• 한국방사선학회논문지
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• 제14권6호
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• pp.755-762
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• 2020

본 연구는 타히보 추출물이 천연 방사선 방호제로써 수컷 쥐의 전립선 내에서 일으키는 영향을 알아보기 위한 연구이다. 타히보 추출물은 유방암, 전립선 암의 세포라인에 대해 세포성장을 억제하는 능력이 있다고 알려져 있다. 수컷 쥐의 전립선을 채택하여 타히보 추출물에 의한 방사선 방호효과를 알아보기 위해 X-선 7 Gy를 조사한 날로부터 1 일, 7 일, 21 일 후의 혈액학적 변화, 외부독성평가, 항산화 효소(SOD)활성 변화 및 조직학적 변화를 관찰하였다. 타히보 투여 후 방사선 조사군은 방사선 조사군에 비해 더 큰 림프구 수치를 나타내었으며, 이 결과는 타히보가 조혈면역계의 회복능력에 영향을 미치는 것으로 사료된다. 외부독성평가결과로 타히보 추출물의 가장 높은 독성은 18.129±5.16 %, 가장 낮은 독성은 13.6945±4.43 %로 나타났다. 이는 타히보 추출물의 독성이 미미한 것으로 판단된다. 대조군 및 타히보 투여군의 전립선 세포핵 및 세포질의 구성은 균질하였으며, 이에 반해 방사선 조사군의 전립선 내 세포 핵 응집현상과 세포질내 염증반응이 나타났다. 타히보 투여 후 방사선 조사군은 방사선 조사군에 비해 전립선 내 세포질 염증반응은 적게 나타났으나 세포핵의 응집현상이 나타났다. 이는 타히보 추출물이 전립선의 세포에 대해 방사선 방호효과가 있음으로 판단된다.

• Applied Biological Chemistry
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• 제49권4호
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• pp.343-348
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• 2006

본 연구에서는 매생이 열수추출물의 항암 및 면역 활성을 알아보기 위하여 적정 추출 및 정제조건, 당 조성, 암세포독성, sarcoma-180 성장저지 효과, 백혈구수 변화, 보체계 활성, 장관 면역 활성, 경구독성 등을 검토하였다. 매생이 보체계 활성물질은 $100^{\circ}C$의 물로 3시간 동안 추출하여 4배량의 주정으로 24시간 침전시킨 다음 투석 및 한외여과하여 분자량 300kDa 이상의 고분자 물질을 분리정제 하였으며 당 조성은 xylose 19.01%, fucose 15.29%, mannose 4.23%, galactose 7.92%로 나타났다. In vitro에서 매생이 보체계 활성물질의 인체 암세포에 대한 독성은 고농도($10-30{\mu}g/ml$)에서만 경미하게 나타났으며, in vivo시험에서는 매생이 추출물의 투여로 마우스 고형암의 성장이 대조군에 비하여 40.13-59.42%가 저해되었다. 그러나 수명 연장율은 실험군간에 통계적 유의차가 없었다. 정제한 매생이 추출물을 마우스의 복강에 투여한 결과, 혈중 백혈구수가 대조군에 비하여 20mg/kg 투여군 39%, 50mg/kg 투여군 70%, 100mg/kg 투여군 83%가 증가하는 것으로 나타났으며, 면역과 관련이 있는 간장, 비장, 흉선의 중량이 증가하였다. 매생이 추출물을 마우스에 경구투여하고 분변으로 배출되는 IgA 항체의 양을 측정한 결과, 대조군이 $2,092{\pm}123.0{\mu}g/mg$인 데에 비하여 매생이 추출물 투여군은 $2,454{\pm}113.8-2,670{\pm}133.1{\mu}g/mg$로 높게 나타났다. 매생이로부터 추출한 면역증강물질은 마우스에 대한 급성독성을 측정한 결과, 체중 1kg당 2,000mg 투여 시 까지도 독성을 나타내지 않아 인체에도 무해할 것으로 사료되었다.

• 대한수의학회지
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• 제46권3호
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• pp.225-234
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• 2006

In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.

