• Clinical Nutrition Research
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• v.12 no.2
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• pp.154-167
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• 2023

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.1
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• pp.18-24
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• 2017

Patient-specific image-based internal dosimetry involves using the patient's individual anatomy and spatial distribution of radioactivity over time to obtain an absorbed dose calculation. Individual absorbed dose was calculated by accumulated activity multiply S-value of each organs. The aim of this study was to calculate the S-values using Monte Carlo simulation in monkey and mouse and evaluation of absorbed dose in each organ. Self-irradiation S-value of monkey heart self-irradiation was 3.15E-03 mGy-g/MBq-s, lung self-irradiation was 8.94E-04 mGy-g/MBq-s and liver self-irradiation S-value was 2.23E-03 mGy-g/MBq-s. Mouse heart self-irradiation S-value was 1.95E-01 mGy-g/MBq-s, lung was 9.59E-02 mGy-g/MBq-s, and liver was 1.40E-03 mGy-g/MBq-s. The results of this study show that the calculation protocol of image based individual absorbed dose of each organ using Monte Carlo simulation. Therefore, this study may be applied to calculate human specific absorbed dose.

• Biomedical Science Letters
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• v.8 no.3
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• pp.179-184
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• 2002

We investigated the morphological changes and TUNEL reaction of apoptotic cells in the liver of D-galactosamine (20 mg/mouse) and lipopolysaccharide (5 $\mu\textrm{g}$/mouse)-treated 30 mice (BALB/c), and in additioa also of apoptotic cells in kidney and spleen. The livers and other some organs of mice at 6, 12, 24, 48 and 72 hrs after treatment were collected and were fixed with 10% neutral formalin and paraffin sections were stained with hematoxylin-eosin or terminal deoxynucleotidly transferase-mediated dUTP nick end labeling (TUNEL) method. Morphological changes in apoptotic hepatocytes were chondensation of nuclei and density of cytoplasms, then the margination and pyknosis of chromatin, the formation of half-moon- or horse-shoe- or ship-like shapes of condensed chromatin mass, lastly formation of apoptotic bodies, disappearance of nuclear envelopes, decrease of stainability, then lysis and disappearance of apoptotic bodies. TUNEL positive reactions of hepatocytes were appeared first moderate in uncondensed hepatocytes, severe in condensed hepatocytes, moderate in chromatin-marginated hepatocytes. These reactions also were appeared moderate in hepatocytes with half-moon- or horse-shoe- or ship-like pyknotic chromatin mass or apoptotic bodies, and mild or negative in hepatocytes with lysed apoptotic bodies or with disappeared nuclear envelopes. Consequently these results suggested that TUNEL positive reactions of hepatocytes appeared at more early stages than appearance of chromatin condensation and disappeared at more early stage than disappearance of histological findings of apoptosis. We also confirmed that the differentiation of apoptotic cells from normal healthy cells of Kupffer cells and vascular endothelial cells in liver, reticular cells and lymphocytes in spleen and epithelial cells of tubules and ducts in kidney was impossible in H-E preparations but was possible in TUNEL preparations.

• Herbal Formula Science
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• v.17 no.2
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• pp.73-83
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• 2009

Objective : In vitro proapoptotic effect of Hangbaek-Tang (HBT) has been documented by one of us. In the present study, we aimed to demonstrate in vivo effect of HBT on tumor growth. Methods : In vitro selective cytotoxicity of HBT was examined by enumeration of viable cell numbers using BC3A mouse leukemic cells and normal spleen cells. In vivo effect of HBT (25 and 50 mg/mouse) on tumor growth was assayed using BC3A cells innoculated subcutaneously in the flank. Annexin-V apoptosis assay and PI staining was performed to determine the effective serum factor in HBT-treated mice. Leukocyte recruitment into peritoneum were analyzed by microscopy with a stained cytosmear of peritoneal lavage fluid. Results : HBT exhibited in vitro selective cytotoxicity to leukemic cells and did not show any toxicity on immune organs. In vivo i.p. administration of HBT induced significant reduction in tumor growth but not complete regression. Sera obtained from HBT-treated mice strongly inhibited BC3A cell growth in vitro and were revealed to markedly enhance apoptosis and accompanying cell death, when compared to those from PBS-treated mice. Abundant extravasation of leukocytes, especially neutrophils, into peritoneum was observed in HBT-treated mice. Conclusions : HBT causes leukemic, BC3A cell death in vivo via apoptosis as well as in vitro, for which functional involvement of leukocytes is suggested.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1585-1593
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• 2005

The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-tang on the stress were studied with cDNA microarray analyses, RT-PCR on hypothalamus using an immobilization-stress mice as an animal model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hrs once a day, and this challenge was repeated for seven· consecutive days. In the change of body weight it showed that the Boshimgeonbi-tang is effected recovery on weight loss caused by the immobilization-stress. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with $CyDye^{TM}$ fluorescence dyes and then hybridized to CDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix4000 series scanner and GenePix $Pro^{TM}$ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis-, stress protein, transcriptional factor, and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosysthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 5.5 fold. The 11 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Ogg1 (DNA repair), Aatk (apoptosis), Dffa (apoptosis), Fkbp5 (protein folding) were restored to the normal one by the treatment of Boshimgeonbi-tang.

