• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1613-1620
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• 2012

Bacterial wilt caused by Ralstonia solanacearum is a devastating disease of many economically important crops. Since there is no promising control strategy for bacterial wilt, phage therapy could be adopted using virulent phages. We used phage PE204 as a model lytic bacteriophage to investigate its biocontrol potential for bacterial wilt on tomato plants. The phage PE204 has a short-tailed icosahedral structure and double-stranded DNA genome similar to that of the members of Podoviridae. PE204 is stable under a wide range of temperature and pH, and is also stable in the presence of the surfactant Silwet L-77. An artificial soil microcosm (ASM) to study phage stability in soil was adopted to investigate phage viability under a controlled system. Whereas phage showed less stability under elevated temperature in the ASM, the presence of host bacteria helped to maintain a stable phage population. Simultaneous treatment of phage PE204 at $10^8$ PFU/ml with R. solanacearum on tomato rhizosphere completely inhibited bacterial wilt occurrence, and amendment of Silwet L-77 at 0.1% to the phage suspension did not impair the disease control activity of PE204. The biocontrol activities of phage PE204 application onto tomato rhizosphere before or after R. solanacearum inoculation were also investigated. Whereas pretreatment with the phage was not effective in the control of bacterial wilt, post-treatment of PE204 delayed bacterial wilt development. Our results suggested that appropriate application of lytic phages to the plant root system with a surfactant such as Silwet L-77 could be used to control the bacterial wilt of crops.

• Toxicological Research
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• v.26 no.2
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• pp.137-147
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• 2010

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

• Molecules and Cells
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• v.37 no.1
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• pp.24-30
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• 2014

Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.111-118
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• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.1-5
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• 2007

Unprecedented amount of genetic information being generated from the result of Human Genome Project (HGP) and advances in genetic research is already forcing changes in the paradigm of health and disease. The ultimate goal of genetic medicine is to use genetic information and technology to develop new ways of treatment or even prevention of the disease on an individual level for 'personalized medicine'. Genetics is play ing an increasingly important role in the diagnosis, monitoring and management of common multifactorial diseases in addition to rare single-gene disorders. While wide range of genetic testing have provided benefits to patients and family, uncertainties surrounding test interpretation, the current lack of available medical options for the diseases, and risks for discrimination and social stigmatization may remain to be resolved. However an increasing number of genetic tests are becoming commercially available, including direct to consumer genetic testing, yet public is often unaw are of their clinical and social implications. The personal nature of information generated by a genetic test, its power to affect major life decisions and family members, and its potential misuse raise important ethical considerations. Therefore appropriate genetic counseling is needed for patient to be informed with the benefits, limitations and risks of genetic tests, prior to informed consent for the tests. Physician also should be familiar with the legal and ethical issues involved in genetic testing to tell patients how w ell a particular genetic risk factor relates with likelihood of disease, and be able to provide appropriate genetic counseling. Genetic counseling become a mandatory requirement as global standard for many genetic testing such as prenatal diagnosis, presymtomatic DNA diagnostic tests and cancer susceptibility gene test for familial cancer syndrome. In oder to meet the challenge of genetic medicine of 21 century in korean health care system, professional education program and certification board for medical genetics specialist including non-MD genetic counselors should be addressed by medical society and regulatory policy of national health insurance reimbursement for genetic counseling to be in place to promote the implementation of clinical genetic service including genetic counseling for proper genetic testing.

• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Nutrition Research and Practice
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• v.13 no.6
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• pp.498-508
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• 2019

