Small Intestinal Mucosal Injury Research Articles

Retraction: Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

Retraction: Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

Interleukin-13 Mediates Non-Steroidal Anti-Inflammatory-Drug-Induced Small Intestinal Mucosal Injury with Ulceration.

Non-steroidal anti-inflammatory drugs (NSAIDs), which are antipyretics and analgesics, cause gastrointestinal disorders, such as inflammation and ulcers. To prescribe NSAIDs more safely, it is important to clarify the mechanism of NSAID-induced gastrointestinal mucosal injury. However, there is a paucity of studies on small intestinal mucosal damage by NSAIDs, and it is currently unknown whether inflammation and ulceration also occur in the small intestine, and whether mediators are involved in the mechanism of injury. Therefore, in this study, we created an animal model in which small intestinal mucosal injury was induced using NSAIDs (indomethacin; IDM). Focusing on the dynamics of immune regulatory factors related to the injury, we aimed to elucidate the pathophysiological mechanism involved. We analyzed the pathological changes in the small intestine, the expression of immunoregulatory factors (cytokines), and identified cytokine secretion and expression cells from isolated lamina propria mononuclear cells (LPMCs). Ulcers were formed in the small intestine by administering IDM. Although the mRNA expression levels of IL-1β, IL-6, and TNFα were decreased on day 7 after IDM administration, IL-13 mRNA levels increased from day 3 after IDM administration and remained high even on day 7. The IL-13 mRNA expression and the secretion of IL-13 were increased in small intestinal LPMCs isolated from the IDM-treated group. In addition, we confirmed that IL-13 was expressed in CD4-positive T cells. These results provided new evidence that IL-13 production from CD4-positive T cells in the lamina propria of the small intestine contributes to NSAID-induced mucosal injury.

Therapeutic effect and mechanism of Daikenchuto in a model of methotrexate-induced acute small intestinal mucositis.

Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-β1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

Protective Effect of Irsogladine against Aspirin-Induced Mucosal Injury in Human Induced Pluripotent Stem Cell-Derived Small Intestine

Background and Objectives: Acetylsalicylic acid (ASA) is widely used for preventing cerebrovascular and cardiovascular diseases. Gastrointestinal (GI) tract injury is one of the major complications of aspirin use, potentially leading to severe GI bleeding. However, no drugs for preventing aspirin-induced small intestinal injury have been developed. The aim of this study was to establish a human experimental model for investigating aspirin-induced small intestinal mucosal injury. In addition, we evaluated the protective effect of Irsogladine against aspirin-induced small intestinal mucosal injury using human induced pluripotent stem cell-derived 2D monolayer crypt-villus structural small intestine (2D-hiPSC-SI). Materials and Methods: Human iPS cell-derived intestinal organoids were seeded and cultured in Air-liquid interface. The permeability of 2D-hiPSC-SI was evaluated using Lucifer yellow. Changes in structure and mucosal permeability of 2D-hiPSC-SI after addition of aspirin were confirmed over time, and changes in intestinal epithelium-related markers were evaluated by real-time qPCR and Immunofluorescence staining. The effect of Irsogladine on prevention of aspirin mucosal injury was examined by adding Irsogladine to the culture medium. Results: Cultured 2D-hiPSC-SI showed multi-lineage differentiation into small intestinal epithelium comprised of absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells, which express CD10, MUC2, chromogranin A, and lysozyme, respectively. RNA in situ hybridization revealed intestinal stem cells that express Lgr5. ASA administration induced an increase in the mucosal permeability of 2D-hiPSC-SI. ASA-injured 2D-hiPSC-SI showed decreased mRNA expression of multi-lineage small intestinal cell markers as well as intestinal stem cell marker Lgr5. Administration of Irsogladine on the basal side of the 2D-hiPSC-SI resulted in significant increases in Mki67 and Muc2 mRNA expression by 2D-hiPSCs at 48 h compared with the control group. Administration of 400 µg/mL Irsogladine to the ASA-induced small intestinal injury model resulting in significantly decreased mucosal permeability of 2D-hiPSC-SI. In immunofluorescence staining, Irsogladine significantly increased the fluorescence intensity of MUC2 under normal conditions and administration of 400 µg/mL ASA. Conclusions: we established a novel ASA-induced small intestinal injury model using human iPSC-derived small intestine. Irsogladine maintains mucosal permeability and goblet cell differentiation against ASA-induced small intestinal injury.

Butyrate Ameliorates Insufficient Sleep-Induced Intestinal Mucosal Damage in Humans and Mice.

