• BMB Reports
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• 제46권9호
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• pp.465-470
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• 2013

Bone morphogenetic proteins (BMPs) have diverse and important roles in the proliferation and differentiation of adult stem cells in our tissues. Especially, BMPs are well known to be the main inducers of bone formation, by facilitating both proliferation and differentiation of bone stem cells. Interestingly, in skin stem cells, BMPs repress their proliferation but are indispensable for the proper differentiation into several lineages of skin cells. Here, we tested whether BMP antagonists have an effect on the prevention of wrinkle formation. For this study we used an in vivo wrinkle-induced mouse model. As a positive control, retinoic acid, one of the top anti-wrinkle effectors, showed a 44% improvement compared to the non-treated control. Surprisingly, bone morphogenetic protein receptor 1a extracellular domain (BMPR1a-ECD) exhibited an anti-wrinkle effect which was 6-fold greater than that of retinoic acid. Our results indicate that BMP antagonists will be good targets for skin or hair diseases.

• BMB Reports
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• 제46권8호
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• pp.383-390
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• 2013

Mammalian neural stem cells (NSCs) are of particular interest because of their role in brain development and function. Recent findings suggest the intimate involvement of programmed cell death (PCD) in the turnover of NSCs. However, the underlying mechanisms of PCD are largely unknown. Although apoptosis is the best-defined form of PCD, accumulating evidence has revealed a wide spectrum of PCD encompassing apoptosis, autophagic cell death (ACD) and necrosis. This mini-review aims to illustrate a unique regulation of PCD in NSCs. The results of our recent studies on autophagic death of adult hippocampal neural stem (HCN) cells are also discussed. HCN cell death following insulin withdrawal clearly provides a reliable model that can be used to analyze the molecular mechanisms of ACD in the larger context of PCD. More research efforts are needed to increase our understanding of the molecular basis of NSC turnover under degenerating conditions, such as aging, stress and neurological diseases. Efforts aimed at protecting and harnessing endogenous NSCs will offer novel opportunities for the development of new therapeutic strategies for neuropathologies.

• 한국정밀공학회지
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• 제31권5호
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• pp.375-380
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• 2014

To enhance biocompatibility between the orthopedic implant stem and obsteoblast cells, bone-forming cells, micro-size holes are patterned in Ti plate surface. Initially, the house built laser power stabilization system is applied to the laser micro patterning machine to convince repeatable result. Various pulse widths are irradiated Ti plate and relationship between diameters of patterned holes and pulsed width is derived. Effect of multi pulse is observed and optimal pulse number is considered to avoid heat affected zone. After MG-63 osbeoblast cells are cultured, micro patterned Ti plates are compared with control plates. In SEM image, cells are well aligned and aggregation is observed in both 60, and $100{\mu}m$ patterned plates. Finally, free form surface stem model is prepared to test micro hole patterning.

• IMMUNE NETWORK
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• 제20권1호
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• 대한조선학회논문집
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• 제29권4호
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• pp.87-97
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• 1992

극지방의 천연자원의 수송에 필수적인 빙해항행선박은 금후 우리나라의 조선산업이 지향해야 할 기술집약형 선박중 하나로서 국제경쟁에 대비하여 독자적인 연구가 요구되는 분야이다. 본 연구는 빙해항행선박 기본설계의 중요한 인자인 선수부 형상과 평탄빙에서의 쇄빙능력 사이의 상관관계를 밝히는데 목적이 있다. 통상 평탄빙(level ice)에서 선박의 전진속도를 3-4 knots로 볼 때, 탄성으로 취급되는 얼음의 재료특성을 고려하여, 파괴시킬 수 있는 얼음의 최대두께와 파괴된 얼음의 특성길이를 수치적으로 추정하는데 주안점을 두고 있다. 본 연구에서는 빙해항행 선박이 평탄빙에서 연속쇄빙을 하고 있는 상황을 탄성지지기반 위에 놓인 유한 길이의 쐐기보에 작용한 충격하중의 문제로 가정하고 굽힘모멘트에 의해 어떤 위치에서 발생한 최대인장응력이 얼음의 굽힘파괴강도에 도달한다면 그 부분에서 파단이 일어날 가능성이 가장 높다고 판단한다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.441-452
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• 2020

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

• International Journal of Stem Cells
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• 제9권2호
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• pp.186-191
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• 2016

Background and Objectives: With the global demand for dairy protein for consumption growing annually, there has been increasing activity in the research field of dairy protein synthesis and production. From a manipulation perspective, it is more difficult to use live cattle for laboratory studies on the production of milk as well as of dairy protein such as casein, as compared with using laboratory animals like rodents. Therefore, we aimed to develop a mouse model of bovine mammary alveolar ducts for laboratory-scale studies. We studied the formation of the bovine mammary gland ductal structure by transplanting the MAC-T bovine alveolar cell line into mice. Methods and Results: MAC-T cells ($1{\times}10^7$) were suspended in Matrigel and injected into the dorsal tissue of 8-week-old male BALB/C nude mice. Histological analysis of tissue dissected from the MAC-T cell-transplanted mice after 6 weeks showed the typical morphology of the tubuloalveolar female gland, as well as glands made up of branching ducts that were surrounded by smooth muscle with small alveoli budding off the ducts. In addition, the epithelial markers CK14 and CK18 were expressed within the duct-like structure. Prolactin was detected in the duct interior in these CK14+ and CK18+ cells but not in the non-transplanted MAC-T cells. Conclusions: These results showed that duct-like tissue had been successfully formed after 6 weeks of transplantation of the CK14+ and CK18+ MAC-T cells into mice dorsal tissue. This mouse model will be a useful tool for further research on the bovine mammary gland.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.432-441
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• 2024

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

• 한국산림과학회지
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• 제98권6호
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• pp.646-651
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• 2009

본 연구는 충북 충주지역 가래나무 조림지에 대한 개체목 및 임분 표준지 조사 자료를 토대로 재적표(수피 포함 및 제외) 및 임분수확표를 조제하고자 하였다. 재적을 산출하기 위한 수간곡선식으로는 Kozak식을 적용하였으며, 식의 적합성지수가 97% 이상으로 매우 높은 정확도를 보였다. 산출된 재적을 이용하여 가래나무에 대한 재적표를 국내 최초로 조제하였다. 임분생산력을 판정할 수 있는 지위지수를 분석하기 위해서 Chapman-Richard 모델을 이용하였으며, 기준 임령은 30년으로 하였다. 분석 결과 지위등급은 평균적으로 16~22의 범위에 분포하는 것으로 나타났다. 본 연구에서 조제된 임분수확표를 지위지수 '중'인 가래나무 70년생 임분에 적용한 결과 축적이 $238m^3$ 이상으로 나타났는데, 이는 가래나무 임분 수확량의 추정을 위해 기존에 적용되어왔던 상수리나무 임분수확표를 적용한 경우에 비해 $100m^3/ha$ 이상 차이가 나타나는 것으로 나타났다. 이러한 연구결과는 활엽수에 대한 수종별 임분수확표 조제의 필요성을 입증하고 있다. 본 연구결과를 토대로 충주지역 가래나무 조림지의 이산화탄소 흡수량을 계산한 결과, 30년생 임분의 경우 연간 $5.84tCO_2/ha$의 탄소를 흡수할 수 있는 것으로 나타났다. 본 연구에서 조제된 가래나무 재적 및 임분수확표는 앞으로 충북 충주지역 가래나무 조림지에 대한 경영의사결정에 주요한 참고자료로 활용될 수 있을 것이다.

• Molecules and Cells
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• 제38권7호
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• pp.643-650
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• 2015

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.