Interferons (IFNs) stimulate the expression of numerous IFN-stimulating genes via the Janus kinase-signal transducers and activators of the transcription (JAK-STAT) signaling pathway, which plays an important role in the host defense against viral infections. In mammals, including humans and mice, a substantial number of IFN-stimulated genes (ISGs) have been identified, and their molecular mechanisms have been elucidated. It is important to note that avian species are phylogenetically distant from mammals, resulting in distinct IFN-induced ISGs that may have different functions. At present, only a limited number of avian ISGs have been identified. In this review, we summarized the identified avian ISGs and their antiviral activities. As gene-editing technology is widely used in avian breeding, the identification of avian ISGs and the elucidation of their molecular mechanism may provide important support for the breeding of avians for disease resistance.

Betaine was found to alleviate inflammation in different studies. Here, newly hatched broilers were randomly divided into control and betaine consumptive groups, who had access to normal drinking water and water with betaine at a dose of 1000 mg/L, respectively. At the age of two weeks, the boilers were intraperitoneally treated with LPS. The protective effects of betaine against LPS-induced skeletal muscle inflammation were studied. Betaine attenuated the LPS-induced overexpression of IL-6 significantly in the leg muscle. Furthermore, LPS lowered the expression of TLR4 and TLR2 but increased the expression of MyD88. Betaine eliminated the effect of LPS on the expression of TLR4 but not TLR2 and MyD88. LPS also increased the expression of Tet methylcytosine dioxygenase 2 (Tet2), and this effect was also eliminated by betaine consumption. MeDIP-qPCR analysis showed that the methylation level in the promoter region of IL-6 was decreased by LPS treatment, whilst betaine cannot prevent this effect. On the contrary, LPS significantly increase the methylation level in the promoter region of TLR4, which was decreased by the consumption of betaine. Our findings suggest that betaine can alleviate LPS-induced muscle inflammation in chicken, and the regulation of aberrant DNA methylation might be a possible mechanism.

Qingqiao is a traditional Chinese medicine widely used for its heat-clearing, detoxifying, antibacterial, and anti-inflammatory properties. Due to these therapeutic effects, it has been commonly employed in the treatment of intestinal inflammatory disorders in China. This study aimed to investigate the therapeutic effects of Qingqiao polyphenols (QP) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and elucidate the underlying mechanisms, particularly the roles of NLRP3 and AIM2 inflammasomes in regulating pyroptosis. Using a DSS-induced murine UC model and an in vitro pyroptosis model in J774A.1 macrophages, we evaluated the protective effects of QP and explored its mechanisms of action. QP can significantly reduce the levels of inflammatory factors and oxidative stress in UC mice. Further investigation revealed that QP improve UC symptoms by inhibiting the NLRP3/AIM2 inflammasomes and pyroptosis. Consistent results were observed in in vitro experiments, where QP reduced lactate dehydrogenase (LDH) levels and pyroptosis occurrence in J774A.1 cells. Intriguingly, upon NLRP3 inhibition, we observed a compensatory upregulation of AIM2, accompanied by increased levels of GSDMD, IL-1β, and LDH release, suggesting that AIM2 may drive pyroptosis in the absence of NLRP3. Furthermore, AIM2 overexpression led to elevated GSDMD and IL-1β while significantly downregulating NLRP3 expression, indicating a competitive interaction between NLRP3 and AIM2 in pyroptotic signaling. We found that QP improve DSS-induced UC by inhibiting NLRP3/AIM2 inflammasome-mediated pyroptosis. Moreover, we uncovered a dynamic crosstalk between NLRP3 and AIM2, where compensatory mechanisms may sustain pyroptosis when one pathway is suppressed.

Background: This study systematically elucidates the mechanism by which Qingqiao polyphenols (QP) alleviate bacterial infectious lesions in poultry by regulating the pyroptosis signaling pathway. Methods: An Escherichia coli ( E. coli ) O157 infection model was established and evaluate the effect of QP on infected chickens. Results: Results showed QP significantly alleviated infection-induced systemic damage, manifested as improved pathological lesions in liver and lungs, and restored mucosal structures in duodenum, jejunum, and ileum. Further studies demonstrated that QP alleviates inflammatory damage in the liver, lungs, and intestines (duodenum, jejunum, ileum) of chickens induced by E. coli , by suppressing the pyroptosis signaling pathway. After gut microbial depletion by antibiotics, a lipopolysaccharide (LPS)-induced chicken enteritis model was used to evaluate whether QP can exert anti-inflammatory effects by inhibiting the pyroptosis pathway. The results demonstrated that QP effectively suppressed pyroptosis and alleviated LPS-induced intestinal inflammation, maintaining efficacy even under antibiotic depleted microbiota group conditions. This suggests that the anti-inflammatory effect of QP may be mediated by a pyroptosis pathway that is independent of the gut microbiota. Conclusion: This study confirms that QP exerts multi-organ protective effects against E. coli -induced inflammatory injury via a gut microbiota-independent pyroptosis-inhibitory mechanism, which provides a new theoretical basis for the application of QP as an antibiotic substitute in poultry bacterial disease prevention and control.