• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.26-35
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• 2006

Background: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-${\kappa}B$ and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. Materials and Methods: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-${\kappa}B$ $cis$-elements. C57BL/6 NF-${\kappa}B^{EGFP}$ mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-${\kappa}B$ activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. Results: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-${\kappa}B$ activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. Conclusions: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.

• Journal of Life Science
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• v.32 no.7
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• pp.532-541
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• 2022

Obesity induced by high-fat diet (HFD) is verified as a strong risk factor and negative prognostic factor for prostate cancer in several genetically engineered mice although it was not examined in the normal mice. To investigate whether HFD-induced obesity can affect the development and progression of cancer in the prostate of normal mice, alterations in the weight and histological structure of the prostate as well as the expression of cancer-related proteins were analyzed in obese C57BL/6N mice fed with 60% HFD for 16 weeks. First, HFD-induced obesity, including an increase in organ weight, body weight, fat accumulation, and serum lipid profile, was successfully induced in C57BL/6N mice after HFD treatment. The total weight of the prostate significantly increased HFD-induced obesity in the model mice compared with the control group. Among the four lobes of the prostate, the weight of the ventral prostate (VP) and anterior prostate (AP) were higher in HFD-induced obesity model mice than in the control group, although the weights of the lateral prostate (DLP) and seminal vesicle (SV) were constantly maintained. In addition, the incidences of hyperplasia and non-hodgkin's lymphoma (NHL) in the histological structure were remarkably increased in HFD-induced obesity model mice, while the epithelial thickness was higher in the same group. A significant increase in the phosphorylation levels of key proteins in the AKT (protein kinase B) signaling pathway was detected in HFD-induced obesity model mice. Therefore, these results suggest that HFD-induced obesity can promote hyperplasia and NHL in the prostates of C57BL/6N mice through the activation of the AKT signaling pathway.

• Journal of Life Science
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• v.33 no.3
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• pp.242-251
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• 2023

The purpose of this study was to investigate the effects of 8-week β-hydroxybutyrate (β-HB) administration with and without endurance exercise training on endurance exercise performance and skeletal muscle protein synthesis and degradation using a mouse model. Forty-eight male wild-type ICR mice (8 weeks old) were randomly divided into four groups: sedentary control (Sed+Con), (Sed+Con), sedentary β-HB (Sed+β-HB), exercise control (Exe+Con), and exercise β-HB (Exe+β-HB). β-HB was dissolved in PBS (150 mg/ml) and injected subcutaneously daily (250 mg/kg) for 8 weeks. Mice performed 5 days/week of a 20 min treadmill running exercise for 8 weeks. The running exercise was carried out at a speed of 10 m/min at a 10° incline for 5 min, and then the speed was increased by 1 m/min for every 1 min of the remaining 15 min. Following 8 weeks of treatments, visceral fat mass and skeletal muscle mass, blood parameters, and the markers for autophagy and protein synthesis were analyzed. The data were analyzed with one-way ANOVA (p<0.05) using the SPSS 21 program. Eight weeks of Exe+β-HB treatment significantly lowered blood lactate levels compared with the other three groups (Sed+Con, Sed+β-HB, and Exe+β-HB) Exe+β-HB) (p<0.05). Eight weeks of Exe+β-HB significantly increased maximal running time (time to exhaustion) compared with the Sed+Con and Exe+Con groups (p<0.05). Eight weeks of β-HB administration significantly decreased autophagy flux and autophagy-related proteins in the skeletal muscle of mice (p<0.05). Conversely, the combined treatment of β-HB and endurance exercise training increased protein synthesis (mTOR signaling and translation) (p<0.05). The 8-week β-HB treatment and endurance exercise training had synergistic effects on the increase in endurance performance, increase in protein synthesis, and decrease in protein degradation in the skeletal muscle of mice.

• Proceedings of the Korean Society of Tobacco Science Conference
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• 1997.10a
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• pp.134-152
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• 1997

Plant viruses of tobacco including tobacco mosaic virus (TMV) and potato virus Y (PVY) cause severe economic losses in leaf-tobacco production. Cultural practices do not provide sufficient control against the viruses. Use of valuable resistant cultivars is most recommendable for the control of the viruses. However, conventional breeding programs are not always proper for the development of virus-resistant plants mostly owing to the frequent lack of genetic sources and introduction of their unwanted properties. Therefore, we tried to develop virus-resistant tobacco plants by transforming commercial tobacco cultivars, NC 82 and Burley 21, with coat protein (CP) or replicase (Nlb) genes of TMV and PVY necrosis strain (PVY-VN) with or without untranslated region (UTR) and with or without mutation. Each cDNA was cloned and inserted in plant expression vectors with 1 or 2 CaMV 35S promotors, and introduced into tobacco leaf tissues by Agrobacterium tumefaciens LBA 4404. Plants were regenerated in kanamycin-containing MS media. Regenerated plants were tested for resistance to TMV and PVY In these studies, we could obtain a TMV-resistant transgenic line transformed with TMV CP and 6 genetic lines with PVY-VN cDNAs out of 8 CP and replicase genes. In this presentation, resistance rates, verification of gene introduction in resistant plants, stability of resistance through generations, characteristics of viral multiplication and translocation in resistant plants, and resistance responses relative to inoculum potential and to various PVY strains will be shown. Yield and quality of leaf tobacco of a promising resistant tobacco line will be presented.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.416-423
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• 2023