Insufficient sleep is a key factor in the occurrence of intestinal diseases. This study was performed to clarify how sleep deficiency mediates the intestinal microbiota, metabolite butyrate disturbance induces intestinal mucosal damage, and butyrate ameliorates it. A questionnaire was launched for sleep and intestinal health issues. Twenty-two healthy volunteers were interviewed, and the influence of insufficient sleep on the gut microbiota and metabolite composition was explored. Moreover, a 72-h sleep deprivation (SD) mouse model with or without butyrate supplementation was used to reveal the effect of butyrate on ameliorating small intestines damage caused by SD. The questionnaire survey of 534 college students showed that among 85.39% of the students who slept less than 7 h, 41.76% were suffering from various bowel disorders. High-throughput 16S rRNA pyrosequencing demonstrated that SD and sleep restriction (SR) resulted in downregulation of Faecalibacterium and butyrate abundance in the feces of college students. Furthermore, we observed that butyrate supplementation markedly reversed sleep-deprivation-induced small intestinal mucosal injury in mice. Meanwhile, butyrate supplementation inverted the SD-caused inflammation response and oxidative stress and the decline of phospho-glycogen synthase kinase 3β (p-GSK-3β), β-catenin, Nrf2, and cyclin D1 and the increase in histone deacetylase 3 (HDAC3) and phospho-P65 (p-P65) proteins in the small intestines. Furthermore, in vitro, the ameliorative effects of butyrate were blocked by treatment with the HDAC3 agonist ITSA-1 and the Nrf2 antagonist ML385 and mimicked by treatment with the HDAC3 antagonist RGFP966 and p-P65 antagonist PDTC. Our study revealed that SD and SR downregulated butyrate production, further causing intestinal homeostasis dysfunction via the HDAC3-p-GSK-3β-β-catenin-Nrf2-NF-κB pathway. IMPORTANCE Radical inflammatory bowel disease (IBD) induced by sleep deficiency is a serious global public health threat. Butyrate, a member of the short-chain fatty acids, exerts multiple effects on it. However, existing research focuses on injury to the colon caused by insufficient sleep, while the changes in the small intestines are often overlooked. This study focused on revealing the influence of insufficient sleep on the intestinal microbiota and its metabolites and further revealed the ameliorative effect of butyrate on sleep deprivation (SD)-induced small intestinal mucosal damage in human and mice. Our studies suggest that butyrate can be used as a probiotic to restore SD-induced IBD and contribute to a better understanding of the mechanisms that govern the beneficial effects of butyrate.

Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge

Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury. This gluten challenge phase 2 trial was double blind and placebo controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine. Fifty patients were randomized, and 43 patients completed the study (IMGX003, n= 21; placebo, n= 22). The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was -0.04 vs -0.35 (P= .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P= .018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P= .231), 0.96 vs 3.29 (bloating, P= .204), and 0.02 vs 3.20 (tiredness, P= .113). The 3× 2-week trend line significance values for these symptoms, respectively, were P= .014, .030, and .002. IMGX003 reduced gluten-induced intestinal mucosal damageand symptom severity. (ClinicalTrials.gov, Number: NCT03585478).

Dietary Glucose Ameliorates Impaired Intestinal Development and Immune Homeostasis Disorders Induced by Chronic Cold Stress in Pig Model.

Endotherms are easily challenged by chronic cold stress. In this study, the development and injury of the small intestine in the Min pig model and Yorkshire pig model under chronic cold stress, and the molecular mechanisms by which glucose supplementation reduces small intestinal mucosal damage were investigated. The results showed that morphological structure lesions of the jejunal mucosa and ileal mucosa were visible in Yorkshire pigs under chronic cold stress. Meanwhile, the Occludin mRNA and protein expression in jejunal mucosa of Yorkshire pigs was decreased. Chronic cold stress enhanced the expression of Toll-like receptor 4 (TLR4), the myeloid differentiation main response 88 (MyD88), nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3), cleaved caspase-1, mature-IL-1β, and high-mobility group box 1 (HMGB 1) mRNA and protein expression in jejunal mucosa of Yorkshire pigs, whereas the mRNA and protein of Bax was triggered in ileal mucosa. In Min pigs, no such deleterious consequences were observed. Dietary glucose supplementation ameliorates small intestinal mucosal injury, declined TLR4 and MyD88 expression in jejunal mucosa. In conclusion, chronic cold stress induced the small intestinal mucosa damage in Yorkshire pigs, whereas glucose supplementation mitigated the deleterious effects of chronic cold stress on the small intestine.

