• Korean Journal of Animal Reproduction
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• v.23 no.1
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• pp.1-12
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• 1999

The present study was conducted to find the effects of different cadmium(Cd) levels in diets on clinical toxicity, sperm capacity and histopathological changes in rats. Thirty male rats of Sprague-Dawley weighing 125.3$\pm$15.2g were randomly blocked into five groups according to body weights. Five levels of Cd in AIN-76 purified diet(0, 25, 50, 100 and 250 ppm) had been fed for 8 weeks. Cadmium was supplemented with a form of CdCl$_2$. 1. After 8 weeks of Cd intake had resulted in apparent cadmium intoxication; reduced growth rate, enlarged kidney and testis, decreased hematocrit value and hemoglobin content in response to supplemented Cd levels in the diets. 2. Cadmium accumulation in liver and kidney showed a tendency to increase in cadmium-exposed groups. The levels of metallothionein were also significantly elevated in the tissues of liver in response to the levels of Cd supplemented(P＜0.05). 3. Although sperm motility was not significantly different among treatments, rats fed Cd tended to have reduced sperm motility but sperm concentration of Cd supplemented groups were significantly lower than that of control(p＜0.05). 4. Based on the findings from gross lesion, rats fed 250ppm of Cd were externally emaciated, had exposed penis and observed atrophies of kidney and testis. Histopathological observation seemed that the liver of groups feeding Cd supplemented diets showed cellular degeneration and accumulation of eosinophilic materials in the capillaries. In kidney, rats fed Cd diets had shown tubular epithelium degeneration and lesions of basophilic materials, while testes were weakened in numbers of spermatid and sporadically enlarged of giant cells.

• Journal of Life Science
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• v.23 no.8
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• pp.989-997
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• 2013

In this study, based on the antioxidative effects in organic solvent fractions obtained from the main methanolic extract of L. japonica, the protective cellular effects and gene expression patterns of ethyl acetate fractions on $H_2O_2$-induced Raw 264.7 cell death ($IC_{50}$) were analyzed. The antioxidant activity of the fractions measured using DPPH free radical scavenging activity increased in a dose-dependent manner, and the $ED_{50}$ exhibited the highest $39.56{\mu}g/ml$ in the ethyl acetate fraction. In addition, the ethyl acetate fractions' cell viability on $H_2O_2$-induced Raw 264.7 cell damage increased in a concentration-dependent manner, showed a visible cell survival rate of 82.49% at a concentration of $100{\mu}g/ml$. The gene expression patterns related to the ethyl acetate fractions' cytoprotective effect in $H_2O_2$-induced Raw 264.7 cell damage presented similar patterns to those of BHA. In comparative analysis for antioxidant activity-related genes affected by ethyl acetate fractions and BHA in $H_2O_2$-induced Raw 264.7 cells, both ethyl acetate fractions and BHA showed very similar gene expression patterns, but the gene expression level of the heme oxygenase 1 (Hmox1) gene making antioxidant enzymes in cells was four times higher in ethyl acetate fractions than BHA. In inflammation-related genes in $H_2O_2$induced Raw 264.7 cells, the T-box transcription factor (Tbx21) gene was expressed about two times more frequently in the ethyl acetate fraction treatment group, while it was expressed half as frequently in the BHA treatment group.

• Molecules and Cells
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• v.42 no.12
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• pp.906-918
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• 2019

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

• Journal of Gifted/Talented Education
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• v.21 no.1
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• pp.57-81
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• 2011

