BACKGROUND: Ionizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection.
METHODS: Survival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle.
RESULTS: The survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP\'s potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs.
CONCLUSIONS: fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR\'s detrimental effects.

The intestine exhibits distinct characteristics along its length, with a substantial immune cell reservoir and diverse microbiota crucial for maintaining health. This study investigates how anatomical location and regional microbiota influence intestinal immune cell abundance. Using conventionally colonized and germ-free mice, segment-specific immune cell composition and microbial communities were assessed. Metagenomic sequencing analyzed microbiome variations, while flow cytometry and immunofluorescence examined immune cell composition. Microbiome composition varied significantly along the intestine, with diversity and abundance increasing from upper to lower segments. Immune cells showed distinct segment-specific patterning influenced by microbial colonization and localization. T cell subsets displayed varied dependence on microbiome presence and anatomical location. This study highlights locoregional differences in intestinal immune cell and microbiome composition, identifying immune subsets susceptible to microbiota presence. The findings provide context for understanding immune cell alterations in disease models.

This study aimed to examine whether dietary supplementation of broiler chickens with turmeric essential could mitigate the effects of cyclic heat stress conditions. Intestinal and immunological parameters and gene expression were evaluated during the grower phase. A total of 320 21-day-old male Cobb 500 broilers were distributed according to a completely randomized design with a 4 (diet) × 2 (environment) factorial arrangement and eight replications of five birds each. Dietary treatments consisted of a basal diet without essential oil (EO, negative control) and three diets containing low (100 mg kg-1), intermediate (200 mg kg-1), or high (300 mg kg-1) levels of turmeric EO. In the heat stress group, dietary supplementation with turmeric EO at 100 and 200 mg kg-1 improved body weight, feed conversion, breast yield, and relative liver weight. These supplementation levels reduced villus width, increased villus/crypt ratio, reduced the H/L ratio, and improved hepatic (HSP70 and SREBP1) and intestinal (OCLN) gene expression in birds under heat stress. These findings support the hypothesis that turmeric EO can be used to improve or restore intestinal integrity, modulate inflammation parameters, and, consequently, enhance the performance of broilers challenged by cyclic heat stress.

Oxidative stress is a major pathogenic factor in many intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). The Nrf2 signaling pathway and mitophagy can reduce reactive oxygen species (ROS) and alleviate oxidative stress, but their relationship is unclear. Hydroxytyrosol (HT), a polyphenolic compound abundant in olive oil, has strong antioxidant activity and may help treat these diseases. We used pigs as a model to investigate HT\'s effect on intestinal oxidative damage and its mechanisms. Diquat (DQ) induced oxidative stress and impaired intestinal barrier function, which HT mitigated. Mechanistic studies in IPEC-J2 cells showed that HT protected against oxidative damage by activating the PI3K/Akt-Nrf2 signaling pathway and promoting mitophagy. Our study highlighted the synergistic relationship between Nrf2 and mitophagy in mediating HT\'s antioxidant effects. Inhibition studies confirmed that disrupting either pathway compromised HT\'s protective effects. Maintaining redox balance through Nrf2 and mitophagy is important for eliminating excess ROS. Nrf2 increases antioxidant enzymes to clear existing ROS, while mitophagy removes damaged mitochondria and reduces ROS generation. This study demonstrates that these pathways collaboratively modulate the antioxidant effects of HT, with neither being dispensable. Targeting Nrf2 and mitophagy could be a promising strategy for treating oxidative stress-related intestinal diseases, with HT as a potential treatment.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage-CD90.2+NK1.1-NKp46-ST2-KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

Strains of the Bacillus cereus (Bc) group are sporulating bacteria commonly associated with foodborne outbreaks. Spores are dormant cells highly resistant to extreme conditions. Nevertheless, the pathological processes associated with the ingestion of either vegetative cells or spores remain poorly understood. Here, we demonstrate that while ingestion of vegetative bacteria leads to their rapid elimination from the intestine of Drosophila melanogaster, a single ingestion of spores leads to the persistence of bacteria for at least 10 days. We show that spores do not germinate in the anterior part of the intestine which bears the innate immune defenses. Consequently, spores reach the posterior intestine where they germinate and activate both the Imd and Toll immune pathways. Unexpectedly, this leads to the induction of amidases, which are negative regulators of the immune response, but not to antimicrobial peptides. Thereby, the local germination of spores in the posterior intestine dampens the immune signaling that in turn fosters the persistence of Bc bacteria. This study provides evidence for how Bc spores hijack the intestinal immune defenses allowing the localized birth of vegetative bacteria responsible for the digestive symptoms associated with foodborne illness outbreaks.

