• 한국식품영양과학회지
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• 제34권5호
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• pp.605-612
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• 2005

방사선 생체손상의 방어 및 회복에 높은 효과를 나타내는 생약조합을 도출하고자 하였다. 이전의 연구에서 6가지 기존 보기${\cdot}$보혈 한약처방제의 방어효과를 검색하여, 재생조직 방어에는 사물탕 및 보중익기탕이, 조혈계 방어에는 보중익기탕 및 사물탕이 높은 효과를 나타내는 것으로 보고된바 있다. 본 연구에서 기존 6가지 처방제의 면역 세포 활성화 효과를 검색한 결과 모두 높은 효과를 나타내지 않았다. 따라서, 처방제의 구성 생약 각각의 효과검증 결과를 바탕으로 재생조직 방어, 조혈계 방어, 면역조혈계 회복 증진 효과를 동시에 높게 나타내는 새로운 생약조합을 도출하였다. 즉, 당귀, 천궁, 백작약을 동일 무게 비율로 혼합하여 열수 추출한 것을 새로운 생약복합물 HIM-I으로 개발하였으며 그 효과를 검정하였다. 본 생약복합물 HIM-I은 면역 세포 활성화에서는 상기한 한약처방제보다 월등하게 높은 효과를 보였으며, 조혈계 촉진효과도 높은 것으로 나타났다. 또한, 재생조직 및 면역조혈계의 방어 측면에서도 사물탕 및 보중익기탕과 같은 높은 효과를 보였다. 한편, 시험관 내에서 높은 항산화 효과를 나타내는 것으로 보아, 이 항산화 작용이 방사선 손상에 대한 방어효과의 작용기전 중의 하나로 생각되었다. 이상의 결과로 보아, 생약복합물 HIM-I은 재생조직방어, 조혈계 방어, 면역조혈계 회복 증진 효과를 동시에 나타냄으로써 방사선뿐만 아니라 여러 가지 원인으로부터 생체를 방호하고 회복시키는데 유용할 것으로 생각된다.

• 대한의생명과학회지
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• 제21권2호
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• pp.51-59
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• 2015

A humanized mice (hu-mice) model is extremely valuable to verify human cell activity in vivo condition and is regarded as an important tool in examining multimodal therapies and drug screening in tumor biology. Moreover, hu-mice models that simply received human $CD34^+$ blood cells and tissue transplants are also overwhelmingly useful in immunology and stem cell biology. Because generated hu-mice harboring a human immune system have displayed phenotype of human $CD45^+$ hematopoietic cells and when played partly with functional immune network, it could be used to evaluate human cell properties in vivo. Although the hu-mice model does not completely recapitulate human condition, it is a key methodological factor in studying human hematological malignancies with impaired immune cells. Also, an advanced humanized leukemic mice (hu-leukemic-mice) model has been developed by improving immunodeficient mice. In this review, we briefly described the history of development on immunodeficient SCID strain mice for hu-and hu-leukemic-mice model for immunologic and tumor microenviromental study while inferring the potential benefits of hu-leukemic-mice in cancer biology.

• IMMUNE NETWORK
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• 제15권3호
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• pp.125-134
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• 2015

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of $CD11b^+Gr-1^+$ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

• 대한한방부인과학회지
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• 제27권2호
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• pp.46-58
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and anti-metastatic effect on cancer cells by orally administered extracts of Boyanghwano-tang. Methods: To observe immunomodulating effects of Boyanghwano-tang on Peyer's patch cells, we measured cytokines GM-CSF, IL-4. In addition to observing effects of Boyanghwano-tang on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in intestinal content and serum was measured to observe the effect of orally administered Boyanghwano-tang on mucosal immune system. After administering ovalbumin (OVA) with Boyanghwano-tang, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Anti-metastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. Results: The amounts of GM-CSF and IL-4 in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regualted with Boyanghwano-tang. These results indicate that oral administration of Boyanghwano-tang enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering OVA with Boyanghwano-tang, IgA induction and Proliferation of peyer's patch cell was up-regulated with Boyanghwano-tang. These results means orally administered Boyanghwano-tang activates intestinal immune system and has an inhibitory effect on tumor metastasis. In addition, We found that orally administered Boyanghwano-tang significantly inhibited tumor metastasis in vivo. Conclusions: Orally administered Boyanghwano-tang appears to have considerable activity on the anti-metastasis by activation of immune system.

