• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.25-32
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• 2021

Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

• Korean Journal of Microbiology
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• v.19 no.3
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• pp.142-152
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• 1981

One hundred and thirteen healed pulmonary tuberculosis patients and 11 patients with other underlying diseases were studied for evidence of pulmonary fungal infection because of persisting hemoptysis or chronic cough. Rediological, mycological and serological investigations revealed that 54 out of 124 patients were evidently infected with one or more species of fungi. A. fumigatus was isolated from 4 out of 70 patients whose sera did not react with antigens from this fungus, while it was isolated from 43 out of 47 serological reactors to this fungus. Chest radiography showed a distinct fungus ball in a cyst of one patient and in a preformed cavity in the lung of 17 healed tuberculosis patients and two other patients. The latter two patients were infected with A.flavus. Two patients, who were under the long period of immunosuppressive therapy, apparently succumbed to invasive aspergillosia due to A.fumigatus. A single or dual infection with A. flavus, A. nidulans, A.nidulans var. latus, C. albicans, and P. boydii were noticed in some patients without mycetomal shadow on chest radiographs. Young mycelial extract (ME) of A.fumigatus detected antibody in 95.8 percent of the sera from patients infected with this fungus, while it was isolated from 43 out of 47 serological reactors to this fungus. Chest radiography showed a distinct fungus ball in a cyst of one patient and in a performed cavity in the lung of 17 healed tuberculosis patients and two other patients. The latter two patients were infected with A. flavus. Two patients, who were under the long period of immunosuppressive therapy, apparently succumbed to invasive aspergillosis due to A.fumigatus. A single or dual infection with A. flavus, A. nidulans, A. niduans var. latus, C. albicans, and P. boydii were noticed in some patients without mycetomal shadow on chest radiographs. Young mycelial extract (ME) of A.fumigatus detected antibody in 95.8 percent of the sera from patients infected with this fungus, while the commercial culture filtrate antigen (GL) yielded 78.7 per cent positive result. Culture filtrate antigen, however, was comparable with ME. There was no single antigen with which all the serum specimens reacted. Fractionation of ME resulted in a loss of some activity although it excluded substances that reacted with C-reactive protein in a loss of some activity although it excluded substances that reacted with C-reactive protein. Most reactive and specific precipitinogens distributed in the fraction (FB) which was precipitable at 75 percent saturation with ammonium sulfate and eluted in a second peak in order from gel-filtration and which contained mostly proteinic components. Glycoproteins or polysaccharides rich fractions (FA and ASI) were relatively less effective in detecting antibody. Demonstration of antibody in the serum from patients using a battery of fungal antigens and of etiologically related fungi from clinical specimens are very useful laboratory procedures for the diagnosis of pulmonary fungal infection which is a common complication of tuberculosis.

• Journal of Food Hygiene and Safety
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• v.33 no.5
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• pp.383-388
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• 2018

In this study, we investigated the effect of bioprocessed polysaccharides (BPPs) from liquid culture of Lentinus edodes fungal mycelia containing rice bran (BPP-RB) on a chicken-derived macrophage cell line, HD-11, when infected with Salmonella Gallinarum, an etiological agent of fowl typhoid. Experimental results demonstrated water extract of BPP-RB did not show growth inhibitory effects on S. Gallinarum 277. Protein expression profiles were also not altered by its treatment. Nonetheless, it could (i) enhance phagocytic activity of HD-11 cells, (ii) activate transcriptional expression of Th1-type cytokines such as tumor necrosis factor-${\alpha}$ and interleukin $(IL)-1{\beta}$, iNOS, as well as an immunosuppressive cytokine IL-10, and (iii) negatively regulate Th2-type cytokines such as IL-4 and IL-6. Together results suggest that BPP-RB may be applicable for preventing fowl typhoid or other Salmonella infections in poultry farms as a potential feed additive.

• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.647-655
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• 1996

To establish the effective ways to prevent bovine mastitis, the study has been performed to investigate the attributable factors causing down-regulation of immune responses in mammary gland of non-lactating cows. Lymphocytes from peripheral blood and mammary gland secretions(MGS) were obtained from normal healthy cows and mastitic cows, respectively. Lymphoblastogenesis were investigated carefully by adding different concentrations of supernatants collected from pure-cultures of neutrophils seperated from peripheral blood and MGS, respectively. The results obtained are as follows ; 1. Lymphoblastogenesis activity stimulated by Con A, PWM and PHA were significantly reduced in MGS from mastitic cows. 2. Supernatants collected from pure-culture of neutrophils separated both from peripheral blood and MGS showed inhibitory effect on mitogenic lymphoblastogenesis. 3. Supernatants from mammary gland neutrophils have shown 7 times more inhibitory activity than those from peripheral blood and this inhibitory effect was increased in proportion to increasing concentrations of supernatants when those were added to lymphoblast cells in culture.