Lactobacillus complex capsules ameliorate aspirin-related small intestinal mucosal injury: a prospective, randomized, controlled clinical trial

Objectives Aspirin can reduce cardiovascular disease risk; however, it can increase the risk of gastrointestinal injury. Lactobacilli have some protective effects; however, there are few studies on their effects on humans. This study investigates the effects of Lactobacillus complex capsule treatment on the aspirin-related small intestinal mucosal injury. Methods This single-center, prospective, randomized controlled clinical trial included 69 patients using enteric-coated aspirin for >1 month between May and December 2019. After baseline magnetically controlled capsule endoscopy (MCCE), patients with aspirin-related small intestinal mucosal injury were randomly assigned (1:1) to receive enteric-coated aspirin and Lactobacillus complex capsules containing a combination of Lactobacillus rhamnosus I, Lactobacillus rhamnosus II, and Enterococcus faecium (probiotics group) or enteric-coated aspirin only (control group) for 2 months. After treatment, the patient underwent MCCE again. The primary outcome was the change in small intestinal mucosal injury scores from baseline to post-intervention. Results Twenty-five patients in the probiotics group and 28 in the control group completed the trial. The decrease in small intestinal mucosal injury scores from baseline to post-intervention was significantly greater in the probiotics group than that in the control group (p < .001). The improvement rates of red spots and erosions in the probiotics group were higher compared with the control group (p = .027 and .022, respectively), and the improvement rate of small intestinal ulcers in the probiotics group was 75.0%; however, there was no improvement in the control group. Conclusion Lactobacillus complex capsules can ameliorate aspirin-related small intestinal mucosal injury.

NSAID-Associated Small Intestinal Injury: An Overview From Animal Model Development to Pathogenesis, Treatment, and Prevention.

With the wide application of non-steroidal anti-inflammatory drugs (NSAIDs), their gastrointestinal side effects are an urgent health burden. There are currently sound preventive measures for upper gastrointestinal injury, however, there is a lack of effective defense against lower gastrointestinal damage. According to a large number of previous animal experiments, a variety of NSAIDs have been demonstrated to induce small intestinal mucosal injury in vivo. This article reviews the descriptive data on the administration dose, administration method, mucosal injury site, and morphological characteristics of inflammatory sites of various NSAIDs. The cells, cytokines, receptors and ligands, pathways, enzyme inhibition, bacteria, enterohepatic circulation, oxidative stress, and other potential pathogenic factors involved in NSAID-associated enteropathy are also reviewed. We point out the limitations of drug modeling at this stage and are also pleased to discover the application prospects of chemically modified NSAIDs, dietary therapy, and many natural products against intestinal mucosal injury.

A Review of Potential Role of Capsule Endoscopy in the Work-Up for Chemotherapy-Induced Diarrhea.

Chemotherapy-induced diarrhea (CID) is a common, severe side effect of chemotherapy, immunotherapy, and targeted therapy. Because patients are more prone to continuing chemotherapy if they do not suffer from CID, appropriate diagnosis and monitoring of this disease are essential. However, suitable monitoring methods are yet to be developed. To date, several studies have shown that small-bowel capsule endoscopy (SBCE) is useful in visualizing the entire small intestinal mucosa and detecting small intestinal abnormalities, including bleeding, malignant tumors, and mucosal injury, associated with the use of nonsteroidal anti-inflammatory drugs and low-dose aspirin. Currently, limited studies have evaluated the small intestinal mucosa using SBCE in patients receiving fluoropyrimidine-based chemotherapy or immune checkpoint inhibitors. These studies have reported that small intestinal mucosal injury is common in patients with severe fluoropyrimidine-induced diarrhea. SBCE might be a useful screening method for the early detection of enterocolitis induced by immune checkpoint inhibitors. SBCE may be a powerful tool for the diagnosis and monitoring of CID, and understanding its indication, contraindication, and capsule-retention risk for each patient is important for clinicians.

Effect of Weikang Capsule () on Aspirin-Related Gastric and Small Intestinal Mucosal Injury.

To investigate the effects of Weikang Capsule (, WKC) on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy (MCCE). Patients taking enteric-coated aspirin aged 40-75 years were enrolled in Beijing Anzhen Hospital, Capital Medical University from January 2019 to December 2019. The patients continued taking aspirin Tablet (100 mg per day) and underwent MCCE before and after 1-month combined treatment with WKC (0.9 g per time orally, 3 times per day). The gastrointestinal symptom score, gastric Lanza score, the duodenal, jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment. Adverse events including nausea, vomiting, abdominal pain, abdominal distension, abdominal discomfort, dizziness, or headache during MCCE and combined treatment were observed and recorded. Twenty-two patients (male/female, 13/9) taking enteric-coated aspirin aged 59.5 ± 11.3 years with a duration of aspirin use of 28.0 (1.0, 48.0) months were recruited. Compared with pre-treatment, the gastrointestinal symptom rating scale scores, gastric Lanza scores, and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment (P<0.05), and jejunal and ileal mucosal injury scores showed no obvious change. No adverse events occurred during the trial. WKC can alleviate gastrointestinal symptoms, as well as gastric and duodenal mucosal injuries, in patients taking enteric-coated aspirin; it does not aggravate jejunal or ileal mucosal injury, which may be an effective alternative for these patients (Clinical trial registry No. ChiCTR1900025451).

