Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

Jejunal Dieulafoy lesion with intraintestinal calcification on computerized tomography: A case report.

RATIONALE: A Dieulafoy lesion is a rare cause of gastrointestinal (GI) bleeding, especially in the jejunum, and the presence of calcifications on CT might be suspicious of the diagnosis. PATIENT CONCERNS: We describe a 72-year-old woman with anemia and melena. Hemoglobin was 6.0 g/dL, and the stools were positive for occult blood (4+). Blood pressure was 116/54 mm Hg. Physical examination showed pale face and pitting edema in both lower limbs. Abdominal computerized tomography showed calcification in the small intestine of the left lower abdomen. Capsule endoscopy showed a blood clot. DIAGNOSES: Dieulafoy lesion. INTERVENTIONS: Single balloon endoscopy was performed via the oral approach and showed a blood clot on the suspected submucosal tumor of jejunum. A hemostatic clip was placed at the base of the lesion to allow the surgeon to locate it during the operation. Laparoscopy was performed, and the lesion was resected. OUTCOMES: The postoperative pathology showed a Dieulafoy lesion. The lower extremity edema subsided. GI bleeding did not recur over 1 year of follow-up, and hemoglobin was 12.2 g/dL. A Dieulafoy lesion is a rare cause of GI bleeding, and it is even rarer in the jejunum. LESSONS: A Dieulafoy lesion does not have special imaging features, but the presence of calcifications in the small intestine on computerized tomography might be suspicious of the diagnosis. When endoscopic treatment is difficult, surgical treatment could be considered.

Neonatal susceptibility to meningitis results from the immaturity of epithelial barriers and gut microbiota.

Neonates are highly susceptible to bacterial meningitis as compared to children and adults. Group B streptococcus (GBS) is a major cause of neonatal meningitis. Neonatal meningitis can result from GBS intestinal colonization and translocation across the intestinal barrier (IB). Here, we show that the immaturity of the neonatal intestinal microbiota leads to low resistance to GBS intestinal colonization and permissiveness of the gut-vascular barrier. Moreover, the age-dependent but microbiota-independent Wnt activity in intestinal and choroid plexus (CP) epithelia results in a lower degree of cell-cell junctions' polarization, which favors bacterial translocation. This study thus reveals that neonatal susceptibility to GBS meningitis results from the age-dependent immaturity of the intestinal microbiota and developmental pathways associated with neonatal tissue growth, which both concur to GBS gut colonization, systemic dissemination, and neuroinvasion. Whereas the activation of developmental pathways is intrinsic to neonates, interventions aimed at maturing the microbiota may help prevent neonatal meningitis.

Challenging Diagnosis and Endoscopic Management of Dieulafoy's Lesion-Induced Small-Bowel Bleeding: A Case Report.

Small-bowel bleeding is a relatively uncommon event of gastrointestinal bleeding. Some causes of small-bowel bleeding, such as vascular lesions, are still challenging to confirm, despite the use of various diagnostic modalities (e.g., capsule endoscopy, deep enteroscopy, and radiographic imaging). Vascular lesion-induced bleeding tends to be insidious and intermittent, but sometimes it can be massive and fatal, so that the timing of an endoscopy is critical. We describe herein the case of an elderly female patient with Dieulafoy's lesion-induced small-bowel bleeding presenting with recurrent melena. In this article, we describe how the cause of her bleeding was found and how the bleeding was stopped endoscopically. Finally, we discuss the characteristics of a small-bowel Dieulafoy's lesion and its endoscopic treatment.

Naringenin prevents TNF-α-induced gut-vascular barrier disruption associated with inhibiting the NF-κB-mediated MLCK/p-MLC and NLRP3 pathways.

