Bisphenol A (BPA), an important chemical raw material, is now a ubiquitous environmental contaminant. As an endocrine disruptor similar to estrogen, BPA increases the risk of various metabolic and chronic diseases. BPA has immunotoxicity to humans and animals. 1,8-cineole (CIN) is a plant-derived monoterpene with antioxidant and antiapoptosis actions. However, there are no reports about whether CIN could antagonize the BPA-induced apoptosis and necroptosis in bursa of Fabricius (BF) of chicken. This study was to elucidate the ameliorative mechanism of CIN on the apoptosis and necroptosis in BF induced by BPA. 120 broilers (1-day-old) were randomly divided into four groups: control group, CIN group, CIN and BPA co-treatment group, and BPA group. TUNEL analysis results, histopathological variations, and the overexpression of proapoptosis biomakers (Caspase 3, Bax, Cyt-c, and p53) and necroptosis pathway-related factors (RIPK1, RIPK3, MLKL, and FADD) indicated that BPA exposure induced the apoptosis and necroptosis in chicken BF. Moreover, BPA treatment elevated the levels of oxidative stress indexes (MDA, iNOS, and NO) and weaken antioxidases activity (SOD, GPx, and CAT) and total antioxidant capacity in chicken BF. BPA administration also lessened the expression of PI3K and AKT and promoted HSPs (HSP27, HSP40, HSP60, and HSP70) activation. whereas CIN supplementation prominently mitigated BPA-caused these changes and the apoptosis and necroptosis damages. In brief, this study illuminated that CIN could protect the chicken BF against BPA-induced apoptosis and necroptosis through restraining oxidative stress and activating PI3K/AKT pathway.

As a protective factor for lipopolysaccharide (LPS)-induced injury, 14-3-3γ has been the subject of recent research. Nevertheless, whether 14-3-3γ can regulate lactation in dairy cow mammary epithelial cells (DCMECs) induced by LPS remains unknown. Here, the anti-inflammatory effect and lactation regulating ability of 14-3-3γ in LPS-induced DCMECs are investigated for the first time, and the molecular mechanisms responsible for their effects are explored. The results of qRT-PCR showed that 14-3-3γ overexpression significantly inhibited the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Enzyme-linked immunosorbent assay (ELISA) analysis revealed that 14-3-3γ overexpression also suppressed the production of TNF-α and IL-6 in cell culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3γ overexpression clearly increased the viability and proliferation of cells. The results of kit methods and western blot analysis showed that 14-3-3γ overexpression promoted the secretion of triglycerides and lactose and the synthesis of β-casein. Furthermore, the expression of genes relevant to nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs) and lactation-associated proteins were assessed by western blot, and the results suggested that 14-3-3γ overexpression inactivated the NF-κB and MAPK signaling pathways by down-regulating extracellular signal regulated protein kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK) and inhibitor of NF-κB (IκB) phosphorylation levels, as well as by inhibiting NF-κB translocation. Meanwhile, 14-3-3γ overexpression enhanced the expression levels of β-casein, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), serine/threonine protein kinase Akt 1 (AKT1), sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor gamma (PPARγ). These results suggest that 14-3-3γ was able to attenuate the LPS-induced inflammatory responses and promote proliferation and lactation in LPS-induced DCMECs by inhibiting the activation of the NF-κB and MAPK signaling pathways and up-regulating mTOR signaling pathways to protect against LPS-induced injury.