The pathogenesis of inflammatory bowel disease (IBD) is not fully elucidated. However, it has been considered that inflammatory macrophages may be involved in the imbalance of the intestinal mucosal immunity to regulate several signaling pathways, leading to IBD progression. The ratio of M1 to M2 subtypes of activated macrophages tends to increase in the inflamed intestinal section. There are challenges in the diagnosis and treatment of IBD, such as unsatisfactory specificity of imaging findings, low drug accumulation in the intestinal lesions, unstable therapeutic efficacy, and drug-related systemic toxicity. Recently developed nanoparticles may provide a new approach for the diagnosis and treatment of IBD. Nanoparticles targeted to macrophages can be used as contrast agents to improve the imaging quality or used as a drug delivery vector to increase the therapeutic efficiency of IBD. This article reviews the research progress on macrophage-targeting nanoparticles for the diagnosis and treatment of IBD to provide a reference for further research and clinical application.
Humans ; Inflammatory Bowel Diseases/therapy* ; Intestines ; Macrophages/metabolism* ; Intestinal Mucosa/pathology* ; Nanoparticles

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls. METHODS: Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test. RESULTS: Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001). CONCLUSIONS Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
Adenosine Triphosphate ; metabolism ; Adult ; Blotting, Western ; Colon ; metabolism ; pathology ; Diarrhea ; enzymology ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; genetics ; physiology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Irritable Bowel Syndrome ; enzymology ; metabolism ; pathology ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism

PURPOSE: Early application of protease inhibitors through the intestinal lumen could increase survival following experimental shock by blocking the pancreatic digestive enzymes. Hence, it was hypothesized that two-route injection (intraintestinal + intravenous) of ulinastatin (UTI), a broad-spectrum protease inhibitor, could better alleviate intestinal injury than single-route injection (either intravenous or intraintestinal). METHODS: A sepsis model induced by lipopolysaccharide on rats was established. The rats were randomly divided into five groups: sham, sepsis, UTI intravenous injection (Uiv), UTI intraintestinal injection (Uii), and UTI intraintestinal + intravenous injection (Uii + Uiv) groups. The mucosal barrier function, enzyme-blocking effect, levels of systemic inflammatory cytokines, and 5-day survival rate were compared among groups. The small intestinal villus height (VH), crypt depth (CD), and two components of mucosal barrier (E-cadherin and mucin-2) were measured to evaluate the mucosal barrier function. The levels of trypsin and neutrophil elastase (NE) in the intestine, serum, and vital organs were measured to determine the enzyme-blocking effect. RESULTS: Compared with the single-route injection group (Uiv or Uii), the two-route injection (Uii + Uiv) group displayed: (1) significantly higher levels of VH, VH/CD, E-cadherin, and mucin-2; (2) decreased trypsin and NE levels in intestine, plasma, and vital organs; (3) reduced systemic inflammatory cytokine levels; and (4) improved survival of septic rats. CONCLUSION Two-route UTI injection was superior to single-route injection in terms of alleviating intestinal injury, which might be explained by extensive blockade of proteases through different ways.
Animals ; Cadherins ; metabolism ; Cytokines ; metabolism ; Disease Models, Animal ; Glycoproteins ; administration & dosage ; pharmacology ; Inflammation Mediators ; metabolism ; Injections, Intralesional ; Injections, Intravenous ; Intestinal Diseases ; drug therapy ; etiology ; metabolism ; Intestinal Mucosa ; metabolism ; pathology ; Intestines ; Leukocyte Elastase ; metabolism ; Male ; Mucin-2 ; metabolism ; Rats, Wistar ; Sepsis ; complications ; Trypsin ; metabolism ; Trypsin Inhibitors ; administration & dosage ; pharmacology

OBJECTIVETo investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).

METHODSMice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.

RESULTSPCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.

CONCLUSIONSRSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.

Amino Acids, Branched-Chain ; metabolism ; Animals ; Female ; Gas Chromatography-Mass Spectrometry ; Intestinal Mucosa ; metabolism ; Intestine, Large ; metabolism ; pathology ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Pneumonia, Viral ; metabolism ; Respiratory Syncytial Virus Infections ; metabolism

To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.
Animals ; Aquaporin 3 ; physiology ; Aquaporins ; Blotting, Western ; Colon ; chemistry ; pathology ; Constipation ; physiopathology ; therapy ; Cyclic AMP ; physiology ; Defecation ; Epithelial Cells ; pathology ; Feces ; chemistry ; Goblet Cells ; pathology ; Intestinal Mucosa ; metabolism ; pathology ; RNA, Messenger ; Rats ; Signal Transduction ; Vasoactive Intestinal Peptide ; administration & dosage ; physiology ; therapeutic use

