Intestinal Injury Research Articles

Pectolinarigenin mitigates 5-FU-induced intestinal mucositis via suppressing ferroptosis through activating PPARγ/GPX4 signaling.

Pectolinarigenin mitigates 5-FU-induced intestinal mucositis via suppressing ferroptosis through activating PPARγ/GPX4 signaling.

Selenium-enriched Kazachstania unispora KU2 ameliorates patulin-induced intestinal injury in mice by mediating the gut microbiota and selenoprotein P synthesis.

Selenium-enriched Kazachstania unispora KU2 ameliorates patulin-induced intestinal injury in mice by mediating the gut microbiota and selenoprotein P synthesis.

Wheat bran supplementation improved polystyrene degradation efficiency of Zophobas atratus larvae by alleviating intestinal injury caused by polystyrene-intake.

Wheat bran supplementation improved polystyrene degradation efficiency of Zophobas atratus larvae by alleviating intestinal injury caused by polystyrene-intake.

Impact of sodium butyrate on stroke-related intestinal injury in diabetic mice: Interference with Caspase-1/GSDMD pyroptosis pathway and preservation of intestinal barrier.

Impact of sodium butyrate on stroke-related intestinal injury in diabetic mice: Interference with Caspase-1/GSDMD pyroptosis pathway and preservation of intestinal barrier.

Hyperoside improves intestinal mucosal immunity against zearalenone-induced intestinal barrier damage by regulating intestinal flora.

Hyperoside improves intestinal mucosal immunity against zearalenone-induced intestinal barrier damage by regulating intestinal flora.

Cortex Dictamni induces cholestatic liver injury via the bile acid-gut-liver axis mediated by FXR signaling pathway in rats.

Cortex Dictamni induces cholestatic liver injury via the bile acid-gut-liver axis mediated by FXR signaling pathway in rats.

Huangqin decoction alleviates chemotherapy-induced intestinal injury by inhibiting ferroptosis via modulation of P53/SLC7A11/GPX4 pathway.

Huangqin decoction alleviates chemotherapy-induced intestinal injury by inhibiting ferroptosis via modulation of P53/SLC7A11/GPX4 pathway.

Polyphyllin Ⅵ modulates macrophage polarization through autophagy-NLRP3 inflammasome to alleviate inflammatory bowel disease.

Polyphyllin Ⅵ modulates macrophage polarization through autophagy-NLRP3 inflammasome to alleviate inflammatory bowel disease.

Qingshu Yiqi decoction ameliorates exertional heat stroke-induced intestinal barrier injury via NF-κB/MLC pathway and gut microbiota.

Qingshu Yiqi decoction ameliorates exertional heat stroke-induced intestinal barrier injury via NF-κB/MLC pathway and gut microbiota.

The Effects of Prebiotic Supplementation on Markers of Exercise-Induced Gastrointestinal Syndrome in Response to Exertional Heat Stress.

