• Journal of Food Hygiene and Safety
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• v.26 no.1
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• pp.49-56
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• 2011

To investigate the toxicological effects of ${\beta}$-glucan, we performed basic studying on ${\beta}$-glucan in Sprague-Dawley (SD) rats. Standard endpoints in this study included mortality, clinical observations, changes of body weights, analysis on food consumption, ophthalmoscopic examination, hematologic examination, serum biochemistry, analysis of organ weights, gross anatomic pathology and histopathology. No clinical signs and mortality were observed in animals treated with beta-glucan throughout the experimental period. The average body weight of each treatment groups showed similar levels at end of experiment. There were no treatment-related changes in mortality, body weights changes, food consumption, ophthalmoscopic examination. Although there were statistically significant differences between the control and treated groups in some relative and absolute organ weights, and hematological and biochemical analysis, the data were in biologically normal ranges and did not show a dose-dependent manner. In the morphological change, hepatic tissue were not showed ballooning degeneration and irregular arrangement of hepatic cell in ${\beta}$-glucan treatment groups with control group. Also, organs weights (liver, heart, kidney and stomach) and hematological indices (WBC, RBC, Hb, Hct and Platelet) did not show statistically significant differences among the experimental groups. In summary of these results, there were no changes in mortality, mean body weight, clinical signs, food consumption. There were no changes in ophthalmological examination, hematology, blood chemistry, necropsy and histopathology. In conclusion, although further investigation of glucan should be performed in the functions registered in many ancient literatures, ${\beta}$-glucan is physiologically safe and may have potential as candidate food for human health.

• Journal of Yeungnam Medical Science
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• v.17 no.2
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• pp.137-145
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• 2000

Background: Hepatocellular carcinomal(HCC) has been considered to be relatively radioresistant. The role of radiotherapy(RT) in the treatment of HCC is controversial. But RT has a role in the treatment of hepatocellular carcinoma as a single or combination modalities. The effect of radiotherapy on HCC was evaluated. Patients and Methods: From January 1984 through January 2000, a total of 18 patients with unresectable HCC underwent radiotherapy alone or in conjunction with transarterial embolization(TAE). We reviewed the medical ecords of patients treated with RT and measured the tumor size using measured the tumor size using planimetry method. The Kaplan-Meier method was used to calculate the survival rate. Results: The RT patients were 15 men and 3 women. The mean age was 51 years. four(22.2%) of them were accompanied with ascites. Eleven(61.1%) of them were accompanied with liver cirrhosis and their functions were 6, 3, 2 in each Child-Pugh A, B, C, respectively. A partial response(PR) was observed in 2 patients(11.1%), minimal response(MR) in 4 patients (22.2%) and no change(NC), in 11 patients(61.1%), whereas progressive disease(PD) was seen in 1 patients(6%), respectively. Conclusions: Although the radiotherapy in HCC did not improve the survival rate. it decreased the tmor size. Radiotherapy strengthens the therapeutic efficacy when combined with TAE, but more studies are needed.

• Journal of Life Science
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• v.21 no.11
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• pp.1625-1630
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• 2011

Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate cellular functions such as cell proliferation, inflammation, and apoptosis. In this study, we investigated the role of NADPH oxidase on the expression of HO-1 in human liver hepatoma cell line HepG2. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, markedly inhibited HO-1 expression and the nuclear translocation of transcription factor Nrf2 in cobalt protoporphyrin (CoPP) or hemin-treated HepG2 cells. Similarly, the knockdown of $p47^{phox}$, a cytosolic factor for NADPH oxidase activity, by siRNA inhibited the CoPP-induced expression of HO-1. In addition, GSHmee, an intracellular antioxidant, blocked the expression of HO-1 in CoPP-treated cells. Based on these results, we conclude that the blockage of NADPH oxidase with DPI or $p47^{phox}$ siRNA inhibits CoPP-induced HO-1 expression in HepG2 cells, and also suggest that the expression of HO-1 in CoPP-induced HepG2 cells is associated with increase of intracellular ROS by NADPH oxidase activity.