• 동의생리병리학회지
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• 제21권5호
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• pp.1210-1218
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• 2007

Recently Atopic Dermatitis(AD) is increasing along with allergic disease. At present, there is no infallible cure for AD. Then AD patients undergo great suffering. This study is carried out to see whether or not the administering Danggwieumja(DG) along with Samhwangseje-gamibang(SG} as a medicine for external aplication, is effective in treating atopic dermatitis. To examine the effectiveness of the above prescription, the author made an observation of diverse immune responses. through the model of NC/Nga atopic mice. Results provided evidence that the DG administration along with SG can be used as a treatment means to atopic dermatitis. The results are as follows: The extent of Clinical skin severities in 13 and 16 week old NC/Nga mice treated with DG and SG, were reduced by 50.9%, 53.9% respectively, compared to the control NC/Nga mice with no drug treatment. IgE, IL-4, IL-5, IL-6, IgM and IgG1 levels in the serum of the NC/Nga mice treated with DG and SG were significantly decreased compared to those of the untreated control mice. In contrary, to the $IFN-{\gamma}$ level, significantly increased. The spleen weight of the NC/Nga mice treated with DG and SG significantly decreased compared to those of the untreated control mice. CCR3 gene expression in the skin tissue of NC/Nga mice treated with DG and SG were highly decreased, and the IL-6 expression significantly decreased, and the $IFN-{\gamma}$ gene expression increased compared to those of the untreated control mice. Histological observation of the ear and dorsal skin tissue of the NC/Nga mice treated with DG and SG, showed that the extents of inflammation and infiltrated immune cells in the epidermal tissue and dermis, were highly reduced compared to those of the untreated control mice. In the model inducing COX-2 activity in RAW 264.7 cell, the denser DG became, the more COX-2 activity was inhibited, compared to those of the untreated control group. $IL-1{\beta}$, and $TNF-{\alpha}$, IL-6 gene expression in RAW 264.7 cell with DG, significantly decreased, compared to those of the untreated control group. According to the assessment of cell toxicity in L929 cell, the rate of cell multiplication increased by 3% in consistency to 100ppm of DG compared to the untreated control group and in more than the 200 ppm consistency, cell toxicity was occurred.

• Nutrition Research and Practice
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• 제9권2호
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• pp.129-136
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• 2015

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

• IMMUNE NETWORK
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• 제4권3호
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• pp.131-142
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• 2004

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

• Journal of Preventive Medicine and Public Health
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• 제32권3호
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• pp.347-354
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• 1999

Objective: This paper examines the possible toxicity to immune system in farmers chronically exposed to pesticides. Methods : We compared 43 male farmers exposed to pesticides with 29 male residents who had neither past nor current pesticides exposure. The selected variables for studying immunotoxicity were WBC, CD3, CD4, CD8, CD19, CD56, IgG, IgA, IgM, and IL-2. As part of the baseline questionnaires for the immunotoxicity, subjects were asked about kinds of farming, posticides exposure and medical history. Results : None of the variables for studying immunotoxicity showed statistically significant difference between the two groups. Although the results were not statistically significant, CD4 and the CD4/CD8 ratio decreased and CD8 increased. These effects showed a dose response change with exposure level. In the exposed group, the values of CD3, CD4, CD4/CD8 and CD19 decreased and those of the CD8 and CD56 increased compared to the non-exposed group. Also there was higher prevalence of self-reported disease in the exposed group compared to the non-exposed group. Conclusions: Although statistically significant differences in indices of immunotoxicity in farmers exposed to pesticides were not shown, the results suggest that pesticides may decrease immune function. More advanced test methods for immunotoxicity need to be developed and tested in larger population to detect immunotoxic effects of pesticides.

• 대한약침학회지
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• 제19권2호
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• pp.114-121
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• 2016

Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

• Nutrition Research and Practice
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• 제10권4호
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• pp.393-397
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• 2016

BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

• 동의생리병리학회지
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• 제32권2호
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• pp.99-105
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• 2018

The aim of this study is to compare the anti-inflammatory and immunological activity of different parts (bone, meat, and rind) of Yeonsan Ogye (YO). In order to evaluate cytotoxicity, MTT assay was performed. We investigated the production of nitric oxide (NO) and pro-inflammatory cytokines, such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$, in LPS-induced RAW264.7 cells. All parts of the YO showed no toxicity at concentrations of 1, 10, and $100{\mu}g/m{\ell}$. Rooster's bone, hen's bone, and rind decreased the production of NO. And rooster's bone, meat, and hen's bone also attenuated TNF-${\alpha}$ production in LPS-induced RAW 264.7 cells. In addition, all parts of the YO decreased IL-$1{\beta}$ and IL-6 production in LPS-induced RAW264.7 cells, whereas they all increased IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in normal RAW264.7 cells. Rooster exhibited higher immune activation and inhibitory activity on inflammation than a hen, and among different parts of the YO, bone showed the highest activity. Our results demonstrated and compared the anti-inflammatory and immunological activity of different parts of the YO. These results suggest that YO may be developed as a raw material for new health supplement food and medicine to attenuate various symptoms related to inflammation and immunity.