Effect of a proton-pump inhibitor on intestinal microbiota in patients taking low-dose aspirin.

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. Thirty-two recruited patients, who received LDA (100mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20mg/day) and 17 patients additionally receiving vonoprazan (10mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI. Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea

BackgroundDiarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID.MethodsIn total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID.ResultsTotal number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06–8.19).ConclusionsDespite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

The Remember/Regeneration Therapy Method as a New Holistic Approach for Celiac Disease: Two Case Reports

Background: celiac disease (cd) is a widespread disorder caused by an intolerance to gluten which is a protein found in many foods in genetically susceptible individuals. The disease is characterized by small-intestinal mucosal injury and nutrient malabsorption. Currently, in spite of a life-long gluten-free diet is the effective and available treatment option for patients with CD, the widespread use of wheat-derived gluten in the food industry limits the effectiveness of treatment. Therefore, it is needed to perform further studies on nondietary therapies which solve the causes of the disease. The Remember/Regeneration Therapy Method (RTM) is a novel holistic medicine approach that targets physiopathological changes in quadruplet body structures and includes various complementary methods such as acupuncture, ozone therapy, and phytotherapy, etc. in different combinations which are determined depending on the disease.

Gluten hydrolyzing activity of Bacillus spp isolated from sourdough

BackgroundCeliac disease is an intestinal chronic disorder with multifactorial etiology resulting in small intestinal mucosal injuries and malabsorption. In genetically predisposed individuals with HLA DQ2/DQ8 molecules, the gluten domains rich in glutamine and proline present gluten domains to gluten reactive CD4+ T cells causing injury to the intestine. In the present experimental design, the indigenous bacteria from wheat samples were studied for their gluten hydrolyzing functionality.ResultsProteolytic activity of Bacillus spp. was confirmed spectrophotometrically and studied extensively on gliadin-derived synthetic enzymatic substrates, natural gliadin mixture, and synthetic highly immunogenic 33-mer peptide. The degradation of 33-mer peptide and the cleavage specificities of the selected isolates were analyzed by tandem mass spectrometry. The gluten content of the sourdough fermented by the chosen bacterial isolates was determined by R5 antibody based competitive ELISA. All the tested isolates efficiently hydrolyzed Z-YPQ-pNA, Z-QQP-pNA, Z-PPF-pNA, and Z-PFP-pNA and also cleaved 33-mer immunogenic peptide extensively. The gluten content of wheat sourdough was found to be below 110 mg/kg.ConclusionIt has been inferred that four Bacillus spp especially GS 188 could be useful in developing gluten-reduced wheat food product for celiac disease prone individuals.

Melatonin alleviates oxidative stress in sleep deprived mice: Involvement of small intestinal mucosa injury

BackgroundPrevious research demonstrated that sleep deprivation (SD) resulted in intestinal homeostasis disorder in colon. The present study was further performed to clarify the role of melatonin in SD-induced small intestinal (SI) mucosal injury. MethodsWe successfully established a multiplatform 72 h SD mouse model with or without melatonin supplementation to explore the improvement of melatonin in the destruction of SI induced by SD. ResultsMelatonin supplementation suppressed an increase of corticosterone level and a decrease of melatonin level caused by SD. Meanwhile, we observed that melatonin supplementation in sleep deprived mice markedly reversed a decrease of the villi length/crypt depth (V/C) ratio and the number of goblet cells, PCNA positive cells, the expressions of MUC2 and tight junction proteins, as well as an upregulation of the expressions of autophagic proteins in the duodenum, jejunum and ileum. Furthermore, melatonin supplementation inverted the SD-induced the decline of antioxidant enzyme activities (T-AOC and CAT etc) and anti-inflammatory cytokines (IL-10 and IFN-γ) and the increase of oxidative product MDA, pro-inflammatory cytokines (IL-6 and TNF-α), p-P65 and p-IκB proteins in the SI. ConclusionsThese findings suggested that melatonin may be used as a probiotic agent to reverse SD-induced SI mucosa injury by suppressing oxidative stress and NF-κB pathway activation.

