• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.196-203
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• 2013

Recent accumulating studies have reported that hypoxic preconditioning during ex vivo expansion enhanced the self-renewal or differentiation of various stem cells and provide an important strategy for the adequate modulation of oxygen in culture conditions, which might increase the functional bioactivity of these cells for cardiac regeneration. In this study, we proposed a novel priming protocol to increase the functional bioactivity of cardiac progenitor cells (CPCs) for the treatment of cardiac regeneration. Firstly, patient-derived c-$kit^+$ CPCs isolated from the atrium of human hearts by enzymatic digestion and secondly, pivotal target molecules identified their differentiation into specific cell lineages. We observed that hCPCs, in response to hypoxia, strongly activated ERK phosphorylation in ex vivo culture conditioning. Interestingly, pre-treatment with an ERK inhibitor, U0126, significantly enhanced cellular proliferation and tubular formation capacities of CPCs. Furthermore, we observed that hCPCs efficiently maintained the expression of the c-kit, a typical stem cell marker of CPCs, under both hypoxic conditioning and ERK inhibition. We also show that hCPCs, after preconditioning of both hypoxic and ERK inhibition, are capable of differentiating into smooth muscle cells (SMCs) and cardiomyocytes (CMs), but not endothelial cells (ECs), as demonstrated by the strong expression of ${\alpha}$-SMA, Nkx2.5, and cTnT, respectively. From our results, we conclude that the functional bioactivity of patient-derived hCPCs and their ability to differentiate into SMCs and CMs can be efficiently increased under specifically defined culture conditions such as short-term hypoxic preconditioning and ERK inhibition.

• Microbiology and Biotechnology Letters
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• v.42 no.4
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• pp.417-421
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• 2014

Sphagnum palustre (SP), a species of moss belong to the Sphagnaceae family, is used as a dwarfed potted plant, in diapers, bandages, and soil additives. Although, SP can be found all over the world and is very cheap, the study of SP components and bioactivities are still at a rudimentary stage. In this study, the hot-water extract of SP (HWSP) and its subsequent organic solvent fractions were prepared, and their in-vitro anti-thrombosis activities were evaluated. The results showed that the water residue of HWSP has a strong anti-coagulation activity with significant extensions of thrombin time, and platelet aggregation activity. Our results suggest that the SP has the potential to be a novel resource for anti-thrombosis agents. This report provides the first evidence of the anti-thrombosis activity of SP.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.123-130
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• 2006

1,4-Naphthoquinones are widely distributed in nature and many clinically important antitumor drugs containing a quinone moiety, such as anthracyclines, mitoxantrones and saintopin, show excellent anticancer activity. In this study, 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) and 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives were synthesized, and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor activity was also assessed in mice bearing S-180 cells in the peritoneal cavity. In comparison with the DMNQ derivatives, the DHNQ derivatives exhibited more potent bioactivities than the DMNQ derivatives against both L1210 and P388 cells in vitro and S-180 cells in vivo. The $ED_{50}$ values of the DHNQ derivatives against P388 cells were in the range of 0.18-1.81 ${\mu}g/mL$ whereas those of the DMNQ derivatives were in the range of 0.26-40.41 ${\mu}g/mL$. The T/C ($\%$) values of the DHNQ derivatives, 8, 17, 18, 19, and 20, were found to be comparable to or even better than that of adriamycin. It was also observed that the 2-substituted derivatives (8, 19, 20) showed better antitumor activity than the 6-substituted derivatives (7, 17, 18) in the mice bearing S-180 cells in the peritoneal cavity.

• Analytical Science and Technology
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• v.32 no.2
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• pp.48-55
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• 2019

The simple and effective analytical method for the quality control of a novel scalp tonic formulation has been developed and optimized in terms of HPLC conditions and sample preparation method, meanwhile, the optimization of preparation condition was using response surface methodology (RSM) based on central composite design (CCD). Oleanolic acid was selected as marker compound because of its bioactivities for alopecia therapy. The developed analytical method and extraction condition were successfully qualified. Coefficient of determination ($r^2$) for the calibration was 0.9997 with a line passing through the origin point in the range of 0.1-100 mg/mL. The limit of detection (LOD) and the limit of quantitation (LOQ) were 17.5 ng/mL and 55.0 ng/mL, respectively. The intra-day and inter-day precision of the method were 0.5-1.4 % and 0.7-1.8 % in relative standard deviation, respectively, while those accuracy were 99.5-100.9 % and 100.0-102.2 %, respectively. The repeatability of oleanolic acid in samples ranged of 0.3-1.9 % based on peak area and 0.3-0.7 % for retention time. Recoveries from samples were 95.0-99.4 % with lower than 1.8 % in relative standard deviation. Overall, the developed analytical method will be used for quality control of this commercial scalp tonic products successfully.