The microvasculature endothelium accurately regulates the passage of molecules across the gut-vascular barrier (GVB), which plays an essential role in intestinal immunity. Naringenin is reported to have therapeutic potential against several intestinal disorders. However, the effect of naringenin on GVB disruption has been rarely studied. This study aims to investigate the effect of naringenin on GVB function and the potential mechanism. In the present study, the in vitro GVB disruption of rat intestinal microvascular endothelial cells (RIMVEC) was induced by 50 ng mL-1 of tumor necrosis factor-α (TNF-α). The integrity of the in vitro GVB was determined by Evans blue (EB)-albumin efflux assay and trans-endothelial electrical resistance (TER). Meanwhile, the expression of tight junction proteins and the related NF-κB, MLCK/p-MLC and NLRP3 pathways were determined using enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence. The results show that naringenin (100 µM) inhibits TNF-α-induced interleukin (IL)-6 hypersecretion, alleviates GVB disruption and mitigates the change in the tight junction protein expression pattern. Naringenin inhibits the GVB-disruption-associated activation of the MLCK/p-MLC system and TLR4/NF-κB/NLRP3 pathways. Furthermore, naringenin shows a similar effect to that of NF-κB inhibitor Bay 11-7082 in reducing the TNF-α-induced activation of NLRP3, p-MLC and secondary GVB disruption. The results suggest that naringenin evidently alleviates TNF-α-induced in vitro GVB disruption via the maintenance of a tight junction protein pattern, partly with the inhibition of the NF-κB-mediated MLCK/p-MLC and NLRP3 pathway activation.

Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease.

Sphingosine-1-phosphate receptors (S1PRs) have an impact on the intestinal inflammation of inflammatory bowel disease (IBD) by regulating lymphocyte migration and differentiation. S1PR modulators as an emerging therapeutic approach are being investigated for the treatment of IBD. However, the role of S1PRs in intestinal vessels has not drawn much attention. Intestinal vascular damage is one of the major pathophysiological features of IBD, characterized by increased vascular density and impaired barrier function. S1PRs have pleiotropic effects on vascular endothelial cells, including proliferation, migration, angiogenesis and barrier homeostasis. Mounting evidence shows that S1PRs are abnormally expressed on intestinal vascular endothelial cells in IBD. Unexpectedly, S1PR modulators may damage intestinal vasculature, for example increase intestinal bleeding; therefore, S1PRs are thought to be involved in the regulation of intestinal vascular function in IBD. However, little is understood about how S1PRs regulate intestinal vascular function and participate in the initiation and progression of IBD. In this review, we summarize the pathogenic role of S1PRs in and the underlying mechanisms behind the intestinal vascular injury in IBD in order for improving IBD practice including S1PR-targeted therapies.

An organoid-based organ-repurposing approach to treat short bowel syndrome.

The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment.

Synergistic Effect of ß-alanine and Aprotinin on Mesenteric Ischemia.

BACKGROUND: Acute mesenteric ischemia arises through sudden interruption of mesenteric blood flow, mostly due to an occlusion of the superior mesenteric artery and is associated with a high mortality of approximately 50% to 90%. In previous studies, the single application of ß-alanine or aprotinin caused an ameliorated intestinal damage but without any systemic effects. METHODS: To analyze the combined effect of ß-alanine and aprotinin on acute ischemia and reperfusion of the small intestine, a model with anesthetized rats was used. Ischemia and reperfusion were initiated by occluding and reopening the superior mesenteric artery. After 120 min of ischemia and 180 min of reperfusion, the intestine was analyzed for tissue damage, the activity of the saccharase, and accumulation of granulocytes. In addition, systemic and metabolic as well as inflammatory parameters were measured in blood at certain points in time. RESULTS: The combination of ß-alanine and aprotinin resulted in a clearly stabilized mean arterial blood pressure and blood glucose level during the reperfusion period. Furthermore, the combined administration resulted in significantly reduced tissue damage parameters, cytokine and cell-free hemoglobin concentrations in blood plasma. In addition, the damage to the small intestine was significantly attenuated, so that the animals ultimately survived the entire test period because of the administration of both substances. CONCLUSIONS: Overall, the simultaneous application of both substances leads to a synergistic protection without the occurrence of undesirable side effects. The combined usage of ß-alanine and aprotinin can be seen as a promising approach to inhibit the onset of acute mesenteric ischemia.

