• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권2호
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• pp.205-212
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• 2008

Genetic variation in the human genome occurs on various levels; from the single nucleotide polymorphism to large, microscopically visible chromosome anomalies. It can be present in many forms, including variable number of tandem repeat (VNTRs; e.g., mini- and microsatellites), presence/absence of transposable elements (e.g., Alu elements), single nucleotide polymorphisms, and structural alterations (e.g., copy number variation, segmental duplication, inversion, translocation). Until recently SNPs were thought to be the main source of genetic and phenotypic human variation. However, the use of methods such as array comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH) have revealed the presence of copy number variations(CNVs) ranging from kilobases (kb) to megabases (Mb) in the human genome. There is great interest in the possibility that CNVs playa role in the etiology of common disease such as HIV-1/AIDS, diabetes, autoimmune disease, heart disease and cancer. The discovery of widespread copy number variation in human provides insights into genetic variability among populations and provides a foundation for studies of the contribution of CNVs to evolution and disease.

• Development and Reproduction
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• 제13권4호
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• pp.297-303
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• 2009

Implantation of blastocyst into the uterine endometrium is established by the existence of histologically and functionally prepared uterine endometrium. Doc-1, an oral cancer suppressor gene, is expressed under the control of steroid hormones and has been suggested as a proliferation regulator of endometrial cells. However, the role is not much clear and in this study we examined the expression modulation of Doc-1 in decidualizing cells in vitro. In vitro decidualization was performed in endometrial stroma cells using progesterone and estrogen. Until 24 hr after decidual induction the proliferation of stroma cell was significantly increased but decreased after then. On the other hand, most of the cells differentiated into decidual cell after 48 hr of induction. The Doc-1 protein was co-localized in a specific deciudal cells and colocalization rate was increased in a parallel manner with the induction time. Based on these results, it is suggested that Doc-1 expression is under the control of both steroid hormones and decidual signals, and Doc-1 protein is involved in suppression of the proliferation of decidualizing cells.

• Clinical and Experimental Pediatrics
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• 제51권11호
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• pp.1211-1216
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• 2008

Purpose : Diamond-Blackfan anemia (DBA) is a rare heterogeneous genetic disorder of infancy and early childhood. It is characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer. Corticosteroids and red cell transfusions are the mainstays of therapy. We describe our experience of 6 cases of DBA that were encountered over a period of 16 years. Methods : Medical records of 6 patients diagnosed to have DBA and admitted to the Chonnam National University Hospital between 1992 and 2008 were retrospectively reviewed. Results : Three patients were males. The age at diagnosis ranged from 3 to 18 months (median, 5.5 months). Heart defects were observed in 4, polydactyly in 2, and strabismus in 1 patient. The median number of transfusions was 3 (range, 2-8). All patients responded to initial treatment with steroids and had a hemoglobin level ${\geq}9g/dL$ with a median of 12.5 days (range, 7-22 days). Three patients are currently not receiving steroid therapy. A minimum dose of oral prednisolone (<5 mg per day) was required to maintain hemoglobin ${\geq}9mg/dL$ in 3 cases. Red cell transfusion was infrequently required in 1 patient. In the median follow-up of 14 years, there was no development of malignancy. No significant side effects of steroids were found, except for short stature in 2. Conclusion : The majority of DBA patients achieved complete response and under maintenance therapy with low dose of steroids. Close observation is needed to monitor steroid side effects, cardiac function, and development of malignancy. A nation-wide survey is necessary to further characterize this rare disease in Korean children.

• Journal of Physiology & Pathology in Korean Medicine
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• 제23권3호
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• pp.685-694
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• 2009

This experimental study was designed to investigate the inhibitory effects of ethanol extract of modified Yukgunja-tang(mYGJT) on high-fat diet-induced obesity and hyperlipidemia in Sprague-Dawley rats, Animals were divided into normal, control, mYGJT(100 mg/kg and 200 mg/kg) treated groups. Obesity with hyperlipidemia was induced by high fat diet treatment for 6 weeks. mYGJT was given to the amimals by oral gavage for 4 weeks, starting at the high-fat diet regimen, The effect of mYGJT on the differentiation of 3T3 L1 adipocytes in vitro and serological paramamters for obesity and hyperlipidemia in vivo were evaluated, mYGJT significnatly inhibited the differentiation of 3T3 L1 adipocytes in a concentration dependent manner. mYGJT treatment siginficantly reduced body weight, abdominal and epididymal fat weight, and FER(Food Efficiency Ratio) compared with control group in a dose dependent manner. It also signficantly inhibited the levels of serum total lipid, triglyceride, phospholipid, total cholesterol, LDL, AI(Atherosclerosis Index) and returned the serum HDL to normal. Total lipids, triglycerides and cholesterols in the liver, as well as malondialdehyde(MDA) and hydroxy radical in the serum were significantly reduced. However, superoxide dismutase(SOD) activity was significantly increased in mYGJT treated group compared with control group. Finally, mYGJT treatment signficantly decreased the MDA and protein carbonyl concentrations of the hepatic homogenate but signficantly increased the activities of SOD, GSH-Px and Catalase. Taken together, these results suggest that mYGJT can be clinically useful in inhibiting high-fat diet-induced obesity and hyperlipidemia.

