• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.24-36
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• 2002

Objectives: The chemotherapeutic potential of Gagamgilgyung-tang for the treatment of human lung cancer, the antitumorigenic effects of Gagamgilgyung-tang on the proliferation and apoptosis of human lung cancer cell line A427 were investigated using molecular biological approaches, Methods: To determine Gagamgilgyung-tang concentrations which do not evoke cytotoxic damage to the cell line, cell viability was examined by MTT assay. To prove Gagamgilgyung-tang's antitumorigenic potential to human lung cancer, [3H]thymidine incorporation assay, trypan blue exclusion and Cpp32 protease activity assays and quantitative RT-PCR analysis were examined. Results: While A427 cells treated with $0.1-2.0{\mu\textrm{g}}/ml$ of Gagamgilgyung-tang showed no recognizable effect, marked reductions of cell viability were detected at concentrations over $5.0{\;}\mu\textrm{g}/ml$. DNA replication of A427 cells was inhibited by Gagamgilgyung-tang in a dose-dependent manner and Gagamgilgyung-tang induced the G1 cell cycle arrest through inhibition of DNA replication. Gagamgilgyung-tang triggered apoptotic cell death of A427 and enhanced the apoptotic sensitivity of the cells that were injured by a DNA damage-inducing chemotherapeutic drug etoposide. Gagamgilgyung-tang induces expression of growth-inhibiting genes such as p53 and p21/Wafl whereas it inhibited expression of growth-promoting genes such as c-Myc and Cyclin D1. Expression of a representative apoptosis-inducing gene Bax was also found to be induced by Gagamgilgyung-tang while apoptosis-suppressing Bcl-2 expression was not changed. Conclusions: Gagamgilgyung-tang could suppress the abnormal growth of tumor cells by suppressing the survival of genetically altered cells via induction of apoptosis. This study suggests that Gagamgilgyung-tang might have an antitumorigenic potential to human lung cancer cells, which might be associated with its growth-inhibiting and apoptosis-inducing properties.

• Transactions of the Korean hydrogen and new energy society
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• v.26 no.2
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• pp.170-178
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• 2015

In this study, we carry out a study on how to improve performance of vanadium redox flow battery (VRFB) through promoting reaction rate of rate determining vanadium reaction ($[VO]^{2+}/[VO_2]^+$). In order to do that, three different carbons like Vulcan (XC-72), CMK3 and MSU-F-C are adopted as the catalysts, while their catalytic activity and reaction reversibility are evaluated using half-cell tests. Their topological images are also measured by TEM. For estimation of the VRFB performance, multiple charge-discharge curves of VRFBs including the catalysts are measured by single cell tests. As a result of that, MSU-F-C shows relatively excellent catalytic activity and reaction reversibility as well as large surface area compared to those of Vulcan (XC-72) and CMK3. Also, in terms of the performance of VRFBs including the catalysts, VRFB including MSU-F-C indicates (i) low charging/discharging overpotentials and low internal resistance, (ii) high charge/discharge capacities and (iii) high energy efficiency. These VRFB performance data are well agreed with results on catalytic activity and reaction reversibility. The reason that MSU-F-C induces superior VRFB performances is attributed to (i) its large surface area and (ii) its hydrophilic surface functional groups that mainly consist of hydroxyl bonds that are supposed to play active surface site role for facilitaing $[VO]^{2+}/[VO_2]^+$ redox reaction. Based on the above results, it is found that adoption of MSU-F-C as catalyst for VRFB results in improvement in VRFB performance by promoting the languid $[VO]^{2+}/[VO_2]^+$ redox reaction.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.30-47
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• 2006

Objective : The present study is aimed to elucidate the effects of Cirsium japonicum var. ussuriense on immunomodulation and the potential as an herbal remedy for cancer treatment. Method : It was performed through measurement of effects Cirsium japonicum var. ussuriense extract (CJE) on NO production, NK cell cytotoxicity and cytokine gene expressions related with macrophage and NK cell activity. Result : 1. CJE did not show any direct cytotoxic effects on 7250, HT1080, Hep G2 and CT-26 cells. 2. CJE activated macrophages partially to product NO and up-regulated gene expressions for iNOS in RAW 264.7 cells. 3. CJE promoted cytotoxicity of NK cells against YAC-1 cells at higher concentration than 200 ${\mu}g/ml$. 4. CJE up-regulated gene expressions for $IL-1{\beta}$, IL-2, iNOS, $IFN-{\gamma}$ and $TNF-{\alpha}$ in mice splenocytes.　５. CJE inhibited lung tumor metastasis induced by CT-26 cell transplantation compared with the control group.　Conclusion : It could be concluded that CJE is an effective herbal drug for immune modulating and anti-cancer treatment by promoting activity of macrophages and NK cells.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.220-228
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• 2024