• Journal of the Korean Chemical Society
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• v.39 no.1
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• pp.66-70
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• 1995

The soil humic acid was subdivided into four subfractions by molecular weight (F1: >100.000 dalton; F2: >100.000 dalton; F3: >10.000 dalton; F4: >2.000 dalton) using MP-dual hollow fiber ultrafiltration system. The characterization using IR, 1H and 13C NMR spectroscopy, showed similar spectroscopic features of HA, demonstrating that the bulk properties of HA subfractions are very similar to one another. IR spectral data showed a decrease in polysaccharide contents and increase in carboxylate functionality as molecular weight become smaller.functions. The structure of (NO) can be described by two interactions (N${\cdot}{\cdot}{\cdot}$N, N${\cdot}{\cdot}{\cdot}$O). One is the ONNO structure with an (N${\cdot}{\cdot}{\cdot}$N) interaction. In this structure, acyclic cis-ONNO with $C_{2v}$-symmetry, acyclic trans-ONNO with $C_{2h}$, and cyclic ONNO with trapezoidal structure ($C_{2v}$) are optimized at the MP2 level. The other structure is the ONON structure with an (N${\cdot}{\cdot}{\cdot}$O) interaction. In the structure, acyclic cis-ONON with Cs$^{-symmetry}$ and cyclic ONON of the rectangular ($C_{2h}$), square $(D_{2h})$, rhombic $(D_{2h})$, and parallelogramic $(D_{2h})$ geometries are also optimized. It is found that acyclic cis-ONNO $(^1A_1$) is the most stable structure and cyclic ONNO ($^3A_1$) is the least stable. Acyclic trans-ONNO ($^3A_1$) with an (N${\cdot}{\cdot}{\cdot}$N) interaction, acyclic trans-ONON and bicyclic ONON $(C_{2v})$ with (N${\cdot}{\cdot}{\cdot}$O) interaction, and acyclic cis- and trans-NOON with an (O${\cdot}{\cdot}{\cdot}$O) interaction can not be optimized at the MP2 level. Particularly, acyclic trans-ONNO with $C_{2h}$-symmetry can not be optimized at the CCSD(T) level. Meanwhile, acyclic NNOO ($^1A_1$, $C_s)$ and trianglic NNOO ($^1A_1$,$C_{2v})$ formed by the (O${\cdot}{\cdot}{\cdot}$N) interaction between $O_2$and $N_2$are optimized at the MP2 level. The binding energies and the relative energy gaps among the isomers are found to be relatively small./sec. Spiral CT scans during the arterial phase were obtained 35 seconds after the injection of contrast medium. CT findings of 78 lesions less than 4cm in diameter were correlated with angiographic findings. Results : The attenuation of lesions was high(n = 69), iso(n = 5), and low(n = 4) compared with liver parenchyma during the arterial phase of spiral CT. In lesions with high-, iso-, and low-attenuation during the arterial phase of spiral CT, hypervascularity on angiograms was found in 63 of 69(91.3%), three of five(60%), and three of four lesions(75%), respectively. Six lesions with high-attenuation on the arterial phase of spiral CT were not seen on angiography. Two iso-attenuated and one low-attenuated lesion were hypovascular on angiograms. Conclusion : The results of this study suggest that with some exceptions there was good correlation between the arterial phase of spiral CT and angiography.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.8
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• pp.1164-1168
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• 2005