The purpose of this study was to explore the quality of life of musically talented students as measured by their external experiences (e.g., activities, companions) and internal experiences (e.g., flow, emotion). The participants in this study were 33 musically talented students (10 males, 23 females) aged 13 to 19. Study data were collected for 7 consecutive days using the Experience Sampling Method (ESM), which employs a cellular-phone as a signaling device. The results were as follows: First, in response to the 1625 random signals, musically talented students reported that 40.9% of their time was spent on productive activities. An additional 33.4% of time was used for maintenance activities and the rest of their time was spent on leisure/social activities. Also, musically talented students reported that 48.5% of their time was spent alone. When they were alone, they spent a lot of time engaging in productive activities (44.3%). Second, in order to measure the flow of their life, two methods were used. One used a 4-channel flow model (i.e. apathy, boredom, flow, anxiety) and the other used 8 dimensions and conditions of the flow experience (i.e. concentration, self-consciousness disappears, action and awareness merge, distorted sense of time, freedom from worry about failure, clear goals, immediate feedback, balance between challenges and skills). According to the former, when engaged in music-related activities, musically talented students usually reported flow (54.0%), while they felt apathy (41.3%) for daily routines activities. According to the latter method, musically talented students experienced flow for most productive activities, while they experienced flow least for maintenance activities. Emotional variables of ESF are comprised of 10 semantic scales (i.e. happy-sad, strong-weak, active-passive, sociablelonely, proud-ashamed, involved-detached, excited-bored, clear-confused, relaxed-worried, cooperative-competitive). Musically talented students reported experiencing the most positive emotion for social activities and experiencing the most negative emotion for maintenance activities. Results of this study assert that musically talented students had to trade off immediate enjoyment for developing their special gifts. They could not afford as much time for socializing with friends, and they had to spend more time alone compared to their peers without such gifts. Consequently, they were found to deprive themselves of the spontaneous good times that teenagers usually thrive on. They were helped in this respect by their autotelic personality traits, especially their strong need for achievement and endurance. The downside, however, is that the moment-to-moment quality of their moods suffered. The argument concerning musically talented students applies for all adolescents. The choices that talented students must make between immediate gratification and long-term development, and between solitude and companionship, are the same choices every young person must make, regardless of her or his level of talent. All of us have gifts that are potentially useful and worthy of being appreciated. But to develop these latent talents we must cultivate them, and this takes time and the investment of mental energy. The lifestyle that musically talented students develop can show us some of the choices all of us must make in order to cultivate our gifts.

• Journal of Embryo Transfer
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• v.16 no.2
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• pp.79-89
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• 2001

Steroid hormones control the expression of many cellular regulators, and a role thor estrogen in mouse oocytes has been well documented. The preovulatory $E_2$increment is generally accepted as the endocrine process regulating induction of in vivo oocyte maturation To address whether the activity of the T-type $Ca^{2+}$ channel is altered by 17 beta-estradiol ( $E_2$), we examined the actions of $E_2$on the calcium channel of mouse oocytes and early embryos. Oocrtes were collected from the oviduct of mice treated with pregnant mare's serum gonadotropin (PMSG) and human choronic gonadotropin (hCG). Whole cell voltage clamp technique and confocal microscopy were used to examine that $E_2$increase intracellular $Ca^{2+}$ concentration ([C $a^{2+}$]$_{i}$ ) via voltage dependent $Ca^{2+}$ channel (VDC) and estrogen receptor (FSR), and $E_2$concentration by the use of radioimmunoassay (RIA) were examined in mouse. The results obtained were as follows: The peak of $Ca^{2+}$ current induced by $E_2$increased 122% to 1.50$\pm$0.03 nA from 1.23$\pm$0.21 nA (n=15) in the presence of 5 mM extracellular $Ca^{2+}$ concentration ([C $a^{2+}$]$_{o}$ ). The increased $Ca^{2+}$ current was temporally associated with $Ca^{2+}$ transients. The intracellular $Ca^{2+}$ level increased 207%~30 s following the addition of 1${\mu}{\textrm}{m}$ $E_2$(relative fluorescence intensity: 836.4$\pm$131.2 for control, n=10, 1736.4$\pm$192.0 in the presence of $E_2$, n=10). $E_2$increased amplitude of $Ca^{2+}$ current and [C $a^{2+}$]$_{i}$ . $E_2$-induced $Ca^{2+}$ current and $E_2$concentration in blood were showed difference on the stage of embryo. These results suggest that $E_2$modulate $Ca^{2+}$ channel to increase $Ca^{2+}$ influx.$Ca^{2+}$ influx.

