• Biotechnology and Bioprocess Engineering:BBE
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• v.8 no.2
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• pp.135-141
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• 2003

The human granulocyte-macrophage colony stimulating factor (hGM-CSF) gene was introduced into tobacco plants. The cell suspension culture was established from leaf-derived calli of the transgenic tobacco plants in order to express and secrete a biologically active hGM -CSF. The recombinant hGM-CSF from the transgenic plant cell culture (prhGM-CSF) was identified as a yield of about 180 ${\mu}$g/L in the culture filtrate, as determined by ELISA. The addition of 0.5 g/L polyvinylpyrrolidone (PVP) to the plant cell culture medium both stabilized the secreted prhGM-CSF and increased the level of production approximately 1.5-fold to 270 ${\mu}$g/L. The biological activity of the prhGM-CSF was confirmed by measuring the proliferation of the hGM-CSF-dependent cell line, TF-1. Interestingly, the specific activity of the prhGM-CSF was estimated to be approximately 2.7 times higher than that of a commercially available preparation from E. coli.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4341-4346
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• 2012

Purpose: The aim of this study was to cast light on initiating molecular events associated with the development of premalignant oral lesions induced by tobacco and/or areca nut. Method: Immunohistochemical analyses of cell cycle regulatory proteins (LIMD1, RBSP3, p16, RB, phosphorylated RB, p53), EGFR and SH3GL2 (EGFR associated protein) were performed with inflammatory/ulcerative epithelium and adjacent hyperplastic/mild dysplastic lesions. Results: No change in expression of the proteins was seen in inflammatory epithelium. Reduced nuclear expression of LIMD1 was evident in ulcerative epithelium. In hyperplastic lesions, reduced expression of RBSP3, p16, SH3GL2 and overexpression of p-RB and EGFR were apparent. Reduced nuclear expression of p53 was observed in mild dysplastic lesions. Conclusion: Our data suggest that inactivation of LIMD1 in ulcerative epithelium might predispose the tissues to alterations of other cell cycle regulatory and EGFR signaling proteins needed for the development of premalignant oral lesions.

• Mycobiology
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• v.46 no.2
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• pp.114-121
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• 2018

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.

• Genomics & Informatics
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• v.12 no.1
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• pp.2-11
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• 2014

After the initial enthusiasm of the human genome project, it became clear that without additional data pertaining to the epigenome, i.e., how the genome is marked at specific developmental periods, in different tissues, as well as across individuals and species-the promise of the genome sequencing project in understanding biology cannot be fulfilled. This realization prompted several large-scale efforts to map the epigenome, most notably the Encyclopedia of DNA Elements (ENCODE) project. While there is essentially a single genome in an individual, there are hundreds of epigenomes, corresponding to various types of epigenomic marks at different developmental times and in multiple tissue types. Unprecedented advances in next-generation sequencing (NGS) technologies, by virtue of low cost and high speeds that continue to improve at a rate beyond what is anticipated by Moore's law for computer hardware technologies, have revolutionized molecular biology and genetics research, and have in turn prompted innovative ways to reduce the problem of measuring cellular events involving DNA or RNA into a sequencing problem. In this article, we provide a brief overview of the epigenome, the various types of epigenomic data afforded by NGS, and some of the novel discoveries yielded by the epigenomics projects. We also provide ample references for the reader to get in-depth information on these topics.

• BMB Reports
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• v.45 no.8
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• pp.464-469
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• 2012

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. MiRNA let-7 family is known to be involved in the regulation of cell apoptosis. However, the function of let-7 in ox-LDL induced ECs apoptosis and atherosclerosis is still unknown. Here, we show that let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (HUVECs). Let-7c over-expression enhanced apoptosis in ECs whereas inhibition of let-7c could partly alleviate apoptotic cell death mediated by ox-LDL. Searching for how let-7c affected apoptosis, we discovered that antiapoptotic protein Bcl-xl was a direct target of let-7c in ECs. Our data suggest that let-7c contributes to endothelial apoptosis through suppression of Bcl-xl.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.35-39
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• 1997

Recent development of human genetics and techniques of gene transfer and expression have opened the way for investigating novel approaches based on the genetic modification of cells to treat both inherited and acquired diseases. This approach is referred to as gene therapy. Over the past few years, gene therapy has moved from the laboratory to phase I clinical trials. Although the clinical performance of gene transfer experiments is still in an early phase of development, the NIH of Health Recombinant DNA Advisory Comittee (RAC) has approved more than 150 protocols that involve gene transfer or putative gene therapy procedures in clinical settings. Many sectors of society in United States have participated in the design and formulation of these clinical trials through local Institutional Review Boards, the National Institutes of Health (NIH) RAC, the Chemotherapy Evaluation Program of the National Cancer institute, and the FDA. Currently, clinical trials involving gene modification are under way at many medical centers throughout the United Slates. The goals of these trials are as follows. (1) The design should be directed to short-term achievable goals. (2) Each clinical trial is best considered as an intermediate step in a multistep process. (3) The design should identify evaluable proximate endpoints for toxicity and for efficacy, (4) The potential benefits and possible risks for patients participating in these trial should be defined.