BACKGROUND/OBJECTIVES: Lower circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with a higher risk of hypertension (HTN); however, it remains unclear whether the relationship is causal. We aimed to evaluate the causal effects of circulating 25(OH)D levels on the prevalence of HTN in the Korean population using the Mendelian randomization (MR) approach. SUBJECTS/METHODS: Epidemiological data, serum 25(OH)D data, and genomic DNA biospecimens were obtained from 2,591 participants, a subset of the study population in the Korea National Health and Nutrition Survey 2011-2012. Five 25(OH)D-related single nucleotide polymorphisms (SNPs; DHCR7 rs12785878, CYP2R1 rs10741657, CYP2R1 rs12794714, CYP24A1 rs6013897, and GC rs2282679), identified a priori from genome-wide association studies, were used as instrument variables (IVs) for serum 25(OH)D levels. In the MR analysis, we performed IV analyses using the two-stage least squares method. RESULTS: In the observational analysis, circulating 25(OH)D levels were found to be inversely associated with the HTN prevalence in ordinary least squares models (odds ratio: 0.97, 95% confidence interval: 0.96, 0.99) after adjusting for the potential confounders. There were differences in the circulating 25(OH)D levels across genotypes of individual SNPs. In the MR analysis, using individual SNPs as IVs, 25(OH)D levels were not associated with the HTN prevalence. CONCLUSIONS: We found no association between genetically determined circulating 25(OH)D levels and HTN in Korean adults. Our results are listed owing to the relatively small sample size and possible weak instrument bias; therefore, further studies are needed to confirm these results.

• ALGAE
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• v.33 no.3
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• pp.269-278
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• 2018

Ocean warming can have significant negative impacts on population genetic diversity, local endemism and geographical distribution of a wide range of marine organisms. Thus, the identification of conservation units with high risk of extinction becomes an imperative task to assess, monitor, and manage marine biodiversity for policy-makers. Here, we surveyed population structure and genetic variation of the red seaweed Gracilaria vermiculophylla along the coast of China using genome-based amplified fragment length polymorphism (AFLP) scanning. Regardless of analysis methods used, AFLP consistently revealed a south to north genetic isolation. Populations at the southern coast of China showed unique genetic variation and much greater allelic richness, heterozygosity, and average genetic diversity than the northern. In particular, we identified a geographical barrier that may hinder genetic exchange between the two lineages. Consequently, the characterized genetic lineage at the southern coast of China likely resulted from the interplay of post-glacial persistence of ancestral diversity, geographical isolation and local adaptation. In particular, the southern populations are indispensable components to explore evolutionary genetics and historical biogeography of G. vermiculophylla in the northwestern Pacific, and the unique diversity also has important conservation value in terms of projected climate warming.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 1997.06a
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• pp.23-49
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• 1997

This is a progress report of rice biotechnology including development of gene transformation system, gene cloning and molecular mapping in rice. The scope of the research was focused on the connection between conventional breeding and biotech-researches. Plant transformation via Agrobacterium or particle bombardment was developed to introduce one or several genes to recommended rice cultivars. Two chimeric genes containing a maize ribosome inactivating protein gene (RIP) and a gerbicide resistant gene (bar) were introduced to Nipponbare, a Japonica cultivar, and transmitted to Korean cultivars. The homozygous progenies of herbicide resistant transgenic plant showed good fertility and agronomic characters. To explore the genetic resourses in rice, over 8,000 cDNA clones from immature rice seed have been isolated and sequenced. About 13% of clones were identified as enzymes related to metabolic pathway. Among them, twenty clones have high homology with genes encoding enzymes in the photorespiratory carbon cycle reaction. Up to now about 100 clones were fully sequenced and registered at EMBL and GenBank. For the mapping of quantitative tarits loci (QTL) and eternal recombinant inbred population with 164 F13 lines (MGRI) was developed from a cross between Milyang 23 and Gihobyeo, Korean rice cultivars. After construction of fully saturated RFLP and AFLP map, quantitative traits using MGRI population were analyzed and integrated into the molecular map. Eighty seven loci were determined with 27 QTL characters including yield and yield components on rice chromosomes. Map based cloning was also tried to isolate semi-dwarf (sd-1) gene in rice. A DNA probe, RG 109, the most tightly linked to sd-1 gene was used to screen from bacterial artifical chromosome (BAC) libraries and five over lapping clones presumably containing sd-1 gene were isolated. Rice genetic database including results of biotech reasearch and classical genetics is provided at Korea Rice Genome Server which is accessible with world wide web (www) browser. The server provides rice cDNA sequences and map informations linked with phenotypic images.