Exercise perturbs various aspects of gastrointestinal integrity and function, which may lead to performance impeding gastrointestinal symptoms (GIS) and/or precipitate clinical issues warranting medical management. This study aimed to determine the impact of prebiotic supplementation on gastrointestinal integrity and functional status in response to exertional heat stress (EHS). Sixteen endurance athletes completed two trials of 3-hr running at 60% V˙O2max in 30°C at baseline (T1) and following an 8-week supplementation period (T2), with 16g/day prebiotic (PREBIOTIC) or matched placebo (PLACEBO). Blood samples were collected pre-EHS and post-EHS and in recovery for determination of stress response (cortisol), intestinal epithelial injury (intestinal fatty acid binding protein), bacterial endotoxemia (sCD14), and systemic inflammation (C-reactive protein). GIS and feeding tolerance variables were assessed throughout the EHS. Orocecal transit time was determined via a lactulose challenge given at 2.5hr into EHS. Plasma cortisol (combined mean: +252ng/ml), intestinal fatty acid binding protein (+800pg/ml), and sCD14 (+487ng/ml) concentrations increased in response to EHS in T1 (p ≤ .05), but not for C-reactive protein (+0.8μg/ml; p > .05), in both PREBIOTIC and PLACEBO. PREBIOTIC supplementation resulted in a blunted intestinal fatty acid binding protein response on T2 (+316pg/ml) compared with an increase (+1,001ng/ml) in PLACEBO (p = .005). Lower sCD14 was observed at T2 (2,799ng/ml) versus T1 (3,246ng/ml) in PREBIOTIC only (p = .039). No intervention effects were observed for C-reactive protein. No difference within or between PREBIOTIC and PLACEBO at T1 and T2 was observed for orocecal transit time, GIS, and feeding tolerance. In conclusion, 8 weeks of prebiotic supplementation modestly attenuates EHS associated perturbations to intestinal integrity, but does not further impair gastrointestinal transit and/or exacerbate EHS associated GIS or feeding tolerance.

Phloretin supplementation ameliorates intestinal injury of broilers with necrotic enteritis by alleviating inflammation, enhancing antioxidant capacity, regulating intestinal microbiota, and producing plant secondary metabolites.

Phloretin supplementation ameliorates intestinal injury of broilers with necrotic enteritis by alleviating inflammation, enhancing antioxidant capacity, regulating intestinal microbiota, and producing plant secondary metabolites.

Comprehensive review of ecological risks and toxicity mechanisms of microplastics in freshwater: Focus on zebrafish as a model organism.

Comprehensive review of ecological risks and toxicity mechanisms of microplastics in freshwater: Focus on zebrafish as a model organism.

Zhi-Zi-chi decoction: A promising remedy for liver inflammation via gut microbiota modulation.

Zhi-Zi-chi decoction: A promising remedy for liver inflammation via gut microbiota modulation.

Sodium/hydrogen exchanger 8 affects sheet migration of human intestinal epithelial cells (HT29MTX) by influencing the actin cytoskeletal rearrangement.

The gastrointestinal Na+/H+ transporter 8 (NHE8) is downregulated in the mucosa of patients with ulcerative colitis, and its deletion in the murine intestine causes a "colitis-like" phenotype. Since ulcerative colitis is characterized by repeated mucosal injury, we investigated the role of NHE8 in intestinal wound repair, by accessing its effect on intracellular pH (pHi) regulation, cell proliferation, and migration. NHE8 expression was downregulated via shRNA lentiviral transduction in HT29MTX cells. The selected clonal cell line (HT29/shNHE8) with ∼80% reduced NHE8 mRNA expression displayed an increased proliferative but reduced migratory rate compared with the mock-transduced cells (HT29/pLKO1). The wound front of the HT29/shNHE8 cells consisted of both migrating and nonmigrating cells, and pHi measured in this segment displayed the following values: pHi(HT29/pLKO.1) = 7.35, pHi(HT29/shNHE8migrating) = 7.27, and pHi(HT29/shNHE8nonmigrating) = 7.1. The migrating HT29/shNHE8 cells exhibited a significantly increased NHE activity compared with migrating mock-transfected and nonmigrating cells, which was abolished by pharmacological NHE3 inhibition. NHE3 localized to the wound front of HT29/shNHE8, but not to that of HT29/pLKO.1 cells. Cell flattening and lamellipodia development were observed at the wound front in HT29/pLKO.1 cells, whereas the HT29/shNHE8 cells formed tight actin bundles and retained their apical-basal architecture. RAC1 and Cofilin-1, required for the generation of actin-based membrane protrusions, were absent at the wound front of HT29/shNHE8 cells but were expressed in migrating HT29/pLKO.1 cells, where RAC1 partially colocalized with NHE8. The results show that NHE8 downregulation reduces the pHi and leads to enhanced epithelial cell proliferation, but impairs migration likely due to altered actin polymerization.NEW & NOTEWORTHY The Na+/H+ exchanger 8 (NHE8) plays an important role in the regulation of intracellular pHi, cell proliferation, and epithelial sheet migration in HT29MTX intestinal cells. NHE8 knockdown cells lack the ability to dynamically rearrange the actin cytoskeleton at the wound front, resulting in a reduced migration rate. These observations provide insights into the molecular mechanism of the downregulation of this transporter in human ulcerative colitis and its role in epithelial restitution.

