Baohong Yuan

Inflammatory bowel disease (IBD) represents a growing global health threat that markedly increases colorectal cancer risk, yet conventional immunosuppressive agents achieve mucosal healing in only a limited subset of patients. M2-polarized macrophages have been recognized as crucial regulators of mucosal repair through their ability to maintain intestinal microenvironment homeostasis. Here, we investigated the potential effects and mechanisms of macrophage-derived exosomes (Exos) on epithelial barrier function in a murine model of IBD. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by treatment with Exos isolated from IL-33-treated macrophages (IL-33-Exos) or untreated macrophages (PBS-Exos). Our findings showed that IL-33-Exos markedly ameliorated inflammatory intestinal mucosal injury and improved intestinal barrier dysfunction. Concurrently, IL-33-Exos mitigated intestinal epithelial cell damage, thereby preserving intestinal mucosal integrity. Mechanistic studies revealed that the beneficial effects of IL-33-Exos were implicated in upregulation of Wnt/β-catenin signaling in intestinal epithelial cells. Translationally, these findings suggest that IL-33-Exos may promote epithelial repair in experimental colitis, offering a novel therapeutic avenue for clinical management of inflammatory bowel disease.

Clostridium perfringens is the etiological agent for necrotic enteritis (NE) in broiler chickens, which causes a substantial economic loss of an estimated USD 6 billion annually in the global poultry industry. Collagen adhesion is involved in the NE pathogenesis in poultry. In this study, the binding capabilities of chicken C. perfringens isolates of various genetic backgrounds (netB⁻tpeL⁻, netB⁺tpeL⁻, netB⁺tpeL⁺) to collagen types I–V and gelatin were examined, and the putative adhesin protein cnaA gene was investigated at the genomic level. In total, 28 C. perfringens strains from healthy and NE-inflicted sick chickens were examined. The results on collagen adhesin-encoding gene cnaA by the quantitative-PCR results indicated that netB⁻tpeL⁻ isolates had much lower copies of the detectable cnaA gene than netB⁺ isolates (10 netB⁺tpeL⁻ isolates, 5 netB⁺tpeL⁺ isolates). Most of the virulent C. perfringens isolates demonstrated collagen-binding abilities to types I–II and IV–V, while some strains showed weak or no binding to collagen type III and gelatin. However, the netB⁺tpeL⁺ isolates showed significantly higher binding capabilities to collagen III than netB⁻tpeL⁻ and netB⁺tpeL⁻ isolates. The data in this study suggest that the collagen-binding capability of clinical C. perfringens isolates correlates well with their NE pathogenicity levels, especially for C. perfringens isolates carrying genes encoding crucial virulence factors and virulence-associated factors such as netB, cnaA, and tpeL. These results indicate that the presence of the cnaA gene may be correlated with C. perfringens virulence (particularly for netB⁺ isolates).

Necrotic enteritis (NE) is a multifactorial and important enteric infectious disease etiologically caused by pathogenic C. perfringens infection, accounting for the estimated loss of around USD 6 billion in the global poultry industry. The increasing incidence of NE was found to be associated with the voluntary reduction or withdrawal of antibiotic growth promoters from animal feed during recent years. Therefore, the development of effective vaccines specific to NE assumes a priority for the poultry industry. This study aimed to identify the potential C. perfringens proteins as vaccine targets for NE. Three recombinant C. perfringens proteins targeting five antigens were prepared: two chimeric proteins (alpha-toxin and NetB, fructose-1,6-bisphosphate aldolase (FBA) and a zinc metalloprotease (Zm)), and one single collagen adhesion protein (Cna). Their protection efficacies were evaluated with a potent challenge model of Eimeria maxima/C. perfringens dual infections using a netB⁺tpeL⁺ C. perfringens strain. Young chicks were immunized twice subcutaneously with adjuvanted C. perfringens proteins on Days 4 and 15. At six days after the second immunization, the chickens immunized with Cna, FBA, and Zm antigens, and alpha-toxin had much higher serum antibody titers than unvaccinated controls prior to the challenge. Following the challenge, the pooled antigen-immunized group demonstrated no mortality and the least lesion scores against virulent challenge. The results indicate that the immunization with multicomponent antigens, including C. perfringens housekeeping protein Cna, may confer partial protection.

Clostridium perfringens is an important opportunistic pathogen that may result in toxin-mediated diseases involving food poisoning/tissue gangrene in humans and various enterotoxaemia in animal species. It is a main etiological agent for necrotic enteritis (NE), the most financially devastating bacterial disease in broiler chickens, especially if raised under antibiotic-free conditions. Importantly, NE is responsible for losses of six billion US dollars annually in the global poultry industry. To investigate the molecular mechanisms of C. perfringens-induced pathogenesis in the gut and its microbiome mRNA levels in C. perfringens-infected and non-infected hosts, we used RNA sequencing technology to perform transcriptional analysis of both host intestine and microbiome using our NE model. The growth rate was significantly impaired in chickens infected by C. perfringens. In total, 13,473 annotated chicken genes were differentially expressed between these two groups, with ninety-six genes showing statistical significance (|absolute fold changes| > 2.0, adjusted p value < 0.05). Genes involved in energy production, MHC Class I antigen, translation, ribosomal structures, and amino acid, nucleotide and carbohydrate metabolism from infected gut tissues were significantly down-regulated. The upregulated genes were mainly engaged in innate and adaptive immunity, cellular processes, genetic information processing, and organismal systems. Additionally, the transcriptional levels of four crucial foodborne pathogens were significantly elevated in a synergic relationship with pathogenic C. perfringens infection. This study presents the profiling data that would likely be a relevant reference for NE pathogenesis and may provide new insights into the mechanism of host-pathogen interaction in C. perfringens-induced NE infection in broiler chickens.

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy.