Nuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidence rate of 46.71% for CMT in China over the past five years, severely threatening the life and health of dogs. Therefore, the search for novel drugs targeting canine mammary cancer is of great significance. This study aims to investigate how the RORγ inhibitors W6134 and XY018 affect the expression of inflammatory genes through histone modifications in CMT-N7 cells. These results show that W6134 and XY018 can upregulate signaling pathways related to inflammation and apoptosis and influence the expression of associated genes. The close link between RORγ and inflammation-related genes further confirms that RORγ may serve as a therapeutic target for canine cancer. Additionally, ChIP-qPCR was used to detect the enrichment of histone markers such as P300, H3K27ac, H3K4me1, H3K9la, and H3K9bhb at the target loci of CXCL10 and MECOM genes. Collectively, our findings provide molecular evidence for the protective role of RORγ in canine mammary cancer, potentially by regulating inflammatory pathways via histone modifications, offering new insights for improving the cure rate and survival of affected dogs.

Fueled by the rapid growth of the global companion animal industry, the development of nutritional additives for improving canine intestinal health has emerged as a prominent research area in pet nutrition. Excessive reactive oxygen species accumulation triggers severe oxidative stress, inducing intestinal inflammation, abnormal epithelial senescence, and tight junction destruction to damage intestinal mucosal integrity. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have proven antioxidative and anti-inflammatory potency, yet divergent functions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on canine ileal epithelial cells (cIECs) remain unclear. Here, an H₂O₂-stimulated oxidative injury model was built to compare their protective capacity. Under all equivalent gradient concentrations ranging from 2.5 to 10 μM in this experiment, Equal-dose DHA failed to alleviate cell damage, while EPA effectively rescued impaired cIEC viability. Biochemical tests showed EPA lowered malondialdehyde and boosted key antioxidant enzyme activities. Transcriptomics confirmed EPA suppressed overactivated TNF-α/IFN-γ inflammatory and senescence pathways. Western blot verified EPA downregulated p-Chk1, p53, p57, and p73 and restored telomere-protective and tight junction proteins. In summary, EPA protects cIECs via antioxidation, anti-inflammation and anti-senescence, supporting its development as a promising functional feed additive for canine intestinal care.

Background: T-2 toxin, a highly toxic Fusarium-derived mycotoxin, frequently contaminates feed and poses significant risks to livestock production and food safety by inducing severe apoptotic damage in the liver, which is the primary organ responsible for toxin metabolism and detoxification. Lycopene, a natural carotenoid antioxidant, exhibits possible hepatoprotective effects against various exogenous toxins; however, there are currently few studies that analyze, from a transcriptomic perspective, how lycopene mitigates T-2 toxin-induced apoptosis in liver tissue. Methods: mouse model of T-2 toxin exposure was established, with low- and high-dose lycopene co-administered for 5 weeks. Results: Transcriptomic analysis and TUNEL staining demonstrated that T-2 toxin stimulation induced marked activation of apoptotic-signaling pathways in liver tissue, while lycopene intervention significantly suppressed this transcriptional activation and alleviated T-2 toxin-provoked hepatocyte DNA-fragmentation signals, together with decreased transcription of pro-apoptotic genes. Comprehensive investigation revealed that T-2 toxin upregulated the RORC (RAR related orphan receptor C) and enhanced its occupancy at the promoter regions of apoptosis-related genes (TNFSF10, PMAIP1, IL18, and RNASEL), as verified by ChIP-qPCR assays. Lycopene strongly reversed the T-2 toxin-induced increase in RORC expression and its binding to apoptosis-related gene promoters. Analysis of the protein—protein interaction network further revealed potential molecular links between RORC and multiple core apoptotic pathway components. Conclusions: Lycopene protects mouse liver from T-2 toxin-induced apoptotic injury, while RORC is identified as a potential candidate regulatory factor associated with this protective effect. This study provides experimental evidence at the transcriptomic level for the use of lycopene in the prevention and treatment of liver tissue damage caused by T-2 toxin.