• Genomics & Informatics
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• v.6 no.4
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• pp.210-222
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• 2008

Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.99-107
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• 2004

The validation of many synthetic chemicals that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, the regulation and evaluation of the chemical hazard playa very important role to environment and human health. The clastogenicity of 11 synthetic chemicals was evaluated in Chinese hamster lung (CHL) fibroblast in vitro. Benzoyl chloride (CAS No. 98-88-4) induced chromosomal aberrations with statistical significance at the concentration of 31-123 $\mug/ml$ and 43 $\mug/ml$ in the absence and presence of S-9 metabolic activation system, respectively. 2-Propyn-l-o1 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed clastogenicity only at the highest concentration in the presence of S-9 mixture. However, 1-naphthol (CAS No. 90-15-3) which is one of the most cytotoxic chemical among 11 chemicals tested revealed no clastogenicity both in the presence and absence of S-9 metabolic activation system. From the results of chromosomal aberration assay with 11 synthetic chemicals in CHL fibroblast in vitro, Benzoyl chloride (CAS No. 98-88-4), 2-Propyn-l-01 (CAS No. 107-19-7) and 2-Phenoxy ethanol (CAS No. 122-99-6) revealed positive clastogenic results in this study.

• Fashion & Textile Research Journal
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• v.6 no.4
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• pp.515-521
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• 2004

The Purpose of this study was to investigate the effect of body fat on thermophysiological responses and subjective sensations under hot environment. Fifteen female college students volunteered as subjects. Subjects were organized into three groups - low body fat group(L group : less than 20% of body fat), medium body fat group(M group : 20%~30% of body fat) and high body fat group(H group : More than 30% of Body fat). The experiment was carried out in a climate chamber of $32^{\circ}C$, 60%RH with the repeat of having 'Exercise' and 'Rest' period. The results of this study are as follows ; Rectal temperature maintained higher in M group and L group than in H group in the period of exercise 1. High body fat was so effective in keeping the core temperature, it seems that as was usually the case in cold environment. The mean skin temperature was the lowest value in H group but the ratio of mean skin temperature change was clearly high value in H group. The above facts indicated that thermophysiological response occurs rapidly in H group. Blood pressure, pulse rate and metabolic rate of H group showed the highest values and those of L group showed the lowest value in all period of experiment. Effective of sweating rate was higher in H group than other groups. In subjective sensations, The H group felt more pleasant and comfortable than M group. With these results in mind, people of H group responses more actively for thermal regulation in a hot environment, and these leads H group to feel more pleasant and comfortable.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Plant Biotechnology Reports
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• v.4 no.4
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• pp.269-280
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• 2010

Lilium ${\times}$ formolongi was genetically engineered by Agrobacterium-mediated transformation with the plasmid pCrtZW-N8idi-crtEBIY, which contains seven enzyme genes under the regulation of the CaMV 35S promoter. In the transformants, ketocarotenoids were detected in both calli and leaves, which showed a strong orange color. In transgenic calli, the total amount of carotenoids [133.3 ${\mu}g/g$ fresh weight (FW)] was 26.1-fold higher than in wild-type calli. The chlorophyll content and photosynthetic efficiency in transgenic orange plantlets were significantly lowered; however, after several months of subculture, they had turned into plantlets with green leaves that showed significant increases in chlorophyll and photosynthetic efficiency. The total carotenoid contents in leaves of transgenic orange and green plantlets were quantified at 102.9 and 135.2 ${\mu}g/g$ FW, respectively, corresponding to 5.6- and 7.4-fold increases over the levels in the wild-type. Ketocarotenoids such as echinenone, canthaxanthin, 3'-hydroxyechinenone, 3-hydroxyechinenone, and astaxanthin were detected in both transgenic calli and orange leaves. A significant change in the type and composition of ketocarotenoids was observed during the transition from orange transgenic plantlets to green plantlets. Although 3'-hydroxyechinenone, 3-hydroxyechinenone, astaxanthin, and adonirubin were absent, and echinenone and canthaxanthin were present at lower levels, interestingly, the upregulation of carotenoid biosynthesis led to an increase in the total carotenoid concentration (+31.4%) in leaves of the transgenic green plantlets.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.227-247
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• 2013

