Layer-by-layer nanoparticle encapsulating all-trans retinoic acid and CpG as a mucosal adjuvant targeting colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent cancers globally, demanding innovative therapeutic strategies. Immunotherapy, a promising avenue, employs cancer vaccines to activate the immune system against tumors. However, conventional approaches fall short of eliciting robust responses within the gastrointestinal (GI) tract, where CRC originates. Harnessing the potential of all-trans retinoic acid (ATRA) and cytosine-phosphorothioate-guanine (CpG), we developed layered nanoparticles using a layer-by-layer assembly method to co-deliver these agents. ATRA, crucial for gut immunity, was efficiently encapsulated alongside CpG within these nanoparticles. Administering these ATRA@CpG-NPs, combined with ovalbumin peptide (OVA), effectively inhibited orthotopic CRC growth in mice. Our approach leveraged the inherent benefits of ATRA and CpG, demonstrating superior efficacy in activating dendritic cells, imprinting T cells with gut-homing receptors, and inhibiting tumor growth. This mucosal adjuvant presents a promising strategy for CRC immunotherapy, showcasing the potential for targeting gut-associated immune responses in combating colorectal malignancies.

Effects of Dietary Glucose Oxidase Supplementation on the Performance, Apparent Ileal Amino Acids Digestibility, and Ileal Microbiota of Broiler Chickens.

This study aimed to investigate the effects of glucose oxidase (GOD) supplementation on growth performance, apparent ileal digestibility (AID) of nutrients, intestinal morphology, and short-chain fatty acids (SCFAs) and microbiota in the ileum of broilers. Six hundred 1-day-old male broilers were randomly allotted to four groups of 10 replicates each with 15 birds per replicate cage. The four treatments included the basal diet without antibiotics (Control) and the basal diet supplemented with 250, 500, or 1000 U GOD/kg diet (E250, E500 or E1000). The samples of different intestinal segments, ileal mucosa, and ileal digesta were collected on d 42. Dietary GOD supplementation did not affect daily bodyweight gain (DBWG) and the ratio of feed consumption and bodyweight gain (FCR) during d 1-21 (p > 0.05); however, the E250 treatment increased DBWG (p = 0.03) during d 22-42 as compared to control. Dietary GOD supplementation increased the AIDs of arginine, isoleucine, lysine, methionine, threonine, cysteine, serine, and tyrosine (p < 0.05), while no significant difference was observed among the GOD added groups. The E250 treatment increased the villus height of the jejunum and ileum. The concentrations of secreted immunoglobulin A (sIgA) in ileal mucosa and the contents of acetic acid and butyric acid in ileal digesta were higher in the E250 group than in the control (p < 0.05), whereas no significant differences among E500, E1000, and control groups. The E250 treatment increased the richness of ileal microbiota, but E500 and E100 treatment did not significantly affect it. Dietary E250 treatment increased the relative abundance of Firmicutes phylum and Lactobacillus genus, while it decreased the relative abundance of genus Escherichina-Shigella (p < 0.05). Phylum Fusobacteria only colonized in the ileal digesta of E500 treated broilers and E500 and E1000 did not affect the relative abundance of Firmicutes phylum and Lactobacillus and Escherichina-Shigella genera as compared to control. These results suggested that dietary supplementation of 250 U GOD/kg diet improves the growth performance of broilers during d 22-42, which might be associated with the alteration of the intestinal morphology, SCFAs composition, and ileal microbiota composition.