• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.402-417
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• 2003

Purpose: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand the receptor mediated uptake into liver and subsequent metabolism of $^{111}In-labeled$ galactosylated MoAb-chelator conjugates were investigated and compared with those of $^{111}In$ labeled MoAb. Materials and Methods : T101 MoAb, $IgG_2$ against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-${\beta}$-D-galactose and then radiolabeled with $^{111}In$. Biodistribution and metabolism study was peformed with two $^{111}In-conjugates$ in mice and rats. Results: $^{111}In-labeled$ T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiornetabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free $^{111}In$ at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. in contrast to DTPA conjugate, the small $^{111}In-DTPA-like$ metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. Conclusion: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.

• Journal of Nutrition and Health
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• v.47 no.4
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• pp.221-228
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• 2014

Purpose: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. Methods: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. Results: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. Conclusion: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.51-57
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• 2006

Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

• Food Science and Preservation
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• v.18 no.6
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• pp.938-945
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• 2011

Epimedium koreanum Nakai is a wild herb commonly consumed in South Korea due to its beneficial health effects. In the present study, the antimutagenic and immunoactivities of extracts from E. koreanum Nakai containing different icariin quantities were investigated for food use. In the Ames test, both the water and ethanol extracts were found not to have a mutagenic effect on Salmonella typhimurium TA98 and TA100, respectively. The E. koreanum Nakai extracts showed over 80 and 90% antimutagenic effects on benzo(${\alpha}$)pyrene (B(a)P) in S. typhimurium TA98 and TA100, respectively. Moreover, all the extracts showed over 70% antimutagenicity on S. typhimurium TA98 and TA100 against 4-nitroquinoline-1-oxide (4NQO). The E. koreanum Nakai extract with ethanol showed strong antimutagenic activity, higher than that of the water extract and the sequenced KE9412, KE9408, and KE9405. In the immunomodulating activity test, the effect of E. koreanum Nakai on the B (Rhamos) and T (Jukat) cells were investigated. The immunoactivity results showed that the growth and viability of the B and T cells increased and were activated more in KE9405 (1.8 times), KE9408 (1.6 times), and KE9412 (1.32 times) in the water extracts, and least in KE9412 (1.74 times), KE9408 (1.52 times), and KE9405 (1.4 times) in the ethanol extracts. In the case of both the water and ethanol extracts ($500{\mu}g/mL$) from E. koreanum Nakai, the highest cell number of the human B (Rhamos) and T (Jukat) cells was observed on day 4 in KE9405 and KE9412, and on day 5 in KE9408. Based on the obtained results, the development of E. koreanum Nakai as a food material is recommended.

• Journal of Food Hygiene and Safety
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• v.38 no.6
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• pp.430-441
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• 2023

Velvet antler is widely used as a traditional medicine, and numerous studies have demonstrated its tremendous nutritional and medicinal values including immunity-enhancing effects. This study aimed to investigate different deer velvet extracts (Sample 1: raw extract, Sample 2: dried extract, and Sample 3: freeze-dried extract) for proximate composition, uronic acid, sulfated glycosaminoglycan, sialic acid, collagen levels, and chemical components using ultra-performance liquid chromatography-quadrupole-time-of-light mass spectrometry. In addition, we evaluated the cytotoxic effect of the deer velvet extracts on BV2 microglia, HT22 hippocampal cells, HaCaT keratinocytes, and RAW264.7 macrophages using the cell viability MTT assay. Furthermore, we evaluated acute toxicity of the deer velvet extracts at different doses (0, 500, 1000, and 2000 mg/kg) administered orally to both male and female ICR mice for 14 d (five mice per group). After treatment, we evaluated general toxicity, survival rate, body weight changes, mortality, clinical signs, and necropsy findings in the experimental mice based on OECD guidelines. The results suggested that in vitro treatment with the evaluated extracts had no cytotoxic effect in HaCaT keratinocytes cells, whereas Sample-2 had a cytotoxic effect at 500 and 1000 ㎍/mL on HT22 hippocampal cells and RAW264.7 macrophages. Sample 3 was also cytotoxic at concentrations of 500 and 1000 ㎍/mL to RAW264.7 and BV2 microglial cells. However, the mice treated in vivo with the velvet extracts at doses of 500-2000 mg/kg BW showed no clinical signs, mortality, or necropsy findings, indicating that the LD50 is higher than this dosage. These findings indicate that there were no toxicological abnormalities connected with the deer velvet extract treatment in mice. However, further human and animal studies are needed before sufficient safety information is available to justify its use in humans.

• The Korean Journal of Mycology
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• v.39 no.1
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• pp.57-67
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• 2011

