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Intestinal ischemia-reperfusion (IIR) injury is caused by the restoration of blood supply after a period of ischemia. It occurs in numerous clinical pathologies, such as intestinal obstruction, incarcerated hernia and septic shock, with mortality rates of 50-80%. Honokiol (HKL), isolated from the herb Magnolia officinalis, is a biphenolic natural product with antioxidative, antibacterial, antitumor and anti-inflammatory properties. Additionally, HKL has protective effects in ischemia-reperfusion injuries, but its role and specific mechanisms in IIR injury are yet to be elucidated. In the present study, the superior mesenteric artery was ligated in rats to establish an IIR model. Hematoxylin and eosin staining and ELISA revealed that HKL administration ameliorated IIR-induced injury in rats, which was demonstrated by a reduced destruction to the intestinal mucosa, as well as a reduced serum intestinal fatty acid-binding protein concentration and Chiu's score in 10 mg/kg HKL treated IIR-induced rats compared with those without HKL treatment. Additionally, immunohistochemical (IHC) staining and western blotting revealed that the occludin and tight junction protein 1 protein levels were increased in the 10 mg/kg HKL treated IIR-induced rats compared with those without HKL treatment. Furthermore, an in vitro hypoxia/reoxygenation (H/R) cell model was established using IEC-6 cells. Cell Counting Kit-8 and lactate dehydrogenase (LDH) assays indicated that HKL mitigated the H/R-inhibited cell viability and decreased the LDH levels in cell supernatants. Mechanistically, immunofluorescent (IF) staining and western blotting revealed that HKL inhibited H/R-triggered pyroptosis. Furthermore, Mito-Tracker, mitochondrial membrane potential and MitoSOX staining as well as western blotting revealed that reducing mitochondrial reactive oxygen species (ROS) inhibited the H/R-induced pyroptosis by mitigating mitochondrial dysfunction. In the present H/R cell model, HKL improved the mitochondrial function by increasing the expression of sirtuin 3 (SIRT3), while IF staining and western blotting indicated that silencing SIRT3 notably reduced the beneficial effect of HKL on pyroptosis. In addition, IHC staining and western blotting revealed that HKL treatment mitigated the IIR-induced pyroptosis in rats. Therefore, HKL treatment may mitigate IIR-induced mitochondrial dysfunction and reduce mitochondrial ROS production by increasing the expression of SIRT3 protein, potentially resulting in an inhibition of pyroptosis during IIR.

Background Lactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus ( L. murinus )-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus -derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism. Methods Liquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids. Results By comparing the fecal contents of three L. murinus -derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury. Conclusions The content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.

Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.

Intestinal ischemia-reperfusion (II/R) injury is a common perioperative complication that occurs during severe infections, trauma, and multiple surgical procedures. II/R not only leads to localized intestinal damage but also disrupts the intestinal mucosal barrier, inducing systemic inflammatory responses and multi-organ failure, especially acute lung injury (ALI). The mechanisms are complex, involving multiple pathological processes such as oxidative stress, systemic inflammatory response, apoptosis, autophagy, and ferroptosis. During II/R, the large amount of reactive oxygen species and inflammatory factors produced rapidly activates immune cells and destroys the alveolar barrier, leading to pulmonary edema and hypoxemia, and in severe cases, acute respiratory distress syndrome (ARDS) may develop, ultimately causing respiratory failure. Current treatments include anti-inflammatory, antioxidant and anti-apoptotic drugs, as well as surgical interventions and traditional Chinese medicine. However, these methods have high drug toxicity and limited efficacy. With the development of nanomedicine, new strategies have emerged for the treatment of II/R-ALI. Nanomedicines, owing to their excellent bioavailability and targeting capabilities, can significantly enhance therapeutic outcomes and reduce side effects. This review summarizes the major mechanisms underlying II/R-ALI and discusses recent advances in the application of nanomaterials for its treatment.

