• 생약학회지
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• 제45권3호
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• pp.214-219
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• 2014

Artemisia apiacea is a traditional herbal medicine using treatment of eczema and jaundice in Eastern Asia including China, Korea, and Japan. In this study, the three phytosterol constituents were isolated and identified from the hexane fraction of 80% aqueous methanol extract of A. apiacea. Compounds were isolated using open column chromatography (silica gel). Their chemical structures were also established using $^1H$-NMR and $^{13}C$-NMR. Moreover, neuroprotective activity of each compound against glutamate-induced neurotoxicity in hippocampal HT-22 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, Inhibition of reactive oxygen species (ROS) and calcium ion ($Ca^{2+}$) accumulation were measured for elucidation of neuroprotective mechanism of isolated compounds. They showed that stigmasterol had neuroprotective activity against the glutamate-induced toxicity by inhibition of ROS and $Ca^{2+}$ production. In conclusion, isolated compound of A. apiacea might be useful for therapeutic agent against neurodegenerative diseases.

• 한국응용과학기술학회지
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• 제27권1호
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• pp.20-28
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• 2010

Melanoma is the most aggressive form of skin cancer and is the fastest growing type of cancer in the United States. We report here the synthesis of a novel series of quinazolinylmethoxybenzene derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line. Among them, urea compound 1a ($IC_{50}\;=\;4.8\;{\mu}M$) having 4-chloro-3-trifluoromethylphenyl moiety showed superior antiproliferative activity to Sorafenib ($IC_{50}\;=\;5.5\;{\mu}M$) as a reference compound. These results will helpful for designing structure of a therapeutic agent for the treatment of melanoma.

• 한국응용과학기술학회지
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• 제26권3호
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• pp.297-305
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• 2009

Melanoma is the most serious type of skin cancer as a malignant tumor of melanocytes. In this work, the syntheses of a novel series of benzaminoquinoline derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line were described. All the compounds ($IC_{50}=0.78-1.02{\mu}M$) showed superior antiproliferative activities to Sorafenib ($IC_{50}=5.58{\mu}M$) as a reference compound. These results suggested that benzaminoquinoline derivatives have potentials as a therapeutic agent for the treatment for melanoma.

• 생체재료학회지
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• 제22권4호
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• pp.221-234
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• 2018

Background: Interest in subcellular organelle-targeting theranostics is substantially increasing due to the significance of subcellular organelle-targeting drug delivery for maximizing therapeutic effects and minimizing side effects, as well as the significance of theranostics for delivering therapeutics at the correct locations and doses for diseases throughout diagnosis. Among organelles, mitochondria have received substantial attention due to their significant controlling functions in cells. Main body: With the necessity of subcellular organelle-targeting drug delivery and theranostics, examples of mitochondria-targeting moieties and types of mitochondria-targeting theranostics were introduced. In addition, the current studies of mitochondria-targeting theranostic chemicals, chemical conjugates, and nanosystems were summarized. Conclusion: With the current issues of mitochondria-targeting theranostic chemicals, chemical conjugates, and nanosystems, their potentials and alternatives are discussed.

• Korean Circulation Journal
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• 제48권11호
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• pp.974-988
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• 2018

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

• 생명과학회지
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• 제20권7호
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• pp.1027-1033
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• 2010

맥문동(Liriope platyphylla)은 한국과 중국에서 전통적으로 당뇨, 비만, 뇌신경질환, 천식 등의 치료를 위해 사용 해온 치료제이다. 최근에 이들 맥문동으로부터 새로운 치료제를 개발하려는 노력이 활발히 진행 중이지만 아직도 유력한 치료후보제는 확보되지 않았다. 따라서 본 연구에서는 맥문동의 새로운 추출물을 이용하여 당뇨치료 제로서의 가능성을 평가하기 위하여 새로운 방법으로 10가지 후보물질을 추출하고 이들의 독성과 효능을 평가하였다. 그 결과 10가지 추출물 중에서 LP9M80-H가 인슐린 분비를 가장 많이 촉진하였고 다음으로는 LP-H, LP-M, LP-E과 LP9M80-C 등의 순서로 촉진을 하였으나 나머지는 인슐린 분비를 촉지하지 못하였다. 그러나 이들 물질은 인슐린 분비를 촉진하는 농도에서 강한 세포 독성을 나타내었다. 따라서 이들 물질 중에서 가장 효능이 좋은 LP9M80-H의 치료용 최적농도를 설정하였으며, 대략 100-25 ug/ml가 최적농도로 결정되었다. 이러한 결과는 맥문동 추출물 중에서 LP9M80-H가 췌장 $\beta$-세포의 인슐린 분비능을 유도하는 새로운 당뇨치료 후보물질로서 향후에 사용될 가능성을 시사하고 있다.

