Severe Mucosal Injury Research Articles

Peucedanum praeruptorum Dunn leaf aqueous extract protects against alcoholic gastric injury by inhibiting inflammation and oxidative stress in mice

Ethnopharmacological relevancePeucedanum praeruptorum Dunn (PPD) was used to treat gastrointestinal disease in China before the Tang Dynasty, and it was considered a “Top-grade” herb in Shennong Bencaojing, known for its ability to relieve the stomach Qi and indigestion. Aim of the studyAlcohol consumption can induce severe gastric mucosal injury that lacks effective and safe interventions. We aimed to investigate the gastroprotective effects of Peucedanum praeruptorum Dunn leaf (PPL) after bolting in alcohol-induced gastric damage in mice. Materials and methodsMice were orally administered PPL aqueous extract at doses of 2.5, 5, and 10 g/kg for 5 consecutive days prior to the induction of gastric damage model with ethanol. Gastric tissue was stained by hematoxylin and eosin (H&E), and the levels of pro-inflammatory cytokines and oxidative stress indicators were determined using ELISA and RT-qPCR. RNA-seq was used to detect differentially expressed genes (DEGs) in the gastric tissue, while Western blotting was employed to measure the expressions of IL-17, TNF-a, and AKT pathways. ResultsTreatment with PPL alleviated alcohol-induced gastric damage in mice, whereas dried root (PPD) and stem (PPS) of Peucedanum praeruptorum Dunn had no gastroprotective function. The content of peucedanocoumarin I was higher in the dried PPL compared to PPD and PPS, with an increase in peucedanocoumarin I content in PPL after boiling. Additionally, PPL administration (5, 10 g/kg) decreased pro-inflammatory factors, such as interleukin-6 (IL-6), IL-8, IL-4, IL-1β, IL-18, and tumor necrosis factor (TNF-a) in alcohol-induced gastric injury mice (p < 0.05), and improved oxidative stress markers, including superoxide dismutase enzymes (SOD), catalase (CAT), and malondialdehyde (MDA) (p < 0.05). RNA-seq data revealed that PPL treatment inhibited alcohol-induced inflammation-related signals, including IL-17 and TNF pathways, and restored alcohol-inhibited gastric digestive and metabolic functions, such as xenobiotics metabolism of cytochrome P450, and protein digestion and absorption pathways. Notably, treatment with PPL downregulated the expressions of IL-17 A, TNF-a, monocyte chemoattractant protein-1 (MCP-1), and AKT-phosphorylation induced by ethanol exposure (p < 0.05). Thus, the aqueous extract of PPL provided protection against alcohol-induced gastric injury by mitigating inflammation and oxidative stress in mice, suggesting a potential novel therapeutic approach for alcohol-induced gastric damage.

Hinesol attenuates DSS-induced ulcerative colitis through the suppression of Src-mediated NF-κB and chemokine signaling pathway.

As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1β, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

The Impact of Early Nutrition Following Peroral Endoscopic Myotomy in Achalasia: A Tertiary Center Experience.

This retrospective single-center study aimed to assess the safety of early feeding in patients who met certain criteria following peroral endoscopic myotomy (POEM). Data from 100 patients who underwent POEM at our center between January and December 2022 were collected. Early feeding was defined as the introduction of clear liquid foods at 4 hours post procedure. At 4 and 24 hours, the pain was rated using the visual analog scale (VAS) in all patients. Patients without intraoperative complications (pneumoperitoneum requiring needle drainage, severe arterial bleeding requiring the use of hemostatic forceps, severe mucosal injury) and severe pain (VAS score > 6) and nausea-vomiting at the fourth postoperative hour were given the early feeding approach. In patients who did not meet these requirements, enteral feeding was initiated after 24 hours (late feeding). Among the 100 patients, 50 patients were categorized early feeding. No patients had a control esophagogram. In the early and late enteral feeding groups, VAS scores were 4 (0-6) and 6 (1-8) (P< 001) at 4 hours and 1 (0-3) and 1 (0-6) (P = .043) at 24 hours, respectively. No severe complications were developed after early feeding. The median hospital stay in the early feeding group was 1 (1-3) day. There was no emergency readmission in any of early feeding patients. Our study showed early feeding following POEM can be begun in achalasia patients who do not have intraoperative complications, severe pain, or nausea/vomiting.

Severe gut mucosal injury induces profound systemic inflammation and spleen-associated lymphoid organ response.