Inflammatory bowel disease (IBD) is a chronic progressive idiopathic inflammatory disorder that involves the digestive tract from the mouth to the anus. Over the past decades, many therapeutic strategies have been developed to manage IBD, but therapeutic strategies based only on relief of clinical symptoms have not changed the natural history of this disease entity. This underlines the importance of understanding the natural history of IBD itself. When we look at the natural history of Crohn's disease (CD), it first begins with inflammation of the intestinal mucosa and this inflammatory reaction proceeds to stenosing or penetrating reaction if not adequately controlled. However, it takes a considerable amount of time before mucosal inflammation proceeds to stenosis of the intestinal lumen or penetration into the adjacent bowel. Therefore, it can be expected that if proper care is given during that period, progression of CD to such a complicated disease could be prevented. Even though the concept of mucosal healing was introduced in the early 1990s, no correlation could be observed between healing of mucosal lesions and relief of clinical symptoms. However, the introduction of biologic agents targeting tumor necrosis factor has changed the way to treat IBD that is refractory to standard medications and has allowed us to aim for a new therapeutic goal, 'deep remission'. Further advances in biologic agents have provided highly effective treatments for IBD, making deep remission a realistic goal. Whether IBD patients may benefit by experiencing a 'deep' remission beyond the control of clinical symptoms need to be evaluated in further investigation. Nevertheless, it can be anticipated that attaining deep remission might ultimately have an impact on important outcomes such as the need for surgery and the quality of life.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Colitis, Ulcerative/drug therapy/metabolism/pathology ; Crohn Disease/drug therapy/metabolism/pathology ; Humans ; Inflammatory Bowel Diseases/drug therapy/metabolism/*pathology ; Intestinal Mucosa/metabolism/pathology ; Mesalamine/therapeutic use ; Tumor Necrosis Factor-alpha/immunology/metabolism

Hemangioma of the esophagus is a rare form of benign esophageal tumor. It usually presents as a single lesion located in the lower third of the esophagus and is mostly asymptomatic. However, it may occasionally cause hematemesis and/or obstruction. Surgical resection is the conventional treatment modality for managing esophageal hemangioma, but less invasive approaches such as endoscopic therapy are recently becoming more widely employed. Herein, we report a case of a 54-year-old man who presented with an esophageal hemangioma that was successfully treated by endoscopic mucosal resection without any complications.
Antigens, CD31/metabolism ; Esophageal Diseases/*diagnosis/surgery ; Esophagoscopy ; Esophagus/diagnostic imaging/metabolism/pathology ; Hemangioma/*diagnosis/surgery ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo observe the effects of astragalus polysaccharide (AP) on the intestinal mucosal morphology, level of secretory IgA (s-IgA) in intestinal mucus, and distribution of T lymphocyte subsets in Peyer's patch in rats with severe scald injury.

METHODSOne hundred and thirty SD rats were divided into sham injury group (SI, sham injured, n = 10), scald group (S, n = 30), low dosage group (LD, n = 30), moderate dosage group (MD, n = 30), and high dosage group (HD, n = 30) according to the random number table. Rats in the latter 4 groups were inflicted with 30% TBSA full-thickness scald on the back. From post injury hour 2, rats in groups LD, MD, and HD were intraperitoneally injected with 0.5 mL AP solution with the dosage of 100, 200, and 300 mg/kg each day respectively, and rats in group S were injected with 0.5 mL normal saline instead. Ten rats from group SI immediately after injury and 10 rats from each of the latter 4 groups on post injury day (PID) 3, 7, 14 were sacrificed, and their intestines were harvested. The morphology of ileal mucosa was examined after HE staining; the level of s-IgA in ileal mucus was determined with double-antibody sandwich ELISA method; the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes in Peyer's patches of intestine were determined with flow cytometer, and the proportion of CD4⁺ to CD8⁺ was calculated. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test.