• Biomaterials and Biomechanics in Bioengineering
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• 제2권2호
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• pp.61-69
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• 2015

Undifferentiated stem cells are being studied to obtain information on the therapeutic potential of isolates that are produced. Dental Pulp Stem Ccell (DPSC) may provide an abundant supply of highly proliferative, multipotent Mesenchymal Stem Cells (MSC), which are now known to be capable of regenerating a variety of human tissues including bone and other dental structures. Many factors influence DPSC quality and quantity, including the specific methods used to isolate, collect, concentrate, and store these isolates once they are removed. Ancillary factors, such as the choice of media, the selection of early versus late passage cells, and cryopreservation techniques may also influence the differentiation potential and proliferative capacity of DPSC isolates. This literature review concludes that due to the delicate nature of DPSC, more research is needed for dental researchers and clinicians to more fully explore the feasibility and potential for isolating and culturing DPSCs extracted from adult human teeth in order to provide more accurate and informed advice for this newly developing field of regenerative medicine.

• Journal of Microbiology and Biotechnology
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• 제23권8호
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• pp.1176-1184
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• 2013

Anti-hepatocyte growth factor (anti-HGF) monoclonal antibodies (mAbs) are potential therapeutics against various cancers. Screening for high-producer clones is a time-consuming and complex process and is a major hurdle in the development of therapeutic mAbs. Here, we describe an efficient approach that allows the selection of high-producer Chinese hamster ovary (CHO) cell lines producing the novel anti-HGF mAb SFN68, which was generated previously by immunizing HGF bound to its receptor c-Met. We selected an SFN68-producing parental cell line via transfection of the dihydrofolate reductase-deficient CHO cell line DG44, which was preadapted to serum-free suspension culture, with an SFN68-expression vector. Subsequent gene amplification via multiple passages of the parental cell line in a methotrexate-containing medium over 4 weeks, followed by clonal isolation, enabled us to isolate two cell lines, 2F7 and 2H4, with 3-fold higher specific productivity. We also screened 72 different media formulated with diverse feed and basal media to develop a suboptimized medium. In the established suboptimized medium, the highest anti-HGF mAb yields of the 2F7 and 2H4 clones were 842 and 861 mg/l, respectively, which were about 10.5-fold higher than that of the parental cell line in a non-optimized basal medium. The selected CHO cell lines secreting high titers of SFN68 would be useful for the production of sufficient amounts of antibodies for efficacy evaluation in preclinical and early clinical studies.

• Journal of Microbiology and Biotechnology
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• 제23권9호
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• pp.1327-1338
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• 2013

The humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% $pO_2$. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.

• 폴리머
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• 제38권2호
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• pp.113-128
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• 2014

Tissue engineering and regenerative medicine strategies could offer new hope for patients with serious tissue injuries or end-stage organ failure. Scientists are now applying the principles of cell transplantation, material science, and engineering to create biological substitutes that can restore and maintain normal function in diseased or injured tissues/organs. Specifically, creation of engineered tissue construct requires a polymeric biomaterial scaffold that serves as a cell carrier, which would provide structural support until native tissue forms in vivo. Even though the requirements for scaffolds may be different depending on the target applications, a general function of scaffolds that need to be fulfilled is biodegradability, biological and mechanical properties, and temporal structural integrity. The scaffold's internal architecture should also enhance the permeability of nutrients and neovascularization. In addition, the stem cell field is advancing, and new discoveries in tissue engineering and regenerative medicine will lead to new therapeutic strategies. Although use of stem cells is still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This review discusses these tissue engineering and regenerative medicine strategies for various tissues and organs.