• Journal of Life Science
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• v.30 no.2
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• pp.211-220
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• 2020

The activity of CAR can be regulated not only by ligand binding but also by phosphorylation of regulatory factors involved in extracellular signaling pathways, cross-talk interactions with transcription factors, and the recruitment, degradation, and expression of coactivators and corepressors. This regulation of CAR activity can in turn have effects on the control of diverse physiological homeostasis, including xenobiotic and energy metabolism, cellular proliferation, and apoptosis. CAR is phosphorylated by the ERK1/2 signaling pathway, which causes formation of a complex with Hsp-90 and CCRP, leading to its cytoplasmic retention, whereas phenobarbital inhibits ERK1/2, which causes dephosphorylation of the downstream signaling molecules, leading to the recruitment to CAR of the activated RACK-1/PP2A components for the dephosphorylation, nuclear translocation, and the transcriptional activation of CAR. Activated CAR cross-talks with FoxO1 to induce inhibition of its transcriptional activity and with PGC-1α to induce protein degradation by ubiquitination, resulting in the transcriptional suppression of PEPCK and G6Pase involved in gluconeogenesis. Regulation by CAR of lipid synthesis and oxidation is achieved by its functional cross-talks, respectively, with PPARγ through the degradation of PGC-1α to inhibit expression of the lipogenic genes and with PPARα through either the suppression of CPT-1 expression or the interaction with PGC-1α each to induce tissue-specific inhibition or stimulation of β-oxidation. Whereas CAR stimulates cellular proliferation by suppressing p21 expression through the inhibition of FoxO1 transcriptional activity and inducing cyclin D1 expression, it suppresses apoptosis by inhibiting the activities of MKK7 and JNK-1 through the expression of GADD45B. In conclusion, CAR is involved in the maintenance of homeostasis by regulating not only xenobiotic metabolism but also energy metabolism, cellular proliferation, and apoptosis through diverse cross-talk interactions with extracellular signaling pathways and intracellular regulatory factors.

• Journal of Plant Biotechnology
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• v.46 no.3
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• pp.236-245
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• 2019

Fruit ripening is a genetically programmed process involving a number of biochemical and physiological processes assisted by variations in gene expression and enzyme activities. This process generally affects the phytochemical profile and the bioactive principles in fruits and vegetables. To appraise the variation in bioactive principles of fruits from Rosa rugosa during its ripening process, we analyzed the changes in antioxidant and anti-elastase activities and polyphenolic compounds during the four ripening stages of fruits. Overall, an extract of unripe fruits contained the highest levels of total phenolic and flavonoid contents, radical scavenging activity, reducing power, oxygen radical antioxidant capacity, and elastase inhibitory activity, compared with the extracts of fruits at other stages of ripening. Additionally, we found that the reduction of flavonoid content occurs because of decreased transcriptional levels of genes involved in flavonoid biosynthesis pathway during the ripening process. Based on HPLC analysis, we found that the extract of unripe fruits contained the highest amount of myricetin, caffeic acid, chlorogenic acid, syringic acid, and p-coumaric acid and suggested that the antioxidant and anti-elastase activities of the extract obtained from stage 1, should be mediated by the presence of these compounds. Additionally, we analyzed the interaction sites and patterns between these compounds and elastase using the structure-based molecular docking approach, and suggested that chlorogenic acid strongly interacted with elastase. Together, these findings suggest that the maturity of fruits has profound effects on the pharmaceutical value of R. rugosa.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.767-774
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• 2011

Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.222-226
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• 2003

Purpose: The interaction of the Fas: Fas ligand has been recognized to play an important role in radiation induced apoptosis. The purpose of this study was to investigate the role of Fas and Fas ligand mutations, in radiation-induced apoptosis in vivo. Materials and Methods: Mice with a mutation in the Fas ($C57BL/6J-Fas^{lpr}$) and its normal control (C57BL/6J) and the Fas ligand ($C3H/HeJ-Fas^{gld}$) and its normal control (C3H/HeJ), were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed at various time intervals, and their spleens collected. Tissue sample was stained with hematoxylin-eosin, and the numbers of apoptotic cells scored. The regulating molecules of apoptosis including the p53, Bcl-2, Bax, $Bcl-X_L\;and\;Bcl-X_s$ genes were also analyzed by Western blotting. Results: With 2.5 Gy and 10 Gy of irradiation, the levels of apoptosis were lower in the $C57BL/6J-Fas^{lpr}\;and\;C3H/HeJ-Fas^{gld}$ mice than in the control mice (p<0.05). With the expression of apoptosis regulating molecules, the Bax was increased in both the C57BL/6J and C3H/HeJ mice in response to radiation; the peak levels of Bax in the C57BL6J and C3H/HeJ were 3 and 3.3-fold higher after 8hr, respectively. However the Bax was not increased in either the $C57BL/6J-Fas^{lpr}\;or\;C3H/HeJ-Fas^{gld}$mice. The p53, Bcl-X_L,\;Bcl-X_S$and Bcl-2 showed no significant changes in the $C57BL/6J-Fas^{lpr},\;C3H/HeJ-Fas^{gld}$, C57BL/6J and C3H/HeJ mice. Conclusion: The levels of radiation-induced apoptosis were lower in the lpr and gld, than the control mice, which seemed to be related to the level of Bax activation due to the radiation in the lpr and gld mice. This result suggests that Fas/Fas L plays an important role in radiation-induced apoptosis in vivo.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Journal of Nutrition and Health
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• v.50 no.1
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• pp.32-40
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• 2017

