• Ocean and Polar Research
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• v.44 no.3
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• pp.209-220
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• 2022

Carbonic anhydrase (CA) is a key controller of the carbon concentrating mechanism (CCM), and is known to be affected by ambient pH and CO₂ compositions. Herein, we characterized three novel CAs genes (PmCA1, 2, and 3) from the marine dinoflagellate Prorocentrum minimum, and evaluated the relative expressions of the PmCAs and photosynthetic genes PmatpB and PmrbcL under different pH conditions. Each PmCA was predicted to have amino acid residues constituting the zinc binding site. With signal peptide, PmCA1 and PmCA2 were predicted to be intracellular CAs located in the cytoplasm and chloroplast membrane, respectively. On the other hand, PmCA3 was predicted to be extracellular CA located in the plasma membrane. Also, PmCA1 was classified into the beta family, and PmCA2 and PmCA3 were classified into the alpha family via phylogenic analysis. The photosynthesis efficiency of P. minimum was similar at pH 7 to 9, and decreased significantly at pH 6 and pH 10. Overall, relative gene expression levels of the three PmCAs decreased at low pH, and increased as pH increased. Photosynthesis related genes, PmatpB and PmrbcL, showed similar expression patterns to those of PmCAs. These results suggest that changes in seawater pH may affect photosynthesis and CO₂ metabolism in marine dinoflagellates.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.83-91
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• 2024

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

• Journal of Integrative Natural Science
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• v.16 no.4
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• pp.123-131
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• 2023

Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

• Journal of Plant Biotechnology
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• v.42 no.3
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• pp.204-214
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• 2015

SHI-RELATED SEQUENCE (SRS) genes are plant-specific transcription factors that contain a zinc-binding RING finger motif, which play a critical role in plant growth and development. Among Brassica rapa SRS genes, BrSRS7 and BrLRP1 genes, isolated from shoot apical regions are important regulators of plant growth and development. In order to explore the function of BrSRS genes in horticultural plant growth and development, two constructs containing BrSRS7 and BrLRP1 under the control of a cauliflower mosaic virus 35S promoter were introduced into petunia by Agrobacterium-mediated transformation. The resulting transgenic plants were dwarf and compact plants with reduced plant height and diameter. Additionally, these transgenic plants had upward-curled leaves of narrow width and short internodes. Interestingly, the flower shapes of petunia were different among transgenic plants harboring different kinds of SRS genes. These phenotypes were stably inherited through generations $T_2$ and $T_3$. Semi-quantitative RT-PCR analyses of transgenic plants revealed that BrSRS7 and BrLRP1 regulate expression of gibberellin (GA)- and auxinrelated genes, PtAGL15- and PtIAMT1-related, involved in shoot morphogenesis. These results indicate that the overexpression of BrSRS7 and BrLRP1 genes suppressed the growth and development of petunia by regulating expression of GA- and auxin-related genes. From these data, we deduce that BrSRS7 and BrLRP1 genes play an important role in the regulation of plant growth and development in petunia. These findings suggest that transformation with the BrSRS genes can be applied to other species as a tool for growth retardation and modification of plant forms.

• Journal of Food Hygiene and Safety
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• v.20 no.2
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• pp.83-88
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• 2005

This study was conducted to estimate the contents of heavy metals including lead, cadmium, zinc, copper as well as iron status(serum iron, total iron binding capacity, feritin etc)in blood samples of middle school students(n=300). The contents of heavy metals were determined using the GF-AAS (Graphite furnace Atomic Absorption Spectrophotometer). The microwave digestion method and dilution method were compared. The dilution method showed the better recovery and detection limit than microwave digestion method. The values of toxic metals in whloe blood of boys & girls were 3.46 & 3.05 for Pb,0.063 & 0.065 for Cd respectively (ug/dL). Also the values of trace metals in serum of boys & girls were 105.9 & 92.6 for Zn, 98.3 & 99.0 for Cu respectively (ug/dL). The prevalence of iron deficiency was $7.5\%$ in 146 boys and $14.3\%$ in 156 girls. The mean values of lead in girls were higher in iron deficiency, iron deficiency anemia and anemia groups than normal group. The mean values of lead and zinc were higher in boys compared to those in girls(P<0.05), the mean values of cadmium and copper in boys were similar to those in girls. Our results of toxic metals such as Pb & Cd showed lower to CDC's(Centers for Disease Control) blood lead levels of concern for children, 10 ug/dL.

• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.212-224
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• 2020

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions: miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2009.06a
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• pp.327-327
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• 2009

ZnO with a large band gap (~3.37 eV) and exciton binding energy (~60 meV), is suitable for optoelectronic applications such as ultraviolet (UV) light emitting diodes (LEDs) and detectors. However, the ZnO-based p-n homojunction is not readily available because it is difficult to fabricate reproducible p-type ZnO with high hall concentration and mobility. In order to solve this problem, there have been numerous attempts to develop p-n heterojunction LEDs with ZnO as the n-type layer. The n-ZnO/p-GaN heterostructure is a good candidate for ZnO-based heterojunction LEDs because of their similar physical properties and the reproducible availability of p-type GaN. Especially, the reduced lattice mismatch (~1.8 %) and similar crystal structure result in the advantage of acquiring high performance LED devices. In particular, a number of ZnO films show UV band-edge emission with visible deep-level emission, which is originated from point defects such as oxygen vacancy, oxygen interstitial, zinc interstitial[1]. Thus, defect-related peak positions can be controlled by variation of growth or annealing conditions. In this work, the undoped ZnO film was grown on the p-GaN:Mg film using RF magnetron sputtering method. The undoped ZnO/p-GaN:Mg heterojunctions were annealed in a horizontal tube furnace. The annealing process was performed at $800^{\circ}C$ during 30 to 90 min in air ambient to observe the variation of the defect states in the ZnO film. Photoluminescence measurements were performed in order to confirm the deep-level position of the ZnO film. As a result, the deep-level emission showed orange-red color in the as-deposited film, while the defect-related peak positions of annealed films were shifted to greenish side as increasing annealing time. Furthermore, the electrical resistivity of the ZnO film was decreased after annealing process. The I-V characteristic of the LEDs showed nonlinear and rectifying behavior. The room-temperature electroluminescence (EL) was observed under forward bias. The EL showed a weak white and strong yellowish emission colors (~575 nm) in the undoped ZnO/p-GaN:Mg heterojunctions before and after annealing process, respectively.

• Korean Journal of Environmental Agriculture
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• v.16 no.1
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• pp.48-54
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• 1997

This study was performed to develop the biological treatment technology of wastewater polluted with heavy metals. The copper-tolerant bacteria, Pseudomonas stutzeri which possessed the ability to accumulate copper, was isolated from mine wastewaters polluted with various heavy metals. The characteristics of copper accumulation in the cells and the recovery of the copper from the cells accumulating zinc, were investigated. Removal rate of copper from the solution containing 100mg/l of copper by copper-tolerant bacteria was more than 78% at 2 days after inoculation with the cells. A large number of the electron-dense granules were found mainly on the cell wall and cell membrane fractions, when determined by transmission electron microscopy. Energy dispersive X-ray spectroscopy revealed that the electron-dense granules were copper complex with the substances binding copper. The copper accumulated into the cells was not desorbed by deistilled water, but more than 80% of the copper accumulated was desorbed by 0.1M-EDTA solution. The residues of the cells after combustion at $550^{\circ}C$ amounted to about 23.2% of the dry weight of the cells. EDS analysis showed that residues were relatively pure copper compound containing more than 78.4% of copper.