• Journal of Periodontal and Implant Science
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• v.30 no.4
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• pp.747-757
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• 2000

Cyclosporin A(CsA) is an immunosuppressive agent widely used for preventing graft rejecting response in organ transplantation. The basic properties of CsA to osteoblast has not been well known yet. A better understanding of the mechanisms of CsA function on bone could provide valuable information regarding basic properties of bone remodeling, pharmacotherapeutic intervention in metabolic bone disease, and the consequences of immunosuppression in bone physiology. The purpose of this study was to investigate the effect of CsA on osteoblast by evaluating parameters of proliferation, collagen synthetic activity, alkaline phosphatase activity, and ALP mRNA expression in mouse calvarial cell. 1. CsA ($3{\mu}g/m{\ell}$) treated mouse calvarial cell showed statistically significant increase in cell proliferation.(P<0.05) 2. CsA($1,\; 3{\mu}g/m{\ell}$) treated MC3T3 cell line showed statistically significant increase in cell proliferation. 3. The amount of collagen of CsA($3{\mu}g/m{\ell}$) treated mouse calvarial cell was decreased statistically significantly. 4. Alkaline phosphatase activity was increased statistically significantly in CsA treated group($1{\mu}g/m{\ell}$). 5. mRNA expression of ALP was increased in CsA treated group These results suggest that CsA could affect bone remodeling by modulating proliferation & differentiation of osteoblast.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.203-212
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• 2001

Background: Rapid advances in neuroendocrine immunology have established the concept of bidirectional communication between the immune and neuroendocrine systems. Capsaicin suppresses the immune function by destroying substance P acting as mediatior of neuroendocrine immune system. Methods and Results: In this study, effect of capsaicin on mature murine lymphocyte functions and lymphoid tissue morphology was examined. Formally, capsaicin showed the strong cytotoxic effect on splenocyte over $10{\mu}g/ml$ concentration in citro. And proliferation and Th1-cytokine expression of splenic cells in mice that received high dose of capsaicin ($100{\mu}g/mouse$) were significantly diminished. However, low dose of capsaicin treatment did not influence these responses in vivo($1{\mu}g/mouse$) and in vitro (under $5{\mu}g/ml$). And the morphology of spleen and lymph nodes after capsaicin treatment was observed. In the spleen of mice injected with high dose of capsaicin (100, $200{\mu}g/mouse$), the size of white pulp was significantly decreased and the length of red pulp was increased, Moreover, vascularity index was diminished in a dose dependent manner. Conclusion: These results implies that immunosuppressive effect of capsaicin is associated with cytotoxic activity on lymphocyte, Th1-cytokine down-regulation and lymphoid tissue abnormalization, and this report is expected to give a hand to the study for the mechanism of action of neurotoxin of the immune system.

• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.131-138
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• 2002

The cyclophilins (Cyps) are family members of proteins that exhibit peptidylprolyl cis-trans isomerase (PPIase, EC 5.2.1.8) activity and bind the immunosuppressive agent cyclosprin A (CsA) in varying degrees. During the process of random sequencing of a cDNA library made from Giardia intestinalis WB strain, the cyclophilin gene (gicypl) was isolated. An open reading frame of gicyp1 gene was 576 nucleotides, which corresponded to a translation product of 176 amino acids (Gicypl). The identity with other Cyps was about 58-71%. The 13 residues that constituted the CsA binding site of human cyclophilin were also detected in the amino acid sequence of Gicypl, including tryptophan residue essential for the drug binding. The single copy of the gicypl gene was detected in the G. intestinalis chromosome by southern hybridization analysis. Recombinant Gicyp 1 protein clearly accelerated the rate of cis ${\rightarrow}$ trans isomerization of the peptide substrate and the catalysis was completely inhibited by the addition of $0.5{\;}{\mu}M$ CsA.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.347-362
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• 2016

Marine sponges have been considered as a drug treasure house with respect to great potential regarding their secondary metabolites. Most of the studies have been conducted on sponge's derived compounds to examine its pharmacological properties. Such compounds proved to have antibacterial, antiviral, antifungal, antimalarial, antitumor, immunosuppressive, and cardiovascular activity. Although, the mode of action of many compounds by which they interfere with human pathogenesis have not been clear till now, in this review not only the capability of the medicinal substances have been examined in vitro and in vivo against serious pathogenic microbes but, the mode of actions of medicinal compounds were explained with diagrammatic illustrations. This knowledge is one of the basic components to be known especially for transforming medicinal molecules to medicines. Sponges produce a different kind of chemical substances with numerous carbon skeletons, which have been found to be the main component interfering with human pathogenesis at different sites. The fact that different diseases have the capability to fight at different sites inside the body can increase the chances to produce targeted medicines.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• Advances in Traditional Medicine
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• v.2 no.1
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.