Effects of Norepinephrine on the Intestinal Vascular System in Rabbits With Endotoxic Shock.

ABSTRACT: We hypothesized that jejunal mucosal tissue blood flow would decrease following norepinephrine (NE) administration in endotoxic shock. We aimed of this study to evaluate changes in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time by administration of NE in rabbits with endotoxic shock. We created four groups (n = 8 each): control group, lipopolysaccharide (LPS; 1 mg/kg) group, NE (2 µg/kg/min) group, and LPS+NE group. As indicators of circulation, we measured mean arterial blood pressure (MAP), cardiac output, SMV blood flow, and jejunal mucosal tissue blood flow every 30 min from 0 to 240 min. The drop in MAP observed in the LPS group was suppressed by NE administration. SMV blood flow dropped temporarily with LPS administration, but then rose thereafter. Administration of NE to the LPS group suppressed the transient decline in SMV blood flow, which did not drop below that of the control group. In the LPS group, jejunal mucosal tissue blood flow transiently dropped and then rose, reflecting the pattern in SMV blood flow. In the LPS+NE group, however, although there was no drop in SMV blood flow, jejunal mucosal tissue blood flow remained low. An interaction between NE and LPS was observed regarding jejunal mucosal tissue blood flow from 90 to 180 min (P = 0.033). We showed that NE maintained MAP and SMV blood flow but decreased jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, NE had a negative effect on jejunal mucosal tissue blood flow.

Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemia-induced intestinal barrier breakdown following hemorrhagic shock.

INTRODUCTION: Hemorrhagic shock (HS) and resuscitation (RES) cause ischemia-induced intestinal permeability due to intestinal barrier breakdown, damage to the endothelium, and tight junction (TJ) complex disruption between enterocytes. The effect of hemostatic RES with blood products on this phenomenon is unknown. Previously, we showed that fresh frozen plasma (FFP) RES, with or without directed peritoneal resuscitation (DPR) improved blood flow and alleviated organ injury and enterocyte damage following HS/RES. We hypothesized that FFP might decrease TJ injury and attenuate ischemia-induced intestinal permeability following HS/RES. METHODS: Sprague-Dawley rats were randomly assigned to groups (n = 8): sham; crystalloid resuscitation (CR) (HS of 40% mean arterial pressure for 60 minutes) and CR (shed blood plus two volumes of CR); CR and DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood plus one volume of FFP); and FFP and DPR (intraperitoneal dialysis fluid plus two volumes of FFP). Fluorescein isothiocyanate-dextran (molecular weight, 4 kDa; FD4) was instilled into the gastrointestinal tract before hemorrhage; FD4 was measured by UV spectrometry at various time points. Plasma syndecan-1 and ileum tissue TJ proteins were measured using enzyme-linked immunosorbent assay. Immunofluorescence was used to visualize claudin-4 concentrations at 4 hours following HS/RES. RESULTS: Following HS, FFP attenuated FD4 leak across the intestine at all time points compared with CR and DPR alone. This response was significantly improved with the adjunctive DPR at 3 and 4 hours post-RES (p < 0.05). Resuscitation with FFP-DPR increased intestinal tissue concentrations of TJ proteins and decreased plasma syndecan-1. Immunofluorescence demonstrated decreased mobilization of claudin-4 in both FFP and FFP-DPR groups. CONCLUSION: Fresh frozen plasma-based RES improves intestinal TJ and endothelial integrity. The addition of DPR can further stabilize TJs and attenuate intestinal permeability. Combination therapy with DPR and FFP to mitigate intestinal barrier breakdown following shock could be a novel method of reducing ischemia-induced intestinal permeability and systemic inflammation after trauma. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level III.

Thalidomide Inhibits Angiogenesis via Downregulation of VEGF and Angiopoietin-2 in Crohn's Disease.

