• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8041-8046
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• 2014

In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4499-4505
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• 2014

Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with $58.6{\mu}g/ml$ for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.102-102
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• 2016

Water, which is most abundant in Earth surface and very closely related to all forms of living organisms, has a simple molecular structure but exhibits very unique physical and chemical properties. Even though tremendous effort has been paid to understand this nature's core substance, there amazingly still lefts much room for scientist to explore its novel behaviors. Especially, as the scale goes down to nano-regime, water shows extraordinary properties that are not observable in bulk state. One of such interesting features is the formation of nanoscale bubbles showing unusual long-term stability. Nanobubbles can be spontaneously formed in water on hydrophobic surface or by decompression of gas-saturated liquid. In addition, the nanobubbles can be generated during electrochemical reaction at normal hydrogen electrode (NHE), which possibly distorts the standard reduction potential at NHE as the surface nanobubble screens the reaction with electrolyte solution. However, the real-time evolution of these nanobubbles has been hardly studied owing to the lack of proper imaging tools in liquid phase at nanoscale. Here we demonstrate, for the first time, that the behaviors of nanobubbles can be visualized by in situ transmission electron microscope (TEM), utilizing graphene as liquid cell membrane. The results indicate that there is a critical radius that determines the long-term stability of nanobubbles. In addition, we find two different pathways of nanobubble growth: i) Ostwald ripening of large and small nanobubbles and ii) coalescence of similar-sized nanobubbles. We also observe that the nucleation and growth of nanoparticles and the self-assembly of biomolecules are catalyzed at the nanobubble interface. Our finding is expected to provide a deeper insight to understand unusual chemical, biological and environmental phenomena where nanoscale gas-state is involved.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.10
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• pp.1515-1521
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• 2016

Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., "modification-dependent protein catabolic process", "proteolysis involved in cellular protein catabolic process", "cellular protein catabolic process", "protein catabolic process", and "ubiquitin-dependent protein catabolic process". In GO analysis, one BP term, "Proteolysis", was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as "Starch and sucrose metabolism" and "Insulin signaling pathway". Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs.

• Herbal Formula Science
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• v.26 no.3
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• pp.237-250
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• 2018

Objectives : This study is a pharmacological network approach, aimed to identify the potential active compounds contained in Curcumae Radix, and their associated targets, to predict the various bio-reactions involved, and finally to establish the cornerstone for the deep-depth study of the representative mechanisms. Methods : The active compounds of Curcumae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : The target information from 32 potential active compounds of Curcumae Radix was collected through TCMSP analysis. The active compounds interact with 133 target genes engaging in total of 885 biological pathways. The most relevant pathway was the lipid-related metabolism, in which 3 representative active compounds were naringenin, oleic acid, and ${\beta}-sitosterol$. The mostly targeted proteins in the lipid pathway were ApoB, AKT1 and PPAR. Conclusions : The pharmacological network analysis is convenient approach to predict the overall metabolic mechanisms in medicinal herb research, which can reduce the processes of various experimental trial and error and provide key clues that can be used to validate and experimentally verify the core compounds.

• Molecules and Cells
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• v.23 no.1
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• pp.108-114
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• 2007

The mitogen-activated protein kinase (MAPK) signaling cascade is critical for regulating plant defense systems against various kinds of pathogen and environmental stresses. One component of this cascade, the MAP kinase kinases (MAPKK), has not yet been shown to be induced in plants following biotic attacks, such as those by insects and fungi. We describe here a gene coding for a blast (Magnaporthe grisea)- and insect (Nilaparvata lugens)-responsive putative MAPK kinase, OmMKK1 (Oryza minuta MAPKK 1), which was identified in a library of O. minuta expressed sequence tags (ESTs). Two copies of OmMKK1 are present in the O. minuta genome. They encode a predicted protein with molecular mass 39 kDa and pI of 6.2. Transcript patterns following imbibition of plant hormones such as methyl jasmonic acid (MeJA), ethephone, salicylic acid (SA) and abscisic acid (ABA), as well as exposure to methyl viologen (MV), revealed that the expression of OmMKK1 is related to defense response signaling pathways. A comparative analysis of OmMKK1 and its O. sativa ortholog OsMKK1 showed that both were induced by stress-related hormones and biotic stresses, but that the kinetics of their responses differed despite their high amino acid sequence identity (96%).

• Molecules and Cells
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• v.27 no.1
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• pp.113-118
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• 2009

In this study, we have shown the transcriptional regulation of the human GD3 synthase (hST8Sia I) induced by valproic acid (VPA) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in VPA-stimulated SK-N-BE(2)-C cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-${\kappa}B$, functions as the VPA-inducible promoter of hST8Sia I in SK-N-BE(2)-C cells. Site-directed mutagenesis and electrophoretic mobility shift assay indicated that the NF-${\kappa}B$ binding site at -731 to -722 was crucial for the VPA-induced expression of hST8Sia I in SK-N-BE(2)-C cells. In addition, the transcriptional activity of hST8Sia I induced by VPA in SK-N-BE(2)-C cells was strongly inhibited by SP600125, which is a c-Jun N-terminal kinase (JNK) inhibitor, and $G{\ddot{O}}6976$, which is a protein kinase C (PKC) inhibitor, as determined by RT-PCR (reverse transcription-polymerase chain reaction) and luciferase assays. These results suggest that VPA markedly modulated transcriptional regulation of hST8Sia I gene expression through PKC/JNK signal pathways in SK-N-BE(2)-C cells.

• The Korean Journal of Food And Nutrition
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• v.30 no.2
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• pp.371-377
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• 2017

Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.149-165
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• 2006

Objectives: This study was done to evaluate the effects of Saengkankunbi-tang on cell-viability, proliferation, cell-cycle, apoptosis and DNA replication on HepG2 cell and to find out by which molecular-biological mechanism by which Saengkankunbi-tang operates. Methods : The MTT assay, cell counting assay, [3H]-thymidine incorporation assay, flow cytometric analysis, tryphan blue exclusion assay, western blot analysis, quantative RT-PCR were taken. Results : Saengkankunbi-tang had no effect on proliferation, cell-cycle and DNA replications of HepG2 cells, while it improved cell viability and reduced apoptosis, and it activated Akt and NFKB. But, it did not produce an effect on cell viability and apoptosis when P13K/Akt pathway was blocked by LY294002 nor when $NF{\kapa}B$ activation was blocked by DN-$I{\kapa}B$. Conclusion : These results suggests that Saengkankunbi-tang improves cell viability and reduces apoptosis of HepG2 cells, by activating $NF{\kapa}B$ through PI3K/Akt pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1028-1035
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• 2004

Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was mutagenic and induced transformation of mouse fibroblast cell lines, whereas it provided inhibiting effects on mutagenesis and carcinogenesis induced by various carcinogens. Furthermore, it has been suggested that imperatorin may have potential anticarcinogenic effects when administered orally in the diet. In addition to its anticarcinogenic properties, imperatorin has been shown to possess anticancer activities. We investigated the macro scale gene expression analysis on the HL-60 cells treated with imperatorin. Imperatorin (10μM) were used to treat the cells for 6h, 12h, 24h, 48h, and 72h. In a human cDNAchip study of 10,000 genes evaluated 6, 12, 24, 48, 72 hours after treated with imperatorin in HL-60 cells. Hierarchical cluster against the genes which showed expression changes by more than 2 fold. Three hundred eighty six genes were grouped into 6 clusters by a hierarchical clustering algorithm. Pathway analysis using gene microarray pathway prof Her that is a computer application designed to visualize gene expression data on screen representing biological pathways and groupings of genes.