• Elastomers and Composites
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• v.57 no.2
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• pp.55-61
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• 2022

In this work, we report a highly deformable covalent adaptable-liquid crystal elastomer (CA-LCE) comprising dynamic thiourea bonds that enable macromolecular network rearrangement at elevated temperatures. The exchange of chain network is verified through stress-relaxation analyses and follows Arrhenius-type behavior. The unique capability of rearranging the chain network in the CA-LCE provides useful properties, such as welding, melt reprocessing, and shape reprogramming, that cannot be achieved by the conventional LCE comprising permanent crosslinks. Reversible actuation is further demonstrated by reprogramming the polydomain CA-LCE into a monodomain via mechanical stretching at elevated temperatures.

• Journal of Embryo Transfer
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• v.33 no.4
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• pp.237-243
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• 2018

Hedgehog (Hh) pathway plays a key role in development from invertebrate to vertebrate. It is known to be involved in cell differentiation, polarity, proliferation, including the development of vertebrate limb and the establishment of flies' body plan. To investigate how the regulation of Hh pathway affects the development of parthenogenetic murine embryos, the parthenogenetically activated murine embryos were treated with either cyclopamine (Cyc), an antagonist of Hh pathway, or purmorphamine, an agonist of Hh pathway. While Cyc did not affect the blastocyst formation and its total cell number, the chemical reduced the hatching rate of embryos and the expression levels of Fn1 mRNA. The results of the present study show the possibility that Cyc may affect the development of embryos at blastocyst stage by blocking Hh pathway and this may cause detrimental effect to the embryos at peri-, and post-implantation stages.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.156-167
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• 2023

Background and Objectives: Cellular reprogramming in regenerative medicine holds great promise for treating patients with neurological disorders. In this regard, small molecule-mediated cellular conversion has attracted special attention because of its ease of reproducibility, applicability, and fewer safety concerns. However, currently available protocols for the direct conversion of somatic cells to neurons are limited in clinical application due of their complex nature, lengthy process, and low conversion efficiency. Methods and Results: Here, we report a new protocol involving chemical-based direct conversion of human fibroblasts (HF) to matured neuron-like cells with a short duration and high conversion efficiency using temporal and strategic dual epigenetic regulation. In this protocol, epigenetic modulation by inhibition of histone deacetylase and bromodomain enabled to overcome "recalcitrant" nature of adult fibroblasts and shorten the duration of neuronal reprogramming. We further observed that an extended epigenetic regulation is necessary to maintain the induced neuronal program to generate a homogenous population of neuron-like cells. Conclusions: Therefore, our study provides a new protocol to produce neurons-like cells and highlights the need of proper epigenetic resetting to establish and maintain neuronal program in HF.

• Molecules and Cells
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• v.46 no.4
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• pp.209-218
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• 2023

In induced pluripotent stem cells (iPSCs), pluripotency is induced artificially by introducing the transcription factors Oct4, Sox2, Klf4, and c-Myc. When a transgene is introduced using a viral vector, the transgene may be integrated into the host genome and cause a mutation and cancer. No integration occurs when an episomal vector is used, but this method has a limitation in that remnants of the virus or vector remain in the cell, which limits the use of such iPSCs in therapeutic applications. Chemical reprogramming, which relies on treatment with small-molecule compounds to induce pluripotency, can overcome this problem. In this method, reprogramming is induced according to the gene expression pattern of extra-embryonic endoderm (XEN) cells, which are used as an intermediate stage in pluripotency induction. Therefore, iPSCs can be induced only from established XEN cells. We induced XEN cells using small molecules that modulate a signaling pathway and affect epigenetic modifications, and devised a culture method which can produce homogeneous XEN cells. At least 4 passages were required to establish morphologically homogeneous chemically induced XEN (CiXEN) cells, whose properties were similar to those of XEN cells, as revealed through cellular and molecular characterization. Chemically iPSCs derived from CiXEN cells showed characteristics similar to those of mouse embryonic stem cells. Our results show that the homogeneity of CiXEN cells is critical for the efficient induction of pluripotency by chemicals.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.35-41
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• 2013

Metabolic analysis of CR6 interacting factor 1 (Crif1) deficient mouse embryonic fibroblasts with impaired oxidative phosphorylation has been carried out using LC-MS/MS and GC-MS methods. Metabolic profiles of the Crif1 deficient cells were comprehensively obtained for the first time. Loss of oxidative phosphorylation functions in mitochondria resulted in cancer-like metabolic reprogramming with consumption of majority of glucose carbon from up-regulated glycolysis to produce lactate, suppressed utilization of glucose carbon in the TCA cycle, increased amounts of amino acids. The changes in metabolic profile of the Crif1 deficient cells are most probably a consequence of metabolic reprogramming to meet the needs of energy balance and anabolic precursors in compensation for the loss of major oxidative phosphorylation functions.

• BMB Reports
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• v.51 no.11
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• pp.557-562
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• 2018

Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

• Proceedings of the Botanical Society of Korea Conference
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• 1999.07a
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• pp.85-89
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• 1999

Somatic embryogendesis is one of good examples of the basic research for plant embryo development as well as an important technique for plant biotechnology. This paper describes the direct somatic embryogenesis from zygotic embryos of Panax ginseng is reversely related to normal axis growth of zygotic embryos by the experiment of various chemical treatments. Under the normal growth condition, the apical tips of embryo axis produced an agar-diffusible substance, which suppressed somatic embryo development from cotyledons. Although the cells of zygotic embryos were released from the restraint of embryo axis, various factors were still involved for somatic embryo development. Electron microscopic observation revealed that the ultrastructure of cells of cotyledon epidermis markedly changed before initiation of embryonic cell division, probably indicating reprogramming events into the cells embryogenically determined state. Polar accumulation of endogenous auxin or cell-cell isolation by plasmolysis pre-treatment is the strong inducer for the somatic embryo development. The cells for the process of somatic embryogenesis might be determined by the physiological conditions fo explants and medium compositions. Direct somatic embryos from cotyledons fo ginseng were originated eithrer from single or multiple cells. The different cellular origin of somatic embryos was originated either from single or multiple cell. The different cellular origin of somatic embryos was depended on various developmental stages of cotyledons. Immature meristematic cotyledons produced multiple cell-derived somatic embryos, which developed into multiple embryos. While fully mature cotyledons produced single cell-derived single embryos with independent state. Plasmolysis pretreatment of cotyledons strongly enhanced single cell-derived somatic embryogenesis. Single embryos were converted into normal plantlets with shoot and roots, while multiple embryos were converted into only multiple shoots. GA3 or a chilling treatment was prerequisite for germination and plant conversion. Low concentration of ammonium ion in medium was necessary for balanced growth of root and shoot of plantlets. Therefore, using above procedures, successful plant regeneration of ginseng was accomplished through direct single embryogenesis, which makes it possible to produce genetically transformed ginseng efficently.