Immune-mediated angiogenesis is important in the pathogenesis of inflammatory bowel disease and targeted treatment could alleviate the disease. Thalidomide is an effective drug in inflammatory bowel disease, which might be related to its multiple role in anti-inflammatory, immunoregulatory, and anti-angiogenesis. This study is to investigate the effect of thalidomide on angiogenesis in tissues from patients and in vitro cells. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), VEGF, and CD31 expressions in intestinal mucosa from pediatric CD patients before and after thalidomide treatment were measured by immunohistochemistry. Western blotting and polymerase chain reaction were performed to characterize the change of angiogenic factors before and after treatment in remission. Human umbilical vein endothelial cells (HUVECs) treated by thalidomide were used to examine its effect on endothelial cell proliferation and migration and capillary-like structures. Results showed that VEGF and Ang-2 levels were significantly greater in CD patients over controls. Thalidomide produced a significant reduction in protein expression of Ang-2 and VEGF, along with a decrease in mRNA expression of Ang-2. While, Ang-1 level did not show a statistically significant change. Thalidomide significantly inhibited cell proliferation in a dose-dependent manner. It also suppressed VEGF- and Ang-2-induced cell migration and capillary-like tube formation in HUVECs. Therefore, our study suggests that VEGF and Ang-2 levels are up-regulated in pediatric CD patients. It also indicated that thalidomide can be able to deactivate endothelium by the downregulation effect on angiogenic factors by targeting VEGF and Ang-2.

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability.

BACKGROUND & AIMS: Increased vascular permeability (VP) has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). However, the pathological causes of increased intestinal VP in IBD remain largely unknown. METHOD: Fibrinogen level was measured in dextran sulphate sodium (DSS)-induced colitis and patients with ulcerative colitis. Gly-Pro-Arg-Pro acetate (GPRP), an Fg inhibitor, was used to detect the effect of Fg inhibition on the pathogenesis of DSS-induced colitis, as indicated by tissue damage, cytokine release and inflammatory cell infiltration. Miles assay was used to detect vascular permeability. RESULTS: Through tandem mass tag-based quantitative proteomics, fibrinogen (Fg) was found to be upregulated in the colon of DSS-treated mice, which was consistent with increased Fg level in colon sample of patients with ulcerative colitis. Gly-Pro-Arg-Pro acetate (GPRP), an Fg inhibitor, significantly alleviated DSS-induced colitis as indicated by improvement of body weight loss and mortality. GPRP decreased colonic inflammation and VP in DSS-treated mice. In vivo, Fg enhanced VP as indicated by Miles assay, which was significantly inhibited by GRPR, AKT (serine/threonine kinase 1) inhibitors and low doses of Jasplakinolide which induced actin polymerization, while was dramatically enhanced by Cytochalasin D (an actin polymerization inhibitor). Moreover, activation of AKT was found in vessels of DSS-treated mice. In vitro, Fg induced activation of AKT and depolymerization of microfilament and promoted cell-to-cell disaggregation. Furthermore, inhibition of AKT decreased Fg-induced microfilament depolymerization. CONCLUSIONS: Our findings highlight the importance of Fg in regulating colitis by modulation of VP via activating AKT and subsequent depolymerization of microfilament and suggest Fg as an attractive target for anti-colitis treatment.

Usefulness of a finger-mounted tissue oximeter with near-infrared spectroscopy for evaluating the intestinal oxygenation and viability in rats.

PURPOSE: To investigate the utility of the device for evaluating intestinal oxygenation and viability using an animal model. METHODS: Sprague-Dawley rats underwent laparotomy under general anesthesia, and the blood vessels in the terminal ileum were clamped to create ischemia. We measured the regional tissue oxygenation saturation (rSO2) using an oximeter after 1, 3, and 6 h of vessel clamping. Ischemic tissue damage was assessed using a histological score. The intestine was reperfused after each clamping period, and intestinal rSO2 and survival rate were evaluated. RESULTS: When reperfusion was performed at 1 and 3 h after ischemia, rSO2 increased after 10 min, and it improved to the same level as for normal intestine after 1 h; all rats survived for 1 week. In contrast, after 6 h of ischemia, rSO2 did not increase after reperfusion, and all animals died within 2 days. The histological scores increased after 1 h of reperfusion, with longer clamping periods. CONCLUSION: A finger-mounted tissue oximeter could evaluate intestinal ischemia and the viability, which is thus considered to be a promising result for future clinical application.

