• Title/Summary/Keyword: Differentiation of Self

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Transcription Factor EB-Mediated Lysosomal Function Regulation for Determining Stem Cell Fate under Metabolic Stress

  • Chang Woo Chae;Young Hyun Jung;Ho Jae Han
    • Molecules and Cells
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    • v.46 no.12
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    • pp.727-735
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    • 2023
  • Stem cells require high amounts of energy to replicate their genome and organelles and differentiate into numerous cell types. Therefore, metabolic stress has a major impact on stem cell fate determination, including self-renewal, quiescence, and differentiation. Lysosomes are catabolic organelles that influence stem cell function and fate by regulating the degradation of intracellular components and maintaining cellular homeostasis in response to metabolic stress. Lysosomal functions altered by metabolic stress are tightly regulated by the transcription factor EB (TFEB) and TFE3, critical regulators of lysosomal gene expression. Therefore, understanding the regulatory mechanism of TFEB-mediated lysosomal function may provide some insight into stem cell fate determination under metabolic stress. In this review, we summarize the molecular mechanism of TFEB/TFE3 in modulating stem cell lysosomal function and then elucidate the role of TFEB/TFE3-mediated transcriptional activity in the determination of stem cell fate under metabolic stress.

Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells

  • Ji-Sun Lee;Ho-Young Lee
    • Journal of Ginseng Research
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    • v.48 no.3
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    • pp.266-275
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    • 2024
  • Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

Shaping Heterogeneity of Naive CD8+ T Cell Pools

  • Sung-Woo Lee;Gil-Woo Lee;Hee-Ok Kim;Jae-Ho Cho
    • IMMUNE NETWORK
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    • v.23 no.1
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    • pp.2.1-2.19
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    • 2023
  • Immune diversification helps protect the host against a myriad of pathogens. CD8+ T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8+ T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8+ T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8+ T cells in a "naive" state, introducing recent studies dealing with the heterogeneity of naive CD8+ T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8+ T cell response.

The effects of nutrient depleted microenvironments and delta-like 1 homologue (DLK1) on apoptosis in neuroblastoma

  • Kim, Yu-Ri
    • Nutrition Research and Practice
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    • v.4 no.6
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    • pp.455-461
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    • 2010
  • The tumor microenvironment, particularly sufficient nutrition and oxygen supply, is important for tumor cell survival. Nutrition deprivation causes cancer cell death. Since apoptosis is a major mechanism of neuronal loss, we explored neuronal apoptosis in various microenvironment conditions employing neuroblastoma (NB) cells. To investigate the effects of tumor malignancy and differentiation on apoptosis, the cells were exposed to poor microenvironments characterized as serum-free, low-glucose, and hypoxia. Incubation of the cells in serum-free and low-glucose environments significantly increased apoptosis in less malignant and more differentiated N-type IMR32 cells, whereas more malignant and less differentiated I-type BE(2)C cells were not affected by those treatments. In contrast, hypoxia (1 % $O_2$) did not affect apoptosis despite cell malignancy. It is suggested that DLK1 constitutes an important stem cell pathway for regulating self-renewal, clonogenicity, and tumorigenicity. This raises questions about the role of DLK1 in the cellular resistance of cancer cells under poor microenvironments, which cancer cells normally encounter. In the present study, DLK1 overexpression resulted in marked protection from apoptosis induced by nutrient deprivation. This in vitro model demonstrated that increasing severity of nutrition deprivation and knock-down of DLK1 caused greater apoptotic death, which could be a useful strategy for targeted therapies in fighting NB as well as for evaluating how nutrient deprived cells respond to therapeutic manipulation.