• Journal of Oral Medicine and Pain
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• v.45 no.4
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• pp.89-96
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• 2020

Purpose: To investigate the expression of malondialdehyde (MDA), lipid peroxidation marker for oxidative stress (OS), in autoimmune Sjögren's syndrome (SjS) by utilizing the SjS-prone C57BL/6.NOD-Aec1Aec2 (B6DC) mouse and the SjS patient plasma samples. Methods: The MDA concentrations in the lysates of the submandibular gland, liver, and serum samples from the SjS-prone B6DC mouse model were compared with those from the C57BL/6J as a control. A thiobarbituric acid reactive substance (TBARS) assay kit was used to measure MDA. Plasma samples from five SjS patients and five control subjects were also evaluated. Results: The MDA concentrations in experimental animals and controls were not significantly different. There were no significant differences between the plasma of SjS patients and of controls. Conclusions: The expression of MDA was investigated in the organs from the SjS-prone B6DC mouse for the first time and in the plasma samples of SjS patients. No significant differences were observed between SjS and control samples when MDA was the target molecule with the TBARS assay. MDA may not be a reliable marker to measure OS contrary to the published studies involving OS of SjS.

• Pediatric Infection and Vaccine
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• v.24 no.2
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• pp.102-107
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• 2017

Purpose: Coronary arterial lesions (CALs) were reported to have developed in children with systemic inflammatory diseases, as well as those with Kawasaki disease (KD). The purpose of this study was to confirm that the CAL development in children with KD occurs in a mouse model of sepsis presenting typical systemic inflammatory response syndrome (SIRS). Methods: To induce the sepsis mouse model with SIRS, 6-week-old C57BL/6 mice were intraperitoneally injected with endotoxin. We compared histological findings of the major organs between the control and the sepsis groups and examined CAL in the heart of the septic mice. Results: Infiltrating inflammatory cells were relatively increased in the heart, liver, and kidneys of the sepsis group, compared with those of the control group. We confirmed lymphocytic infiltration in the myocardium (myocarditis) and the pericardial soft tissue of the heart. Furthermore, coronary artery of the septic mouse was identified, but CAL was not observed. Conclusions: In this study, we failed to confirm the existence of CAL in a mouse model of sepsis. However, it is well-known that CALs are seen in many kinds of diseases that cause SIRS. Our findings suggest further investigation into the clinical significance of CAL in various systemic inflammatory diseases, including KD.

• Journal of Photoscience
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• v.9 no.2
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• pp.415-417
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• 2002

Juvenile visceral steatosis (JVS) mouse is an animal model of the systemic camitine deficiency. JVS mice first develop fatty liver following cardiac hypertrophy. hyperammonemia, etc. To clarify the relationship between fatty liver and other symptoms. lipid hydroperoxides levels of peripheral oragans in JVS mice at 1 month were determined by the use of phosphine derivatives. We also report here a new method to quantitate the lipid components level in fatty liver of JVS mice.

• Proceedings of the Korean Society of Toxicology Conference
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• 1997.05a
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• pp.20-27
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• 1997

Chinin is the second most plentiful natural polymer. Currently, chitin and chitosan are manufactured commercially in large scale from crab and shrimp shell as fish processing waste. They is being used in many commercial application because of their various functional properties. Chitosan, in particular, is being evaluated as biomedical materials in a number of food and pharmaceutical industries. Despite their potential abilities, the perfect safety had been demonstrated until now. However, the long-term feeding with chitin was not any negative effect the body weights and serum enzymatic activities in mice. And, in rats supplied with $5\%$ of chitosan diet for 450 days, there was no changes of Ca concentration in blood, bone and other organs except for in muscle. Consequently, there was no direct toxicity of chitin and chitosan against some animals such as rat and mouse by recently reports.

• Biomolecules & Therapeutics
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• v.10 no.2
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• pp.89-98
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• 2002

In this study general pharmacological profiles of KI-60606 on the central nervous system, the cardiovascular system and the other organs were investigated. The dosages given were 0,5, 10 and 25 mg/kg and drugs were administered intravenously. The animals used for this study were mice, rats, cats and guinea pigs. KI-60606 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital-induced hypnosis time, body temperature, analgesic activity, anticonvulsant activity and contraction of nictitating membrane in cats. Furthermore KI-60606 showed no effects on blood pressure, heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP(double product), CFR(coronary flow rate), smooth muscle contraction using guinea pig ileum and gastric secretion at all dosage tested except the increase of gastrointestinal transport and urinary $K^+$ excretion.