The intestine is the largest organ in terms of surface area in the human body. It is responsible not only for absorbing nutrients but also for protection against the external world. The gut microbiota is essential in maintaining a properly functioning intestinal barrier, primarily through producing its metabolites: short-chain fatty acids, bile acids, and tryptophan derivatives. Ethanol overconsumption poses a significant threat to intestinal health. Not only does it damage the intestinal epithelium, but, maybe foremostly, it changes the gut microbiome. Those ethanol-driven changes shift its metabolome, depriving the host of the protective effect the physiological gut microbiota has. This literature review discusses the impact of ethanol consumption on the gut, the gut microbiota, and its metabolome, providing a comprehensive overview of the mechanisms through which ethanol disrupts intestinal homeostasis and discussing potential avenues for new therapeutic intervention.

Prediction of intestinal drug absorption and drug-induced intestinal toxicity is critical for the development of orally-administered drugs. However, it is difficult to accurately predict these events because of large species differences and a lack of appropriate in vitro assay. Then, we proposed the use of human crypt-derived intestinal cells for the prediction of intestinal absorption and the risk of intestinal toxicity. 3D human intestinal spheroids were established from fresh surgical specimens of proximal jejunum and terminal ileum using the conditioned media containing Wnt3a, R-spondin 3, and noggin. To generate 2D monolayer, spheroids were enzymatically dissociated into single cells and plated onto Matrigel-precoated culture plates/inserts. We have confirmed the activities of typical drug-metabolizing enzymes and uptake/efflux transporters in human jejunal spheroid-derived differentiated cells. Intestinal availability (Fg) estimated from the apical-to-basal permeation clearance across the jejunal monolayer showed a good correlation with in vivo human Fg values for five CYP3A substrate drugs. As for the prediction of intestinal toxicity, we found that the degree of ATP decreases in intestinal spheroids incubated with different EGFR-TKIs varied greatly depending on the drugs and the rank order of the extent of ATP decrease corresponded with that of frequency of clinically-observed diarrhea. We also constructed enterochromaffin (EC) cell-rich spheroids and quantified serotonin release from EC cells upon exposure to drugs for the prediction of drug-induced nausea and vomiting. As a result, we found that the serotonin release was related to the high/low risk of nausea and vomiting of each ALK/ROS1 kinase inhibitors.

Fecal incontinence (FI) referred to the inability to control the leakage of solid, liquid, or gaseous feces, the artificial anal sphincter (AAS) was the last resort for patients with FI except enterostomy. In order to the clinical application value of AAS was improved, the detection and analysis of intestinal pressure information was very necessary. Biaxial actuated artificial anal sphincter (BAAS) was a new type of AAS, which not only had a stable, long-term and safe energy supply, but also could provide real-time feedback of intestinal pressure information. In this paper, the BAAS was implanted into piglets for a long-term animal experiment. Piglets\' life habits, defecation habits and intestinal pressure were analyzed. The analysis results showed that the BAAS system had good feces control effect, when the actuator of the BAAS system was closed, there was basically no fecal leakage of piglets, and when the actuator of the BAAS system was opened, the piglets could defecate normally. Under the normal condition of the piglets\' health state and the BAAS\'s operating state, the accuracy of the defecation perception reached to 65.79%. This study realized the in-depth study of the mechanism of piglets\' defecation, and provided guidance for the development of a new generation of AAS.

This work aimed to describe and quantify the tissue components of the digestive tube of the neotropical freshwater stingray, Potamotrygon wallacei. For this, conventional histology and stereological methods were used to estimate tissue volume. The volumes of the four fundamental layers and the tissue components in the stomach (cardiac and pyloric) and spiral intestine were also estimated. In the cardiac stomach, the mucosa layer occupies 44.7% of the total volume of the organ wall. The gastric glands are the main components, and these structures alone represent 49.7% of this layer. This large number of gastric glands suggests a high potential for processing food items with a high protein content. The stereological methods were sensitive enough to show a reduction in the volume of the gastric glands from the cardiac region toward the pyloric region. Gastric glands are absent in the pyloric region of the stomach. However, the muscularis becomes thicker towards the pyloric region. The increase in smooth muscle thickness is due to the thickening of the inner muscular layer. This suggests that the role of the pyloric stomach may be related to the mixing of the chyme and assisting its passage to the spiral intestine. In the spiral intestine, data on the volume of the mucosa layer (and epithelial lining) suggest that the spiral valve has a large absorptive area. In several respects, the morphology of the digestive tube of P. wallacei is similar to that of other batoids. However, its slight morphological variations may be related to the habitat specificity of this species.