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Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly (P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin, claudin1, and claudin2. However, pretreatment with CS-GT significantly increased (P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4. In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo. This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury. [Display omitted] [ABSTRACT FROM AUTHOR]

The mechanism underlying the intestinal transport of COS is not well understood. Here, transcriptome and proteome analyses were performed to identify potential critical molecules involved in COS transport. Enrichment analyses revealed that the differentially expressed genes in the duodenum of the COS-treated mice were mainly enriched in transmembrane and immune function. In particular, B2 m, Itgb2, and Slc9a1 were upregulated. The Slc9a1 inhibitor decreased the transport efficiency of COS both in MODE-K cells (in vitro) and in mice (in vivo). The transport of FITC-COS in Slc9a1-overexpressing MODE-K cells was significantly higher than that in empty vector-transfected cells (P < 0.01). Molecular docking analysis revealed the possibility of stable binding between COS and Slc9a1 through hydrogen bonding. This finding indicates that Slc9a1 plays a crucial role in COS transport in mice. This provides valuable insights for improving the absorption efficiency of COS as a drug adjuvant. [Display omitted] [ABSTRACT FROM AUTHOR]