• Journal of Life Science
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• v.26 no.6
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• pp.689-697
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• 2016

Kefir is an acidic-alcoholic fermented milk product originating from the Caucasian mountains. Kefir has long been known for its probiotic health benefits, including its immunomodulatory effects. The objectives of this study were to investigate the properties of a fermented whey product and to examine the effects of kefir grains on the in vitro immune-modulation of human mast cell-1 (HMC-1). The results showed that the whey fermented by kefir grains contained the maximum lactic acid bacteria and yeast for 16 hr by 1.83×10⁸ and 6.5×10⁵ CFU/ml, respectively, and lactose and whey proteins were partially hydrolyzed. The experimental whey fermented by kefir grains exhibited an in vitro anti-inflammatory effect on the HMC-1 line for 8, 16, and 24 hr, and this effect induced the expression of interleukin (IL)-4 as a pro-inflammatory cytokine, but not for 48 hr by RT-PCR in HMC-1 cells. In addition, the same phenomenon was observed for the expression of IL-8 as a pro-inflammatory cytokine by the kefir-fermented whey during the same periods of 8-48 hr under the same conditions. These cytokines resulted in the production of IL-4 at 20-25 ng in HMC-1 cells for 8, 16, and 24 hr, whereas 5 ng was produced for 48 hr by the fermented whey. In contrast, IL-8 was produced at 15-20 ng in HMC-1 cells during 4, 8, 16, and 24 hr, while 7 ng was produced at 48 hr. It was concluded that the whey fermented by kefir grains possesses a potential anti-inflammatory function, which could be used for an industrial application as an ingredient of functional foods and pharmaceutical products.

• Journal of Life Science
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• v.28 no.11
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• pp.1361-1368
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• 2018

Inflammation is the most common condition in the human body. Tissue damage triggers inflammation, together with vasodilation and increased blood flow at the inflamed site, resulting in edema. Inflammatory responses are also triggered by lipopolysaccharide (LPS), a Toll-like receptor Enterococcus faecalis, a gram-positive organism, has been reported to possess immunomodulatory and preventive activities; however, its use may present risks of sepsis and other systemic infections. Heat-killed Enterococcus faecalis (EF-2001) has been reported to induce antitumor activity, but its effects on inflammation are not known. In the present study, we investigated the effect of EF-2001 on LPS-induced macrophage inflammatory responses. EF-2001 treatment reduced nitric oxide (NO) production, indicating suppression of inflammatory reactions. EF-2001 showed no cytotoxicity in macrophages. Further investigation of the anti-inflammatory mechanism of EF-2001 indicated that EF-2001 reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. EF-2001 also reduced f the LPS induction of several inflammatory molecules involved in the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) and mitogen-activated protein kinase pathways, including ERK, JNK, and p38 phosphorylation, in a concentration-dependent manner. Additionally, EF-2001 inhibited Akt phosphorylation and increased the expression of the inhibitory ${\kappa}B$ ($I{\kappa}B$) protein, an inhibitor of $NF-{\kappa}B$. EF-2001 also inhibited the nuclear translocation of p65. These results suggest that EF-2001 has anti-inflammatory properties and may be useful for treating inflammatory diseases.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.533-541
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• 2004

