• IMMUNE NETWORK
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• v.16 no.1
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.505-513
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• 2017

Objective: This study was performed to evaluate whether ambient temperature and dietary glycerol addition affect growth performance, and blood metabolic and immunological parameters, in beef cattle. Methods: Twenty Korean cattle steers ($405.1{\pm}7.11kg$ of body weight [BW], $14.2{\pm}0.15$ months of age) were divided into a conventional control diet group (n = 10) and a 2% glycerol- added group (n = 10). Steers were fed 1.6% BW of a concentrate diet and 0.75% BW of a timothy hay diet for 8 weeks (4 weeks from July 28th to August 26th and 4 weeks from August 27th to September 26th). Blood was collected four times on July 28th, August 11th, August 27th, and September 26th. Results: The maximum indoor ambient temperature-humidity index in August (75.8) was higher (p<0.001) than that in September (70.0), and in August was within the mild heat stress (HS) category range previously reported for dairy cattle. The average daily gain (ADG; p = 0.03) and feed efficiency (p<0.001) were higher in hotter August than in September. Glycerol addition did not affect ADG and feed efficiency. Neither month nor glycerol addition affected blood concentrations of cortisol, triglyceride, or non-esterified fatty acid. Blood concentrations of cholesterol, low-density lipoprotein, high-density lipoprotein, glucose, and albumin were lower (p<0.05) on August 27th than on September 26 th, and blood phosphorus, calcium and magnesium concentrations were also lower on August 27th than on September 27th. Glycerol addition did not affect these blood parameters. Percentages of $CD4^+$ T cells and $CD8^+$ T cells were higher (p<0.05) on July 28th than on August 27th and September 26th. The blood $CD8^+$ T cell population was lower in the glycerol supplemented-group compared to the control group on July 28th and August 27th. Conclusion: Korean cattle may not be significantly affected by mild HS, considering that growth performance of cattle was better in hotter conditions, although some changes in blood metabolic and mineral parameters were observed.

• Journal of the Speleological Society of Korea
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• no.95
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• pp.35-49
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• 2009

Ever since the beginning of time, caves not only have offered a place to live for humans but they have also been used as cultural spaces. That is, in the event of making some sounds in a location within the cave, the sound that is created is greatly magnified and sounds out as if it is being amplified from a giant megaphone. This, as we well know it, is known as the resonance effect. Here, the cave itself appears to function as a massive wind instrument. Especially in cases like the Altamira Cave (Spain) where cave paintings were found, the point where the cave drawings were found has commonalities in that it is a wide space and that it is usually discovered together with flutes and drums that are made with mammoth bones. We need to focus on this point. We can infer from these facts that the prehistoric people have carried out cultural activities along with their incantation rituals within those caves. In the meantime, amongst the Korean traditional arts, in the case of pansori which is a representative vocal genre, there have been examples where caves were used as practicing locations for those people who are training to perfect their singing. This is known as toguldoggong(土窟獨功) which literally means 'obtaining one's own art by oneself in the earth cave by practicing incessantly'. This process along with pokpodoggong (瀑布獨功) (same as above except that the location is by the waterfall) is the final training stage in order to become a recognized virtuoso on the part of the apprentice. This could be compared to the final annealing and finishing process of producing a metalwork. This has been a long tradition followed by most Korean traditional artists in order to perfect their sound which is harmonious with nature within natural surroundings. By honing in on this point, I have come to think about this matter repeatedly while coaching the university students in vocal singing. In short, I came to the conclusion that "the making of natural sounds will be obtained naturally within natural surroundings like caves!" Consequently, The Society for Studying Cave Sounds was inaugurated on January 1992 along with some of my students. We made use of times like vacations to go around exploring caves all over Jeju and carried out investigations of sounds along with cave exploration on an experimental basis. After 5 years, in September of 1997, we were able to host the first ever cave concert domestically at the Whale Nostril Cave(東岸鯨窟) on Wu-do. After that, we have been hosting the cave concert once every year. We have achieved a record of a total of 14 cave concerts until 2009 of this year. Out of these, 2 were held in Seokhwaeam Cave in Kangwon Province, another two were held in Manjang Cave which is a lava cave, and the remaining 10 were held in the Whale Nostril Cave of Wu-do. Along with that, I have carried out a special recording for the production of a cave music CD in May of 1999. This paper was written and organized by using the main materials that were derived from the experiences of using caves as concert halls in the past. It is hoped that this cave concert will offer a very unique experience to tourists who come to Jeju every year and give them the best possible superior natural sound effect that only Jeju caves can offer.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.169-177
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• 2016

There is a growing interest in the application of primary hepatocytes for treatment of liver diseases in humans and for drug development. Several studies have focused on long-term survival and di-differentiation blocking of primary hepatocytes in an in vitro culture system. Therefore, the present study also aimed to optimize an in vitro culture system using primary rat hepatocytes. Primary rat hepatocytes from 6-week-old male Crl:CD rats were isolated using a modified two-step collagenase perfusion. Healthy $3.5{\times}10^6$ primary rat hepatocytes were seeded into a 2 dimensional (2D) culture in a 25T culture flask coated with collagen type I or into a 3D culture in a 125-ml spinner flask for 7 days. Production of plasma protein (ALB and TF), apoptosis (BAX and BCL2), and CYP (CYP3A1) related genes were compared between the 2D and 3D culture systems. The 3D culture system had an advantage over the 2D system because of the relatively high expression of ALB and low expression of BAX in the 3D system. However, the level of CYP3A1 did not improve in the 3D culture with and without the presence of a dexamethasone inducer. Therefore, 3D culture has an advantage for albumin production and primary rat hepatocyte survivability, but a low expression of CYP3A1 indicated that primary rat hepatocytes require a high-density culture for stress reduction by continuous flow.

