• Journal of Nutrition and Health
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• 제48권2호
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• pp.157-166
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• 2015

골기능 개선용 흑염소 액상제품을 개발하기 기초연구로서 흑염소 및 약용식물 복합추출물이 MG-63 조골세포 및 마우스 골수세포 유래 파골세포의 분화에 미치는 영향을 분석하였다. 흑염소 원료육의 일반성분, 휘발성 염기질소, 무기질함량, 유리아미노산 조성 및 지방산 조성 등의 영양성분을 분석하여 기초자료를 마련하였다. 흑염소에 첨가할 약용식물의 종류와 배합을 달리한 두 그룹의 한약재 첨가군에 대해 증탕추출액과 증류액을 제조하여 총 6개 시료군 (흑염소육 (BG-E, BG-D), 6종 한약재 첨가군 (BG-E6, BG-D6) 및 8종 한약재 첨가군 (BG-E8, BG-D8)을 대상으로 골강화 활성을 분석하였다. 식품공전상 식품의 원료로 사용이 가능한 원료 중 황기, 홍화씨, 당귀, 황정, 속단, 우슬 각각 2/2/2/2/1/1의 배합비를 지닌 한약재 6종 첨가군 및 동일배합에 녹용과 녹각을 각각 0.3/1.2 로 추가배합한 한약재 8종 첨가군을 사용하였다. 조골세포 MG-63의 증식 촉진 활성에 대해 시료별 및 농도별로 유의적인 차이가 나타났으며 한약재 무첨가 흑염소군보다 6종 및 8종 등 한약재 첨가량이 많을수록 활성이 증가하였다. 증탕추출액과 달리 증류액은 모두 유의한 효과가 없었다. 조골세포의 골석회화 촉진활성시험 결과 대조군에 비해 모든 시료 처리군에서 칼슘함량이 유의적으로 증가하여 MG-63 세포의 석회화 결절 형성을 농도 의존적으로 유의하게 증가시켰다. BG-E6는 대조군에 비해 석회화 형성을 170.3% 증가시켰고, 증류액인 BG-D와 BG-D6는 각각 168.5% 및 159.8%의 증가를 나타내었다. 시료별 차이에 있어 한약재 첨가군이 무첨가군보다 높았고, 증탕추출액이 증류액보다 높은 활성을 보였다. 세포의 칼슘 흡수량을 측정한 결과 모든 증탕추출액에서 활성이 증가하였고 특히 BG-E6와 BG-E8은 각각 615.5%와 628.1%로 유의적으로 가장 높은 증가율을 보였다. 증류액은 BG-D6의 1/10 농도군외에 효과가 없었다. 마우스 골수세포 유래 파골세포의 증식억제 실험결과 TNF-${\alpha}$ 만을 처리한 대조군에 비해 모든 시료군이 TRAP활성을 억제하는 경향을 나타내었다. 특히 BG-D 및 BG-E6, BG-E8은 유의하게 파골세포로의 분화를 억제하였다. 종합적으로 흑염소육을 비롯하여 황기, 홍화씨, 당귀, 황정, 속단, 우슬, 녹용 및 녹각 등 한약재의 복합추출물은 골 기능 강화에 매우 효과적인 기능성 원료가 될 수 있을 것으로 사료된다.

• Journal of Chest Surgery
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• 제34권6호
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• pp.506-510
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• 2001

Langerhans 세포 조직구증(LCH, Langerhans\` Cell Histiocytosis)은 Langerhans\` cell histiocyte의 이상 증식을 특징으로 하는 원인 불명의 질환이다. 이 질환은 eosinophilic granuloma, Hand-Sch ller-Christian씨 병, Letterer-Siwe병을 포함하는 것으로 과거에는 histiocytosis X로 불리던 질환이다. 피부, 림프절, 골, 골수 및 체내 모든 조직과 기관을 침범할 수 있으나 국내에서 흉벽에서 발생된 예는 보고된 증례가 많지않다. 18개월 된 남자 환아에서 흉벽의 늑골에서 기원하여 골용해 소견을 동반한 종괴가 있어 수술적 절제한 후 LCH로 확진된 증례가 있어 문헌고찰과 함께 보고하는 바이다

• International Journal of Stem Cells
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• 제15권4호
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• pp.405-414
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• 2022

Background and Objectives: Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods and Results: BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions: CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

• 대한구강악안면병리학회지
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• 제42권6호
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• pp.159-165
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• 2018

The Hippo pathway was originally discovered in Drosophila by genetic screening and it has been shown to be conserved in various organisms including human. Until now, the essential roles of Hippo pathway in regulating cell proliferation, apoptosis, tumorigenesis, and organ size control is extensively studied. Currently, Mats1/2 (Mob1a/1b), one of the important components in Hippo pathway, mutant mice were generated which has abnormal phenotype such as resistance to apoptosis and spontaneous tumorigenesis. Of note, Mats1/2 mutant mice also showed dental malocclusion. Therefore, in this study, we have evaluated the bone phenotype of Mats1/2 mutant mice. Although the mRNA expressions of Mats1 or Mats2 were observed in both osteoclastogenesis and osteoblastogenesis, the increase of Mats1 level was most prominent during osteoblastogenesis. The RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) was unaltered upon Mats1/2 mutation; however, the osteoblast differentiation using calvarial pre-osteoblasts was significantly reduced in Mats1/2 mutant mice compare to that of wild type mice. In accordance with in vitro results, Mats1/2 mutant mice showed decreased bone volume as well as increased trabecular separation in ${\mu}CT$ analyses. These results may provide novel prospect of the probable linkage between Hippo pathway and bone homeostasis.