• Proceedings of the Microbiological Society of Korea Conference
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• 2008.05a
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• pp.39-41
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• 2008

The yeast Saccharomyces cerevisiae has been shown to contain three isoforms of citrate synthase (CS). The mitochondrial CS, Cit1, catalyzes the first reaction of the TCA cycle, i.e., condensation of acetyl-CoA and oxaloacetate to form citrate [1]. The peroxisomal CS, Cit2, participates in the glyoxylate cycle [2]. The third CS is a minor mitochondrial isofunctional enzyme, Cit3, and related to glycerol metabolism. However, the level of its intracellular activity is low and insufficient for metabolic needs of cells [3]. It has been reported that ${\Delta}cit1$ strain is not able to grow with acetate as a sole carbon source on either rich or minimal medium and that it shows a lag in attaining parental growth rates on nonfermentable carbon sources [2, 4, 5]. Cells of ${\Delta}cit2$, on the other hand, have similar growth phenotype as wild-type on various carbon sources. Thus, the biochemical basis of carbon metabolism in the yeast cells with deletion of CIT1 or CIT2 gene has not been clearly addressed yet. In the present study, we focused our efforts on understanding the function of Cit2 in utilizing $C_2$ carbon sources and then found that ${\Delta}cit1$ cells can grow on minimal medium containing $C_2$ carbon sources, such as acetate. We also analyzed that the characteristics of mutant strains defective in each of the genes encoding the enzymes involved in TCA and glyoxylate cycles and membrane carriers for metabolite transport. Our results suggest that citrate produced by peroxisomal CS can be utilized via glyoxylate cycle, and moreover that the glyoxylate cycle by itself functions as a fully competent metabolic pathway for acetate utilization in S. cerevisiae. We also studied the relationship between Cit1 and apoptosis in S. cerevisiae [6]. In multicellular organisms, apoptosis is a highly regulated process of cell death that allows a cell to self-degrade in order for the body to eliminate potentially threatening or undesired cells, and thus is a crucial event for common defense mechanisms and in development [7]. The process of cellular suicide is also present in unicellular organisms such as yeast Saccharomyces cerevisiae [8]. When unicellular organisms are exposed to harsh conditions, apoptosis may serve as a defense mechanism for the preservation of cell populations through the sacrifice of some members of a population to promote the survival of others [9]. Apoptosis in S. cerevisiae shows some typical features of mammalian apoptosis such as flipping of phosphatidylserine, membrane blebbing, chromatin condensation and margination, and DNA cleavage [10]. Yeast cells with ${\Delta}cit1$ deletion showed a temperature-sensitive growth phenotype, and displayed a rapid loss in viability associated with typical apoptotic hallmarks, i.e., ROS accumulation, nuclear fragmentation, DNA breakage, and phosphatidylserine translocation, when exposed to heat stress. Upon long-term cultivation, ${\Delta}cit1$ cells showed increased potentials for both aging-induced apoptosis and adaptive regrowth. Activation of the metacaspase Yca1 was detected during heat- or aging-induced apoptosis in ${\Delta}cit1$ cells, and accordingly, deletion of YCA1 suppressed the apoptotic phenotype caused by ${\Delta}cit1$ mutation. Cells with ${\Delta}cit1$ deletion showed higher tendency toward glutathione (GSH) depletion and subsequent ROS accumulation than the wild-type, which was rescued by exogenous GSH, glutamate, or glutathione disulfide (GSSG). Beside Cit1, other enzymes of TCA cycle and glutamate dehydrogenases (GDHs) were found to be involved in stress-induced apoptosis. Deletion of the genes encoding the TCA cycle enzymes and one of the three GDHs, Gdh3, caused increased sensitivity to heat stress. These results lead us to conclude that GSH deficiency in ${\Delta}cit1$ cells is caused by an insufficient supply of glutamate necessary for biosynthesis of GSH rather than the depletion of reducing power required for reduction of GSSG to GSH.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.265-274
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• 2002