• BMB Reports
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• v.45 no.2
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• pp.79-84
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• 2012

In asthma, T helper 2 (TH2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated $CD^{4+}$ T cells. Dendritic cells played an important role in determining the fate of naive T cells into either $T_H1$ or $T_H2$ cells. We determined whether RG-II regulates the $T_H1/T_H2$ immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon-gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.115-125
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• 2012

Objectives : The purpose of this study is to observe the inhibitory effects of $Chrthami$ semen oil pharmacopuncture(CSOP) on CIA (collagen-induced arthritis) mice. Materials and Methods : Two types of experiments were conducted: $in$ $vitro$ assay, inhibition of MIF mRNA and TNF-${\alpha}$ mRNA expressions in synovial membranes was observed, and $in$ $vivo$ assay, $1{\mu}{\ell}/kg$ CSOP was injected every day to the left $Weizhong$ ($BL_{40}$) from day 3 to 21 after induction of CIA, and changes in paw edema, apical surface morphology, neovascularization in synovial membranes, fibrosis, pro-inflammatory cytokines production, Th-1 differentiation, and anti-inflammatory effect were investigated. Results : 1. In synoviocytes of the CIA mice treated with CSOP, MIF mRNA and TNF-${\alpha}$ mRNA expressions were down-regulated in a dose-dependent manner. 2. Paw edema of the CIA mice treated with CSOP was diminished. 3. Tissue injury in the synovial membranes, capillary distribution and fibrosis were reduced in CSOP-treated mice. 4. MIF, TNF-${\alpha}$, IL-6, MMP-9 expressions were repressed in CSOP-treated mice during the experiment to observe the inhibitory effect on cytokines production in early stage RA. 5. IL-12 and CD28 were reduced in CSOP-treated mice during the observation of inhibitory effect on Th 1 differentiation. 6. PPAR-${\gamma}$ was increased during the experiment to observe the anti-inflammatory effect of CSOP. Conclusions : The results may suggest that administration treatment using $Chrthami$ semen oil pharmacopuncture decreases the inflammatory response on an Animal Model with CIA.

• Journal of Oriental Neuropsychiatry
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• v.17 no.2
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• pp.91-122
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• 2006

Objective : This research investigates the effect of the Jangwon-Dan,(JWD) on Alzheimer's disease. Method : The effects of the JWN extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA, the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA, (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : 1. The JWN extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The JWN extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The JWN extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the JWN extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The JWN extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and CD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The JWN extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion : These results suggest that the JWN extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the JWN extract for Alzheimer's disease is suggested for future research.

• Journal of Oriental Neuropsychiatry
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• v.15 no.2
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• pp.119-139
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• 2004

This research investigates the effect of the Hibiscus syriacus(HSS) on Alzheimer's disease. Specifically, the effects of the HSS extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and reactive oxygen species(ROS); (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized below ; 1. The HSS extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-l cells treated with LPS. 2. The HSS extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The HSS extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the HSS extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The HSS extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ and $TNF-{\alpha}$ mRNA, CD68/GFAP, ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The HSS extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the HSS extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the HSS extract for Alzheimer's disease is suggested for future research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.420-427
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• 2006

Immunological activities of the combined-administration of Ginseng Radix Rubra and Vitis Fructus were examined in C57BL/6 mice. Ginseng Radix Rubra and Vitis Fructus were extracted with distilled water or 40% ethyl alcohol. Ginseng Radix Rubra water extracts (GW), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:1)], the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:3)], 40% ethyl alcohol extracts of Ginseng Radix Rubra (GE), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:1)] and the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:3)] were administered p.o. once a day for 7 days, respectively. GVW(1:1) and GVW(1:3) decreased the viability of thymocytes increased by GW, but GVE(1:1) and GVE(1:3) increased the viability of thymocytes decreased by GE. GVW(1:1) and GVW(1:3) increased the viability of splenocytes decreased by GW or GE. Also, GVW(1:1) and GVE(1:1) enhanced the population of helper T cell in thymocytes, and GVE(1:1) and GVE(1:3) decreased the population of cytotoxic T cells increased by GE. Furthermore, GVW(1:1), GVW(1:3), GVE(1:1) and GVE(1:3) enhanced the population of $B220^+$ cells decreased by GW or GE, and decreased the population of $Thyl^+$ cells increased by GW or GE, and decreased the population of splenic $CD4^+$ cells increased by GW or GE. In addition, GVW(1:1) and GVW(1:3) decreased the phagocytic activity and the production of nitric oxide in peritoneal macrophages increased by GW, but GVE(1:1) and GVE(1:3) enhanced the phagocytic activity and the production of nitric oxide in peritoneal macrophages decreased by GE. These results suggest that Vitis Fructus has an regulative action on immune response of Ginseng Radix Rubra.