Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na₂SeO₃) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na₂SeO₃. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na₂SeO₃ treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na₂SeO₃ treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na₂SeO₃ can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na₂SeO₃ and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.

Our previous study has demonstrated that porcine pulmonary microvascular endothelial cells (MVECs) are susceptible to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). The innate immune response of MVECs infected with HP-PRRSV would play important roles in controlling virus proliferation, resisting cellular injury, and preventing the virus from spreading to other tissues and organs. Type I interferon is one of the most effective antiviral cytokines in the innate immune response, and interferon-induced proteins with tetratricopeptide repeats (IFITs) are members of interferon-stimulated genes induced by viruses and other pathogens, which are crucial in inhibiting virus proliferation and regulating the innate immune response. However, their effects on HP-PRRSV-induced innate immunity in porcine pulmonary MVECs remain unclear. Here, the roles of IFITs in porcine pulmonary MVECs infected with the HP-PRRSV HN strain were investigated, and the effects of astragalus polysaccharides (APS), a widely used traditional Chinese herbal ingredient with the immunopotentiating effect, on them were studied. The results showed that more autophagosomes were observed in HP-PRRSV-infected MVECs, and the expression of IFN-α, IFIT3, and IFIT5 decreased or increased at different time points after infection. When silencing the genes of IFIT3 or IFIT5, the HP-PRRSV replication in MVECs was significantly increased. The expression of IFIT3 and IFIT5 could be upregulated by APS, whose inhibitory effects on the HP-PRRSV replication significantly declined when the genes of IFIT3 or IFIT5 were silenced. The results suggest that IFIT3 and IFIT5 play an important role in inhibiting the HP-PRRSV replication in porcine pulmonary MVECs, and APS suppress the multiplication of HP-PRRSV by upregulating their expression.

Background: Traditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear.Methods: In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS’s action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis.Results: Network pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway.Conclusion: We conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.

In the current study, Bacillus coagulants had a role in combating oxidative stress by inhibiting the growth of intestinal pathogens. However, there are few studies on reducing the mechanisms of oxidative stress. Therefore, this study aimed to explore the effects and underlying mechanisms of B. coagulant HYI (BC-HYI) treatment on growth and intestinal functions in laying chickens under LPS-induced oxidative stress. The in vivo experimental group included five groups of laying chicks: normal control, LPS group, B6 group, B7 group and B8 group. The test consisted of six repetitions in each group, with six animals in each repetition. In the in vitro experiment, an LPS-induced oxidative stress model of chicken fibroblast DF-1 cells was established, and the DF-1 cells were divided into control group, LPS-treated group, B5 group, B6 group and B7 group. On the one hand, we found that BC-HYI can inhibit pathological changes in some intestinal tissues. On the other hand, BC-HYI supplementation has a dual effect on the gut microbiota, promoting the proliferation of beneficial microbes such as Barbarella, Lactobacillus, and Antibacterial while maintaining symbiotic balance. The abundance of Barbarella, Bactericide, and Cloistral was significantly different between the LPS group and the BC-HYI group (p < 0.01). Moreover, compared with the LPS group, BC-HYI significantly decreased reactive oxygen species levels and prevented cell apoptosis (p < 0.01). It used to prevent oxidative stress by activating the Nrf2-ARE/HO-1 signaling pathway, enhancing the scavenging of free radicals, and reducing oxidative damage. BC-HYI alleviated oxidative stress in laying chickens by modulating the gut microbiota and activating the Nrf2-ARE/HO-1 signaling pathway. In summary, laying chickens and cell experiments indicate that BC-HYI supplementation can improve the enzyme function of antioxidants, regulate intestinal barrier function and activate the Nrf2-ARE/HO-1 signaling pathway to regulate intestinal barrier function.

Purpose: Streptococcus agalactiae is one of the primary pathogens responsible for subclinical mastitis, a significant economic burden for dairy farms. An essential component of the immune response to infection is ubiquitination, which plays important roles in the complex interactions between the pathogen and host. Materials and Methods: In the present study, quantitative ubiquitylomics was performed to profile changes in the global ubiquitinome of bovine mammary gland epithelial cells (BMECs) infected with S. agalactiae. Results: The most notable changes in the BMEC ubiquitinome were related to the adherens junction, ribosome, and tight junction pathways. Ubiquitination of CTNNB1, EGFR, ITGB1, CTNNA1, CTNNA2, CDH1, YES1, and SLC9A3R1 appears to be fundamental for regulating multiple cellular processes in BMECs in response to S. agalactiae infection. In addition, broad ubiquitination of various effectors and outer membrane proteins was observed. Ubiquitinated proteins in S. agalactiae-infected BMECs were associated with regulating cell junctions in the host, with potential implications for susceptibility to infection. Conclusion: The preliminary findings suggest that extensive ubiquitination of CTNNB1, CDH1 and SLC9A3R1 and proteins closely related to cell junctions might play an important role in mastitis progression in dairy cows. The results provide evidence that ubiquitin modification of certain proteins in S. agalactiae-infected BMECs could be a promising therapeutic strategy for reducing mammary gland injury and mastitis.