Atopic dermatitis, also called congenital fever, is a allergic eczema of chronic itching disease. It is a recurrent and familial disease and appears on a wide age group from infant to adult. It is very common, and the ratio of occurrence is about $9{\~}l2\%$ of a child. However. it is showing trend of continuous increase by social and natural environment, food culture, and life style, recently. The human skin plays a barrier role against a physical and chemical stimulus from external environment. According to the latest study, the decreased amount of ceramide in horny layer impairs the bier function and moisture-maintaining function of skin in atopic dematitis patient. Ceramide is a kind of the sphingolipid in which a fatty acid is connected to sphingosin. Ceramide constitutes about $40\%$ of total lipid between keratinocytes and has the function of defense wall and building regular structure to suppress moisture vaporization in horny layer. In horny layer of skin a comified cell is composed of multi-layer structure of a brick shape, and, as for this cornified cell, it is strongly connected by ceramide, cholesterol, and free fatty acid. Here, we described the effects of a cream containing ceramide on the recovery of skin harrier function of atopic dermatitis patient. The safety and efficacy of latex and liquid formula were evaluated as cosmetics for atopic dermatitis. The latex products was composed of intercellular lipid components-ceramide, cholesterol, and free fatty acid-to restore skin barrier function in atopic dermatitis patients. The liquid one contained beta-glucan, magnolia extracts, and licolice extracts, which have skin immunomodulatory and anti-inflammatory effects. It is also confirmed that their possibility on new cosmetic market of atopic dermatitis.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.274-279
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• 2009

Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-$\gamma$) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-$\gamma$ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.879-885
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• 2008

Purpose : The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. Methods : Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-${\beta}$ (TGF-${\beta}$), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. Results : 1) The release of VEGF was significantly increased after stimulation with TGF-${\beta}$, and its release was augmented when co-stimulated with PDGF and TGF-${\beta}$. 2) VEGF release induced by PDGF or TGF-${\beta}$ was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-${\beta}$ nor PDGF induced TARC release from lung fibroblasts. Conclusion : Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.

• Molecules and Cells
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• v.42 no.12
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• pp.906-918
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• 2019

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.522-527
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• 2008

Low molecular peptides were isolated from Asterias amurensis via SDS-PAGE. The peptides were separated via consecutive gel filtration as five fractions (F1-F5) according to molecular weights, based on the results of MALDI-TOF MS analysis. The molecular weight of the most active peptide was estimated as 15,000 daltons. The peptide showed cytotoxicity on normal human fibroblast cells at levels as low as 20% when 1.0 mg/mL of the samples was added. The peptide also exhibited higher levels of nitric oxide production from macrophages than the lipopolysaccaharides. It was determined that prostaglendin $E_2$ production was significantly inhibited, up to 127.8% as compared to the control. The low molecular peptide inhibited hyaluronidase activity as 535.7 ${\mu}g/mL$ of $IC_{50}$. It can be concluded that the relatively low molecular weight peptide, fucoidan, from A. amurensis has excellent cosmetic and immunomodulatory activities, which can be considered as a possible resource of new cosmetic agents for skin immunomodulation.

• Journal of Life Science
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• v.26 no.10
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• pp.1207-1213
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• 2016

Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Food Science and Industry
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• v.51 no.4
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• pp.278-301
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• 2018

Although more than 80% of living organisms are found in marine ecosystems, only less than 10% of marine resources have been utilized for human food consumptions and other usages. It is well known that marine resources (fish, shellfish and algae) have exceptional nutritional properties; however, their functional characteristic has not been completely discovered. It is believed that metabolites (organic compounds, proteins, peptides, lipids, minerals, etc.) play an important role to show its biological properties. Marine proteins and peptides are considered to be future drugs due to their excellent biological activities with a fewer adverse side effect. Marine peptides show several biological activities, including antimicrobial, antioxidant, anti-inflammatory, anti-cancer, anti-viral, anti-tumor, anti-diabetic, anti-hypertensive, anti-coagulant, immunomodulatory, appetite suppressing and neuroprotective effects. Therefore, the pharmaceutical, nutraceutical, and cosmeceutical companies have been paid attention to the marine peptides to commercialize into products. This current review mainly focused on the above mentioned biological activities of marine peptides and protein hydrolysates as a functional food and pharmaceutical applications. To commercialize these materials in industrial level required large quantity in high-purity level, and it is complicated to produce huge quantity from the marine resources due to insufficient raw materials, unavailability of raw materials through a year, hinder the growth with geographical variations, and availability of compounds in extreme small quantities. The best solution for these issues is to introduce new modern technologies such as artificial intelligence robots, drones, submersibles and automated raw material harvesting vessels in farming industries instead of man power, which will lead to 4th industrial revolution.