• Journal of Ginseng Research
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• v.42 no.4
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• pp.455-462
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• 2018

Background: Ginsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes. Methods: The effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2. Results: LINE1 showed induction of hypomethylation at specific CpGs by 1.6-9.1% (p < 0.05). Genome-wide methylation analysis identified the "cell-mediated immune response"-related pathway as the top network. Cell proliferation of MCF-7 was retarded by Rh2 in a dose-dependent manner. Hypermethylated genes such as CASP1, INSL5, and OR52A1 showed downregulation in the Rh2-treated MCF-7, while hypomethylated genes such as CLINT1, ST3GAL4, and C1orf198 showed upregulation. Notably, a higher survival rate was associated with lower expression of INSL5 and OR52A1 in breast cancer patients, while with higher expression of CLINT1. Conclusion: The results indicate that Rh2 induces epigenetic methylation changes in genes involved in immune response and tumorigenesis, thereby contributing to enhanced immunogenicity and inhibiting the growth of cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.25-33
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• 1991

The immune staus is known to be decreased in malignant disease and radiation therapy (RT), used as a therapeutic tool, further decrease this-attenuated immune status. We measured the number of peripheral lymphocytes, its subsets and lymphoblast transformation for PPD, PHA, monoclonal antibodies including anti-CD3 and anti-CD2 before and after RT in 19 patients with squamous cell lung cancer to search the fine mechanism behind the RT-induced attenuation of lymphoblast transformtion for mitogens and antigen. The results were as follows; 1) The number of lymphocytes and its subsets decreased significantly after RT, but the percentages of lymhocyte subsets did not change aftr RT except interleukin-2 receptor positive T lymphocytes. 2) The function of lymphoctes, measured by lymphoblast tranformation for PHA and PPD, decrased after RT and the compositions of PBMC used for lymphoblast transformtion were not different before and after RT. 3) The mitosis of lymphocytes to anti-CD2 or anti-CD3 decreased significantly after RT. And IL-2 plus anti-CD3 increased the mitosis than that of anti-CD3 only after RT, but before RT there was no difference. In conclusion, we suggested the fine mechanism behind the RT-induced attenuation of immune response might be the dysfunction of lymphocytes in terms of impaired synthesis of IL-2 rather than the decrease of circulating lymphocyte numbers.

• Development and Reproduction
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• v.24 no.3
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• pp.187-196
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• 2020

The caspase10 encodes an initiating caspase that plays an important role in the maintaining the cellular homeostasis by regulating the steps involved in the immune response and cell death. We investigated the expression of caspase10 during the different developmental stages and in olive flounder tissues. Caspase10 increased in the late stage of the formation of immune tissue, and high expression was observed in the gills, kidney, skin, and spleen. The current study analyzed the expressional changes of caspase10 in olive flounder infected with viral hemorrhagic septicemia virus (VHSV). One of the major causes of mass mortality, VHSV infection in olive flounder attributes to significant expression of caspase10 in the gills, spleen, skin, and kidneys. The results indicate a close association of caspase10 expression with the immune response to VHSV infection in olive flounder. The observations could form the basis data for exploration of other fish immune system.

• Korean Journal of Pharmacognosy
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• v.41 no.4
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• pp.275-281
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• 2010

To evaluate the immunomodulatory activity of a water extract (KMF-WE) of Korean mistletoe (Viscum album var. coloratum) fruit, we examined its ability to induce humoral and cellular immune response against keyhole limpet hemocyanine (KLH). Immunized mice with KLH admixed with KMF-WE (KLH/KMF-WE) showed significant induction of KLH-specific antibodies compared to mice immunized with KLH alone. The assay for determining isotypes of antibodies revealed that KMFWE augmented KLH-specific-IgG1 and -IgG2a production. In vitro T lymphocyte proliferation analysis against KLH revealed that the splenocytes of mice immunized with KLH/KMF-WE showed a significantly higher proliferative ability than those from mice immunized with KLH alone. The culture supernatants of splenocytes, which were harvested from mice immunized with KLH/KMF-WE, showed higher levels of both Th-1 type (IL-2, IFN-${\gamma}$) and Th-2 type (IL-4) cytokines in response to KLH stimulation compared to those from mice immunized with KLH alone. Also, in delayed-type hypersensitivity (DTH) assay, mice immunized with KLH/KMF-WE showed a significantly higher reaction to KLH than mice treated with KLH alone. These results suggest that KMF-WE possess immunoadjuvant activity to enhance both antigen-specific humoral and cellular immune responses against protein antigens (KLH).

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1181-1194
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• 2015

Tuberculosis (TB) is an infectious disease transmitted by aerosol droplets and characterized by forming granulomatous lesions. Although the number of people infected in the population is high, the vast majority does not exhibit symptoms of active disease and only 5-10% develop the disease after a latent period that can vary from weeks to years. The bases of the immune response for this resistance are unknown, but it depends on a complex interaction between the environment, the agent, and the host. The analysis of cellular components of M. tuberculosis shows important host-pathogen interactions, metabolic pathways, virulence mechanisms, and mechanisms of adaptation to the environment. However, the M. tuberculosis proteome still remains largely uncharacterized in terms of virulence and pathogenesis. Here, we summarize some of the major proteomic studies performed to scrutinize all the mycobacterial components.

