• 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.

• Journal of Life Science
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• v.29 no.3
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• pp.354-361
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• 2019

The red pepper (Capsicum annuum L.) is one of the most important vegetables in traditional Korean food, containing vitamins A, C, and E, polyphenol, and flavonoids. In addition, red peppers have high anti-oxidant ability and are known to be effective in preventing obesity, diabetes, hypertension, digestive disorders, stress, and aging. In this study, we investigated the effects against obesity and diabetes of both fermented and non-fermented red pepper. C57BL/6N mice with induced obesity from an eight-week 45% high fat diet (HFD) were then fed either an HFD or diets containing 2.5% non-fermented red pepper marc (NRM), 1.25% fermented red pepper marc (FRM), or 2.5% FRM for a further eight weeks. An oral glucose tolerance test was performed seven weeks after dietary intake, and body weight, liver, epididymal fat weight, serum insulin level, and HOMA-IR were measured and a lipid content test performed at eight weeks. The results show that the 2.5% FRM diet reduced body and tissue weight, lipid content, serum insulin levels, and HOMA-IR compared to the 2.5% NRM and HFD diets. These results suggest that fermented red pepper is effective against obesity and diabetes. We will use this information as the basic data for the development of health food materials using red pepper.

• Journal of Life Science
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• v.21 no.8
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• pp.1163-1167
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• 2011

Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer's disease and Parkinson's disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.

• Clinical and Experimental Reproductive Medicine
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• v.16 no.2
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• pp.139-146
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• 1989

The purpose of this study was to examine the qualitative variation of human fetal-cord sera (HCS) and to accept the sera in human lVF-ET program. One hundred and sixteenth RCS were tested with 1772 2-cell embryos of F1 (C57BL x CBA) virgin mice, Ten to sixteenth embryos were cultured in m-KRB medium with a aliquot of each serum (10%, v/v) or with bovine serum albumin(O.4%, w/v) as a control medium. Embryonic development were recorded at every 24hr for 4 days by such events as cellular compaction, cavitation, and hatching. In the control groups of eight assays, 98.1%(106/ 108) of 2-ce1l embryos developed above expanded blastocyst and the embryonic development was unified through the tests. But the developmental pattern in medium with each serum was various. Namely, the sera that supported development of 100% 2-cell embryos to above morula, early blastocyst, expanded blastocyst and hatching blastocyst was 45,7%(53/116) , 35.3%(41/116), 15.5%08/116.) and 6.9-%(8/116), respectively. And the sera that supported development of above 80% 2-cell embryos to the each embryonic stage was 92.2% (107/116), 83.6%(97/116), 63.8%(74/116) and 36.2%(42/116), respectively. Meanwhile two kinds of toxic pattern to the embryonic development were observed in some sera. The first pattern is that some sera arrested development of most embryos in pre- or post-stage of morula or blastocyst. The second pattern is that some sera promoted or arrested a part of embryos in the same dish. The ability of serum was depended on the batch of serum. Finally we could accept 69%(80/116) of the tested sera for human IVF-ET program. The base line for acceptance was the ability that supported above 80% 2-ce1l embryos to blastocyst. But some deterious sera were contained in this range. We cut off about 10% of the sera (83.6% , 97/116) that passed the baseline. This final percent of sera was similar to that of grade N of this study.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.583-590
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• 2021

Background: Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca²⁺]_i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods: C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results: qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion: The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• Journal of Environmental Health Sciences
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• v.43 no.4
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Nutrition Research and Practice
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• v.4 no.1
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• pp.3-10
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• 2010

This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, tree radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3035-3042
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• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• Journal of Nutrition and Health
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• v.46 no.4
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• pp.307-314
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• 2013

Resveratrol (RSV) exerts several beneficial effects on metabolism and metaflammation-related diseases, including diabetes and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate whether RSV affects pathophysiology of diabetes and NAFLD as well as hepatic autophagy in a rodent model of diet induced obesity (DIO). DIO was induced in a subset of C57BL/6J mice fed a high fat (HF, 45% kcal fat) diet. After six weeks of HF diet treatment, RSV (8 mg/kg/day) was administered via an osmotic pump for a period of four weeks. Therefore, the experimental groups were as follows: 1) lean control (CON), 2) HF diet-induced obese control (HF), and 3) HF_RSV. Body weight and food intake were monitored daily. Fasting glucose, insulin, and adiponectin in serum and lipid profiles in serum and liver were analyzed. In addition, the autophagic process was investigated using transmission electron microscopy (TEM). Body weight and food intake were not affected by RSV treatment. Impaired glucose control accompanied by DIO was recovered with RSV as shown by lower levels of fasting serum glucose and insulin when compared with HF obese controls. In addition, RSV treatment resulted in increased levels of serum adiponectin, however, indices of lipid profile in serum and livers were reduced. Results of TEM analysis showed that a HF diet induced excessive autophagy with the presence of double-membrane autophagosomes, which was ameliorated by RSV. The regulatory effect of RSV on autophagy was confirmed by the altered LC3-II formation, which increased with a HF diet and was decreased by RSV treatment. These results suggest that RSV treatment improves glucose control and lipid profile and these beneficial effects may be mediated by an altered autophagic process.