Microarray Profiling and Functional Identification of LncRNA in Mice Intestinal Mucosa Following Intestinal Ischemia/Reperfusion.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. METHODS: The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. RESULTS: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. CONCLUSIONS: Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

circ-PRKCB acts as a ceRNA to regulate p66Shc-mediated oxidative stress in intestinal ischemia/reperfusion.

Background: Oxidative stress has emerged as an essential factor in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. The adaptor protein p66Shc is a key regulator of reactive oxygen species (ROS) generation and a mediator of I/R damage in the intestine, but the upstream mechanisms that directly regulate p66Shc expression during intestinal I/R remain largely unknown. Recent studies have suggested that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their versatile regulatory roles in gene expression. The aim of this study was to elucidate the contribution of p66Shc to oxidative damage in intestinal I/R and to investigate the regulation of p66Shc by circRNA sponges. Methods: Intestinal I/R was induced in mice via superior mesenteric artery (SMA) occlusion. A miR-339-5p agomir or circ-protein kinase C beta (PRKCB) siRNA was injected intravenously before I/R challenge. In addition, Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. Results:In vitro, p66Shc deficiency significantly reduced H/R-induced ROS overproduction by attenuating mitochondrial superoxide anion (O2-) levels, suppressing NADPH oxidase activity and enhancing antioxidant enzyme expression. Moreover, miR-339-5p was identified to directly regulate p66Shc expression in the intestine. Furthermore, we found that a circRNA transcribed from the PRKCB gene, named circ-PRKCB, acted as an endogenous miR-339-5p sponge to regulate p66Shc expression. circ-PRKCB silencing or miR-339-5p overexpression significantly downregulated p66Shc expression and attenuated oxidative stress levels and I/R injury in vivo and in vitro. Notably, the increased circ-PRKCB levels and decreased miR-339-5p levels associated with murine intestinal I/R were consistent with those in patients with intestinal infarction. Conclusions: Our findings reveal a crucial role for the circ-PRKCB/miR-339-5p/p66Shc signaling pathway in regulating oxidative stress in the I/R intestine. This pathway may be a potential therapeutic target for intestinal I/R injury.

Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

OBJECTIVE: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. RESULTS: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. CONCLUSION: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Utility of narrow band imaging in predicting histology in celiac disease.

BACKGROUND: Narrow band imaging (NBI) with magnification better visualizes the duodenal microsurface and mucosal vascularity. NBI delineates villous atrophy better than conventional white light endoscopy. AIMS: This study was conducted to evaluate the diagnostic accuracy of narrow band imaging with magnification (NBI-ME) in celiac disease (CD). METHODS: In this prospective study, consecutive patients of suspected CD and controls were subjected to tissue transglutaminase antibody test and endoscopic evaluation initially with white light followed by NBI-ME, and biopsies were taken from duodenum. Duodenal villous patterns on NBI were interpreted as normal, blunted distorted, and absent. Severity of villous atrophy was reported according to the modified Marsh criteria. RESULTS: One hundred and twenty-two patients (mean age of 27.53 ± 13.37 years and a male to female ratio of 1:1.26) and 40 controls were studied. The sensitivity and specificity of NBI-ME in predicting villous atrophy were found to be 95.54% and 90%, respectively. The specificity and negative predictive value of NBI-ME in predicting villous atrophy amongst controls was 100% and 97.5%, respectively. Abnormal findings (blunted and absent villous patterns) combined with elevated transglutaminase antibody (> 5-fold) were found to have high accuracy in predicting villous atrophy. CONCLUSION: NBI with magnification has high sensitivity and specificity in predicting villous atrophy in patients with celiac disease.