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The gut microbiota plays an important role in intestinal immune system development and in driving inflammation. Antibiotic administration for therapeutic purposes causes an imbalance in the gut microbiota. Antimicrobial peptides can regulate the gut microbiota and maintain intestinal homeostasis. The aim of this study was to investigate the anti-inflammatory effects and regulation of the gut microbiota by the orally administered antimicrobial peptide mastoparan X (MPX). In this study, Escherichia coli was used to induce intestinal inflammation, and the results showed that MPX+ E. coli alleviated weight loss and intestinal pathological changes in necropsy specimens of E. coli–infected mice. MPX+ E. coli reduced the serum levels of the inflammation-related proteins interleukin-2, interleukin-6, tumour necrosis factor-α, myeloperoxidase, and lactate dehydrogenase on days 7 and 28. Furthermore, MPX+ E. coli increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum and colon post infection. Scanning electron microscopy and transmission electron microscopy results showed that MPX could improve the morphology of jejunum villi and microvilli and increase tight junction protein levels. 16S rRNA sequencing analysis of caecal content samples showed that the species diversity and richness were lower in the E. coli–infected group. At the genus level, MPX+ E. coli significantly reduced the abundance of Bacteroidales and Alistipes and enhanced the relative abundance of Muribaculaceae. Alpha-diversity analyses (Shannon index) showed that MPX significantly increased the microbial diversity of mice. Overall, this study is the first to investigate the effects of oral administration of MPX on intestinal inflammation and the gut microbiota, providing a new perspective regarding the prevention of enteritis and maintenance of intestinal homeostasis. [ABSTRACT FROM AUTHOR]

Halofuginone (HF) is an extract from the widely used traditional Chinese medicine (TCM) Dichroa febrifuga that facilitates the recovery of wounds and attenuates hepatic fibrosis. However, the role of HF in the epithelial-mesenchymal transition (EMT) of IPEC-J2 cells remains unclear. The current study explored the anti-EMT effect of HF in IPEC-J2 cells and illustrates its molecular mechanism. Transforming growth factor β1 (TGF-β1), as a recognized profibrogenic cytokine, decreased the level of the epithelial marker E-cadherin and increased the level of the mesenchymal markers, such as N-cadherin, fibronectin (FN), vimentin (Vim), and α-smooth muscle actin (α-SMA), in IPEC-J2 cells depending on the exposure time and dose. HF markedly prevented the EMT induced by TGF-β1. Dissection of the mechanism revealed that HF inhibited IPEC-J2 cell EMT via modulating the phosphorylation of SMAD2/3 and the SMAD2/3-SMAD4 complex nuclear translocation. Furthermore, HF could promote the phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which modulates the SMAD signaling pathway. These results suggested that HF inhibits TGF-β1-induced EMT in IPEC-J2 cells through the eIF2α/SMAD signaling pathway. Our findings suggest that HF can serve as a potential anti-EMT agent in intestinal fibrosis therapy. [ABSTRACT FROM AUTHOR]

Salmonella is an important zoonotic pathogen and is a major cause of gastrointestinal diseases worldwide. The current serious problem of antibiotic abuse has prompted the search for new substitutes for antibiotics. JH-3 is a small antimicrobial peptide with broad-spectrum bactericidal activity. In this study, we showed that JH-3 has good bactericidal activity towards the clinical isolate Salmonella enterica serovar Typhimurium strain CVCC541. The minimum inhibitory concentration (MIC) of JH-3 against this bacterium was determined to be 100 μg/mL, which could decrease the number of CVCC541 cells by 1000-fold in vitro within 5 h. The transmission electron microscopy (TEM) results showed that JH-3 can damage the cell wall and membrane of CVCC541, leading to the leakage of cell contents and subsequent cell death. To measure the bactericidal activity of CVCC541-infected mice were treated intraperitoneally 40 or 10 mg/kg JH-3 at 2 h or 3 days postinfection. Our results showed that treatment with 40 mg/kg JH-3 at 2 h postinfection had the best therapeutic effect and could significantly protect mice from a lethal dose of CVCC541. Furthermore, the clinical symptoms, bacterial burden in blood and organs, and intestinal pathological changes were all decreased and were close to normal. This study examined the therapeutic effect of the antimicrobial peptide JH-3 against S. enterica CVCC541 infection for the first time and determined the therapeutic effect of different JH-3 doses and treatment times, laying the foundation for studies of new antimicrobial agents. [ABSTRACT FROM AUTHOR]