Korean traditional deer decoction (Nogjungtang), composed of oriental herbs and almost deer parts, has been used as an important resource for human health. For basic studying on Nogjungtang, this experiment was conducted to evaluate nutritional effects of Nogjungtang, and estimate its effect on growth, food efficiency, organ development and hematological indices in growing and adult Sprague-Dawley rats. The rats were divided into three groups as follows; control: non-supplementation, Notiungtang I: recommended dose, and Nogjungtang II: thrice recommended dose. Nogjungtang was composed of various general nutrients with up 93$\%$ moisture.Crude protein is the highest value as 22.78$ \%$, Mg is a major mineral as 0.48$\%$ compared to other minerals, and methionine and proline are higher by 1.31 and 1.67$\%$ than other amino acids based on dry matter, re-spectively. In both growing and adult rats, there were no significant difference in body weight gain and feed intake between the control and Nogjungtang groups. Also, organs weights (liver, heart, kidney and stomach) and hematological indices (WBC, RBC, Hb, Hct and Platelet) did not show statistically significant differences among the experimental groups. However, all of experimental rats were normal growth without hypertrophy or negative development of organs by Nogjungtang. Hematological indices maintained in normal value by thrice recommended dose of Nogjungtang. The average body weight of each treatment groups showed similar levels at end of experiment. In case of the feed efficiency ratio (feed intake/body gain), the growing rats showed 6.00, 5.81 and 5.99 and adult rats showed 9.03, 8.98 and 9.10 in control, Nogjungtang I and Nogjungtang II, respectively. In conclusion, although further investigation of Nogjungtang should be performed in the functions registered in many ancient literatures, Nogjungtang is physiologically safe and may have potential as candidate food for human health.

• Journal of Life Science
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• v.24 no.6
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• pp.686-693
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• 2014

Restricted supply of nutrients may affect genes at the molecular level as well as physiological functions. Understanding the cellular responses during starvation is necessary for developing strategies to reduce damage caused by starvation stress. After 1 h of starvation, Got1 gene expression was increased but its expression returned to the normal state after 24 h. Mat1 gene expression continuously increased with starvation from 1 h until 24 hr. Rats starved for 1-3 days showed significant changes in expression of the Got1 and Mat1 genes, which were significantly reduced in the cerebral cortex and cerebellum. In the lung, gene expression was increased by starvation for 1-2 days but decreased on the third day. No differences were observed in gene expression in the heart. Strong Got1 lung gene expression was seen in the starvation group one day after restoration of the food supply. Muscle mass was significantly reduced at the start of starvation and remained the same after two days of starvation and one day after the food supply was restored. The Mat1 gene expression did not change. The Got1 was induced by NaCl and showed strong expression in the lung and the thymus, but the apparent decrease of the remaining changes were not observed in male rats. The Mat1 gene was not as sensitive as the Got1 gene to induction by NaCl. However, differences in gene induction by NaCl were evident between males and females, indicating that diet control of gene expression is associated with hormones.

• Journal of Life Science
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• v.26 no.7
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• pp.764-771
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• 2016

Extracts from Artemisia annua Linné (AAE) have been known to possess various functions, including anti-bacterial, anti-virus, and anti-oxidant effects. However, the mechanism of those effects of AAE is not well-known. The aim of this study was to analyze the inhibitory effects of AAE on cell proliferation of the human hepatoma cell line (Hep3B) and to examine its effects on apoptosis. Activation by phosphorylation of Akt is cell proliferation through the phosphorylation of TSC2, mTOR, and GSK-3β. We suggested that AAE may exert cancer cell apoptosis through Akt/mTOR/GSK-3β signal pathways and mitochondria-mediated apoptotic proteins. For this, we examined the effects of extracts of AAE on cell proliferation according to treatment concentration. Treatment with AAE not only reduced cell viability, but also resulted in the induced release of lactate dehydrogenase (LDH). These results were determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay. Furthermore, we determined the effects of apoptosis through Hoechst 33342 staining, annexinⅤ-propidium iodide (PI) staining, 5,5′, 6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining, and Western blotting. Our study showed that the treatment of liver cancer cells with AAE resulted in the inhibition of Akt, TSC2, GSK-3β-phosphorylated, Bcl-2, and pro-caspase 3 and the activation of Bim, Bax, Bak, and cleaved PARP expressions. These results indicate that AAE induced apoptosis by means of a mitochondrial event through the regulate of Akt/mTOR/GSK-3β signaling pathways.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.99-116
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• 2016

We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.