• Journal of Mushroom
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• v.2 no.4
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• pp.169-174
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• 2004

A hot water extract(HWE-P4) was separated from the fruit bodies of PMO-P4, and its antitumor and immunomodulatory activities against sarcoma-180 in ICR mice were investigated. The internal transcribed spacer(ITS) regions from PMO-P4 were amplified using polymerase chain reaction(PCR) and sequenced. The results revealed that PMO-P4 was belong to the Phellinus baumii. When oral administration at the dose of 160mg/kg/day in the mice until the end of the experiment with 2 week's pre-feeding of the HWE-P4, the survival rate of the mice was 152% for 50days after the inoculation of sarcoma-180 and the suppression rate of the tumor growth was 35.3%(p<0.05) for 28 days after inoculation of sarcoma-180. The HWE-P4 increased 71.4% of the CD4/CD8 ratio and 5-fold of the expression of CD25(IL-2 receptor chain) compared with the control. From these results, the antitumor activity of HWE-P4 is exerted through its immunomodulating activity on the host's immune system.

• Journal of Periodontal and Implant Science
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• v.40 no.4
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• pp.153-163
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• 2010

Periodontal disease, as a polymicrobial disease, is globally endemic as well as being a global epidemic. It is the leading cause for tooth loss in the adult population and has been positively related to life-threatening systemic diseases such as atherosclerosis and diabetes. As a result, it is clear that more sophisticated therapeutic modalities need to be developed, which may include vaccines. Up to now, however, no periodontal vaccine trial has been successful in satisfying all the requirements; to prevent the colonization of a multiple pathogenic biofilm in the subgingival area, to elicit a high level of effector molecules such as immunoglobulin sufficient to opsonize and phagocytose the invading organisms, to suppress the induced alveolar bone loss, or to stimulate helper T-cell polarization that exerts cytokine functions optimal for protection against bacteria and tissue destruction. This article reviews all the vaccine trials so as to construct a more sophisticated strategy which may be relevant in the future. As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, $CD_{4+}$, $CD_{25+}$, $FoxP_{3+}$) have also been introduced. Targeting not only a single pathogen, but polymicrobial organisms, and targeting not only periodontal disease, but also periodontal disease-triggered systemic disease could be a feasible goal.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.40-51
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• 2006

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and occurrence of grossly deleted nef genes ($g{\Delta}nef$), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined whose the annual decrease in CD4 T cells was less than $20/{\mu}l$ over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and products were sequenced directly. Patient CD4 T cell counts decreased from $444{\pm}207/{\mu}l$ to $294{\pm}177/{\mu}l$ over $136{\pm}23$ months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of $13.3/{\mu}l$. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 92 out of the 479 genes revealed $g{\Delta}nef$. The deletion extended outside the nef gene in 25 $g{\Delta}nef$ obtained from 6 patients. The proportion of samples with $g{\Delta}nef$ (34.3%) was significantly higher than 4.8% in control patients (P<0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P<0.01). These data suggest the possibility that occurrence of $g{\Delta}nef$ might be associated with long-term intake of KRG.

• Parasites, Hosts and Diseases
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• v.55 no.4
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• pp.375-384
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• 2017

Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis ${\alpha}$-actinin 2, $Tv{\alpha}$-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of $Tv{\alpha}$-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-$Tv{\alpha}$-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or $Tv{\alpha}$-actinin 2 protein. Both T. vaginalis and $rTv{\alpha}$-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, $CD4^+CD25^-$ regulatory T cells (Treg cells) incubated with $rTv{\alpha}$-actinin 2-treated DCs produced high levels of IL-10. These data indicate that $Tv{\alpha}$-actinin 2 modulates immune responses via IL-10 production by Treg cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.251-258
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• 2021

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

• Journal of Animal Science and Technology
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• v.51 no.1
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• pp.25-32
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• 2009

This study was conducted to determine the effects of probiotics supplementation on growth performance, nutrient digestibility, occurrence of diarrhea and immune response in weaning pigs. Treatments were 1) NC (basal diet), 2) PC (basal diet + 0.12% avilamycin) and 3) A (basal diet + 0.2% Aspergillus oryzae), 4) B (basal diet + 0.2% Lactobacillus casei), 5) C (basal diet + 0.2% Bacillus subtilis), 6) D (basal diet + 0.2% Lactobacillus crispatus). A total of 120 pigs ($7.16\pm0.01$ kg average body weight, weaned at $23\pm3$days of age) were assigned to 6 treatments, 5 replicates and 4 pigs per pen in a randomized complete block (RCB) design. During the whole experimental period, body weight (P<0.01), average daily gain (ADG; P<0.01), and average daily feed intake (ADFI; P<0.05) of treatment PC were higher than other treatments. However, the probiotics treatments tended to increase ADG and G:F ratio compared to treatment NC. The G:F ratio in treatment A (Aspergillus oryzae) was similar to treatment PC during the whole experimental period (P<0.05). The supplementation of probiotics in the diet of weaning pig did not change nutrient digestibility (dry matter, crude protein, crude fat and ash) and nitrogen retention of weaning pigs. In blood urea nitrogen (BUN) concentration, treatment B had lower value than other treatments at 2 and 4 weeks (P<0.05). Treatments PC and C tended to decrease diarrhea score than other treatments (P=0.18). At 3h after lipopolysaccharide (LPS) injection, treatments NC and PC had higher count of $CD^{4+}$ T-cells than probiotics treatments, and treatment C showed the lowest value (P<0.01). There were no differences on count of $CD^{8+}$ T-cells and $CD^{4+}:CD^{8+}$ ratio among all treatments (P>0.10). These results suggest that the dietary probiotics are likely able to improve the growth performance, occurrence of diarrhea and immune response although they do not have similar effects like antibiotics in weaning pigs.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.354-361
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• 2002

Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.261-268
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• 2016

$Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

• Korean Journal of Food Science and Technology
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• v.45 no.4
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• pp.508-514
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• 2013

2Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However, it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model. Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation, similar to INCA-6.

• Gut and Liver
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• v.12 no.6
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.