• Journal of Radiation Industry
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• v.17 no.1
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• pp.83-92
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• 2023

When assessing the risk of radioactive wastes transportation on land, computer codes such as RADTRAN and RISKIND are used as deterministic methods. Transportation risk assessment using the deterministic method requires a relatively short assessment time. On the other hand, transportation risk assessment using the probabilistic method requires a relatively long assessment time, but produces more reliable results. Therefore, a study is needed to evaluate the exposure dose using a deterministic method that can be evaluated relatively quickly, and to compare and analyze the exposure dose result using a probabilistic method. The purpose of this study is to evaluate the exposure dose during transportation of radioactive wastes using deterministic and probabilistic methods, and to compare and analyze them. For this purpose, the main exposure factors were selected and various exposure situations were set. The distance between the radioactive waste and the receptor, the size of the package, and the speed of vehicle were selected as the main exposure factors. The exposure situation was largely divided into when the radioactive wastes were stationary and when they were passing. And the dose (rate) model of the deterministic overland transportation risk assessment computer code was analyzed. Finally, the deterministic method of the RADTRAN computer code and the RISKIND computer code and the probabilistic method of the MCNP 6 computer code were used to evaluate the exposure dose in various exposure situations during transportation of radioactive wastes. Then we compared and analyzed them. As a result of the evaluation, the tendency of the exposure dose (rate) was similar when the radioactive wastes were stationary and passing. For the same situation, the evaluation results of the RADTRAN computer code were generally more conservative than the results of the RISKIND computer code and the MCNP 6 computer code. The evaluation results of the RISKIND computer code and the MCNP 6 computer code were relatively similar. The results of this study are expected to be used as basic data for establishing the radioactive wastes transportation risk assessment system in Korea in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• The korean journal of orthodontics
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• v.33 no.6 s.101
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• pp.485-497
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• 2003

The form and function of the craniofacial structure critically depend on genetic information. With recent advances in the molecular technology, genes that are important for normal growth and morphogenesis of the craniofacial skeleton are being rapidly uncovered, shaping up modem craniofacial biology. One of them is fibroblast growth factor receptor 2 (FGFR2). Specific point mutations in the. FGFR2 gene have been linked to Apert syndrome, which is characterized by premature closure of cranial sutures and craniofacial anomalies as well as limb deformities. To study pathogenic mechanisms underlying craniosynostosis phenotype of Apert syndrome, we used a transgenic approach; an FGFR2 minigene construct containing an Apert mutation (a point mutation that substitute proline at the position 253 to arginine; P253R) was introduced into fertilized mouse germ cells by DNA microinjection. The injected cells were then allowed to develop into transgenic mice. We used a bone-specific promoter (a DNA fragment from the type I collagen gene) to confine the expression of mutant FGFR2 gene to the bone tissue, and asked whether expression of mutant FGFR2 in bone is sufficient to cause the craniosynostosis phenotype in mice. Initial characterization of these mice shows prematurely closed cranial sutures with facial deformities expected from Apert patients. We also demonstrate that the transgene produces mutant FGFR2 protein with increased functional activities. Having this useful mouse model, we now can ask questions regarding the role of FGFR2 in normal and abnormal development of cranial bones and sutures.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.78-88
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• 2005

Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.

• Development and Reproduction
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• v.11 no.1
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• pp.49-54
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• 2007

Ethane 1,2-dimethane sulfonate(EDS), a toxin which specifically kills Leydig cells(LC), has been widely used to prepare the reversible testosterone(T) depletion rat model. In the present study, we monitored the gene expression profiles of pituitary gonadotropins, LH and FSH, up to 7 weeks after EDS injection. Adult male Sprague-Dawley rats($300{\sim}350\;g$ B.W.) were injected with a single dose of EDS(75 mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Total RNAs were purified from each pituitary, and the message levels of common alpha subunit($C{\alpha}$) of pituitary glycoprotein hormones, LH beta subunit($LH{\beta}$), FSH beta subunit($FSH{\beta}$) and GnRH receptor(GnRH-R) were evaluated by semi-quantitative RT-PCRs. The message levels of $C{\alpha}$ increased sharply during weeks 1-4, then return to the control level on week 5. The mRNA levels of $LH{\beta}$ were elevated after week 2, reached the peak at week 4, then declined to the control level after week 5. The message levels of $FSH{\beta}$ were elevated after week 2, reached the peak at week 3, then declined to the nadir at week 5. Similarly, the mRNA levels of GnRH-R were elevated after week 2, reached the peak at week 3, then gradually declined to the control level after week 5. The present study indicated that EDS treatment could induce reversible alterations in the transcriptional activities of gonadotropin subunits and GnRH-R in the anterior pituitary from male rats. EDS injection model might be useful to understand the mechanism of hormonal regulation of hypothalamus- pituitary neuroendocrine axis in male rats.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Food Science of Animal Resources
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• v.33 no.3
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• pp.411-416
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• 2013

This study aimed to examine the mechanisms underlying the effects of Garcinia cambogia extract on the adipogenic differentiation of 3T3-L1 cells and long-chain saturated fatty acid-induced lipotoxicity of HepG2 cells. 3T3-L1 preadipocytes, mouse embryonic fibroblast-adipose like cell line, were treated with MDI solution (0.5 mM IBMX, 1 ${\mu}M$ dexamethasone, 10 ${\mu}g/mL$ insulin) to generate a cellular model of adipocyte differentiation. Using this cellular model, the anti-obesity effect of Garcinia cambogia extract was evaluated. MDI-induced lipid accumulation and expression of adipogenesis-related genes were detected by Oil red O staining, Nile Red staining, and Western blot analysis. Effects Garcinia cambogia extract on palmitate-induced lipotoxicity was also analyzed by MTT assay, LDH release, and DAPI staining in HepG2 cells. Garcinia cambogia extract significantly suppressed the adipogenic differentiation of preadipocytes and intracellular lipid accumulation in the differentiating adipocytes. Garcinia cambogia extract also markedly inhibited the expression of peroxisome proliferator- activated receptor ${\gamma}2$ ($PPAR{\gamma}2$), CCAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), and adipocyte protein aP2 (aP2). In addition, Garcinia cambogia extract significantly attenuated palmitate-induced lipotoxicity in HepG2 cells. Palmitateinduced cellular damage and reactive aldehydes were also significantly reduced in the presence of Garcinia cambogia extract. These findings suggest that the Garcinia cambogia extract inhibits the adipogenic differentiation of 3T3-L1 preadipocytes, probably by regulating the expression of multiple genes associated with adipogenesis such as $PPAR{\gamma}2$, $C/EBP{\alpha}$, aP2, and thereby modulating fatty acid-induced lipotoxicity to reduce cellular injury in hepatocytes.

• Journal of Life Science
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• v.29 no.6
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

• Journal of Life Science
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• v.29 no.1
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• pp.9-17
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• 2019

As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.