Agaricus brasiliensis, one of edible mushroom belonging to Basidiomycota, has been used for curing gastric ulcer and stomach cancer of human beings and also known to have good inhibitory effects on sarcoma 180 and Ehrlich carcinoma of mice. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were prepared from fruiting body of the mushroom. ${\beta}$-glucan and total protein contents were identify from fractions of edible mushrooms extract. The ${\beta}$-glucan and protein contents of all fractions of the mushrooms ranged from 21.54~32.31% and 0.16~9.34%, respectively. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, NIH3T3 and RAW 264.7 at the concentration of 10~2000 ${\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of 18.8~50.6% in mice previously inoculated with Sarcoma 180. Fr. HW increased the numbers of spleen cell by 1.2 fold at the concentration of 200 ${\mu}g/ml$ compared with control. Fr. MeOH and Na improved the immuno-potentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by 1.6 fold compared with control at the concentration of 50~500 ${\mu}g/ml$. Fr. Na generated 15.9 ${\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7 at the concentration of 200 ${\mu}g/ml$, while lipopolysaccharide, a positive control, produced 3.7 ${\mu}M$. The Fr. NaCl, Fr. HW and Fr. MeOH increased the secretion of TNF-${\alpha}$, IL-$1{\beta}$, Il-2 and IL-6 by 2.2 times compared with the control group. Fr. Na increased the numbers of peritoneal exudate cells by 4 folds at the concentration of 50mg/kg compared with control. Circulating leukocytes increased by 2.7 folds when Fr. HW from A. brasiliensis was inoculated at the concentration of 50 mg/kg body weight. The hematological and blood chemical analysis of the 3 fractions did not show any difference in blood compositions and enzyme activities compared with the control group (p<0.05). Therefore, the experimental results suggested that crude polysaccharides extracted from A. brasiliensis contain antitumor and immuno-potentiating activities against Sarcoma 180 in ICR mice.

• Development and Reproduction
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• v.12 no.3
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• pp.289-296
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• 2008

BPES (Blepharophimosis/Ptosis/Epicanthus inversus Syndrome) is an autosomal dominant disorder caused by mutations in FOXL2. Affected individuals have premature ovarian failure (POF) in addition to small palpebral fissures, drooping eyelids, and broad nasal bridge. FOXL2 is a member of the forkhead family transcription factors. In FOXL2-deficient ovaries, granulosa cell differentiation dose not progress, leading to arrest of folliculogenesis and oocytes atresia. Using yeast two-hybrid screening of rat ovarian cDNA library with FOXL2 as bait, we found that small ubiquitin-related modifier (SUMO)-conjugating E2 enzyme UBE2I protein interacted with FOXL2 protein. UBE2I also known as UBC9 is an essential protein for processing SUMO modification. Sumoylation is a form of post-translational modification involved in diverse signaling pathways including the regulation of transcriptional activities of many transcriptional factors. In the present study, we confirmed the protein-protein interaction between FOXL2 and UBE2I in human cells, 293T, by in vivo immunoprecipitation. In addition, we generated truncated FOXL2 mutants and identified the region of FOXL2 required for its association with UBE2I using yeast-two hybrid system. Therefore, the identification of UBE2I as an interacting protein of FOXL2 further suggests a presence of novel regulatory mechanism of FOXL2 by sumoylation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.605-610
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• 2003

According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

• Journal of Life Science
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• v.16 no.6
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• pp.1052-1059
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• 2006

The heat shock response is induced by environmental stress, pathophysiological state and non-stress conditions and wide spread from bacteria to human. Although translations of most proteins are stopped under a heat shock response, heat shock proteins (HSPs) are produced to protect cell from stress. When heat shock response is induced, conformation of HSF1 was changed from monomer to trimer and HSF1 specifically binds to DNA, which was called a heat shock element(HSE) within the promoter of the heat shock genes. Human HSF1(hHSFl) contains five cysteine(Cys) residues. A thiol group(R-SH) of Cys is a strong nucleophile, the most readily oxidized and nitrosylated in amino acid chain. This consideration suggests that Cys residues may regulate the change of conformation and the activity of hHSF1 through a redox-dependent thiol/disulfide exchange reaction. We want to construct role of five Cys residues of hHSF by redox reagents. According to two studies, Cys residues are related to trimer formation of hHSF1. In this study, we want to demonstrate the correlation between structural change and DNA-binding activity of HSF1 through forming disulfide bond and trimerization. In this results, we could deduce that DNA binding activity of DNA binding domain wasn't affected by redox for always expose outside to easily bind to DNA. DNA binding activity of wild-type HSF's DNA binding domain was affected by conformational change, as conformational structure change (trimerization) caused DNA binding domain.

• Korean Journal of Animal Reproduction
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• v.22 no.4
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• pp.419-424
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• 1998

The present study was carried out to examine the efficiency of cloning of transgenic embryos by nuclear transfer(NT) using gene-injected rabbit embryos. The rabbit embryos at pronuclear stage were microinjected with methallothionein-human growth hormone(MT-hGH) gene and cultured to 8- and 16-cell in TCM-199 containing 10% FCS with a monolayer of rabbit oviductal epithelial cells in a 5% $CO_2$incubator. The recipient oocytes were collected from the oviducts 14~16 h after hCG injection. The oocytes were enucleated and activated with 5$\mu$M ionomycin and 2mM 6-dimethylaminopurine. Blastomeres form gene-injected embryos were transferred into the enucleated oocytes by micromanipulation. The nuclear transplant oocytes were electrofused and co-cultured with rabbit oviductal cells. Following 120 h of culture, blastocysts were prepared for gene analysis by polymerase chain reaction(PCR). In previous experiment, the rate of gene-positive embryos detected by the nested PCR analysis was significantly decreased while developing to blastocyst(25%)(Kang et al., 1998). The fusion rate of gene-injected blastomeres was significantly(P＜0.05) lower than non-injected blastomeres(66% vs 80%). However, the NT embryos that were derived from gene-injected donor embryos did not differ from control embryos in development to the blastocyst stage(39% vs 31%). Of the 43 NT blastocysts developed from the gene-injected donor embryos, twelve(28%) were positive for the injected DNA. The results indicate that NT with gene-injected embryos can be successfully used for cloning and multiplication of transgenic embryos, furthermore applicable to improvement of transgenic animal production.