Clinical evidence indicates a connection between gut injuries, infections, inflammation, and an increased susceptibility to systemic inflammation. Nevertheless, the animal models designed to replicate this progression are inadequate, and the fundamental mechanisms are still largely unknown. This research explores the relationship between gut injuries and systemic inflammation using a Dextran Sulfate Sodium (DSS)-induced colonic mucosal injury mouse model. Continuous treatment of adult mice with 4% DSS drinking water yielded a remarkable mortality rate by day 7, alongside intensified gut injury and detectable peripheral inflammation. Moreover, RNAscope in situ hybridization with 16S rRNA probe noted bacterial penetration into deeper colon compartments of the mice following treatment with DSS for 7 days. Histological analysis revealed inflammation in the liver and lung tissues of DSS-treated mice. In addition, we found that DSS-treated mice exhibited elevation of Alanine transaminase (ALT) and Aspartate transaminase (AST) in peripheral blood and pro-inflammatory cytokine levels in the liver. Notably, the DSS-treated mice displayed a dampened metabolic profile, reduced CD45 marker expression, and an increase in apoptosis within the lymphoid organ such as spleen. These findings suggest that high-dose DSS-induced gut injury gives rise to sepsis-like systemic inflammation characterized by multiple organ injury and profound splenocyte apoptosis and dysfunction of CD45+ cells in the spleen, indicating the role of the spleen in the pathogenesis of gut-derived systemic inflammation. Together, the severe colonic mucosal injury model facilitates research into gut damage and associated peripheral immune responses, providing a vital framework for investigating mechanisms related to clinically relevant, gut-derived systemic inflammation.

Anatomic Considerations of esophageal button battery ingestion for outcomes and imaging

IntroductionButton batteries (BB) are a source of significant morbidity and mortality in young children. Little data is available regarding associations between esophageal impaction location and outcomes or need for surveillance imaging. MethodsAll patients treated at a single institution following BB ingestion between 2018 and 2022 were included for retrospective chart review. ResultsTwenty patients were treated at our institution BBs were located, or most significant damage observed, in the cervical esophagus (n = 10, 50 %), followed by thoracic esophagus (n = 6, 30 %), and abdominal esophagus (n = 4, 20 %). Patients with cervical esophageal impaction were younger (482 [370–866] days), than those with thoracic (1395 [871–2369] days) or abdominal esophageal impaction (2021.5 [1230.5–3419.5] days) (p = 0.003). Zargar Mucosal Injury Grade was significantly more severe in patients with cervical button battery impaction; 8/10 (80 %) had a ≥Grade IIIB injury, compared to 2/6 (33.3 %) thoracic impactions and 0/4 (0 %) abdominal impactions (p = 0.002). All patients who developed persistent esophageal stenosis (n = 6) had cervical battery impactions (6, 60 %, p = 0.015). Both TEFs (2/2) had anterior facing anode, while both (2/2) esophageal perforations had posterior. Only 1/20 (5 %) patients, and 1/7 (14.3 %) with serious complications, had a serious complication detected on routine, rather than clinically indicated follow-up surveillance. ConclusionsIn our population, cervical BB impaction occurred more frequently in younger children, was associated with more severe mucosal injury, and had higher risk of stenosis. Nearly all complications were detected on clinically indicated rather than postoperative surveillance imaging.

Ginseng Stem-and-Leaf Saponins Mitigate Chlorpyrifos-Evoked Intestinal Toxicity In Vivo and In Vitro: Oxidative Stress, Inflammatory Response and Apoptosis.

