• Proceedings of the PSK Conference
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• 2003.10a
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• pp.79-80
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• 2003

A lot of polyketide antibiotics have been isolated from natural sources like microorganism, fungi and plant. The polyketide natural products have biologically and medically important activities, including antibacterial, anticancer, antiparasitic, and immunosuppressant properties. The diversified activities of polyketides are originated from their structural variety of which have been took advantage by several research groups for development of new drugs. (omitted)

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Journal of Microbiology and Biotechnology
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• v.7 no.1
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• pp.56-61
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• 1997

A strain producing immunosuppressive substances was isolated from a soil in Cheju island. By morphological, cultural, and physiological studies, the strain was identified as Streptomyces lydicus MCY-524. Cultured broth was purified by silica gel, sephadex LH-20 and preparative HPLC and gave two immunosuppressive compounds, MCH-22 and MCH-32. They dramatically suppressed the B cell activation with lipopolysaccharide, T cell activation by mixed lymphocyte response, and primary T-dependent antibody response at a final concentration of 1 ${\mu}g$/ml. They also markedly suppressed the proliferation of lymphocytes induced by lipopolysaccharide, pokeweed mitogen, and concanavaline A at the same concentration. Their suppressive activities, which were comparable to those of cyclosporin A, suggested that they were potent and broad immunotoxic agents on the immune functions of murine lymphocytes.

• Journal of Microbiology and Biotechnology
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• v.28 no.3
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• pp.418-424
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• 2018

${\text\tiny{D}}-Allose$ is a potential medical sugar because it has anticancer, antihypertensive, antiinflammatory, antioxidative, and immunosuppressant activities. Allose production from fructose as a cheap substrate was performed by a one-pot reaction using Flavonifractor plautii ${\text\tiny{D}}-allulose$ 3-epimerase (FP-DAE) and Clostridium thermocellum ribose 5-phosphate isomerase (CT-RPI). The optimal reaction conditions for allose production were pH 7.5, $60^{\circ}C$, 0.1 g/l FP-DAE, 12 g/l CT-RPI, and 600 g/l fructose in the presence of 1 mM $Co^{2+}$. Under these optimized conditions, FP-DAE and CT-RPI produced 79 g/l allose for 2 h, with a conversion yield of 13%. This is the first biotransformation of fructose to allose by a two-enzyme system. The production of allose by a one-pot reaction using FP-DAE and CT-RPI was 1.3-fold higher than that by a two-step reaction using the two enzymes.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.471-477
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• 1998

Cyclosporin A (CsA), a widely used immunosuppressant, is well known to cause nephrotoxicity and hypertension as major side effects. The present study was aimed at investigating the effects of CsA-pretreatment on the activities of cytosolic guanylate cyclase (cGC) in relation to the alteration of relaxant responses in the rat thoracic aorta. CsA $(10\;{\mu}M)-preincubation$ for 90 min significantly attenuated the vasodilatation induced by sodium nitroprusside (SNP), a cytosolic guanylate cyclase activator, shifting the dose-response curve to the right. The increase in cGMP contents induced by SNP was markedly attenuated by CsA. SNP ($1\;{\mu}M{\sim}\;mM$) increased the cGC activity dose-dependently, and the increase was completely abolished by CsA. CsA attenuated the SNP-induced cGC activation dose-dependently. The abolishing effect of CsA-pretreatment on the SNP-induced cGC activation was not affected by washing the preparation, suggesting that the inhibition is irreversible. When CsA was added simultaneously with SNP, cGC activation was not attenuated. 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H-7), a protein kinase C (PKC) inhibitor, decreased SNP-induced cGC activation and blocked the CsA-attenuation of cGC activation. These results suggest that CsA directly inhibits cGC participating in the CsA-induced impairment of vasodilatation, and that PKC is involved in the inhibitory action of CsA on cGC.

• Journal of Periodontal and Implant Science
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• v.24 no.2
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• pp.238-254
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• 1994