The relationship between immune-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) and intestinal necrosis in different types of acute intestinal ischemia remains unclear. A total of 138 patients with acute intestinal ischemia were divided into a nonnecrosis group (  = 65) and a necrosis group (  = 73). Least absolute shrinkage and selection operator (Lasso)-logistic regression model was used to identify independent risk factors for intestinal necrosis. Multivariate logistic regression was conducted to assess the associations between NLR and SII levels and intestinal necrosis. Sensitivity analyses were performed using smooth curve fitting, threshold effect analysis, subgroup analysis, and propensity score matching (PSM). . The optimal thresholds of NLR and SII for differentiating intestinal necrosis were 8.85 and 1492.11, respectively, while PLR showed no significant association. In Lasso-logistic regression analysis, vascular intestinal ischemia, NLR ≥ 8.85, SII≥ 1492.11, C-reactive protein (CRP), and D-dimer > 0.5 mg/L were independent risk factors for intestinal necrosis. After adjusting for potential confounding variables, the multivariate logistic regression analysis showed a positive correlation between natural logarithm (Ln)-NLR (OR = 20.187, 95% CI = 3.788-107.578,   < 0.001) and Ln-SII (OR = 5.375, 95% CI = 1.141-25.313,   < 0.033) and intestinal necrosis. Subgroup analysis showed a significant interaction between NLR, intestinal necrosis, and coronary heart disease ( interaction = 0.016). Smooth curve fitting indicated the relationship between Ln-NLR and Ln-SII and intestinal necrosis was nonlinear, with inflection points at 1.78 (NLR = 5.93) and 7.32 (SII = 1510.20), respectively. When NLR > 5.93 or SII < 1510.20, the risk of intestinal necrosis significantly increased. The associations remained robust after PSM. This study demonstrates that elevated levels of NLR and SII are significantly associated with intestinal necrosis, suggesting that these biomarkers may help identify patients at higher risk of intestinal necrosis in acute intestinal ischemia. However, prospective studies are needed to validate their predictive value.

Intestinal pneumatosis (IP) is an infrequent radiological sign defined as pathological gas infiltration into the bowel wall. It may be associated to different underlying clinical conditions—inflammatory bowel diseases, malignancies, chemotherapy, infections, immune deficiency status, trauma, intestinal ischemia, and necrosis—that are often related to emergency state and require a prompt diagnosis. All the imaging techniques, especially abdominal radiography and Computed Tomography, could detect the presence of IP and discern the forms related to emergency conditions. The differential diagnosis is essential to start an immediate clinical or surgical management and treatment. The aim of this article is to review the radiological features of IP in different illnesses, with particular attention to differential diagnosis.

Background Intestinal ischemia–reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intestinal I/R (II/R) injury and elucidate the underlying mechanisms. Methods C57BL/6 mice and Caco-2 cells were used for in vivo and in vitro studies. We established an animal model of II/R injury by temporarily occluding superior mesenteric artery. We constructed an oxygen–glucose deprivation/reoxygenation (OGD/R) cell model using a hypoxia-reoxygenation incubator. Different doses of Emodin were explored to determine the optimal therapeutic dose. Additionally, inhibitors targeting the protein kinase B (Akt) or Heme oxygenase-1 (HO-1) were administered to investigate their potential protective mechanisms. Results Our results demonstrated that in animal experiments, Emodin mitigated barrier disruption, minimized inflammation, reduced oxidative stress, and inhibited apoptosis. When Akt or HO-1 was inhibited, the protective effect of Emodin was eliminated. Inhibiting Akt also reduced the level of HO-1. In cell experiments, Emodin reduced inflammation and apoptosis in the OGD/R cell model. Additionally, when Akt or HO-1 was inhibited, the protective effect of Emodin was weakened. Conclusions Our findings suggest that Emodin may protect the intestine against II/R injury through the Akt/HO-1 signaling pathway.