RESULTS(1) Villi in normal form and intact villus epithelial cells were observed in rats of group SI immediately after injury, while edema of villi and necrosis and desquamation of an enormous amount of villi were observed in groups with scalded rats on PID 3, with significant infiltration of inflammatory cells. On PID 7, no obvious improvement in intestinal mucosal lesion was observed in groups with scalded rats. On PID 14, the pathology in intestinal mucosa of rats remained nearly the same in group S, and it was alleviated obviously in groups LD and MD, and the morphology of intestinal mucosa of rats in group HD was recovered to that of group SI. (2) On PID 3, 7, and 14, the level of s-IgA in intestinal mucus significantly decreased in groups S, LD, MD, and HD [(43 ± 5), (45 ± 5), (46 ± 5) µg/mL; (47 ± 5), (48 ± 5), (49 ± 6) µg/mL; (50 ± 6), (51 ± 5), (52 ± 5) µg/mL; (53 ± 6), (54 ± 5), (55 ± 5) µg/mL] as compared with that of rats in group SI immediately after injury [(69 ± 4) µg/mL, with P values below 0.05]. The level of s-IgA in intestinal mucus of rats in group MD was significantly higher than that in group S at each time point (with P values below 0.05), and that of group HD was significantly higher than that in groups S and LD at each time point (with P values below 0.05). (3) Compared with those of rats in group SI immediately after injury, the proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes significantly decreased in groups with scalded rats at each time point (with P values below 0.05), except for those in group HD on PID 14. The proportion of CD4⁺ T lymphocytes of rats in group LD was significantly higher than that in group S on PID 3 (P < 0.05). The proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes were significantly higher in groups MD and HD than in groups S and LD (except for the proportion of CD4⁺ T lymphocytes in group MD on PID 3 and 14) at each time point (with P values below 0.05). The proportion of CD3⁺ T lymphocytes on PID 7 and 14 and that of CD4⁺ T lymphocytes on PID 3 were significantly higher in group HD than in group MD (with P values below 0.05). Compared with that of rats in group SI immediately after injury, the proportion of CD8⁺ T lymphocytes significantly increased in the other 4 groups at each time point (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group LD on PID 7 and 14 and groups MD and HD at each time point than in group S (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group MD on PID 7 and 14 and group HD at each time point than in group LD (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group HD on PID 7 and 14 than in group MD (with P values below 0.05). On PID 3, 7, and 14, the proportion of CD4⁺ to CD8⁺ was significantly lower in groups S, LD, MD, and HD (0.65 ± 0.11, 0.68 ± 0.13, 0.73 ± 0.22; 0.76 ± 0.15, 0.78 ± 0.14, 0.90 ± 0.10; 0.85 ± 0.21, 0.89 ± 0.18, 1.08 ± 0.19; 0.99 ± 0.20, 1.05 ± 0.21, 1.25 ± 0.23) as compared with that of rats in group SI immediately after injury (1.74 ± 0.20, with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group HD than in group MD on PID 7 (P < 0.05), and the proportion was significantly higher in these two groups than in group S at each time point (with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group MD on PID 14 and group HD at each time point than in group LD (with P values below 0.05). Compared within each group, the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes and the proportion of CD4⁺ to CD8⁺ of rats in groups LD, MD, and HD showed a trend of gradual elevation along with passage of time.

CONCLUSIONSAP can improve the injury to intestinal mucosa and modulate the balance of T lymphocyte subsets in Peyer's patch in a time- and dose-dependent manner, and it can promote s-IgA secretion of intestinal mucosa in a dose-dependent manner.

Animals ; Astragalus Plant ; adverse effects ; Burns ; immunology ; pathology ; physiopathology ; Dose-Response Relationship, Drug ; Immunity, Mucosal ; Immunoglobulin A ; metabolism ; Intestinal Mucosa ; metabolism ; physiology ; Intestine, Small ; metabolism ; Peyer's Patches ; immunology ; physiopathology ; Polysaccharides ; Rats ; Rats, Sprague-Dawley ; Soft Tissue Injuries ; T-Lymphocyte Subsets ; immunology

BACKGROUND/AIMS: Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis. METHODS: This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunohistochemical analysis of the colonic mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-kappaB, interferon-gamma, inducible nitric oxide synthase, and tumor necrosis factor-alpha. We compared the quantity score of immunohistochemical staining among the groups. RESULTS: The microscopic colitis group showed significantly higher expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-kappaB, and interferon-gamma compared with the control group. Cytokine expression was similar between collagenous colitis and lymphocytic colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous colitis. CONCLUSIONS: Proinflammatory cytokines, including interleukin-17 and interferon-gamma, are highly expressed in microscopic colitis. The expression of cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis. This study is the first on interleukin-17 expression in microscopic colitis patients.
Biopsy ; Colitis, Microscopic/*metabolism ; Colon/pathology ; Cyclooxygenase 2/*metabolism ; Cytokines/metabolism ; Diarrhea/metabolism ; Humans ; Interferon-gamma/metabolism ; Interleukin-17/*metabolism ; Intestinal Mucosa/pathology ; NF-kappa B/metabolism ; Nitric Oxide Synthase Type II/*metabolism ; Tumor Necrosis Factor-alpha/metabolism