Intestinal NF-κB pathway-mediated pyroptosis contributes to endotoxemia-induced intestinal injury.

Pyroptosis contributes to activation of the innate immunity system and defense against infection by pathogens. Endotoxemia is the host inflammatory storm occurring in response to severe and life-threatening infections caused by endotoxin from gram-negative bacilli. However, whether pyroptosis is involved in intestinal epithelial cell (IEC) or intestinal stem cell (ISC) injury induced by endotoxemia remains unclear. Mice with NF-κB p65 deletion in IECs (p65IEC - KO) were used to investigate the role of NF-κB-mediated pyroptosis in endotoxemia-induced intestinal injury. Morphology, pyroptosis, permeability, inflammation, endoplasmic reticulum stress in the intestine and survival were evaluated in WT and p65IEC - KO mice. Pyroptosis was found in intestinal epithelial cells of mice treated with lipopolysaccharide (LPS), but was significantly reduced in p65IEC - KO mice. Mice with endotoxemia exhibited morphological alterations in intestinal tissue, with a shortened villus length and crypt depth, increased intestinal permeability, increased inflammatory factors, and reduced survival rate, all of which were markedly improved in p65IEC - KO mice. Importantly, ER stress was found to be downregulated in IECs of p65IEC - KO mice with endotoxemia. Furthermore, the ER stress activator tunicamycin markedly enhanced IEC pyroptosis and aggravated intestinal injury in p65IEC - KO mice with endotoxemia. NF-κB p65-mediated pyroptosis participates in IEC injury in response to endotoxemia via regulation of ER stress. It may provide a potential therapeutic target for protecting against endotoxemia-induced intestinal injury.

Fecal Microbiota Transplantation Modulates Th17/Treg Balance via JAK/STAT Pathway in ARDS Rats.

This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.

Mitochondrial alanyl-tRNA synthetase 2 mediates histone lactylation to promote ferroptosis in intestinal ischemia-reperfusion injury.

Ferroptosis is a newly recognized form of regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species. It has been extensively studied in various diseases, including cancer, Parkinson's disease, and stroke. However, its precise role and underlying mechanisms in ischemia/ reperfusion injury, particularly in the intestinal ischemia-reperfusion (IIR), remain unclear. In current work, we aimed to investigate the participation of histone lactylation during IIR progression. To investigate the role of mitochondrial alanyl-tRNA synthetase 2 (AARS2) in ferroptosis and its epigenetic regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) through histone lactylation during IIR injury. We established a mouse model to mimic IIR and conducted AARS2 knockdown as treatment. The expression of AARS2 in intestinal tissues was measured by western blot. The integrity of intestinal tissues was detected by hematoxylin and eosin staining, serum fatty acid-binding protein, protein levels of ZO-1 and occluding. An in vitro hypoxia-reperfusion (H/R) cell model was established, and cell viability was measured by CCK-8. The in vitro and in vivo ferroptosis was determined by the accumulation of Fe2+ and malondialdehyde (MDA). The epigenetic regulation of ACSL4 by AARS2 was detected by chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay. We observed a notable elevated AARS2 level in intestinal tissue of mice in IIR model group, which was reversed by shAARS2 treatment. Knockdown of AARS2 repressed alleviated intestinal barrier disruption and repressed the accumulation of ferroptosis biomarker Fe2+ and MDA during IIR. The in vitro results showed that shAARS2 alleviated impaired cell viability caused by H/R, as well as repressed ferroptosis. Knockdown of AARS2 notably downregulated the RNA and protein expression of ACSL4. Mechanistically, knockdown of AARS2 downregulated the enrichment of H3K18 La modification on AARS2, as well as suppressed its promoter activity. Overexpression of AARS2 could abolish the protective effects of shACSL4 in vitro. The elevation of AARS2 during IIR led to cell ferroptosis via epigenetically upregulating the expression of ACSL4. Our findings presented AARS2 as a promising therapeutic target for IIR.