Cyclosporine A is an immunosuppressant commonly used for patients receiving organ transplants. Gingival overgrowth is an adverse side-effect seen in about 8-26% of patients taking cyclosporine A which have been shown to increase the DNA synthesis of gingival fibroblast at the concentration of $10^{-9}g/ml$ in vitro. Glycyrrhetinic acid is the active pharmacological ingredients of licorice which exerts steroid-like action and anti-viral activity. Oleanolic acid, which were isolated from Glechoma hederacea, has been shown to act as inhibitors of tumor promotion in vivo and to be less cytotoxic retinoic acid. This study has been performed to evaluate the effects of glycyrrhetinic acid and oleanolic acid on cyclosporine A induced cell activity in vitro. Human gingival fibroblasts were isolated from explant cultures of healthy gingiva of orthodontic patients. Gingival fibroblasts were trypsinized and transferred to the walls of microtest plates. Fibroblasts were cultured in growth medium added $10^{-9}g/ml$ cyclosporineA and $50{\mu}l/ml$ lipopolysaccharides. Cells between the 4th and 6th transfer in culture were used for this study. The morphology of gingival fibroblst were examined by inverted microscope. The effects of cyclosporine A on the time course of DNA sythesis by human gingival fibroblasts were assessed by $[^3H]-thymidine$ uptake assays. Cyclosporine A was found to stimulate DNA synthesis of human gingival fibroblast at a concentration of $10^{-9}g/ml$. In the presence of lipopolysaccharide derived from Fusobacterium nucleatum, addition of cyclosporine A results in reversal of inhibition at the concentration which normally inhibits gingival fibroblast proliferation. The cell acitivities in the presence of glycyrrhetinic acid and oleanolic acid were decreased, and increased cell acitivities by cyclosporine A were decreased by glycyrrhetinic acid and oleanolic acid at the concentration of $200{\mu}g/ml$. These results suggested that the increased cell activities by cyclosporine A modulated by glycyrrhetinic acid and oleanolic acid.

• Journal of Life Science
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• v.25 no.1
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• pp.29-36
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• 2015

Prodigiosin, a member of natural red pigment family, is produced by Serratia marcescens, and characterized by a common pyrrolylpyrromethane skeleton. This pigment has been reported with the effects of anticancer, immunosuppressant, antifungal, and algicidal activities. Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital infections. In this study, anti-MRSA properties of prodigiosin isolated from Serratia sp. PDGS 120915 were investigated. We identified and purified prodigiosin using high performance liquid chromatography (HPLC) and evaluated anti-MRSA activity. Purified prodigiosin inhibited the growth of MRSA. The minimum inhibitory concentrations (MICs) of prodigiosin were determined to $32{\mu}g/ml$ against the MRSA strains. Fractional inhibitory concentration (FIC) indices of ampicillin and penicillin were indicated synergistic effects of prodigiosin on MRSA.

• Journal of Life Science
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• v.34 no.6
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• pp.377-384
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• 2024

Prodigiosin is a red pigment characterized by a common pyrrolylpyrromethane skeleton. It is produced by Serratia marcescens, Vibrio psychroerythrus, Hahella chejuensis, etc. Prodigiosin has been reported to possess anticancer, immunosuppressant, antifungal antimalarial, and algicidal activities. However, despite prodigiosin's diverse range of activities, its production rate is significantly low and biosynthesis conditions are difficult. Consequently, the selling price is high, and its usability is limited. This study aimed to increase the efficiency of prodigiosin production according to the culture conditions of Serratia. In this study, a bacterial strain PDGS¹²⁰⁹¹⁵ producing prodigiosin was isolated from lightly contaminated stream water in Busan and identified as a strain of Serratia sp. based on 16S rDNA gene sequence analysis and physiological characteristics. The reddish pigment from PDGS¹²⁰⁹¹⁵ was directly extracted using acidified ethanol, and a characterization analysis confirmed that it was a prodigiosin compound. The optimal conditions for pigment production were 25℃, pH 7, and 0% NaCl concentration for a duration of 14 hr. Furthermore, by treating carbon and nitrogen sources, such as fructose and beef extract, respectively, prodigiosin production increased approximately six-fold and four-fold. Among the minerals tested, 0.1% KCl was found to be the most effective for prodigiosin production. Moreover, casein was identified as the most suitable source for prodigiosin production.

• Korean journal of applied entomology
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• v.59 no.1
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• pp.41-54
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• 2020

Two mosquito species were collected in still-water near farming area in Andong, Korea. Based on morphological characters, these two mosquitoes were identified as Aedes koreicus and Culex vagans, respectively. DNA barcode analyses supported the identification. An entomopathogenic bacterium, Bacillus thuringiensis subsp. israelensis (BtI), exhibited insecticidal activities against the two mosquito species and its virulence was more potent than that of B. thuringiensis subsp. kurstaki. It has been known that the bacterial metabolites of Xenorhabdus spp. suppress insect immunity and enhance pathogenicity of B. thuringiensis. This study tested the effect of the bacterial culture broth of Xenorhabdus spp. on enhancing BtI pathogenicity. Among three Xenorhabdus spp., culture broth of X. ehlersii (Xe) was relatively effective to enhance BtI pathogenicity against both mosquito species. Indeed, organic extracts of Xe culture broth suppressed the hemocyte-spreading behavior, suggesting the presence of immunosuppressant in the culture broth. These results suggest a formulation of BtPlus by mixing BtI spore and Xe culture broth to be applied to control the two mosquito species.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.284-289
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• 2017

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.