Background Intestinal ischemia–reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments. Methods We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu’s score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3. Results It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu’s score (− 1.96, 95% CI − 2.72 to − 1.19, P  < 0.00001), less intestinal inflammation (IL-6 (− 2.73, 95% CI − 4.19 to − 1.27, P  = 0.0002), TNF-α (− 3.00, 95% CI − 4.74 to − 1.26, P  = 0.0007)) and oxidative stress (MDA (− 2.18, 95% CI − 3.17 to − 1.19, P  < 0.0001)), and decreased serum levels of DAO (− 1.39, 95% CI − 2.07 to − 0.72, P  < 0.0001), D-Lactate (− 1.54, 95% CI − 2.18 to − 0.90, P  < 0.00001) and TNF-α (− 2.42, 95% CI − 3.45 to − 1.40, P  < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells. Conclusions Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

Intestinal ischemia-reperfusion (I/R) injury is a clinical condition that leads to severe intestinal damage, inflammation and oxidative stress. While cathepsin B (CTSB) has been implicated in these pathophysiological processes, its precise role in mediating I/R-induced injury remains poorly understood. The present study aimed to elucidate how CTSB knockdown influences oxidative stress, inflammatory responses and the integrity of the intestinal epithelial barrier in intestinal epithelial Caco-2 cells subjected to I/R injury. To identify key genes implicated in I/R injury, a comprehensive analysis was conducted using differential expression profiling and protein-protein interaction network analysis of the GSE37013 dataset. To simulate I/R damage in vitro, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was employed in Caco-2 cells. Subsequently, inflammation was induced by stimulating the cells with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). To investigate the role of CTSB in this context, small interfering RNA was utilized to knock down CTSB expression. In vitro assays were then performed to evaluate NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, oxidative stress levels, inflammatory cytokine production and cell survival. The results revealed that intestinal tissues from the I/R group in the GSE37013 dataset showed markedly higher CTSB expression, and the Caco-2 cells subjected to OGD/R model resulted in a considerable increase in CTSB expression. However, the expression levels of tight junction proteins were enhanced, cell survival was improved and lactate dehydrogenase release was reduced by CTSB knockdown. This reduction in CTSB levels also reduced malondialdehyde levels, and alleviated oxidative stress by increasing the activities of glutathione peroxidase and superoxide dismutase. Furthermore, pro-inflammatory cytokine production was reduced, and NLRP3 inflammasome activation was inhibited by CTSB knockdown, although a modest increase was still observed after LPS + ATP stimulation. Notably, although CTSB knockdown significantly reduced the inflammatory response, LPS + ATP stimulation still elicited a modest reversal in cytokine levels, suggesting that a CTSB-independent pathway of inflammatory activation may exist. In conclusion, CTSB knockdown effectively mitigates I/R injury by reducing inflammation, preserving barrier integrity and alleviating oxidative stress, positioning CTSB as a promising therapeutic target. Future work should validate these findings in in vivo models and explore CTSB-targeted therapies to improve clinical outcomes in I/R-related diseases.

Purpose: Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and [alpha]-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. Methods: i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), [alpha]-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 [micro]g/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. Results: The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 [+ or -] 0.75; curcumin, 1.54 [+ or -] 0.8; DEX5, 1.47 [+ or -] 0.7; DEX20 1.14 [+ or -] 0.5; and [alpha]-tocopherol, 1.01 [+ or -] 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 [+ or -] 0.07 [micro]g/mL; non-treated, 1.18 [+ or -] 0.07 [micro]g/mL; curcumin 1.76 [+ or -] 0.3 [micro]g/mL; DEX5, 2.29 [+ or -] 0.2 [micro]g/mL; DEX20, 2.25 [+ or -] 0.26 [micro]g/mL; and [alpha]-tocopherol 1.66 [+ or -] 0.21 [micro]g/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. Conclusion: All drugs were effective in reducing HID, although a-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals. Keywords: intestinal ischemia-reperfusion, i-IRI, female rat, [alpha]-tocopherol, curcumin, dexmedetomidine, intestinal mucosal damage, absorptive function, antioxidant therapy