• Journal of Life Science
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• v.31 no.11
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• pp.980-986
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• 2021

Natural products have always been an attractive source in terms of novel anti-metastatic compounds which can hinder MMP expression and activity. Corydalis heterocarpa is a salt marsh plant found in the seashores throughout Korea. Its yellow flowers and spikes have been an ingredient in folk medicine to treat spasm and contractions. The present study assessed the potential of different solvent-based fractions from the crude extract of Corydalis heterocarpa (CHE), a halophyte with reported bioactivities, to suppress the PMA-induced MMP expression in human fibrosarcoma HT-1080 cells. The solvent fractions which were named after the solvent used for fractionation (n-hexane, 85% aqueous (aq.) methanol (MeOH), n-butanol (BuOH), and H₂O were shown to inhibit the both elevated mRNA and protein expression levels of MMP-2 and MMP-9 and simultaneously relieved the suppression on the expression of the endogenous MMP inhibitors TIMP-1 and TIMP-2. Results indicated that the CHE fractions might intervene with the PMA-induced activation of the MAPK signaling which is the upstream activator of MMP overexpression. Among tested samples, 85% aq. MeOH and n-hexane fractions of CHE was determined to be the most active and future studies to isolate the bioactive substances responsible for the regulation of the MMP expression are, therefore, urged. In conclusion, C. heterocarpa was shown to be a potential source of anti-metastatic compounds and n-Hexane and MeOH fractions might yield lead molecules to develop novel MMP inhibitors.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.203-213
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• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

• Fisheries and Aquatic Sciences
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• v.24 no.1
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• pp.19-31
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• 2021

Seaweeds are a potential source of minerals, essential amino acids, fatty acids, proteins, and various bioactive compounds such as antioxidants. The higher water content of seaweeds reduces the shelf life and this requires the appropriate drying method. The drying conditions play a major role in the conservation of nutrient composition in dried seaweeds. In recent years, the seaweed industry has used many different drying methods with advantages and limitations. Hybrid hot-water Goodle dryer (HHGD) which is a special dryer mixed with hot-water and a Korean traditional heating system (Goodlejang) might be a solution to avoid these limitations. The present study evaluated the effect of drying conditions in HHGD on nutrient composition and bioactivities of brown seaweeds. Moreover, freeze-dryer (FD) and HHGD were employed in this study to compare the dried outputs obtained from four brown seaweed species. The present study aims to evaluate the effect of the hybrid hot-water Goodle drying method (HHGDM) on the nutritional composition and antioxidant activity of dried seaweeds. AOAC standard methods were used to analyze the proximate composition of dried samples and their 70% ethanol extract. The intracellular and extracellular antioxidant activities were evaluated using Vero cells and electron spin resonance (ESR) spectrometer respectively. High performance liquid chromatography, apoptotic body formation, and in-vivo experiments were used for further confirmation of the quality of dried output. The proximate composition results obtained from drying in HHGD and FD did not exhibit any significant difference. Moreover, the seaweed extracts from the dried seaweeds by HHGD and FD dryings were also not different and both significantly down-regulated in-vivo and in-vitro oxidative stress. Furthermore, the high performance liquid chromatography results revealed that the two dryers did not make the major peaks different in the chromatograms. Freeze-drying method (FDM) provides elevated quality for dried output, but there are limitations such as high cost and low capacity. The results from a novel HHGD did not provide any significant difference with the results in FD and expressed a potential to avoid the limitations in FD. Overall, these findings solidified the applicability of HHGD over FD.