In recent years, the phenomenon of acute poisoning and organ damage caused by organophosphorus pesticides (OPs) has been a frequent occurrence. Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides. The main active components of ginseng stems and leaves are total ginseng stem-and-leaf saponins (GSLSs), which have various biological effects, including anti-inflammatory, antioxidant and anti-tumor activities. We speculate that these could have great potential in the treatment of severe diseases and the relief of organophosphorus-pesticide-induced side effects; however, their mechanism of action is still unknown. At present, our work aims to evaluate the effects of GSLSs on the antioxidation of CPF in vivo and in vitro and their potential pharmacological mechanisms. Mice treated with CPF (5 mg/kg) showed severe intestinal mucosal injury, an elevated diamine oxidase (DAO) index, the decreased expression of occlusive protein-1 (ZO-1) and occlusive protein, an impaired intestinal mucosal oxidation system and intestinal villi relaxation. In addition, chlorpyrifos exposure significantly increased the contents of the inflammatory factor TNF-α and the oxidative-stress-related indicators superoxide dismutase (SOD), catalase (CAT), glutathione SH (GSH), glutathione peroxidase (GSH-PX), reactive oxygen species (ROS) and total antioxidant capacity (T-AOC); elevated the level of lipid peroxide malondialdehyde (MDA); reversed the expression of Bax and caspase; and activated NF-κB-related proteins. Interestingly, GSLS supplementation at doses of 100 and 200 mg/kg significantly reversed these changes after treatment. Similar results were observed in cultured RAW264.7 cells. Using flow cytometry, Hoechst staining showed that GSLSs (30 μg/mL, 60 μg/mL) could improve the cell injury and apoptosis caused by CPF and reduce the accumulation of ROS in cells. In conclusion, GSLSs play a protective role against CPF-induced enterotoxicity by inhibiting NF-κB-mediated apoptosis and alleviating oxidative stress and inflammation.

The Potential Gastro-Protective Effect of Qaysum (Achillea fragrantissima) Against Ethanol-Induced Gastric Ulcer in Wistar Albino Rats.

Gastric ulcer (GU) is among the peak prevalent syndromes. This study investigates the defensive properties of Achillea fragrantissima (Forssk.) Sch.Bip. extract (AFE) against ethanol-induced stomach lesions. Twenty-eight rats were allocated into negative control, positive control, AFE + ethanol, and omeprazole ethanol. In serum and gastric homogenates, oxidative stress displays (e.g., malondialdehyde (MDA), decreased glutathione (GSH), superoxide dismutase enzyme (SOD), and catalase enzyme (CAT)) and inflammatory parameters (e.g., tumor necrosis factor-alpha (TNF-α)) were estimated. GU markers (gastric lesions, ulcer index (UI), pH) were evaluated, and gastric histopathological examinations were performed. The positive control cluster exhibited severe gastric mucosal injuries, reduced stomach mucus secretion, and pH of gastric content. Furthermore, AFE-pretreated rats displayed meaningfully increased periodic acid-Schiff (PAS) countenance in their stomach epithelial layers. Pretreatment with AFE reduced stomach lesions, UI, MDA, and TNF-α levels, while mucus, pH, CAT, GSH, and SOD levels increased. Stomach examination showed significant improvement in gastric mucosa reduced edema and leukocyte infiltration of the submucosal level in pretreatment with the AFE and omeprazole groups versus the ethanol group. Additionally, AFE extracts increase the intensity of the stomach epithelium's PAS. The acute toxicity experiment with an advanced dosage of 5 g/kg AFE did not exhibit any signs of toxicity in the rats. In conclusion, the AFE reduced the effect of ethanol on the gastric mucosa, which may be due to its antioxidants and anti-inflammatory properties.

Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

Honokiol, an inducer of sirtuin-3, protects against non-steroidal anti-inflammatory drug-induced gastric mucosal mitochondrial pathology, apoptosis and inflammatory tissue injury.

Mitochondrial oxidative stress, inflammation and apoptosis primarily underlie gastric mucosal injury caused by the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Alternative gastroprotective strategies are therefore needed. Sirtuin-3 pivotally maintains mitochondrial structural integrity and metabolism while preventing oxidative stress; however, its relevance to gastric injury was never explored. Here, we have investigated whether and how sirtuin-3 stimulation by the phytochemical, honokiol, could rescue NSAID-induced gastric injury. Gastric injury in rats induced by indomethacin was used to assess the effects of honokiol. Next-generation sequencing-based transcriptomics followed by functional validation identified the gastroprotective function of sirtuin-3. Flow cytometry, immunoblotting, qRT-PCR and immunohistochemistry were used measure effects on oxidative stress, mitochondrial dynamics, electron transport chain function, and markers of inflammation and apoptosis. Sirtuin-3 deacetylase activity was also estimated and gastric luminal pH was measured. Indomethacin down-regulated sirtuin-3 to induce oxidative stress, mitochondrial hyperacetylation, 8-oxoguanine DNA glycosylase 1 depletion, mitochondrial DNA damage, respiratory chain defect and mitochondrial fragmentation leading to severe mucosal injury. Indomethacin dose-dependently inhibited sirtuin-3 deacetylase activity. Honokiol prevented mitochondrial oxidative damage and inflammatory tissue injury by attenuating indomethacin-induced depletion of both sirtuin-3 and its transcriptional regulators PGC1α and ERRα. Honokiol also accelerated gastric wound healing but did not alter gastric acid secretion, unlike lansoprazole. Sirtuin-3 stimulation by honokiol prevented and reversed NSAID-induced gastric injury through maintaining mitochondrial integrity. Honokiol did not affect gastric acid secretion. Sirtuin-3 stimulation by honokiol may be utilized as a mitochondria-based, acid-independent novel gastroprotective strategy against NSAIDs.