• Korean Journal of Veterinary Research
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• 제52권2호
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• pp.125-131
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• 2012

Rabbit hemorrhagic disease is a highly acute and fatal viral disease caused by rabbit hemorrhagic disease virus (RHDV). Since first outbreak in Korea 1987, RHDV has been continually affected in the country, but the pattern of outbreak seem to be changed. In this study, to understand the pathogenesis of the new RHDVa serotype, we therefore carried out to inoculate RHDVa to rabbits, and to examine the sequential histopathologic changes and viral distribution. Macroscopically, various sized dark red or white spots or appearance were observed in the liver, lung, kidney uterus and ureter. In euhanized rabbits, significant pathologic findings such as infiltration of heterophils and mononuclear cells were observed at 24 hours after inoculation (HAI), and these were sequentially extended periportal to centrilobular area. However, in dead rabbits, severe hepatic degeneration and/or necrosis with relatively weak inflammatory responses were observed. RHDV antigens began to detect in liver, spleen, and lung from 12 HAI by PCR. Immunohistochemically, RHDV positive cells were seen in only liver from 24 HAI, and the degree of immunogen reactivity was stronger in dead rabbits than in euthanized ones. In conclusion, RHDVa caused the subacute or chronic infection accompanying low mortality and moderate to severe inflammatory reaction in rabbits, suggesting the possibility that RHD could become endemic.

• Journal of Ginseng Research
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• 제11권2호
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• pp.145-252
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• 1987

Isolated rat adipocytes are well known to possess opposite pathways of lipid metabolism: lipolysis and ipogenesis. Both of the metabolism respond to various biologically active substances such as epinephrine, ACTH and insulin. Epinephrine and ACTH stimulate lipolysis and insulin accelerates lipogenesis. Recently, Korean red ginseng powder was found to contain adenosine and an acidic poptide which inhibited epinephrine-induced lipolysis and sl imulated insulin-mediated lipogenesis from added glucose. The acidic peptide is consisted mainly of glutamic acid and glucose. Ginsenosides Rb1 and Re inhibited ACTH-induced lipolysis in isolated rat adipocytes, while they did not affect insulinstimulated lipogenesis, Thus, all these substances extracted from Korean red ginseng exhibited selective modulations toward the opposite metabolic pathways in rat adipocyte; They inhibited the lipolysis but not the lipogenesis. We call these substances"selective modulators". Recently, we isolated a toxic substance named "toxohormone-L " from ascites fluid of patients with various malignant tumors. The toxohormone-L stimulated lipolysis in rat adipocytes and induced anorexia in rats. Both the lipolytic and the anorexigenic actions of toxohormone-L were found to be inhibited by ginsenoside Rb2 in Korean red ginseng. Based on these results, physiological signifi¬cances of these substances in Korean red ginseng were discussed. Pan ax ginseng is a medicinal plant long used in treatment of various pathological states including general complaints such as head ache, shoulder ache, chilly constitution and anorexia in cancer patients, There have been many pharmacological studies on Panax ginseng roots. Petkovllreported that oral administration of an aqueous alcoholic extract of ginseng roots decreased the blood sugar levtl of rabbits. Saito2lreported that Panax ginseng suppressed hyperglycemia induced by epinephrine and high carbohydrate diets. These findings suggest that Panax ginseng roots contain insulin-like substances. Previously, we demonstrated that gin¬seng roots contain an insulin-like peptide which inhibits epinephrine-induced lipolysis and stimulated insulin-mediated lipogenesis. In 1984, we suggested that such an insulin-like substance should be called a selective modulator4). Present investigation describes the details of the selective modulators in ginseng roots. During progressive weight loss in patients with various neoplastic disease, depletion of fat stores have been observed. The depletion of body fat during growth of neoplasms is associated with increase in plasma free fatty acids. Recently, we found that the ascites fluid from patients with hepatoma or ovarian tumor and the pleural fluid from patients with malignant lymphoma elicited fatty acid release in slices of rat adipose tissue in vitro. The lipolytic factor, named"toxohormone-L". was purifed from the ascites fluid of patients with hepatoma. The isolated preparation gave a single band on both disc gel electrophoresis and sodium dodecyl sulfate(SDS)-acrylamide gel electrophoresis in the presence of ${\beta}$-mercaptoethanol. Its molecular weight was determined to be 70,000-75,000 and 65,000 by SDS-acrylamide gel electrophoresis and analytical ultracentrifugation, respectively. Injection of toxohormone-L into the lateral ventricle of rats significantly suppressed food and water intakes. There was at least 5 hr delay between its injection and appearance of its suppressive effect. In the present study, we also tried to find a inhibitory substance toward toxohormone-L from root powder of ginseng.

• Journal of Physiology & Pathology in Korean Medicine
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• 제21권4호
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.

• Journal of Ginseng Research
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• 제39권1호
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• pp.29-37
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• 2015

Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• Journal of Life Science
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• 제19권8호
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• pp.1152-1158
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• 2009

For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.