Background: Panax ginseng, one of the valuable perennial medicinal plants, stores numerous pharmacological substrates in its storage roots. Given its perennial growth habit, organ regeneration occurs each year, and cambium stem cell activity is necessary for secondary growth and storage root formation. Cytokinin (CK) is a phytohormone involved in the maintenance of meristematic cells for the development of storage organs; however, its physiological role in storage-root secondary growth remains unknown. Methods: Exogenous CK was repeatedly applied to P. ginseng, and morphological and histological changes were observed. RNA-seq analysis was used to elucidate the transcriptional network of CK that regulates P. ginseng growth and development. The HISTIDINE KINASE 3 (PgHK3) and RESPONSE REGULATOR 2 (PgRR2) genes were cloned in P. ginseng and functionally analyzed in Arabidopsis as a two-component system involved in CK signaling. Results: Phenotypic and histological analyses showed that CK increased cambium activity and dormant axillary bud formation in P. ginseng, thus promoting storage-root secondary growth and bud formation. The evolutionarily conserved two-component signaling pathways in P. ginseng were sufficient to restore CK signaling in the Arabidopsis ahk2/3 double mutant and rescue its growth defects. Finally, RNA-seq analysis of CK-treated P. ginseng roots revealed that plant-type cell wall biogenesis-related genes are tightly connected with mitotic cell division, cytokinesis, and auxin signaling to regulate CK-mediated P. ginseng development. Conclusion: Overall, we identified the CK signaling-related two-component systems and their physiological role in P. ginseng. This scientific information has the potential to significantly improve the field-cultivation and biotechnology-based breeding of ginseng.

• International Journal of Industrial Entomology and Biomaterials
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• v.27 no.2
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• pp.303-311
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• 2013

In this study, we compared the efficiency of osteoblast differentiation media (ODM) containing three distinct reagent combinations in osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in monolayer culture. In addition, we analyzed growth and differentiation of hBMSCs on silk scaffolds and examined the bone-forming activity of a nanofibrous silk scaffold in a tibia diaphysis defect model of a rat hind limb with intramedullary nailing. Although all three ODM increased alkaline phosphatase activity to a comparable extent, the ODM containing bone morphogenetic protein-2 (BMP-2) was found to be significantly less effective in promoting mineral deposition than the others. Growth of hBMSCs on sponge-form silk scaffolds was faster than on nanofibrous ones, while osteoblastic differentiation was apparent in the cells grown on either type of scaffold. By contrast, bone formation was observed only at the edge of the nanofibrous scaffold implanted in the tibia diaphysis defect, suggesting that use of the silk scaffold alone is not sufficient for the reconstitution of the long bone defect. Since silk scaffolds can support cell growth and differentiation in vitro, loading MSCs on scaffolds might be necessary to improve the bone-forming activity of the scaffold in the long bone defect model.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2002.08a
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• pp.64-71
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• 2002

Rice(Oryza stiva L.) is a major cereal food providing nourishment to over half of the world's populations and was considered only as a source of energy. However, The recent many researches have been made to suggest that rice may relate to prevention chronic disease and health-promoting properties such as postprandial glucose response, hypocholesterolemic effect and blood pressure-lowering effect. There has been numerous observation supporting that rice has hypocholesterolemic effect. Rice, rice bran, rice bran oil and unsaponifiable matter of rice bran oil reduced plasma cholesterol in rat, hamster as well as human. Components of rice showing hypocholesterolemic effect include dietary fiber(hemicellulose, phytic acid). protein, ${\gamma}$-oryzanol, $\beta$-sitosterol, and tocotrienols. Crapo et al has been studied that the effect of various of starchy foods on the postprandial blood glucose and insulin responses in healthy and diabetic humans. The results showed that rice had lower blood glucose and insulin responses compared to potato, bread and dextrose. The different physical forms in the same starch also produce the different postprandial glucose and insulin responses. In recent years, several studies have shown that some components of rice have potent antioxidant activity against Fe$^{2+}$ -ascorbate induced lipid peroxidation in rat liver microsomal membranes. Cell culture and animal studies have shown that some components of rice have inhibitory effect on the growth and proliferation of several types of human cancer cell. It was also reported that the methanol extract of brown rice has antimutagenic activity against various mutagens. In addition, the pepsine hydrolysate from rice protein is reported to inhibit angiotensin converting enzyme activity. GABA (${\gamma}$ - aminobutyric acid) and GABA enriched rice germ is also effective for lowering blood pressure and triglyceride levels.s.