Dual Drug-Loaded Liposomes for Synergistic Efficacy in MCF-7 Breast Cancer Cells and Cancer Stem Cells

  • Park, Hee-Bin;Kim, Yun-Ji;Lee, Seong-Min;Park, James S.;Kim, Keun-Sik
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.159-169
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    • 2019
  • Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

Absolute Differentiated Services for Optical Burst Switching Networks Using Dynamic Wavelength Assignment (동적 파장 할당 기법을 이용한 광 버스트 스위칭 네트워크에서의 절대적 QoS 제공)

  • 김성창;최진식;강민호
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.40 no.10
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    • pp.8-15
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    • 2003
  • In this paper, we address how to provide absolute differentiated services for optical burst switching (OBS) networks based on dynamic wavelength assignment. Unlike existing quality of service (QoS), such as buffer-based and offset-time based scheme, our proposed dynamicvirtual lambda partitioning (DVLP) scheme does not mandate any buffer or extra offset time, but can achieve absolute service differentiation between classes. This new DVLP scheme shares wavelength resources based on several different priority of classes in an efficient and QoS guaranteed manner. The performance results show that the proposed scheme effectively guarantees a target blocking probability of each traffic classes both in Poisson and Self-similar traffic environment.

Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment

  • Park, Min Hee;Min, Woo-Kie;Jin, Hee Kyung;Bae, Jae-sung
    • BMB Reports
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    • v.48 no.12
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    • pp.645-646
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    • 2015
  • The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

Analysis on mathematical behavior characteristics of a mathematically gifted student in independent study (독자적 연구에서 나타난 수학영재의 수학적 행동특성 분석)

  • Jeong, Jin-Yeong;Kang, Soon-Ja
    • The Mathematical Education
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    • v.53 no.4
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    • pp.479-492
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    • 2014
  • According to Krutetskii, the education of mathematically gifted students must be focused on the improvement of creative mathematical ability and the mathematically gifted students need to experience the research process like mathematician. Independent study is highly encouraged as the self-directed activity of highest level in the learning process which is similar to research process used by experts. We conducted independent study as a viable differentiation technique for gifted middle school students in the 3rd grade, which participated in mentorship program for 10 months. Based on the data through the research process, interview with a study participant and his parents, and his blog, we analyzed mathematical behavior characteristics of a study participant. This behavior characteristics are not found in all mathematically gifted students. But through this case study, we understand mathematically gifted students better and furthermore obtain the message for the selection and education of the mathematically gifted students and for the effective method of running mentorship program particularly.

Global Proteomic Analysis of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells via Connective Tissue Growth Factor Treatment under Chemically Defined Feeder-Free Culture Conditions

  • Seo, Ji-Hye;Jeon, Young-Joo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.126-140
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    • 2022
  • Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.

A Study on the Repositioning of Korean Character/Career Women's Wear Brands - Focused on the Comparative Analysis with Import Masstige Brands - (국내 여성 캐릭터.커리어 브랜드의 리포지셔닝에 관한 연구 - 수입 매스티지 브랜드와의 비교 분석을 중심으로 -)

  • Shin, Su-Yun;Cho, Jeong-A
    • The Research Journal of the Costume Culture
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    • v.17 no.1
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    • pp.120-131
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    • 2009
  • The purpose of this study was to suggest the repositioning strategy for Korean character/career women's wear brands by comparing them with masstige brands. The subjects were 240 Women in their twenties and early forties in Seoul and the metropolitan area. The data had been collected by self-administered questionnaire and analyzed by frequency and biplot. The results of the study were as follows: (1) The brand preference was 'Time'(33.3%), 'Michaa'(12.5%), and then 'Mine'(8.8%) in sequence; (2) For brand differentiation, the attributes of 'store image', 'comfortableness', 'brand reputation', and 'promotion' were found out to be important in sequence; (3) The national character/career brands were favored by theirs 'store image', 'quality', and 'design', while imported masstige brands were favored by theirs 'comfortableness', 'brand reputation', 'promotion', and 'perceived price'; (4) Among brands, 'Time' had been highly evaluated, but comparatively showed weakness on 'perceived price', 'comfortableness', and 'promotion'.

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