Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.

To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.

NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.

We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.

These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.

• Necrotizing enterocolitis
• Autophagy
• Umbilical cord mesenchymal stem cell
• Exosomes
• Intestinal epithelial cell
• Intestinal barrier function

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.

To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.

NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.

We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.

These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.

• Necrotizing enterocolitis
• Autophagy
• Umbilical cord mesenchymal stem cell
• Exosomes
• Intestinal epithelial cell
• Intestinal barrier function

• Autophagy
• Biochemical characteristics
• Gastrointestinal diseases
• Morphological study
• Subcellular structure
• Transmission electron microscopy

• Humans
• Gastrointestinal Diseases
• Autophagy
• Microscopy, Electron, Transmission

• NLRP3 inflammasome
• deoxynivalenol
• enterotoxigenic Escherichia coli
• intestinal injury
• macroautophagy

• Animals
• Cell Line
• Enterotoxigenic Escherichia coli
• Escherichia coli Infections/microbiology
• Inflammasomes/genetics
• Inflammasomes/metabolism
• Inflammation/metabolism
• Intestinal Mucosa/metabolism
• Macroautophagy
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Swine
• Trichothecenes

Remifentanil (RFT), extensively used for general anesthesia, is a synthetic ultra-short-acting opioid used as an anti-inflammatory oxidant to alleviate a plethora of diseases. This study was designed to determine whether RFT would provide protective effects on sepsis-induced intestinal injury.The determination of cell viability and inflammation of LPS-treated IEC-6 cells influenced by RFT was conducted by Cell counting Kit-8 (CCK-8), RT-qPCR, and western blot, while the detection of LDH, diamine oxidase (DAO), and intestinal-type fatty acid binding proteins (I-FABP) was conducted for determining the intestinal cytotoxicity in these cells. The apoptosis of these cells was detected by TUNEL, with autophagy-related protein expression measured by western blot to confirm whether autophagy was activated. Finally, the aforementioned assays were conducted again after 3-Methyladenine (3-MA), an autophagy inhibitor, was used on these cells to investigate whether RFT exerted its effects on LPS-treated IEC-6 cells via modulation of autophagy.RFT alleviates LPS-induced IEC-6 cell inflammation, cytotoxicity and apoptosis, and autophagy-related proteins were expressed at higher levels when RFT was used on these cells. Nevertheless, further treatment of 3-MA weakened the restorative impacts of RFT on the inflammation, cytotoxicity and apoptosis of these cells.To conclude, this paper is the first to present evidence that RFT attenuates sepsis-induced intestinal injury by inducing autophagy, which will provide instructions for the future investigations into the use of RFT in treatment of intestinal injury.

• Remifentanil
• autophagy
• sepsis-induced intestinal injury

Lipopolysaccharide (LPS) is the key factor in various intestinal inflammation which could disrupt the epithelial barrier function. Deoxynivalenol (DON), a well-known mycotoxin, can induce intestinal injury. However, the combined enterotoxicity of LPS and DON has rarely been studied. In this study, IPEC-J2 cell monolayers were exposed to LPS and nontoxic-dose DON for 12 and 24 h to investigate the effects of DON on LPS-induced inflammatory response and tight junction variation, and specific inhibitor and CRISPR-Cas9 were used to explore the underlying mechanisms. Our results showed that nontoxic-dose DON aggravated LPS-induced cellular inflammatory response, reflecting on more significant changes of inflammatory cytokines mRNA expression, higher protein expression of NOD-like receptor protein 3 (NLRP3) and procaspase-1. Moreover, nontoxic-dose DON aggravated LPS-induced mRNA and protein expression decreased, and distribution confused of tight junction proteins. We found that DON further enhanced LPS-induced phosphorylation and nucleus translocation of p65, and expression of LC3B-Ⅱ. NF-κB inhibitor and CRISPR-Cas9-mediated knockout of LC3B attenuated the effects of combination which indicated nontoxic-dose DON aggravated LPS-induced intestinal inflammation and tight junction disorder through activating NF-κB signaling pathway and autophagy-related protein LC3B. It further warns that ingesting low doses of mycotoxins may exacerbate the effects of intestinal pathogens on the body.

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Nontoxic-dose DON aggravates LPS-induced cellular inflammatory response in IPEC-J2 cell monolayers.

• Deoxynivalenol
• Inflammation
• LC3B
• LPS
• NF-κB signaling pathway
• Tight junction

It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal injury was constructed in wild‐type and Deptor knockout (KO) mice. Haematoxylin‐eosin staining, Chiu's score and diamine oxidase were utilized to detect intestinal damage. RT‐qPCR assay was used to detected miR‐182 expression. Electronic microscopy was used to detect autophagosome. Western blot was applied to detect the expression of Deptor, S6/pS6, LC3‐II/LC3‐I and p62. Dual‐luciferase reporter assay was used to verify the relationship between miR‐182 and Deptor. The results showed miR‐182 was down‐regulated following intestinal I/R. Up‐regulation of miR‐182 reduced intestinal damage, autophagy, Deptor expression and enhanced mTOR activity following intestinal I/R. Moreover, suppression of autophagy reduced intestinal damage and inhibition of mTOR by rapamycin aggravated intestinal damage following intestinal I/R. Besides, damage of intestine was reduced and mTOR activity was enhanced in Deptor KO mice. In addition, Deptor was the target gene of miR‐182 and was indispensable for the protection of miR‐182 on intestine under I/R condition. Together, our research implicated up‐regulation of miR‐182 inhibited autophagy to alleviate intestinal I/R injury via mTOR by targeting Deptor.

• Deptor
• autophagy
• ischaemia reperfusion injury
• mTOR
• miR-182

The current climate changes have increased the prevalence and intensity of heat stress (HS) conditions. One of the initial consequences of HS is the impairment of the intestinal epithelial barrier integrity due to hyperthermia and hypoxia following blood repartition, which often results in a leaky gut followed by penetration and transfer of luminal antigens, endotoxins, and pathogenic bacteria. Under extreme conditions, HS may culminate in the onset of “heat stroke”, a potential lethal condition if remaining untreated. HS-induced alterations of the gastrointestinal epithelium, which is associated with a leaky gut, are due to cellular oxidative stress, disruption of intestinal integrity, and increased production of pro-inflammatory cytokines. This review summarizes the possible resilience mechanisms based on in vitro and in vivo data and the potential interventions with a group of nutritional supplements, which may increase the resilience to HS-induced intestinal integrity disruption and maintain intestinal homeostasis.

• heat stress (HS)
• intestinal integrity
• nutritional supplements
• reactive oxygen species (ROS)
• resilience pathways