Purpose: Obesogenic environments in children, in particular excessive intake of sodium, generate hypertension, which is a major risk factor for chronic diseases. Methods: In all, 725 children, 379 boys and 373 girls, aged 8~9 years were recruited from seven elementary schools in Kuro-ku, Seoul. To evaluate whether or not obesity risk was modulated by salt-sensitive genes, Solute Carrier Familiy 12 member 3 (SLC12A3) was used as the target. After children were assigned into obese (BMI > 85 percentile) or non-obese groups, anthropometry, blood biochemistry, and dietary intakes were measured according to the genotypes GG (wild) or GA+AA (hetero+mutant). Results: Without gender differences, high TG and low HDLc were detected in the obese group compared to the non-obese group. Regardless of obesity, weight gain and blood pressure (BP) increased in the SLC12A3 GA+AA genotype rather than in the GG type. HDLc was associated with obesity risk without genotype difference. Odd ratios for risk of obesity were 15.57 (95% CI 2.192~110.654), 22.84 (95% CI 1.565~333.469), and 9.32 (95%CI 1.262~68.817) in boys and girls with GA+AA genotypes as sodium intake increased above 4,000 mg/day. Dietary calcium, sodium, folate, and vit C were associated with obesity risk according to gender or genotype differences. Since high folate intake reduced obesity risk in only boys with GG type. Risk for overweight and obesity increased in boys with GA+AA genotypes and dietary habits with high sodium and cholesterol and low folate. Conclusion: The A allele of SLC12A3 rs11643718 was sensitive to development of obesity in children as sodium intake increased.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.4 no.1
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• pp.115-124
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• 1968

It was shown that the most desirable characters for kenaf are high-fiber weight and moderately early maturity. Therefore, the objectives of this research on this crop is to find varieties possessing these characteristics. The experiments covered in this report provided new information relative to segregation, mode of inheritance, estimate of the number of genes involved in fiber weight and their response to short day length of 10 hours and the qualitative characters, such as, color of stem, capsule, petiole and shape of leaves. The associations which exist among these characters are also indicated. Fiber weight per plant, days to flowering, Stem color, Petiole color, Capsule color, and shape of leaves were studied in parental, $F_1$.$F_2$and backcross populations of a cross between Dashkent, a low-fiber weight but early maturing kenaf variety, and G 38 F-1, a high-fiber weight but late maturing kenaf variety. Crosses were made using the varieties, Dashkent and G 38 F-1 as parents. The Dashkent parent had the following characteristics: green stems, capsules and petioles and lobed shaped leaves; 105.8234 mean-days to flowering in the field, and 106.9222 mean-days under 10 hours short day treatment. The other parent, G 38 F-1 had red stems yellow capsules and red petioles and unlobed shaped leaves; 149.8921 mean-days to flowering in the field, and 62.3684 mean-days under 10 hours short day treatment. Both of the parents, $F_1$, $F_2$, $BC_1$ ($F_1$ X Dashkent, ) and $BC_2$($F_1$ ${\times}$ G38F-1) of the kenaf cross were grown at the Crops Experiment Station, Suwon, Korea in 1965. Color of stems, petioles and capsules, and shape of leaves were noted to be simply inherited as a single factor. Red stem color was dominant over green stem color, red petiole color was dominant over green petiole, lobed shaped leaves were dominant over unlobed shaped leaves and yellow capsules were dominant over green capsule. It was, also, noted that the factor for color of petiole was linked with the factor for shape of leaf with a 11.9587 percent recombination value, however no interaction or linkage were found among the color of stem and capsule color. Using Powers partitioning method, theoretical means and frequency distributions for each population, the days to flowering were calculated with the assumption that two gene pairs were involved. The values obtained fitted the theoretical values. In general this would indicate that Dashkent and G 38 F -1 were differentiated by two gene pairs. Heritability values were calculated as the percent of additive genetic variance. Heritability value of days to flowering, 89.5% in the broad sense and 79.91% in the narrow sense, indicated that the selection for this character would be effective in relatively early generations. Particularly, high positive correlations were found between days to flowering and the color of petioles and shape of leaves. However, there was no relation between days to flowering and capsule color nor between these and stem color. On the basis of the results of this experiment there is evidence that the hereditary factor for shape of leaves and the color of petioles is linked with an effective factor or factors for the characters of days to flowering. The association was sufficiently close to offer a possible simple and efficient means of selection for moderately early mat. uring plants by leaf shape and petiole color selection. Again using Powers partitioning method the frequency distribution for each population to the fiber weight were calculated with the assumption that two gene pairs, AaBb, were involved. Both phenotypic and genotypic dominance were complete. The obtained value did not agree with the theoretical value for $F_2$ and $BC_1$ ($F_1$ ${\times}$ Dashkent.) It seems that Dashkent and G 38 F-1 were differentiated by two major gene pairs but some the other minor genes are necessary. It is certain that the hereditary factor for shape of leaves and color of petioles is linked with an effective factor or factors for fiber weight. Also, high. yielding plants with moderately early maturity were found in the $F_2$ population. Thus, simultaneous selection for high-fiber yield and moderately early maturing plants should be possible in these populations. Phenotypic and genotypic correlation coefficients between fiber weight per plant and days to flowering, stem height and stem diameter were calculated. In general, genotypic correlations are higher than the phenotypic correlation. The highest correlation is found between stem height and fiber weight per plant (0.7852 in genotypic and 0.4103 in phenotypic) and between days to flowering and fiber weight per plant (0.7398 in genotypic and 0.3983 in phenotypic.) It was also expected that the selection of high stem height and moderately early maturing plants were given the efficient means of selection for high fiber weight.

