• The Korea Journal of Herbology
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• v.29 no.4
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• pp.29-34
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• 2014

Objectives : Ulcerative colitis (UC) is an inflammatory bowel disease, which is one of chronic gastrointestinal disorders. Orostachys japonicus (OJ) has been used as a traditional medicine for various diseases including gastric cancer, gastric ulcers and intoxication. However, the regulatory effect of OJ on intestinal inflammation has not been fully understood, yet. The aim of this study was to investigate the effect of OJ on dextran sulfate sodium (DSS)-induced colitis in mice. Methods : To ascertain the pharmacological effects of OJ, the colitis mice were induced by drinking water containing 5% DSS for 7 days. Mice were randomized into groups receiving OJ (100 mg/kg), sulfasalazine (150 mg/kg) as a positive control, or water as a negative control. We evaluated the effects of OJ on DSS-induced the clinical signs, measuring weight loss and colon length. In addition, the inhibitory effect of OJ on the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level was determined by enzyme-linked immunosorbent assay in colitis tissue. Results : The results indicated that mice treated with DSS showed remarkable clinical signs, including weight loss, and reduced colon length. However, treatment with OJ significantly improved the weight loss and DAI as clinical symptoms. Moreover, OJ reduced the TNF-${\alpha}$ levels in DSS-treated colon tissues. Conclusions : Collectively, the findings of this study provide us with novel insights into the pharmacological actions of OJ as a potential medicine for use in the treatment of ulcerative colitis.

• BMB Reports
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• v.56 no.2
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• pp.96-101
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• 2023

Particulate matter is an air pollutant composed of various components, and has adverse effects on the human body. Particulate matter is known to induce cell death by generating an imbalance in the antioxidant system; however, the underlying mechanism has not been elucidated. In the present study, we demonstrated the cytotoxic effects of the size and composition of particulate matter on small intestine cells. We found that particulate matter 2.5 (PM_2.5) with extraction ion (EI) components (PM_2.5 EI), is more cytotoxic than PM containing only polycyclic aromatic hydrocarbons (PAHs). Additionally, PM-induced cell death is characteristic of ferroptosis, and includes iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) generation. Furthermore, ferroptosis inhibitor as liproxstatin-1 and iron-chelator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, and ROS production after PM_2.5 EI treatment in human small intestinal cells. These results suggest that PM_2.5 EI may increase ferroptotic-cell death by iron accumulation and ROS generation, and offer a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.

• Journal of Life Science
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• v.26 no.9
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• pp.1082-1087
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• 2016

The intestinal tight junction (TJ) plays an important role as a paracellular barrier. Impaired TJ permeability and enhanced proinflammatory cytokine production are crucial pathophysiological mechanisms in inflammatory bowel diseases (IBDs). Although proinflammatory cytokines, tumor necrosis factor-alpha and interluekin-1 beta, which are markedly increased in IBD patients, have been reported to increase intestinal TJ permeability, the role of interleukin-1 alpha (IL-1α) in the TJ has not been studied. Phytochemicals could prevent proinflammatory cytokine-caused TJ alteration. Curcumin (CCM), a biologically active component of turmeric, has a strong anti-inflammatory activity. The purpose of this study was to elucidate the effect of IL-1α on intestinal epithelial TJ permeability and the role of CCM in IL-1α′s action on TJ in an in vitro intestinal epithelial system, Caco-2 monolayers. The TJ integrity of Caco-2 monolayers was estimated by measuring the flux of FITC-labeled dextran and transepithelial electrical resistance (TEER). Apical IL-1α (100 ng/ml) treatment elevated TJ permeability and suppressed TEER of Caco-2 monolayers. Pretreatment with CCM (20 μM) for 30 min significantly inhibited IL-1α-induced TJ alterations, such as increased TJ permeability and decreased in TEER values. These results demonstrated that IL-1α-induced increases in Caco-2 TJ permeability and CCM blocked the action of IL-1α in the TJ.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.339-344
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• 2004

Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.205-214
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• 2005

Background: We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (DC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. Methods: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the micro array analysis. Real time-PCR (RT-PCR) was performed to verify the results of micro array. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. Results: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A>G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g. -1,706 G>A (p=0.000000055), g. -1,458 G>A (p=0.0048), and g. -962C>A (p=0.0006) were found to be significantly associated with the susceptibility of Uc. Conclusion: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of Uc.

• Pediatric Infection and Vaccine
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• v.27 no.3
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• pp.158-170
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• 2020

Purpose: We evaluated the incidence and characteristics of Clostridioides difficile infection (CDI) in Korean children. Methods: Medical records of patients aged 2-18 years and diagnosed with CDI at a tertiary hospital between 2009 and 2018 were analyzed. The patients were classified into three CDI groups: community-acquired (CA), community onset-health care facility-associated (CO-HCFA), and healthcare facility onset (HO). Results: The incidence of CDI increased from 1.00 to 10.01 cases per 10,000 admissions from 2009 to 2018 (P<0.001). As compared to the CA group, the HO group had a higher frequency of operation and malignancy as predisposing factors (40.4% vs. 0.0%, P=0.001; and 27.7% vs. 0.0%, P=0.027, respectively), frequency and number of previous antibiotic use (97.9% vs. 31.3%, P<0.001; and 2 vs. 0, P<0.001, respectively), and median postdiagnosis hospital stay (13 vs. 5 days, P=0.008). The CO-HCFA group had a lower median age and higher frequency of malignancy than the CA group (5 vs. 13 years, P=0.012; and 30.8% vs. 0.0%, P=0.030, respectively). As compared to the HO group, the CA group had a higher frequency of abdominal pain and hematochezia (56.3% vs. 10.6%, P=0.001; and 50.0% vs. 10.6%, P=0.002, respectively), inflammatory bowel disease (68.8% vs. 2.1%, P=0.001), and intravenous metronidazole treatment (37.5% vs. 2.1%, P=0.001). Conclusions: With the increasing incidence of pediatric CDI, awareness regarding its epidemiology and clinical characteristics is important to manage nosocomial infections.