• IMMUNE NETWORK
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• 제9권1호
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• pp.27-33
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• 2009

Macrophages generated in vitro using macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 from bone marrow cells (BM-Mp) are defective in antigen presenting cell (APC) function as shown by their ability to induce the proliferation of anti-CD3 mAb-primed syngeneic T cells. However, they do express major histocompatibility (MHC) class I and II molecules. accessory molecules and intracellular adhesion molecules. Here we demonstrate that the defective APC function of macrophages is mainly due to production of $TGF-{\beta}1$ by BM-Mp. Methods: Microarray analysis showed that $TGF-{\beta}1$ was highly expressed in BM-Mp, compared to a macrophage cell line, B6D. which exerted efficient APC function. Production of $TGF-{\beta}1$ by BM-Mp was confirmed by neutralization experiments of $TGF-{\beta}1$ as well as by real time-polymerase chain reaction (PCR). Results: Addition of $anti-TGF-{\beta}1$ monoclonal antibody to cultures of BM-Mp and anti-CD3 mAb-primed syngeneic T cells efficiently induced the proliferation of syngeneic T cells. Conversely, the APC function of B6D cells was almost completely suppressed by addition of $TGF-{\beta}1$. Quantitative real time-PCR analysis also confirmed the enhanced expression of $TGF-{\beta}1$ in BM-Mp. Conclusion: The defective APC function of macrophages generated in vitro with M-CSF and IL-6 was mainly due to the production of $TGF-{\beta}1$ by macrophages.

• 혜화의학회지
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• 제10권2호
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• pp.1-10
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• 2002

In review of "invigorating spleen and supplementing qi" of clinical and experimental studies on malignant tumor, we obtained the conclusions as follows 1. Asthenic splenic qi is an important factor in mutation, occurrence and development of tumor. 2. The anti-tumor mechanism of "invigorating spleen and supplementing qi" is improvement of immune suveillance, controling cell proliferating period and enhancing body metabolism. 3. "Invigorating spleen and supplementing qi" is often used with "nourishing kidney" or "expelling pathogen" for treating cnacer. 4. In experimental studies, "invigorating spleen and supplementing qi" has effects on inhibiting occurrence and development of tumor, protecting mutation, inhibiting recurrence and metastasis, immune activity, enhancing metabolism, promoting bone marrow hemopoietic cell proliferation, increasing anti-tumor effect and protecting normal cells. 5. In clinical studies, "invigorating spleen and supplementing qi" has effects on prolonging the survival period of cancer patients, improving clinical symptoms and quality of life of cancer patients, degrading the side effects of western therapie(operation, chemotherapy and radiotherapy). 6. "Invigorating spleen and supplementing qi" is an extensive discipline of syndrome differentiation used to inhibit occurence, development, recurrence and metastasis.

• IMMUNE NETWORK
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• 제4권1호
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• pp.44-52
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• 2004

Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

• Journal of Microbiology and Biotechnology
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• 제13권3호
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• pp.422-428
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• 2003

Umbilical cord blood (UCB), a rich source of hematopoietic stem/progenitor cells, has been proposed as an alternative to bone marrow and peripheral blood for transplantation treatment. Ex vivo expansion of cord blood stem cells could make the use of cord blood transplant feasible even for adult patients. However, the optimal cytokine cocktail for expansion of stem cells is yet to be established. This study compares proliferation, apoptosis, and telomerase activities in human cord blood stem cells cultured ex vivo with FLT3 ligand (FL)/thrombopoietin (TPO) or FL/TPO/stem cell factor (SCF), with a view to determine optimal combination of cytokines. CD34+ cells were cultured in DMEM containing either FL (50 ng/ml) and TPO (10 ng/ml) (FT group) or FL (50 ng/ml), TPO (10 ng/ml) and SCF (50 ng/ml) (FTS group). The cell proliferation rate was ten times higher in the FTS group. Although cells cultured with the two different combinations of cytokines were maintained for a long term (up to 8 weeks), a large number of cells underwent differentiation during this period. Cells cultured in FTS displayed lower levels of apoptosis compared to those of the FT group during the Initial 7 days of culture. The CD34+ fraction in both groups was markedly decreased to $21-30\%$ , and only $5-6\%$ was detected at 14 days of culture. Telomerase activity detected in human CD34+ cord blood at low levels was upregulated during the early phase of culture and decreased to baseline levels in the later phase. The telomerase activity of cord blood cultured in FT was lower than that of the FTS group. Our results suggest that, on adding stem cell factors to the FT cytokines, cultured CD34+ cord blood cells display a greater degree of cell proliferation and decreased apoptosis. However, during CD34+ cord blood cell culture, a Barge number of cells undergo differentiation, indicating that more potent novel cytokines or new culture conditioning methods should be developed to maintain their ability to engraft and sustain long-term hematopoiesis.

• IMMUNE NETWORK
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• 제5권1호
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• BMB Reports
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• 제56권9호
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.