• Journal of Wetlands Research
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• v.18 no.4
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• pp.474-480
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• 2016

In this study, formation background of biodiversity and its changes in the process of geologic history, and effects of climate change on biodiversity and human were discussed and the alternatives to reduce the effects of climate change were suggested. Biodiversity is 'the variety of life' and refers collectively to variation at all levels of biological organization. That is, biodiversity encompasses the genes, species and ecosystems and their interactions. It provides the basis for ecosystems and the services on which all people fundamentally depend. Nevertheless, today, biodiversity is increasingly threatened, usually as the result of human activity. Diverse organisms on earth, which are estimated as 10 to 30 million species, are the result of adaptation and evolution to various environments through long history of four billion years since the birth of life. Countlessly many organisms composing biodiversity have specific characteristics, respectively and are interrelated with each other through diverse relationship. Environment of the earth, on which we live, has also created for long years through extensive relationship and interaction of those organisms. We mankind also live through interrelationship with the other organisms as an organism. The man cannot lives without the other organisms around him. Even though so, human beings accelerate mean extinction rate about 1,000 times compared with that of the past for recent several years. We have to conserve biodiversity for plentiful life of our future generation and are responsible for sustainable use of biodiversity. Korea has achieved faster economic growth than any other countries in the world. On the other hand, Korea had hold originally rich biodiversity as it is not only a peninsula country stretched lengthily from north to south but also three sides are surrounded by sea. But they disappeared increasingly in the process of fast economic growth. Korean people have created specific Korean culture by coexistence with nature through a long history of agriculture, forestry, and fishery. But in recent years, the relationship between Korean and nature became far in the processes of introduction of western culture and development of science and technology and specific natural feature born from harmonious combination between nature and culture disappears more and more. Population of Korea is expected to be reduced as contrasted with world population growing continuously. At this time, we need to restore biodiversity damaged in the processes of rapid population growth and economic development in concert with recovery of natural ecosystem due to population decrease. There were grand extinction events of five times since the birth of life on the earth. Modern extinction is very rapid and human activity is major causal factor. In these respects, it is distinguished from the past one. Climate change is real. Biodiversity is very vulnerable to climate change. If organisms did not find a survival method such as 'adaptation through evolution', 'movement to the other place where they can exist', and so on in the changed environment, they would extinct. In this respect, if climate change is continued, biodiversity should be damaged greatly. Furthermore, climate change would also influence on human life and socio-economic environment through change of biodiversity. Therefore, we need to grasp the effects that climate change influences on biodiversity more actively and further to prepare the alternatives to reduce the damage. Change of phenology, change of distribution range including vegetation shift, disharmony of interaction among organisms, reduction of reproduction and growth rates due to odd food chain, degradation of coral reef, and so on are emerged as the effects of climate change on biodiversity. Expansion of infectious disease, reduction of food production, change of cultivation range of crops, change of fishing ground and time, and so on appear as the effects on human. To solve climate change problem, first of all, we need to mitigate climate change by reducing discharge of warming gases. But even though we now stop discharge of warming gases, climate change is expected to be continued for the time being. In this respect, preparing adaptive strategy of climate change can be more realistic. Continuous monitoring to observe the effects of climate change on biodiversity and establishment of monitoring system have to be preceded over all others. Insurance of diverse ecological spaces where biodiversity can establish, assisted migration, and establishment of horizontal network from south to north and vertical one from lowland to upland ecological networks could be recommended as the alternatives to aid adaptation of biodiversity to the changing climate.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.