Background : Tumor associated antigens, which are produced specifically by tumor cells, are promising targets for the early diagnosis and immunotherapy. Among the tumor associated antigens, MAGE (a melanoma antigen), BAGE, GAGE, PRAME and NY-ESO were named as cancer/testis specific antigens they are detected exclusively in the testis or cancer cells If MAGE is easily detectable in the sputum, it would become a convenient method for diagnosing lung cancer. This study was undertaken to investigate MAGE expression in the induced sputum obtained from lung cancer patients. Materials and Methods : In 14 control patients and 30 lung cancer patients, the induced sputum was collected after inhaling 3% saline(5 cc) delivered by nebulizer for approximately 5 minutes after a mouth rinse and bronchodilator inhalation. The induced sputum was placed in a conservative-mixed solution (guanidinium isothiocyanate, Triton X-100). The total cellular mRNA was extracted from the cells and RT PCR and nested PCR were run in 30 and 35 cycles respectively, with two different types of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results : MAGE expression was not detected in the 14 controls, but in the 30 cancer patients, MAGE was found in 24 patients (80%, p=0.001). In the cancer patients, there were no differences in the expression level according to the tissue types (squamous cell cancer 13/17, adenocarcinoma 7/9, and small cell cancer 4/4, p-0.56). Among the 24 MAGE-positive patients, the tumor was not visible on a bronchoscopy in 11 patients (45.8%). Conclusion : A study of MAGE in induced sputum appears to be a useful and complementary method in the diagnosis of lung cancer. A further prospective study with more patients is recommended.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.145-154
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• 2004

Purpose : To examine whether a synthetic bile acid derivatives (HS-1200) sensitizes the radiation-induced apoptosis in human breast cancer cells (MCF-7) and to investigate the underlying mechanism. Materials and Methods : Human breast cancer cells (MCF-7) in exponential growth phase were treated with HS-1200 for 24 hours at 37$^{\circ}C$ with 5$\%$ CO$_{2}$ in air atmosphere. After removal of HS-1200, cells were irradiated with 2$\~$8 Gy X-ray, and then cultured Ii drug-free media for 24-96 hours. The effect of radiation on the clonogenicity of MCF-7 cells was determined with clonogenic cell survival assay with 16$\mu$M of HS-1200. The induction of apoptosis was determined using agarose gel electrophoresis and Hoechst staining. The expression level of apoptosis-related molecules, such as PARP, Bax, Bcl-2, Bak and AIF, were assayed by Western blotting analysis with 40$\mu$M of HS-1200 combined with 8 Gy irradiation. To examine the cellular location of cytochrome c, bax and AIF immunofluorescent stainings were undertaken. Results : Treatment of MCF-7 cells with 40$\mu$M of HS-1200 combined with 8 Gy irradiation showed several changes associated with enhanced apoptosis by agarose gel electrophoresis and Hoechst staining. HS-1200 combined with 8 Gy irradiation treatment also enhanced production of PARP cleavage products and increased Bax/Bcl-2 ratio by Western blotting. Loss of mitochondrial membrane potential ($\Delta$$\psi$$_{m}$) and increased cytochrome c staining indicated that cytochrome c had been released from the mitochondria in HS-1200 treated cells. Conclusion : We demonstrated that combination treatment with a synthetic chenodeoxycholic acid derivative HS-1200 and irradiation enhanced radiation-induced apoptosis of human breast cancer cells (MCF-7). We suggest that the increased Bax/Bcl-2 ratio In HS-1200 co-treatment group underlies the increased radio sensitivity of MCF-7 cells. Further futures studies are remained elusive.

