• Korean Journal of Pharmacognosy
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• v.52 no.4
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• pp.234-241
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• 2021

Dermal papilla cells (DPCs) are present throughout the hair cycle and play an essential role in hair cycle and hair growth. In this study, we investigated the effect of Carex dispalata on the activation of anagen pathway in DPCs. C. dispalata extract increased the proliferation of DPCs and induced changes in the levels of cell cycle-related proteins. To elucidate the mechanism by which C. dispalata extract stimulates the anagen pathway related to the proliferation of DPCs, we evaluated the effect of C. dispalata extract on the activation of Akt signaling. The increase in the level of phospho-Akt by C. dispalata extract was inhibited by PI3K inhibitor (wortmannin). Wortmannin reduced the effects of C. dispalata extract on the levels of cell cycle-related proteins and proliferation of DPCs. C. dispalata extract increased the levels of Wnt/β-catenin proteins. Wnt/β-catenin inhibitor (XAV939) inhibited changes in cell cycle, cell cycle-related proteins, Wnt/β-catenin proteins, and proliferation induced by C. dispalata extract. C. dispalata extract increased the level of autophagy protein (LC3I/II), and this change was inhibited by XAV939. These results suggest that C. dispalata extract can activate PI3K/Akt, Wnt/β-catenin, and autophagy pathways in DPCs to induce cell proliferation, and thereby promote hair growth phase.

• Journal of Life Science
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• v.31 no.2
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• pp.158-163
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• 2021

In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.52-68
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• 2008

Objectives and Methods : Salviae miltiorrhizae Radix (SMR) promotes blood circulation to remove blood stasis, cools the blood to relieve carbuncle, clears away heat from the heart and tranquilizes the mind. This study was designed to investigate the effects of SMR on immuno-potentiative action in terms of changes in the genetic profile of dendritic cells (DC) using by microarray analysis. Results and Conclusion: In this experiment, treatments with more than 250 ${\mu}g/ml$ upto 1000 ${\mu}g/ml$ of SMR elevated the proliferation rates of DC. Microscopic observations confirmed the tendency on proliferation rates. Expression levels of genes related with cellular methabolic process, cell communication, and macromolecule metabolic process were elevated by treatment with SMR in comparison of functional distribution in a Biological Process. In molecular functions, expression levels of genes related with receptor activation, nucleotide binding and nucleic acid binding were elevated. In cellular components, expression levels of genes related to cellular membrane-bound organelles were elevated. In addition, expression levels of genes related to Wnt signalling pathways and the glycerophospholipid metabolism were elevated through analysis using pathway analysis between up-and down-regulated genes in cells treated with SMR. Finally, genes related to JAK2, GRB2, CDC42, SMAD4, B2M, FOS and ESRI located the center of Protein interaction network of genes through treatment with SMR.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4793-4799
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• 2012

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.231-237
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• 2007

Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.82-83
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• 2003

Plants have evolved differently from animals having mobile activities. Thus, plants should have developed unique defense mechanisms against biotic/abiotic stresses to which plants are differently exposed, according to seasons. Most organisms have an conserved signaling network using mitogen-activated protein kinase (MAPK) cascade(s). The phenomenon implied that they are functionally very important in all organisms. In fact, they constitute one of the major components of signaling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. Recently, complete MAPK cascade was first characterized in Arabidopsis from the receptor kinase (FLS2) through fellowing MEKKI -MKK4/MKK5-MPK3/MPK6-WRKY22/MRKY29 pathway. Whereas, MAPK cascade signaling pathway in monocot plant including rice (0ryza sativa L.), the most important of all food crops and an established monocot plant research model, MAPKinase kinase kinases (MAPKKK) of rice are the first upstream component of the MAPK cascade, but MAPKKK has been first identified and characterized in our lab and designated as, OsEDRl based on its homology with the Arabidopsis EDRI. The Arabidopsis EDRl was regarded as a negative regulator of defense response and the role of rice OsEDRl was analyzed. Transcriptional regulation of OsEDRl was detected under various stresses and immunoblotting analysis is going on to detect the level of OsEDRl protein in the mutants showing unique phenotype. We also introduced the constitutively active and the dominant negative forms of the OsEDRl for characterizing biological function.