• Plant Biotechnology Reports
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• v.2 no.3
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• pp.213-218
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• 2008

Swertia chirata is an endangered gentian species that prefers to grow at higher altitudes. This ethnomedicinal herb is known primarily for its bitter taste caused by the presence of important phytochemicals that are directly associated with human health benefits. Due to a continuous loss of habitat and inherent problems of seed viability and seed germination, alternative strategies for propagation and conservation are urgently required to prevent the possible extinction of this species. We have formulated a reproducible protocol for the rapid propagation and conservation of this plant using leaves taken from in vitro shoot cultures. Direct induction of more than seven shoot buds per explant was achieved for the first time when the explants were placed on MS medium supplemented with $2.22{\mu}M$ N-6-benzyladenine, $11.6{\mu}M$ kinetin, and $0.5{\mu}M$ ${\alpha}-naphthalene$ acetic acid. Direct organogenesis was noted exclusively from the adaxial surface of the basal segments of leaves. Leaves closer to the apical meristem were more responsive than those farther away from the meristem. Plants raised through direct organogenesis were evaluated for their clonal fidelity by chromosomal analysis and DNA fingerprinting. Complete plants were successfully transferred to the field condition and produced viable seeds. Given the enormous potential of this age-old medicinal plant in terms of potential health-benefitting drugs, this protocol can be used for commercial propagation purposes and to initiate future genetic improvement studies.

• Korean Journal of Cleft Lip And Palate
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• v.10 no.2
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• pp.81-88
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• 2007

Cleft lip and palate (CLP) is one of the most prevalent congenital craniofacial anomalies. It has a significantly greater incidence of dental abnormalities in number, size, shape, and eruption of the teeth. Knout-out mouse model can identify several genes which play an important role in tooth agenesis. Since disruption of these genes has been confirmed to result in tooth agenesis in humans, CLP associated with hypodontia may be the best models for isolated tooth agenesis. According to the studies of dental abnormalities in CLP, the severity of dental defect is known to be influenced by the CLP phenotype. The cumulative data obtained from mouse and human genetic studies indicated that MSX1, PAX9 and AXIN2 are considered as candidate genes in non-syndromic hypodontia, while Shh, Pitx2, Irf6, p63 and EDA pathway genes are involved in syndromic one. We expect that genetic approach of CLP can offer the basis for tooth regeneration and be a new target in hypodontia therapy.

• BMB Reports
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• v.34 no.2
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• pp.166-171
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• 2001

The levels of $\gamma$-aminobutyric acid (GAGA) have been analyzed from pharbitis seeds by an AccQ-Tag amino acid analysis procedure. The GABA level of the pharbitis seeds was 125 nmole per gram fresh weight. To investigate the effects of pharbitis seed diets on serum and hepatic lipid levels, as well as enzyme activities of rats administered with ethanol chronically, Sprague-Dawley male rats were fed with either a AIN-76 diet (control), a control diet plus ethanol, a control plus pharbitis seed diet, or a control plus pharbitis seed diet plus ethanol for 30 days. Pharbitis seed diets decreased the serum total cholesterol, triglyceride, LDL-cholesterol, and $\gamma$-GTP levels that were increased by the chronic ethanol administration. In addition, pharbitis seed diets decreased the liver triglyceride and total lipid levels that were increased by the ethanol administration. However, ethanol metabolism was not retarded by the pharbitis seed supplemented diets. The present Endings, plus previous data showing the differences in the effects of cabbage diets having a high or a low level of GABA on the lipid levels and the enzyme activities of rats (Cha and Oh [2000] J. Korean Soc. Food Sci. Nutr. 29, 500-505), raise the possibility that GABA in plants could have a nutraceutical role in the recovery of chronic alcohol-related diseases.

• Toxicological Research
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• v.17
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• pp.289-292
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• 2001

Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. Models of essential hypertension have been produced by mutated genes relating renin angiotensin system. The most significant contribution to understanding the genetic etiology of essential hypertension is probably the demonstration that discrete alterations in the expression of a variety of different genes can individually cause changes in the blood pressures of mice, even when the mice have all their compensatory mechanisms intact. These effects are readily detected in animals having moderate decreases in gene function due to heterozygosity for gene disruptions or modest increases due to gene duplication. As a species the mouse is highly resistant to atherosclerosis. However. through induced mutations it has been possible to develop lines oj mice that are deficient in apolipoprotein E, a ligand important in lipoprotein clearance, develop atherosclerotic lesions resembling those observed in humans. The atherosclerotic lesions in apoE-deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. Other promising models are mice that are deficient in the low-density lipoprotein receptor. Considerable work still remains to be done in dissecting out in a rigorous manner the effects of alterations in single genes on the induction or progression of atherosclerosis and on the control of blood pressures. Perhaps even more exciting is the opportunity now becoming available to breed animals in which the effects oj precise differences in more than one gene can be studied in combination.