MicroRNAs (miRNAs) are a class of recently discovered non-coding small RNA molecules, on average approximately 21 nucleotides in length, which underlie numerous important biological roles in gene regulation in various organisms. The miRNA database (release 18) has 18,226 miRNAs, which have been deposited from different species. Although miRNAs have been identified and validated in many plant species, no studies have been reported on discovering miRNAs in Panax ginseng Meyer, which is a traditionally known medicinal plant in oriental medicine, also known as Korean ginseng. It has triterpene ginseng saponins called ginsenosides, which are responsible for its various pharmacological activities. Predicting conserved miRNAs by homology-based analysis with available expressed sequence tag (EST) sequences can be powerful, if the species lacks whole genome sequence information. In this study by using the EST based computational approach, 69 conserved miRNAs belonging to 44 miRNA families were identified in Korean ginseng. The digital gene expression patterns of predicted conserved miRNAs were analyzed by deep sequencing using small RNA sequences of flower buds, leaves, and lateral roots. We have found that many of the identified miRNAs showed tissue specific expressions. Using the insilico method, 346 potential targets were identified for the predicted 69 conserved miRNAs by searching the ginseng EST database, and the predicted targets were mainly involved in secondary metabolic processes, responses to biotic and abiotic stress, and transcription regulator activities, as well as a variety of other metabolic processes.

• Molecules and Cells
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• v.40 no.3
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• pp.186-194
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• 2017

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.

• International Journal of Industrial Entomology and Biomaterials
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• v.14 no.2
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• pp.121-126
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• 2007

Obesity is a major risk factor for cardiovascular disease. In our case study using animal models for disease states such as obesity or hypertension, we found that, Isaria sinclairii remarkably reduced body weight and ameliorated metabolic abnormalities in Zucker and SHR rats. Genetically obese (fa/fa) Zucker rats were one animal model chosen for this study. Four groups of rats received a standard diet and were treated orally with the following test samples daily for 8 weeks: saline (negative control), ethanol extracts of I. sinclairii, hot water extract of I. sinclairii, or $Xenical^{(R)}$ (30 mg/kg, positive control). Mild reductions (6.3%) in body weight gain were observed in the groups treated with the hot water extract of I. sinclairii compared to the control after 8 weeks. Interestingly, organ weight was greatly reduced by this Dongchunghacho (I. sinclairii), in parallel with the mild reductions in body weight gain and reductions in abdominal fat (adipose tissue). Also observed was a 4.1 % decrease in the ratio of heart weight/body weight compared to the control group. As a hypertensive animal model, SHR (spontaneously hypertensive rat) and WKY (Wistar Kyoto) rats were also administered these extracts for one month. Treatment with the hot water extract of I. sinclairii caused greater reductions in body weight gain for the SHR group (10.9%) compared to the WKY group's (5.2%). Based on these results, I. sinclairii extracts contain selective action for anti-obesity activity, naturally occurring candidate for regulation of body weight increase, as demonstrated in the present study.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.585-592
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• 2021

Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise (CC, n = 8), cisplatin (1 mg/kg) + resistance exercise (CRE, n = 9) group, and cisplatin (1 mg/kg) + aerobic exercise (CAE, n = 11). The CRE group performed progressive ladder exercise (starting with 10% of body weight on a 1-m ladder with 2-cm-interval grids, at 85°) for 8 weeks. The CAE group exercised by treadmill running (20 m/min for 60 min daily, 4 times/week) for 8 weeks. Compared with the CC group, the levels of the autophagy-related factors BNIP3, Beclin 1, LC3-II/I ratio, p62, and FOXO3a in the gastrocnemius and soleus muscles were significantly decreased in the CRE and CAE groups. The CRE and CAE groups further showed significantly decreased MuRF 1 and Atrogin-1 levels and increased phosphorylation of AKT, FOXO3a, and PGC1-α. These results suggest that both ladder and aerobic exercise directly affected muscle wasting by modulating the AKT/PGC1-α/FOXO3a signaling pathways regardless of the skeletal muscle type.