• Genes and Genomics
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• v.40 no.12
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• pp.1383-1388
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• 2018

The development of therapeutic bacteriophages will provide several benefits based on an understanding the basic physiological dynamics of phage and bacteria interactions for therapeutic use in light of the results of antibiotic abuse. However, studies on bacteriophage therapeutics against microbes are very limited, because of lack of phage stability and an incomplete understanding of the physiological intracellular mechanisms of phage. The major objective of this investigation was to provide opportunity for development of a novel therapeutic treatment to control respiratory diseases in swine. The cytokine array system was used to identify the secreted cytokines/chemokines after Bordetella bronchiseptica infection into swine nasal turbinate cells (PT-K75). We also performed the real-time quantitative PCR method to investigate the gene expression regulated by B. bronchiseptica infection or bacteriophage treatment. We found that B. bronchiseptica infection of PT-K75 induces secretion of many cytokines/chemokines to regulate airway inflammation. Of them, secretion and expression of IL-$1{\beta}$ and IL-6 are increased in a dose-dependent manner. Interestingly, membrane-bound mucin production via expression of the Muc1 gene is increased in B. bronchiseptica-infected PT-K75 cells. However, cytokine production and Muc1 gene expression are dramatically inhibited by treatment with a specific B. bronchiseptica bacteriophage (Bor-BRP-1). The regulation of cytokine profiles in B. bronchiseptica-induced inflammation by B. bronchiseptica bacteriophage is essential for avoiding inappropriate inflammatory responses. The ability of bacteriophages to downregulate the immune response by inhibiting bacterial infection emphasizes the possibility of bacteriophage-based therapies as a novel anti-inflammatory therapeutic strategy in swine respiratory tracts.

• Journal of Microbiology and Biotechnology
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• v.18 no.7
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• pp.1278-1285
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• 2008

The intestinal epithelial cell (IEC) layer of the intestinal tract makes direct contact with a number of microbiota communities, including bacteria known to have deleterious health effects. IECs possess innate protective strategies against pathogenic challenge, which primarily involve the formation of a physicochemical barrier. Intestinal tract mucins are principal components of the mucus layer on epithelial surfaces, and perform a protective function against microbial damage. However, little is currently known regarding the interactions between probiotics/pathogens and epithelial cell mucins. The principal objective of this study was to determine the effects of Lactobacillus on the upregulation of MUC2 mucin and the subsequent inhibition of E. coli O157:H7 attachment to epithelial cells. In the current study, the attachment of E. coli O157:H7 to HT-29 intestinal epithelial cells was inhibited significantly by L. acidophilus A4 and its cell extracts. It is also important to note that the expression of MUC2 mucin was increased as the result of the addition of L. acidophilus A4 cell extracts (10.0 mg/ml), which also induced a significant reduction in the degree to which E. coli O157:H7 attached to epithelial cells. In addition, the mRNA levels of IL-8, IL-1$\beta$, and TNF-$\alpha$ in HT-29 cells were significantly induced by treatment with L. acidophilus A4 extracts. These results indicate that MUC2 mucin and cytokines are important regulatory factors in the immune systems of the gut, and that selected lactobacilli may be able to induce the upregulation of MUC2 mucin and specific cytokines, thereby inhibiting the attachment of E. coli O157:H7.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.469-474
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• 2016

Liriopogons (Liriope and Opiopogon) species are used as a main medicinal ingredient in several Asian countries. The Liriopes Radix (tuber, root of Liriope platyphylla) has to be a promising candidate due to their source of phytochemicals. Steroidal saponins and their glycosides, phenolic compounds, secondary metabolites are considered of active constituents in Liriopes Radix. Spicatoside A, a steroidal saponin, could be more efficacious drug candidate in future. In this review, we summarized the available knowledge on phytochemical and pharmacological activities for spicatoside A. It significantly suppressed the level of NF-${\kappa}B$, NO, iNOS, Cox-2, IL-$1{\beta}$, IL-6 and MAPKs in LPS-stimulated inflammation. The production of MUC5AC mucin was increased. MMP-13 expression was down-regulated in IL-$1{\beta}$-treated cells and reduced glycosaminoglycan release from IL-$1{\alpha}$-treated cells. The neurite outgrowth activity, PI3K, Akt, ERK1/2, TrkA and CREB phosphorylation and neurotropic factors such as NGF and BDNF were upregulated with increased latency time. It also showed cell growth inhibitory activity on various carcinoma cells. From this, spicatoside A exerts anti-inflammation, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anticancer activities. Further studies are needed on spicatoside A in order to understand mechanisms of action to treat various human diseases.

• The Journal of Internal Korean Medicine
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• v.38 no.3
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• pp.353-366
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• 2017

Objective: This study aimed to use a mouse model to evaluate the effects of Gwaruhaengryeon-hwan (GHH) on chronic obstructive pulmonary disease (COPD) and particulate matter induced lung injury. Materials and Methods: The study was carried out in two ways (in vitro, in vivo). In vitro RAW 264.7 cells (mouse macrophage) were used and analyzed by flow cytometry, ELISA. In vivo lipopolysaccharide (LPS) and cigarette smoke solution (CSS), or coal, fly ash, diesel exhaust particle (CFD) challenged mice were used and its BALF was analyzed by ELISA, lung tissue by real-time PCR. Results: In vitro, GHH maintained an 80-100% rate of viability. So cytotoxicity was not shown. In the ELISA analysis with RAW 264.7 cells, GHH significantly decreased NO over $30{\mu}g/ml$. In the ELISA analysis, GHH significantly decreased $TNF-{\alpha}$, IL-6 over $300{\mu}g/ml$. In the COPD model, the GHH 200 mg/kg dosage group, the application of GHH significantly decreased the increasing of neutrophils, $TNF-{\alpha}$, IL-17A, MIP2, CXCL-1 in BALF, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA expression in lung tissue and histological lung injury. In the CFD induced lung injury model, the GHH 200 mg/kg dosage group, the application of GHH significantly decreased the increase of neutrophils, $TNF-{\alpha}$, IL-17A, MIP2, CXCL-1 in BALF, MUC5AC, $TGF-{\beta}$ mRNA expression in lung tissue and histological lung injury. Conclusion: This study suggests the usability of GHH for COPD patients by controlling lung tissue injury.

• Development and Reproduction
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• v.22 no.4
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• pp.379-391
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• 2018

Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or $500{\mu}g/L$) or DEHP (133 or $1,330{\mu}g/L$) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known $17{\beta}$-estradiol ($E_2$)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in $133{\mu}g/L$ DEHP. Endometrial and myometrial thickness increased in 133 and $1,330{\mu}g/L$ DEHP treated groups, and in 50, $500{\mu}g/L$ NP and $133{\mu}g/L$ DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in $50{\mu}g/L$ DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known $17{\beta}$-estradiol ($E_2$) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.