• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.161-167
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• 2015

These commensal intestinal bacteria can enhance the immune system and aid in nutrient absorption but can also act as opportunistic pathogens. Among these intestinal bacteria, the anaerobic Bacteroides fragilis are divided into enterotoxigenic B. fragilis (ETBF) which secrete the B. fragilis toxin (BFT) and non-enterotoxigenic B. fragilis (NTBF) which do not secrete BFT. ETBF can cause diarrhea and colitis in both humans and livestock but can also be found in asymptomatic individuals. ETBF is predominantly found in patients with inflammatory diarrheal diseases and traveller's diarrhea. Several clinical studies have also reported an increased prevalence of ETBF in human patients with inflammatory bowel disease (IBD), colitis and colorectal cancer. In small animal models (C57BL/6 wild-type mice, germ-free mice, multiple intestinal neoplasia (Min) mice, rabbits and Mongolian gerbils), ETBF have been found to initiate and/or aggravate IBD, colitis and colorectal cancer. BFT induces E-cadherin cleavage in intestinal epithelial cells resulting in loss of epithelial cell integrity. Subsequent activation of the ${\beta}$-catenin pathway leads to increased cellular proliferation. In addition, ETBF causes acute and chronic colitis in wild-type mice as well as enhances tumorigenesis in Min mice via activation of the Stat3/Th17 pathway. Currently, ETBF can be detected using a BFT toxin bioassay and by PCR. Advances in molecular biological techniques such as real-time PCR have allowed both researchers as well as clinicians to rapidly detect ETBF in clinical samples. The emergence of more sensitive techniques will likely advance molecular insight into the role of ETBF in colitis and cancer.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.3-10
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• 2015

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. MATERIALS/METHODS: An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. RESULTS: Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), IL-6, and IL-$1{\beta}$ in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-${\alpha}$ were down-regulated in response to inhibition of $I{\kappa}B{\alpha}$ phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. CONCLUSIONS: SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.96-104
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• 2022

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener's disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn's disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1506-1512
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• 2023

Quantitative analysis of adenosine triphosphate (ATP) has been widely used as a diagnostic tool in the food and medical industries. Particularly, the pathogenesis of a few diseases including inflammatory bowel disease (IBD) is closely related to high ATP concentrations. A bioluminescent D-luciferin/luciferase system, which includes a luciferase (FLuc) from the firefly Photinus pyralis as a key component, is the most commonly used method for the detection and quantification of ATP. Here, instead of isolating FLuc produced in recombinant Escherichia coli, we aimed to develop a whole-cell biocatalyst system that does not require extraction and purification of FLuc. To this end, the gene coding for FLuc was introduced into the genome of probiotic Saccharomyces boulardii using the CRISPR/Cas9-based genome editing system. The linear relationship (r² = 0.9561) between ATP levels and bioluminescence generated from the engineered S. boulardii expressing FLuc was observed in vitro. To explore the feasibility of using the engineered S. boulardii expressing FLuc as a whole-cell biosensor to detect inflammation biomarker (i.e., ATP) in the gut, a colitis mouse model was established using dextran sodium sulfate as a colitogenic compound. Our findings demonstrated that the whole-cell biosensor can detect elevated ATP levels during gut inflammation in mice. Therefore, the simple and powerful method developed herein could be applied for non-invasive IBD diagnosis.

• Journal of Yeungnam Medical Science
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• v.38 no.3
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• pp.251-257
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• 2021

Vedolizumab (VDZ) has been approved for the treatment of inflammatory bowel diseases (IBDs) in patients aged ≥18 years. We report a case of a pediatric patient with Crohn disease (CD) who was successfully treated with VDZ. A 16-year-old female developed severe active pulmonary tuberculosis (TB) during treatment with infliximab (IFX). IFX was stopped, and TB treatment was started. After a 6-month regimen of standard TB medication, her pulmonary TB was cured; however, gastrointestinal symptoms developed. Due to the concern of the patient and parents regarding TB reactivation on restarting treatment with IFX, VDZ was started off-label. After the second dose of VDZ, the patient was in clinical remission and her remission was continuously sustained. Ileocolonoscopy at 1-year after VDZ initiation revealed endoscopic healing. Therapeutic drug monitoring conducted during VDZ treatment showed negative antibodies to VDZ. No serious adverse events occurred during the VDZ treatment. This is the first case report in Korea demonstrating the safe and effective use of VDZ treatment in a pediatric CD patient. In cases that require recommencement of treatment with biologics after recovery of active pulmonary TB caused by anti-tumor necrosis factor agents, VDZ may be a good option even in pediatric IBD.

• BMB Reports
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• v.52 no.5
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6923-6928
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• 2015

Background: Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. Materials and Methods: Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls. The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0.45 with AUC 0.812. Conclusions: These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals.

• Food Science of Animal Resources
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• v.32 no.4
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• pp.434-440
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• 2012

It has been suggested that probiotics could be useful for the prevention of symptomatic relapse in patients with inflammatory bowel disease (IBD). Interleukin (IL)-8 has been well recognized as one of the pro-inflammatory cytokines that could trigger inflammation and epithelial barrier dysfunction. In this study, the anti-inflammatory effects of probiotics were investigated using a human epithelial cell line (HT-29). Probiotics from infant feces and kimchi were tested for their cytotoxicity and effects on adhesion to epithelial cells. The present results show that seven strains could form 70 % adhesion on HT-29. The probiotics used in this study did not affect HT-29 cell viability. To screen anti-inflammatory lactic acid bacteria, HT-29 cells were pretreated with live and heat-killed probiotics, and lipopolysaccharide (LPS) ($1{\mu}g/mL$) was then added to stimulate the cells. The cell culture supernatant was then used to measure IL-8 secretion by ELISA, and the cell pellet was used to determine IL-8 and toll-like receptor (TLR-4) mRNA expression levels by RT-PCR. Some probiotics (KJP421, KDK411, SRK414, E4191, KY21, and KY210) exhibited anti-inflammatory effects through the repression of IL-8 secretion from HT-29 cells. In particular, Lactobacillus salivarius E4191, originating from Egyptian infant feces, not only decreased IL-8 mRNA expression, but also decreased TLR-4 expression. These results indicate that Lactobacillus salivarius E4191 may have a protective effect in intestinal epithelial cells.

• Nutrition Research and Practice
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• v.13 no.2
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• pp.95-104
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• 2019

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to $12.5-50{\mu}g/mL$ extract. However, absence of XBP1 or $IRE1{\alpha}$ in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an $IRE1{\alpha}$-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.6
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• pp.255-260
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• 2021

Crohn's disease (CD) is an idiopathic inflammatory bowel disease (IBD) with unknown etiopathogenesis. Currently there are no definitive treatment modalities for CD. This case report presents clinical remission and its maintenance of CD induced by Korean herbal medicine treatment. A 56-year-old male patient diagnosed as CD by capsule endoscopy presented to a Korean Medicine clinic with severe abdominal pain as a chief complaint. Despite taking 5-aminosalicylic acid and immunosuppressant for 2 years, his abdominal pain was worsening at the time of visit. Treatment was initiated with Jinmoo-tang based on pattern identification and continued for approximately a year with some modifications according to patient's symptom changes. He was mainly given Jinmoo-Tang for a year and clinical remission was achieved; he could stop taking western medications. For 6 years since then, he took Korean medicine from time to time when he felt his condition went down and he is still maintaining remission. There were no adverse events reported. This case report suggests that individualized Korean herbal medicine treatment may have the potential for induction and maintenance of clinical remission of CD. Further research is warranted to establish an evidence-base for such approach.