A51 INTESTINAL MICROBIOTA DETERMINES ARYL HYDROCARBON RECEPTOR ACTIVATION AND SUSCEPTIBILITY TO COLITIS

Abstract Background Intestinal microbiota, diet, and the immune system have been proposed to contribute to the development of inflammatory bowel diseases (IBD). The aryl hydrocarbon receptor (AhR) is a critical regulator of intestinal immunity and mucosal barrier homeostasis that is activated by agonists such as host and microbial tryptophan metabolites. IBD patients have altered microbiota and reduced AhR agonists in intestinal content resulting in the downregulation of AhR. These findings necessitate further study to understand how diet-microbiota interactions contribute to intestinal inflammation. Purpose To study the influence of intestinal microbiota on tryptophan metabolism, AhR activation, and colitis severity. Method 8- to 10-week-old germ-free C57BL/6 mice were colonized with cecal content of mice harbouring specific pathogen-free (SPF) or a limited and well-defined altered Schaedler flora (ASF) microbiota. Germ-free mice were used as controls. Three weeks following colonization, mucosal injury was induced in a subset of mice with dextran sulfate sodium (DSS) in drinking water for five days followed by two days of water recovery. Activation of AhR was measured in stool using an in vitro AhR luciferase reporter assay. Stool AhR agonists were determined using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Colonic expression of AhR pathway genes Cyp1a1, Il22, Ahrr, Ahr, and Il17 was evaluated by RT-qPCR. Susceptibility to colitis was assessed by analysing stool consistency and stool blood, colonic microscopic damage, immune infiltration by immunohistochemistry, and pro-inflammatory gene expression (NanoString). Fecal microbiota was analysed by 16S rRNA gene sequencing (Illumina). Result(s) AhR agonists, AhR activation in vitro, and AhR pathway gene expression were elevated in mice colonized with SPF microbiota in comparison to mice colonized with ASF microbiota and germ-free mice. In ASF-colonized mice, DSS induced more severe inflammation than in SPF-colonized mice, as demonstrated by worsened mucosal injury, greater weight loss, and softer stools. SPF-colonized mice developed less mucosal immune cell infiltration and pro-inflammatory gene signaling. Conclusion(s) Our findings suggest that intestinal microbiota composition determines the metabolic capacity to degrade tryptophan into agonists that homeostatically activate AhR. When mucosal injury is induced, mice with elevated microbiota-derived AhR agonists and AhR activation develop less severe mucosal injury and signs of colitis. This study presents a useful tool for evaluating dietary and microbial therapies in the context of a microbiota with impaired tryptophan metabolism. Please acknowledge all funding agencies by checking the applicable boxes below CCC, CIHR Disclosure of Interest None Declared

HLA-DQ genotype distribution and risk evaluation of celiac disease in Northwest China

Background Celiac disease (CD) is an autoimmune small bowel disease. Genetic susceptibility for CD is mainly determined by the human leukocyte antigen (HLA)-DQ haplotypes. The risk of CD conferred by HLA genotypes varies geographically and across populations, however, this has not yet been documented in Chinese patients with CD. Aims To investigate the distribution of HLA-DQ and the related risks of CD development in Northwest China. Methods A total of 75 CD patients and 300 healthy individuals were genotyped for HLA-DQ using the Illumina NextSeq, and the relative risks of the different genotypes were evaluated. Results In total, 68.00% of CD patients and 21.00% of controls carried HLA-DQ2.5 heterodimers (p < 0.001). We identified four CD risk gradients. Individuals carrying a double dose of DQB1*02 had the highest risk of developing CD (1:16); however, with heterozygosis (DQB1*02:02/DQB1*02:01) having the highest risk (1:9). HLA-DQ2.5 individuals with a single copy of HLA-DQB1*02, in either the cis or trans configuration, were at a medium risk (1:38). Non-DQ2.5 carriers of DQ8 or DQ2.2 were at low risk, while only carriers of DQ7.5 or DQX.5 were at very low risk. Patients with the HLA-DQ2.5 genotype had more severe mucosal damage compared with the HLA-DQ2.5 genotype negative CD patients (70.59% vs. 41.67%, p = 0.016). Conclusion Genetic susceptibility to CD is highly prevalent in the Northwest Chinese population and the highest risk of developing CD was associated with the DQ2.5/DQ2.2 genotype. The DQ2.5 allele is involved in the severity of mucosal injury.

