulate viral replication and host immunity, yet its regulatory role and molecular mechanism regarding PEDV infection outside the gastrointestinal tract remain unexplored. In this study, we demonstrate that PEDV can infect porcine lung tissue and the 3D4/21 alveolar macrophage cell line, and the key m6A demethylase ALKBH5 is remarkably induced after PEDV infection. Interestingly, the disruption of ALKBH5 expression remarkably increases the infection's capacity for PEDV. Transcriptome profiling identified dozens of putative targets of ALKBH5, including GAS6, which is known to regulate virus infectivity. Further, MeRIP-qPCR and mRNA stability analyses suggest that ALKBH5 regulates the expression of GAS6 via an m6A-YTHDF2-dependent mechanism. Overall, our study demonstrates that PEDV can infect porcine lung tissue and 3D4/21 cells and reveals the crucial role of ALKBH5 in restraining PEDV infections, at least partly, by influencing GAS6 through an m6A-YTHDF2-dependent mechanism. [ABSTRACT FROM AUTHOR]