• 대한한방부인과학회지
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• 제27권2호
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• pp.34-45
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and antimetastatic effect of Ojeok-san on cancer cells by oral administration. Methods: Cell viability of Ojeok-san was tested with colon 26-M3.1 carcinoma cells and Peyer's patch cells in vitro. Antimetastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. To observe immunomodulating effects of Ojeok-san on Peyer's patch cells, we measured interleukin (IL)-4, GM-CSF. In addition to observing effects of Ojeok-san on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in serum and intestinal content was measured to observe the effect of orally administered Ojeok-san on mucosal immune system. After administering Ovalbumin (OVA) with Ojeok-san, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Results: in vitro cytotoxicity analysis, the inhibitory concentration $(IC)_{50}$ of the colon 26-M3.1 carcinoma cell was $890{\mu}g/ml$. $IC_{50}$ of the Peyer's patch cells with LPS was $990{\mu}g/ml$. We found that orally administered Ojeok-san significantly inhibited tumor metastasis in vivo. In addition, the amounts of IL-4 and GM-CSF in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regulated with Ojeok-san. These results indicate that oral administration of Ojeok-san enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering Ovalbumin (OVA) with Ojeok-san, IgA induction and Proliferation of peyer's patch cell was up-regulated with Ojeok-san. These results means orally administered Ojeok-san activates intestinal immune system and has an inhibitory effect on tumor metastasis. Conclusions: Orally administered Ojeok-san appears to have considerable activity on the anti-metastasis by activation of immune system.

• IMMUNE NETWORK
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• 제11권6호
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• pp.324-335
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• 2011

The human leukocyte antigen (HLA), the major histocompatibility complex (MHC) in humans has been known to reside on chromosome 6 and encodes cell-surface antigen-presenting proteins and many other proteins related to immune system function. The HLA is highly polymorphic and the most genetically variable coding loci in humans. In addition to a critical role in transplantation medicine, HLA and disease associations have been widely studied across the populations worldwide and are found to be important in prediction of disease susceptibility, resistance and of evolutionary maintenance of genetic diversity. Because recently developed molecular based HLA typing has several advantages like improved specimen stability and increased resolution of HLA types, the association between HLA alleles and a given disease could be more accurately quantified. Here, in this review, we have collected HLA association data on some autoimmune diseases, infectious diseases, cancers, drug responsiveness and other diseases with unknown etiology in Koreans and attempt to summarize some remarkable HLA alleles related with specific diseases.

• BMB Reports
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• 제56권8호
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• pp.417-425
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• 2023

In various organisms, the Hippo signaling pathway has been identified as a master regulator of organ size determination and tissue homeostasis. The Hippo signaling coordinates embryonic development, tissue regeneration and differentiation, through regulating cell proliferation and survival. The YAP and TAZ (YAP/TAZ) act as core transducers of the Hippo pathway, and they are tightly and exquisitely regulated in response to various intrinsic and extrinsic stimuli. Abnormal regulation or genetic variation of the Hippo pathway causes a wide range of human diseases, including cancer. Recent studies have revealed that Hippo signaling plays a pivotal role in the immune system and cancer immunity. Due to pathophysiological importance, the emerging role of Hippo signaling in blood cell differentiation, known as hematopoiesis, is receiving much attention. A number of elegant studies using a genetically engineered mouse (GEM) model have shed light on the mechanistic and physiological insights into the Hippo pathway in the regulation of hematopoiesis. Here, we briefly review the function of Hippo signaling in the regulation of hematopoiesis and immune cell differentiation.