Mucosal Injury During Per-oral Endoscopic Myotomy: A Single-Center Experience.

Peroral endoscopic myotomy is associated with a low risk of adverse events. Mucosal injury is the most common intraprocedural adverse event of peroral endoscopic myotomy. Severe mucosal injury may cause serious consequences, such as esophageal leak and mediastinitis, which affect the outcome of the procedure and prolong hospital stay. The aim of the present study was to determine the characteristics, predictors, and management approaches for unintended mucosal injury during peroral endoscopic myotomy. A total of 211 patients who underwent peroral endoscopic myotomy between November 2014 and June 2019 were enrolled in this study. Mucosal injury was defined according to a previous study and maintained in the endoscopy database. Patient-related and procedure-related factors were compared between patients with and without mucosal injury. Multivariate analysis was performed after adjusting for confounding factors. A total of 206 patients were eligible for study enrollment. Of these, 44 experienced mucosal injury, with an overall frequency of 21.4% (44/206). On multivariable analysis, mucosal injury was associated with submucosal fibrosis (odds ratio, 8.33; P = .024), intraprocedural bleeding (OR, 14.29; P < .001), endoscopic diameter of 9.9 mm (OR, 4.389; P = .006), and procedure duration over 60 minutes (OR, 1.016; P = .034). Mucosal injury is a significant event encountered during peroral endoscopic myotomy, affecting its short- and long-term outcomes. Intra-procedural bleeding, endoscopic submucosal fibrosis, and use of an endoscope with a large outer diameter have been found to be significant predictors of mucosal injury. Endoscopists should pay more attention to risk factors associated with mucosal injury to avoid adverse events.

Decompression Illness in a Scuba Diver With Significant Esophageal Injury

Scuba divers are at risk of decompression illness, of which arterial gas embolism is the most feared consequence. Severe complications involving the gastrointestinal tract are rare. In this report, we describe a case of an experienced scuba diver who was forced to rapidly ascend because of a mechanical failure. His course was complicated by severe esophageal mucosal injury including multiple ulcerations. Although he improved clinically, an esophageal stricture subsequently formed, which required dilation. This seems to be the first case report of significant esophageal injury resulting from decompression illness in a scuba diver.

Battery Ingestion in Children, an Ongoing Challenge: Recent Experience of a Tertiary Center.

IntroductionMorbidity related to childhood battery ingestions (BI) has increased recently due to the expanding use of larger lithium cells. A prompt endoscopic removal is vital to prevent severe complications in cases of esophageal batteries (EB).Materials and MethodsA retrospective, descriptive study of admissions for BI requiring endoscopic removal in a tertiary hospital's pediatric emergency department (Jan. 2011/Dec. 2020).ResultsWe had 35 cases, with an increasing incidence in the last 6 years; median age, 26 m (8 m-10 years), witnessed ingestion in 86%. On the X-ray: 14 (40%) had an EB, 21 (60%), a gastric battery (GB). Symptoms were present in 57% (100% EB/24% GB), and vomiting was the most frequent (50%). Endoscopy revealed: EB, 13 (37%); GB, 17 (49%); duodenal battery, 1 (3%); no battery, 4 (11%). Median time to removal: EB, 7 h (2 h-21days); GB, 12 h (2 h-3 days). All the patients with EB on the X-ray (14) had severe mucosal injury (Zargar classification): Grade IIIa, 7 (50%); IIIb, 5 (36%); IV, 2 (14%). CT-scan showed perforation in 2 patients (total, 4; 29% of EB). In patients with GB (21), 14 (67%) had mucosal damage; 13 (93%), mild (< Grade III, two esophageal erosions); 1 (7%) IIIa (esophageal ulceration). A statistically significant association between exposure time, younger age or battery size and severity of endoscopic lesions was found in EB location. There were no mortality cases. Acute complications occurred in 57% of EB: infection, 50%; perforation, 29%; pneumomediastinum/stridor, 14%; pneumothorax/subglottic stenosis/hemodynamic instability, 7 vs. 0% GB. Stenosis subsequently developed in 6 (43%) of EB: mild, 4 cases (29%); severe, 2 cases (14%, one resolved after endoscopic dilation; one needed a gastrostomy and esophagocoloplasty).ConclusionWe verified recent increase in admissions due to battery ingestions and associated complications, despite the availability of an emergency pediatric endoscopy team. The patients with EB had more severe mucosal injury and poorer short/long-term outcomes. Children with GB had milder lesions, although the presence of a GB did not exclude esophageal injury. The availability of actual data from national referral centers will support advocacy efforts among stakeholders, including industry representatives and policy makers, in preventing worldwide button battery injury.