• Molecules and Cells
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• v.44 no.5
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• pp.363-373
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• 2021

Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.

• Korean journal of applied entomology
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• v.40 no.1
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• pp.51-58
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• 2001

Entomopathogenic fungus, Paecilomyces japonicus, has been commercially used as medicinal purpose . The silkworm, Bombyx mori, as an optimal host for the fungi, has been selected and used for the production of the fungal fruit bodies. In current method, newly molted fifth instal larvae should be exposed to the adverse stress environment of high temperature (3$0^{\circ}C$), high relative humidity ( 90%), and starvation for 24h for better fungal inoculation to the host insects. In this study, an alternative method using chemical agent, dexamethasone (DEX: an eicosanoid biosynthesis inhibitor), was tried to get the immunodepressive effect on the larvae to elevate the inoculation rate of the fungi to the silkworm without any harsh rearing environment. DEX (100$\mu\textrm{g}$) showed significantly synergistic effect on the hemocyte lethality of the fungus, and was effective to decrease cellular immune responses measured by the number of hemocyte microaggregation and phenoloxidase activity of the fifth instar larvae in response to the fungal injection. A detergent of 0.05% Triton-X was effective to increase the in- oculation rate of the fungi to the larvae and used in all fungal spraying solutions. Without any environ- mental stress treatment, only DEX (100$\mu\textrm{g}$) injection to the fifth instar larvae followed by the fungal spray was effective to get the inoculation rate equivalent to the current fungal spray method requiring harsh rearing environment. These results suggest that the inoculation of P. japonicus can be elevated by the help of DEX and that the silkworms use eicosanoids to elicit cellular immune response against fungal pathogen.

• Korean journal of applied entomology
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• v.51 no.4
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• pp.349-356
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• 2012

Eicosanoid mediates various cellular immune responses in insects. This study aimed to discover its novel action on the modulation of hemocyte populations in response to an immune challenge. Upon bacterial challenge, the last instar larvae of the beet armyworm, Spodoptera exigua, increased their total hemocyte density in 2 h, and then decreased it to a basal hemocyte density level. This rapid increase in total hemocyte density was explained by an increase of plasmatocyte and spherulocyte densities. When larvae were treated with dexamethasone (a specific phospholipase $A_2$ ($PLA_2$) inhibitor), they did not show any increase in hemocyte density in response to bacterial challenge. However, the addition of arachidonic acid (a catalytic product of $PLA_2$) to larvae treated with dexamethasone recovered the up-regulation of hemocyte density in response to bacterial infection. Among eicosanoid, cyclooxygenase (COX), but not lipoxygenase (LOX), products seemed to mediate the increase of hemocyte density in response to bacterial infection because naproxene (a COX inhibitor) inhibited the hemocyte density increase, though esculetin (a LOX inhibitor) did not. Prostaglandin $E_2$, a COX product, significantly increased the hemocyte density even without bacterial infection. These results suggest that eicosaniod mediates a rapid increase in total hemocyte density in response to immune challenge.

• Environmental Analysis Health and Toxicology
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• v.6 no.1_2
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• pp.39-57
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• 1991

The effect of red ginseng ethanol extract on the immunotoxicity of diethylstilbestrol (DES) was studied in ICR mice. ICR male mice were divided into S groups (10 mice/group), and red ginseng ethanol extract (50, 100 and 200 mg/kg body wt., respectively) and DES (1 mg/kg body wt.) were injected intraperitoneally (i.p.) to ICR mice once a day for 2 weeks. Mice were sensitized and challenged with sheep red blood cells (S-RBC). Immune response were evaluated by humoral immunity, cell-mediated immunity, non-specific immunity, and circulating leukocyte counts. The results of this study were summarized as followings: 1. The DES-treated control group as compared with normal group showed the tendency to decrease body weight rate and relative liver weight, decreased both humoral and cellular immune responses, phagocyte activity, and circulating leukocyte counts, but increased the natural killer (NK) cell activity. 2. Compared with the DES-treated control group, DES plus red ginseng ethanol extract-treated groups significantly decreased the body weight rate (P<0.01). Relative liver weight was significantly decreased in DES plus red ginseng ethanol extract (50mg/kg)-treated group (P<0.01), but significantly increased in DES plus red ginseng ethanol extract (100mg/kg)-treated group (P<0.01). Relative spleen and thymus weights were significantly enhanced in DES plus red ginseng ethanol extract (100 mg/kg)-treated group (P<0.01), but significantly decreased in DES plus red ginseng ethanol extract (200 mg/kg)-treated group (P<0.01). 3. Both humoral and cellular immune responses were significantly decreased in DES plus red ginseng ethanol extract-treated groups rather than in the DES-treated control group (P<0.01). Especially, it weakened the decrease in DES plus red ginseng ethanol extract (100 mg/kg)-treated group. 4. Phagocyte activity and circulating leukocyte counts were significantly decreased in DES plus red ginseng ethanol extract-treated groups rather than in the DES-treated control group (P<0.01). Especially, it weakened the decrease in DES plus red ginseng ethanol extract (100 mg/kg)-treated group. NK cell activity was significantly enhanced in DES plus red ginseng ethanol extract (100 mg/kg)-treated group (P<0.01), but significantly decreased in DES plus red ginseng ethanol extract (50 and 200 mg/kg)-treated groups (P<0.01).