• IMMUNE NETWORK
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• 제11권1호
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• pp.68-78
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• 2011

Background: Graft-versus-host disease (GVHD) is a huddle for success of hematopoietic stem cell transplantation. In this study, effects of irradiation dose on immune kinetics of GVHD were investigated using B6 ${\rightarrow}$ BALB.B system, a mouse model for GVHD after MHC-matched allogeneic transplantation. Methods: BALB.B mice were transplanted with bone marrow and spleen cells from C57BL/6 mice after irradiation with different doses. Leukocytes residing in the peripheral blood and target organs were collected periodically from the GVHD hosts for analysis of chimerism formation and immune kinetics along the GVHD development via flow cytometry. Myeloid cells were tested for production of IL-17 via flow cytometry. Results: Pre-conditioning of BALB.B hosts with 900 cGy and 400 cGy resulted in different chimerism of leukocytes from the blood and affected survival of GVHD hosts. Profiles of leukocytes infiltrating GVHD target organs, rather than profiles of peripheral blood leukocytes (PBLs), were significantly influenced by irradiation dose. Proportions of IL-17 producing cells in the infiltrating $Gr-1^+$ or $Mac-1^+$ cells were higher in the GVHD hosts with high does irradiation than those with low dose irradiation. Conclusion: Pre-conditioning dose affected tissue infiltration of leukocytes and cytokine production by myeloid cells in the target organs.

• 한국식품과학회지
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• 제33권1호
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• pp.135-141
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• 2001

십전대보탕의 10가지 구성 천연물을 열수추출하여 장관면역 활성을 비교 검토한 결과, 창출(Atractylodes lancea DC., ALR)과 인삼(Panax ginseng C.A. Meyer, PG)에서는 높은 활성을 나타내었으나 약한 활성을 갖는 황기(Astragalus membranacues, ASR)와 당귀(Angelica aculiloba Kitagawa, AR)를 제외하고는 어떤 생약에서도 거의 활성을 갖지 않았다. 한편 이러한 활성을 가진 생약(ALR, PG와 ASR) 중에서도 특히 ALR만이 종류, 생산지 및 육종조건에 관계없이 항상 일정하게 높은 활성을 보여주어 창출의 열수추출물 획분(ALR-0)이 십전대보탕의 장관면역 활성에 중요하게 관여하는 시료로 선정되었다. ALR-0 획분은 다시 용매별로 분획되어 메탄올-가용성 획분(ALR-1), 메탄올-불용성/에탄올-가용성 획분(ALR-2) 및 조다당 획분(ALR-3)으로 조제되었으며 이들의 활성을 측정한 결과, 단지 ALR-3 획분만이 Peyer's patch를 통한 골수세포의 증식을 활성화시키는 장관면역 활성을 시료농도에 의존적으로 나타내었으며 그 외의 획분에는 활성이 거의 없었다. 한편 ALR-3 획분을 $NaIO_4,\;NaClO_2$ 및 pronase로 처리한 후 활성을 측정한 결과, 모든 처리군에서 활성이 감소되었으며 특히 periodate 산화에 의해 심한 활성감소를 보였다. 이러한 결과를 토대로 십전대보탕의 장관면역 활성은 10종의 생약 중에서도 특히 창출이 중요하게 활성에 관여하는 것으로 보이며 다양한 용매별 분획을 통해 저분자보다는 에탄올에 침전된 고분자가 주요 함유물질인 조다당 획분이 장관면역 활성에 관여하는 것으로 추정되었다. 또한 periodate 산화에 의해 활성이 크게 감소되는 것으로 보아 주로 다당류가 창출의 장관면역에 중요한 활성물질인 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2935-2941
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• 2012

Biological response modifiers (BRMs) can alter interactions between the immune system and cancer cells to boost, direct, or restore the body's ability to fight disease. Mice with ethylnitrosourea- (ENU) induced leukemia were here used to monitor the therapeutic efficacy of lipopolysaccaride (LPS), Bacillus Calmette Guerin (BCG) and sheep erythrocytes (SRBC). Flow cytometry based CD34+ positivity analysis, clonogenicity, proliferation and ultrastructure studies using scanning electron microscopy (SEM) of stem cells in ENU induced animals with and without BRMs treatment were performed. BRMs improved the stem-stromal relationship structurally and functionally and might have potential for use as an adjunct in human stem cell therapy.