• Korean Journal of Microbiology
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• v.41 no.1
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• pp.67-73
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• 2005

Photoautotrophic bacteria are promising candidates for the production of poly(3-hydroxybutyrate) (PHB) since they can address the critical problem of substrate costs. In this study, we isolated 25 Tn5-inserted mutants of the Synechocystis sp. PCC 6803 which showed enhanced PHB accumulation compared to the wild-type strain. After 5-days cultivation under nitrogen-limited mixotrophic conditions, the intracellular levels of PHB content in these mutants reached up to $10-30\%$ of dry cell weight (DCW) comparable to $4\%$ of DCW in the wild-type strain. Using the method of inverse PCR, the affected genes of the mutants were mapped on the completely known genome sequence of Synechocystis sp. PCC 6803. As a result, the increased PHB accumulation in 5 mutants were found to be resulted from defects of genes coding for NADH-ubiquinone oxidoreductase, O-succinylbenzoic-CoA ligase, photosystem II PsbT protein or histidine kinase, which are involved in photosystem in thylakoid inner membrane of the cell. The values of $NAD(P)H/NAD(P)^+$ ratio in the cells of these mutants were much higher than that of the wild-type strain as measured by using pulse-amplitude modulated fluorometer, suggesting that PHB synthesis could be enhanced by increasing the level of cellular NAD(P)H which is a limiting substrate for NADPH-dependent acetoacetyl-CoA reductase. From these results, it is likely that NAD(P)H would be a limiting factor for PHB synthesis in Synechocystis sp. PCC 6803.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.540-548
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• 2001

Backgrounds : Because ventilator-induced lung injury is partly dependent on the intensity of vascular flow, we hypothesized that hypothermia may attenuate the degree of such an injury through a reduced cardiac output. Methods : Twenty-seven male Sprague-Dawley rats were randomly assigned to normothermia ($37{\pm}1^{\circ}C$)-injurious ventilation (NT-V) group (n=10), hypothermia ($27{\pm}1^{\circ}C$)-injurious ventilation (HT-V) group (n=10), or nonventilated control group (n=7). The two thermal groups were subjected to injurious mechanical ventilation for 20 min with peak airway pressure 30 cm $H_2O$ at zero positive end-expiratory pressure, which was translated to tidal volume $54{\pm}6\;ml$ in the NT-V group and $53{\pm}4\;ml$ in the HT-V group (p>0.05). Results : Pressure-volume (P-V) curve after the injurious ventilation was almost identical to the baseline P-V curve in the HT-V group, whereas it was shifted rightward in the NT-V group. On gross inspection, the lungs of the HT-V group appeared smaller in size, and showed less hemorrhage especially at the dependent regions, than the lungs of the NT-V group. [Wet lung weight (g)/body weight (kg)] ($1.6{\pm}0.1$ vs $2.4{\pm}1.2$ ; p=0.014) and [wet lung weight/dry lung weight] ($5.0{\pm}0.1$ vs $6.1{\pm}0.8$ ; p=0.046) of the HT-V group were both lower than those of the NT-V group, while not different from those of the control group($1.4{\pm}0.4$, $4.8{\pm}0.4$, respectively). Protein concentration of the BAL fluid of the HT-V group was lower than that of the NT-V group($1,374{\pm}726\;ug/ml$ vs $3,471{\pm}1,985\;ug/ml$;p=0.003). Lactic dehydrogenase level of the BAL fluid of the HT-V group was lower than that of the NT-V group ($0.18{\pm}0.10\;unit/ml$ vs $0.43{\pm}0.22\;unit/ml$;p=0.046). Conclusions : Hypothermia attenuated pulmonary hemorrhage, permeability pulmonary edema, and alveolar cellular injuries associated with injurious mechanical ventilation, and preserved normal P-V characteristics of the lung in rats.