Intestinal microplastic debris, flora dysbiosis, and insidious combined hazards across diverse aquatic and terrestrial organisms.

Intestinal microplastic debris, flora dysbiosis, and insidious combined hazards across diverse aquatic and terrestrial organisms.

The Role of TLR4 in the Intestinal Barrier and Its Relationship With Nanoparticle-Induced Intestinal Injury.

In recent years, the increasing application of nanomaterials in the medical, food additives, and drug delivery fields is attributed to their unique physical and chemical properties, particularly their significant potential in drug delivery, disease diagnosis, and treatment. As a critical immune organ and barrier in the human body, the intestine plays a vital role in defending against harmful external factors. Toll-like receptor 4 (TLR4) expressed on intestinal cells is essential for maintaining intestinal barrier function and modulating immune responses. Studies have indicated that nanoparticles (NPs) can directly interact with intestinal cells upon entering the intestine, stimulating the TLR4 signaling pathway and initiating a cascade of biological reactions, including inflammation, autophagy, and immune dysregulation. Aberrant activation of TLR4 exacerbates the disruption of the intestinal microenvironment, potentially contributing to systemic inflammatory diseases. This process involves mechanisms such as the secretion of pro-inflammatory factors and recruitment of immune cells, ultimately resulting in intricate toxic effects, including impairment of intestinal barrier function. However, current research predominantly focuses on canonical TLR4 signaling, yet key NPs-specific molecular mechanisms remain poorly understood at the single-cell level. However, despite numerous studies on NPs-TLR4 interactions, the lack of systematic summaries and in-depth analysis has led to unclear mechanisms and conflicting findings. This review aims to comprehensively examine the regulatory effects of NPs on the TLR4 signaling pathway and investigate their toxicological implications on intestinal barrier dysfunction. The objective is to offer novel insights and theoretical foundations for future research on the mechanisms underlying NP-induced intestinal injury.

Targeting TREM1 Ameliorates Necrotizing Enterocolitis in Neonatal Mice by Inhibiting Endoplasmic Reticulum Stress and Regulating Macrophage Polarization.

This study aims to investigate the role of TREM1 in necrotizing enterocolitis (NEC). A mouse model of NEC was established through artificial feeding combined with hypoxia-cold stress. Intestinal injury was assessed via H&E staining. Inflammatory cytokines were measured by ELISA, and reactive oxygen species (ROS) activity was evaluated using DHE staining. Intestinal permeability was determined by the fluorescein-isothiocyanate-dextran (FITC-dextran) method. Tight junction proteins were analyzed through immunohistochemistry and western blotting. The expression of CD86 and CD206 in M1 and M2 macrophages was assessed by immunofluorescence, and the mRNA levels of M1 and M2 markers (CD86, iNOS, CD206, and Arg-1) were detected by RT-qPCR. Proteins involved in ER stress were analyzed using western blotting. Inhibition of TREM1 was found to reduce intestinal injury, inflammation, and oxidative stress, improve intestinal barrier function, suppress M1 macrophage polarization, and attenuate ER stress in NEC mice. Moreover, we found that treatment with the ER stress inducer tunicamycin reversed these protective effects of TREM1 inhibition. TREM1 inhibition protects against intestinal injury, inflammation, oxidative stress, intestinal barrier damage, and M1 macrophage polarization in NEC mice by suppressing ER stress.