• Genomics & Informatics
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• v.12 no.3
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• pp.114-120
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• 2014

Bone mineral density (BMD) is one of the quantitative traits that are genetically inherited and affected by various factors. Over the past years, genome-wide association studies (GWASs) have searched for many genetic loci that influence BMD. A recent meta-analysis of 17 GWASs for BMD of the femoral neck and lumbar spine is the largest GWAS for BMD to date and offers 64 single-nucleotide polymorphisms (SNPs) in 56 associated loci. We investigated these BMD loci in a Korean population called Korea Association REsource (KARE) to identify their validity in an independent study. The KARE population contains genotypes from 8,842 individuals, and their BMD levels were measured at the distal radius (BMD-RT) and midshaft tibia (BMD-TT). Thirteen genomic loci among 56 loci were significantly associated with BMD variations, and 3 loci were involved in known biological pathways related to BMD. In order to find putative functional variants, nearby SNPs in relation to linkage equilibrium were annotated, and their possible functional effects were predicted. These findings reveal that tens of variants, not a single factor, may contribute to the genetic architecture of BMD; have an important role regardless of ethnic group; and may highlight the importance of a replication study in GWASs to validate genuine loci for BMD variation.

• Korean Journal of Environmental Agriculture
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• v.15 no.2
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• pp.246-261
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• 1996

Organophosphorus pesticides, which are an important part of synthetic pesticides in current use contain sulfur atom in their molecules and can be activated or detoxified by environmental and/or biological metabolism. Among the related metabolic reactions, oxidative processes are particularly important with their final products and the study on the reactive intermediates formed in those reactions is essential to elucidate the metabolic pathways and mechanisms and to understand the toxicological properties. This review dealt with the reactive intermediates formed in various reactions from the structural and mechanistic point of view for organophosphorus pesticides and related compounds.

• Korean Journal of Environmental Biology
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• v.30 no.3
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• pp.157-163
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• 2012

Oxidative stress has been reported to be one of causes of neuritis. This study examined antioxidative activities of methanol extracts of six amphibian species known to be medicinal animals (Rana catesbeiana, R. coreana, R. rugosa, R. dybowskii, R. nigromaculata, and Hyla japonica) and investigated their effects of inhibiting nitric oxide (NO) production and cytotoxicity on the murine macrophage RAW264.7 cells. As inflammation is closely associated with reactive oxygen species, assays on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, xanthine oxidase inhibitory activity, superoxide anion radical scavenging activity and NO scavenging activity of the extracts of the six species were performed to investigate their antioxidative activity. The results obtained were as follows; All extracts showed antioxidative activity, and the activity of R. dybowskii was the highest in comparison among those. Anti-inflammatory effects of the extracts were also examined, the five extracts except that of R. rugosa did not show cytotoxicity for RAW264.7 cells at the maximal concentration ($1,000{\mu}g\;mL^{-1}$). Selectivity index, meaning NO scavenging activity compared to cytotoxicity, showed the highest level in the extract of R. dybowskii. These results will be very useful basic data for future studies on prevention and treatment of human diseases to understand the biological roles of amphibian extracts throughout the antioxidative or anti-inflammatory pathways.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.100-105
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• 2014

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of apigenin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Apigenin significantly relaxed fluoride-, thromboxane $A_2$ mimetic- or phorbol ester-induced vascular contraction, which suggests that apigenin could be an anti-hypertensive that reduces agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, apigenin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels, which suggests the mechanism involving the inhibition of Rho-kinase and MEK activity and the subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of apigenin on agonist-induced vascular contraction regardless of endothelial function.