Carbon monoxide-releasing molecule-2 protects intestinal mucosal barrier function by reducing epithelial tight-junction damage in rats undergoing cardiopulmonary resuscitation

BackgroundIschemia-reperfusion injury (IRI) to the small intestine is associated with the development of systemic inflammation and multiple organ failure after cardiopulmonary resuscitation (CPR). It has been reported that exogenous carbon monoxide (CO) reduces IRI. This study aimed to assess the effects of carbon monoxide-releasing molecule-2 (CORM-2) on intestinal mucosal barrier function in rats undergoing CPR. MethodsWe established a rat model of asphyxiation-induced cardiac arrest (CA) and resuscitation to study intestinal IRI, and measured the serum levels of intestinal fatty acid-binding protein. Morphological changes were investigated using light and electron microscopes. The expression levels of claudin 3 (CLDN3), occludin (OCLN), zonula occludens 1 (ZO-1), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and nuclear factor kappa B (NF-κB) p65 were detected by western blotting. ResultsCompared with the sham-operated group, histological changes and transmission electron microscopy revealed severe intestinal mucosal injury in the CPR and inactive CORM-2 (iCORM-2) groups. In contrast, CORM-2 alleviated intestinal IRI. CORM-2, unlike iCORM-2, markedly decreased the Chiu's scores (2.38 ± 0.38 vs. 4.59 ± 0.34; P < 0.05) and serum intestinal fatty acid-binding protein level (306.10 ± 19.22 vs. 585.64 ± 119.84 pg/mL; P < 0.05) compared with the CPR group. In addition, CORM-2 upregulated the expression levels of tight junction proteins (CLDN3, OCLN, and ZO-1) (P < 0.05) and downregulated those of IL-10, TNF-α, and NF-кB p65 (P < 0.05) in the ileum tissue of rats that received CPR. ConclusionsCORM-2 prevented intestinal mucosal damage as a result of IRI during CPR. The underlying protective mechanism was associated with inhibition of ischemia-reperfusion-induced changes in intestinal epithelial permeability and inflammation in intestinal tissue.

Effect of minimally invasive premeasured suctioning on airway mucosal injury and suction-induced stress among mechanically ventilated neonates: A clinical challenge for nurses

PurposePerforming ETS to fragile neonates presents a clinical challenge and a dilemma facing nurses. The challenge is how to clear secretions successfully without causing complications. This study aimed to investigate the effect of Minimally Invasive Premeasured Suctioning (MIPS) on airway mucosal injury and suction-induced stress among mechanically ventilated neonates. Designand methods: A quasi-experimental, two groups, pre-post-test study was carried out in the NICU of University Specialized Hospital in Smouha, Alexandria. Sixty mechanically ventilated neonates were randomly assigned to two equal groups. A suction catheter was inserted into the Endotracheal Tube (ETT) until it reached the measured length then the negative pressure was applied. ResultsThe majority of neonates who received MIPS (83.3%) had no airway mucosal injury (clear secretion), while 44.4% of neonates in the deep suctioning group developed severe airway mucosal injury (bloody secretion). Moreover, 71.1% of neonates who received deep ETS developed a high-stress level compared to only 10% of the neonates in the MIPS group. ConclusionMeasuring the exact depth of suction catheter insertion effectively reduced airway mucosal injury and the subsequent level of stress among mechanically ventilated neonates.

Protective effect of polysaccharides isolated from the seeds of Cuscuta chinensis Lam. on 5-fluorouracil-induced intestinal mucositis in mice.