Prevalence of Gastric and Small-Intestinal Mucosal Injury in Elderly Patients Taking Enteric-Coated Aspirin by Magnetically Controlled Capsule Endoscopy.

Objective To investigate aspirin-related gastric and small-intestinal mucosal injury in elderly patients by magnetically controlled capsule endoscopy (MCCE). Methods Patients taking enteric-coated aspirin attending the outpatient department of Beijing Anzhen Hospital, Capital Medical University, from September 2017 to July 2019 underwent MCCE to assess injury to the gastric and small-intestinal mucosa. The patients were divided into the elderly group (age ≥ 60 years) and middle-aged group (45 years ≤ age < 60 years), and their clinical data were evaluated. Results Sixty-eight patients (34 per group) taking enteric-coated aspirin were recruited, and the elderly and middle-aged groups did not differ significantly in sex, history of smoking, history of alcohol consumption, body mass index, or accompanying diseases. In the elderly and middle-aged groups, the gastric Lanza scores were 2.0 (2.0, 3.0) and 2.0 (1.0, 3.0; P = 0.192), the numbers of patients with small-intestinal mucosal injuries (at least one erosion and/or ulcer) were 30 (88.2%) and 15 (44.1%; P < 0.001), the numbers of patients with more severe small-intestinal mucosal injuries (larger erosion and/or ulcer) were 11 (32.4%) and 3 (8.8%; P = 0.033), the numbers of patients with ileal erosion were 22 (64.7%) and 8 (23.5%; P = 0.001), and the durations of aspirin use were 30.0 (12.0, 120.0) and 10.5 (2.0–48.0) months (P = 0.007), respectively. Conclusions The rate of small-intestinal mucosal injury was significantly higher in elderly than in middle-aged patients taking enteric-coated aspirin, especially the rate of ileal erosion. MCCE enables the monitoring of aspirin-related gastric and small-intestinal mucosal injury in elderly patients, which can guide treatment decision making.

A bis-resorcinol resveratrol congener prevents indomethacin-induced gastric ulceration by inhibiting TNF-α as well as NF-κB and JNK pathways

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3′,5,5′-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been established using a mice model. HST-1 reversed the adverse effects of IND on several inflammatory (myeloperoxidase, cytokines, adhesion molecules etc.) and ulcer-healing (cyclooxygenases, prostaglandin, growth factors and their receptors etc.) parameters in mice. More importantly, HST-1 down-regulated TNF-α and the TNF-α-mediated activation of NF-κB and JNK/MAPK pathways that are the key determinants in the IND-gastropathy. The effect of HST-1 on all these factors was significantly better than that of Resv, misoprostol, and omeprazole. HST-1 also did not induce small intestinal mucosal injury, unlike some of the proton pump inhibitors. On the other hand, Resv reduced activation of the prosurvival ERK1/2 pathway that may explain its contraindicative property in the gastrointestinal tract.

MicroRNAs: Novel Markers in Diagnostics and Therapeutics of Celiac Disease.

microRNAs (miRNAs) are a novel class of single-stranded RNAs with a key role in the regulation of gene expression. miRNA main mechanism of action involves interaction with the mRNA transcribed from the genes, leading to the target mRNA silencing and degradation. Indeed, it is easy to conceive that a defective miRNA-based mRNA regulation may compromise normal cell function and cause genetic diseases. A wide spectrum of studies has focused on the identification and introduction of regulatory diseases-specific miRNAs for the past decade. Overexpression or downregulation of several miRNAs can potentially stimulate or inhibit pathways related to the pathogenesis of celiac disease (CD). CD is a chronic inflammatory disease characterized by small intestinal mucosal injury and nutrient malabsorption in genetically susceptible individuals after the dietary ingestion of gluten. The disease is characterized by villous atrophy, intraepithelial lymphocyte infiltration, and chronic inflammation and activation of lamina propria T cells. The common genetic background in CD is the presence of heterodimeric human leukocyte antigen class II molecules DQ2 or DQ8 that account for ∼40% of the genetic predisposition in this disease. In fact, by minute identification of these miRNAs and related targets and mechanisms, specific therapeutics can be developed to suppress these pathophysiological pathways through the enhancement or inhibition of miRNAs. This development can open a new prospect for personalized medicine.

Sa1743 – Investigation of the Relationship Between Aspirin-Induced Small Intestinal Mucosal Injury and Heme Oxygenase-1

Sa1743 – Investigation of the Relationship Between Aspirin-Induced Small Intestinal Mucosal Injury and Heme Oxygenase-1