• Journal of Life Science
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• v.32 no.1
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• pp.51-55
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• 2022

Matrix metalloproteinase (MMP) enzymes are responsible for the degradation and formation of the extracellular matrix (ECM), and overproduction of MMPs is observed in several diseases, such as cancer and asthma, that progress with metastatic characteristics. Natural products, especially phytochemicals, have been an important source of MMP inhibitors with reduced side effects. Although the majority of phytochemicals inhibit the enzymatic activity of MMPs, some suppress MMP production. In this context, the current study evaluated the potential of Corydalis heterocarpa, a halophyte with reported bioactivities, to inhibit MMP expression in PMA-stimulated HT-1080 cells. A crude C. heterocarpa extract was shown to decrease the mRNA and protein expression of MMP-2 and MMP-9 while increasing the endogenous MMP inhibitors TIMP-1 and TIMP-2 which regulate MMP expression in healthy tissues. In addition, our results show that the inhibitory effects of C. heterocarpa might occur through suppression of the phosphorylation of MAPK signaling, the upstream activator of MMP overexpression. In conclusion, C. heterocarpa is a potential source of antimetastatic compounds that might serve as lead molecules to develop novel MMP inhibitors.

• Journal of Life Science
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• v.32 no.2
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• pp.155-160
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• 2022

Kenaf (Hibiscus cannabinus L.), one of the four major fiber crops, is attracting attention for its efficient CO₂-absorbing ability and versatility for producing daily supplies, including textiles. In Korea, a new cultivar 'Jangdae' was established in 2013. The ease of cultivation and seed gathering of 'Jangdae' has led to its nationwide cultivation. However, evaluation of the bioactivities of the different parts of kenaf, and especially the 'Jangdae' cultivar, remains rudimentary. In this study, the antithrombosis and antioxidant activities of extracts prepared from different parts of the 'Jangdae' cultivar were evaluated by determining their effects on blood clot formation. Extracts prepared from seeds (HC-SD), seedpods (HC-SP), leaves (HC-L), stems (HC-S), and roots (HC-R) of the 'Jangdae' cultivar strongly inhibited blood clot formation. In particular, the HC-SD, HC-SP, and HC-S extracts showed strong inhibition against the coagulation factors prothrombin, and thrombin. The HC-SP extract showed strong antioxidant activities, such as scavenging ability against DPPH anion, ABTS cation, nitrite, and reducing power. Since blood clot formation is closely related to oxidative stress, the HC-SP extract could be developed as a novel anticoagulation and antioxidant resource. This is the first report of the antithrombosis activities of different parts of H. cannabinus L. cv. 'Jangdae'.

• Journal of Life Science
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• v.27 no.2
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• pp.131-138
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• 2017

In this study, for the efficient use of the byproduct of the omija (Schizandra chinensis Baillon: SC) processing industry, the ethanol extracts of the fruit (F), seed (S), and pomace (P) of SC were prepared, and their useful bioactivities were evaluated. For F-SC, S-SC, and P-SC, the extraction yields were 28.3%, 22.1%, and 7.2%, respectively, and the polyphenol contents were 8.81, 37.22, and 9.20 mg/g, respectively. The total flavonoid content in P-SC (4.31 mg/g) was 3.5-fold higher than that in F-SC (0.76 mg/g). In an antioxidation activity assay, P-SC showed stronger radical scavenging activities against DPPH anion, ABTS cation, and nitrite and stronger reducing power activities than the other extracts. The calculated concentration required for 50% radical scavenging activity, $RC_{50}s$, of P-SC for DPPH anion, ABTS cation, and nitrite was 226.2, 192.5, and $92.5{\mu}g/ml$, respectively. In an antimicrobial activity assay, F-SC, S-SC, and P-SC showed similarly strong growth inhibitions against Bacillus subtilis and P. vulgaris at a concentration of 0.5 mg/disc. F-SC and P-SC showed 15-fold extended time in thrombin, prothrombin, and activated partial thromboplastin time assays at a concentration of 5 mg/ml. The anticoagulation activity of P-SC (2.5 mg/ml) was comparable to that of aspirin (1.5 mg/ml). Furthermore, F-SC and S-SC showed very good platelet aggregation inhibitory activities. F-SC, S-SC, and P-SC did not show significant hemolysis against human red blood cell up to a concentration of 0.5 mg/ml. These results suggest that S-SC and P-SC, both of which are byproducts of the omija processing industry, show strong potential as novel antioxidant, antimicrobial, and antithrombosis agents.