ABSTRACTPurpose:To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice.Methods:PCCL was orally administered at a dose of 20 mg·kg–1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg–1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1β levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2.Results:The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression.Conclusions:PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Effect of Trianthema triquetra Rottl. ex Willed (Aizoaceae) on ethanol-induced gastric ulcers in experimental rats

Trianthema triquetra Rottl. Ex.Willed (T. triquetra) is a medicinal plant that belongs to the family Aizoaceae. The plant has been used traditionally as fodder, as a remedy for chronic ulcer, fever, and healing wounds. Therefore, the present study was intended to investigate the anti-ulcer ability of different fractions of T. triquetra to verify its folklore use in ulcer cure. Acute oral toxicity of all the fractions of T. triquetra was evaluated at a dose of 2g/kg b.wt. Anti-ulcer potential of nbutanol (TTB), chloroform (TTC), ethyl acetate (TTEA) and aqueous (TTA) fraction of crude methanolic extract of T. triquetra was assessed by using ethanol- induced gastric ulcer model in rats. Omeprazole at a dose of 20 mg/kg b.wt. was used as standard drug. After 1 hour of administration of all the fractions of T. triquetra, at a dosage of 300mg/kg b.wt., the gastric ulcer was induced in all animals by administering absolute ethanol (1mL/animal) orally except normal control group. After an hour, all the rats were sacrificed. Ulcer index, % age of ulcer inhibition, gastric pH, gastric volume, total acidity, gastric wall protein, gastric wall mucus and histopathology of the stomach wall of rats were assessed. All fractions of T. triquetra showed a substantial decrease in ulcer index and improvement in percentage inhibition compared to the disease control group. There was a rise in the amount of gastric wall mucus content, total protein content, gastric pH and a decrease in gastric volume and total acidity. Histopathological studies showed severe mucosal injury, leucocyte infiltration and edema in the disease control group compared to omeprazole and plant fractions treated animal groups. The present work encourages the conventional use of T. triquetra in the cure of ulcers.

Acute Cold Water-Immersion Restraint Stress Induces Intestinal Injury and Reduces the Diversity of Gut Microbiota in Mice.

Growing evidence has demonstrated that stress triggers gastrointestinal (GI) disorders. This study aimed to investigate how the acute cold water-immersion restraint (CWIR) stress affects intestinal injury and gut microbiota (GM) distribution. Male C57BL/6 mice were used to establish a CWIR animal model. Hematoxylin–eosin and periodic acid–Schiff staining were performed to assess intestinal histopathological changes. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and immunofluorescence staining were used to evaluate the expression of inflammatory cytokines and immune cell infiltration in the intestinal tissues. The gut permeability and intestinal occludin protein expression were determined through fluorescein isothiocyanate-dextran detection and western blot, respectively. GM profiles were analyzed via high-throughput sequencing of the fecal bacterial 16S rRNA genes. Results showed that CWIR induced more severe intestinal mucosal injury compared to the control, leading to a significant increase in tumor necrosis factor-α expression, but no infiltration of neutrophil and T cells. CWIR also resulted in GI disruption and increased the permeability of the intestinal mucosa. GM profiles showed that CWIR reduced GM diversity of mice compared with the control group. Specifically, aerobic and gram-negative bacteria significantly increased after CWIR, which was associated with the severity of gut injury under stress. Therefore, acute CWIR leads to severe intestinal damage with inflammation and disrupts the GM homeostasis, contributing to decreased GM diversity. Our findings provide the theoretical basis for the further treatment of intestinal disorders induced by CWIR.

Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis

SummaryImmune checkpoint blockade using PD-1 inhibition is an effective approach for treating a wide variety of cancer subtypes. While lower gastrointestinal (GI) side effects are more common, upper gastrointestinal adverse events are rarely reported. Here, we present a case of nivolumab-associated autoimmune gastritis. To elucidate the immunology underlying this condition, we leverage multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to identify the presence and proportion of infiltrating immune cells from a single section of biopsy specimen. Using MIBI-TOF, we analyze formalin-fixed, paraffin-embedded human gastric tissue with 28 labels simultaneously. Our analyses reveal a gastritis characterized by severe mucosal injury, interferon gamma (IFN-γ)-producing gastric epithelial cells, and mixed inflammation that includes CD8 and CD4 T cell infiltrates with reduced expression of granzyme B and FOXP3, respectively. Here, we provide a comprehensive multiplexed histopathological mapping of gastric tissue, which identifies IFN-γ-producing epithelial cells as possible contributors to the nivolumab-associated gastritis.