• The Korea Journal of Herbology
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• v.36 no.5
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• pp.59-67
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• 2021

Objectives : Hibiscus (Hibiscus sabdariffa L.) is rich in antioxidants such as flavonoids and anthocyanins and is known to have anti-inflammatory activity and anti-aging function of the skin, but there is no study on its effect on the skin barrier. This study aim to investigate the positive effect on the skin barrier by confirming the effect of water extracts of Hibiscus sabdariffa L. (WEHS) on the tight junction-related gene expression. Methods : The antioxidant efficacy of WEHS was investigated through ABTS and DPPH assays, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium was performed to examine the effect on cell viability. quantitative Reverse transcription polymerase chain reaction and immunoblot analysis were performed to confirm the effect of WEHS on the expression of tight junction-related genes, and immunofluorescence microscopy was used to confirm the movement of Claudin 1 protein into tight junctions. Results : WEHS showed strong antioxidant activity and induced an increase in both mRNA and protein expression levels of Claudin 1 among tight junction-related genes. The strong localization of Claudine 1 protein increased by WEHS to the tight junction was confirmed by immunofluorescence microscopy. Conclusions : Hibiscus was confirmed through this study to show antioxidant activity and the function of promoting the expression of the tight junction Claudin 1 gene, suggesting that Hibiscus can be used as a material for the prevention and treatment of skin moisturizing and atopy, which have an important influence on tight junction.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.131-138
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• 2017

In most mammals, metaphase II (MII) oocytes having high maturation promoting factor (MPF) activity have been considered as good oocytes and then used for assisted reproductive technologies including somatic cell nuclear transfer (SCNT). Caffeine increases MPF activity in mammalian oocytes by inhibiting p34cdc2 phosphorylation. The objective of this study was to investigate the effects of caffeine treatment during in vitro maturation (IVM) on oocyte maturation and embryonic development after SCNT in pigs. To this end, morphologically good (MGCOCs) and poor oocytes (MPCOCs) based on the thickness of cumulus cell layer were untreated or treated with 2.5 mM caffeine during 22-42, 34-42, or 38-42 h of IVM according to the experimental design. Caffeine treatment for 20 h during 22-42 h of IVM significantly inhibited nuclear maturation compared to no treatment. Blastocyst formation of SCNT embryos was not influenced by the caffeine treatment during 38-42 h of IVM in MGCOCs (41.1-42.1%) but was significantly improved in MPCOCs compared to no treatment (43.4 vs. 30.1%, P<0.05). No significant effects of caffeine treatment was observed in embryo cleavage (78.7-88.0%) and mean cell number in blastocyst (38.7-43.5 cells). The MPF activity of MII oocytes in terms of p34cdc2 kinase activity was not influenced by the caffeine treatment in MGCOCs (160.4 vs. 194.3 pg/ml) but significantly increased in MPCOCs (133.9 vs. 204.8 pg/ml). Our results demonstrate that caffeine treatment during 38-42 h of IVM improves developmental competence of SCNT embryos derived from MPCOCs by influencing cytoplasmic maturation including increased MPF activity in IVM oocytes in pigs.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.5
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• pp.726-731
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• 2003

The aim of this research was to identify candidate probiotic lactic bacteria among indigenous dadih lactic isolates. Dadih is an Indonesian traditional fermented milk of West Sumatra which is fermented naturally. Viability of the strain is critical in determining the capacity of lactic bacteria to induce immune stimulation as well as to colonize in the intestinal tract. Therefore, LAB are proposed to exert health promoting or probiotic effects in human, such as inhibition of pathogenic microflora, antimutagenic, and the reduction of cholesterol levels. This manuscript reports in vitro probiotic properties of indigenous dadih lactic bacteria, especially some important colonization factors in GI tract, such as lysozyme, acid and bile tolerance. Bile Salt Hydrolase (BSH) activity, spectrum of bacteriocin, and antimutagenic activity of bacterial cells were also assessed. Twenty dadih lactic isolates were screened further for their tolerance to low pH, at pH 2 and 3 as well as their bile tolerance. There were ten isolates classified as acid and bile acid tolerant, and further screened for lysozyme tolerance, BSH activity. The spectrum of bacteriocin activity of isolates was assayed using cell-free neutralized supernatants by agar spot test against variety of pathogens. Lc. lactis subsp. lactis IS-10285, IS-7386, IS-16183, IS-11857 and IS-29862, L. brevis IS-27560, IS-26958 and IS-23427, Leu.mesen.mesenteroides IS-27526, and L. casei IS-7257 each has good survival rate at low pH values and in the presence of lysozyme, and short lag time in the presence of 0.3 % oxgall. Lc. lactis subsp. lactis IS-11857 and IS-29862 each has high BHS activity, Lc. lactis subsp. lactis IS-10285 and IS-16183 each had a positive spectrum of bacteriocin activity against E. coli 3301 and Lysteria monocytogenes ATCC 19112, while L. brevis IS-26958 has high BHS activity as well as positive spectrum of bacteriocin against E. coli 3301, Lysteria monocytogenes ATCC 19112, and S. aureus IFO 3060. All of the ten dadih lactic strains performed in vitro acid and bile tolerance, indicating a possibility to reach the intestine alive, and display probiotic activities.