Figs has known to have antioxidant, whitening, anti-inflammatory, and antibacterial effects in their leaves, roots, stems, latex, and fruits. In order to develop cosmetic materials based on natural products, we have studied on the skin activity of the ficin in latex as well as the whitening function of the fruit extract with 70% ethanol, and used it as a raw material for released cosmetic product. However, there is little research on the demand for the development of new eutectic solvent extraction methods and its ability to control skin inflammation and psoriasis regulation. Thus, in this study, we evaluated the effectiveness of fig fruit extracts and fractions using eutectic solvent extraction for skin inflammation control and psoriasis. First, fig fruits were extracted under optimal eutectic solvent conditions and fractionated with n-hexane, dichloromethane, ethyl acetate, and butanol. First, the antioxidant activity and inhibition of nitric oxide (NO) production were confirmed in mouse macrophage RAW264.7 cells. In addition, as a result of observing the mRNA expression through RT-PCR, pro-inflammatory cytokines such as TNF-α, IL1α, and IL-1β were suppressed significantly in the hexane, dichloromethane, and ethyl acetate fractions. In addition, it was confirmed in TNF-α stimulated HaCaT keratinocyte model. Finally, chemokine CC motif ligand 20 (CCL20), marker gene of human psoriasis skin disease, was significantly suppressed in the hexane, dichloromethane, and ethyl acetate fractions. These results suggested its anti-inflammatory and skin soothing effect and the possibility of development as an excellent skin soothing natural cosmetic material in the future through future clinical trials.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.45-52
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• 2001

Purpose : Granulocyle-colony stimulating factor (G-CSF) has been widely used to treat neutropenia caused by chemotherapy or radiotherapy. The efficacy of recombinant human hematopoietic growth factors in improving oral mucositis after chemotherapy or radiotherapy has been recently demonstrated in some clinical studies. This study was designed to determine whether G-CSF can modify the radiation injury of the intestinal mucosa in mice. Materials and Methods : One hundred and five BALB/c mice weighing 20 grams were divided into nine subgroups including G-CSF alone group $(I:10\;{\mu}g/kg\;or\;II:100\;{\mu}g/kg)$, radiation alone group (7.5 or 12 Gy on the whole body), combination group with G-CSF and radiation (G-CSF I or II plus 7.5 Gy, G-CSF I or II plus 12 Gy), and control group. Radiation was administered with a 6 MV linear accelerator (Mevatron Siemens) with a dose rate of 3 Gy/min on day 0. G-CSF was injected subcutaneously for 3 days, once a day, from day -2 to day 0. Each group was sacrificed on the day 1, day 3, and day 7. The mucosal changes of jejunum were evaluated microscopically by crypt count per circumference, villi length, and histologic damage grading. Results : In both G-CSF I and II groups, crypt counts, villi length, and histologic damage scores were not significantly different from those of the control one (p>0.05). The 7.5 Gy and 12 Gy radiation alone groups showed significantly lower crypt counts and higher histologic damage scores compared with those of control one (p<0.05). The groups exposed to 7.5 Gy radiation plus G-CSF I or II showed significantly higher crypt counts and lower histologic damage scores on the day 3, and lower histologic damage scores on the day 7 compared with those of the 7.5 Gy radiation alone one (p<0.05). The 12 Gy radiation plus G-CSF I or II group did not show significant difference in crypt counts and histologic damage scores compared with those of the 12 Gy radiation alone one (p>0,05). Most of the mice in 12 Gy radiation with or without G-CSF group showed intestinal death within 5 days. Conclusion : These results suggest that G-CSF may protect the jejunal mucosa from the acute radiation damage following within the tolerable ranges of whole body irradiation in mice.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.1-6
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• 1991

The effect of 2-deoxy-d-glucose (2-DDG) on $C_3H$ mouse fibrosarcoma(FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo $^{31}P$-MRS, proliferative capacity was observed on flow cytometry(FC) and growth rate was measured after transplantation of $10^6$ viable tumor cells in the dorsum of foot of $C_3Hf/Sed$ mice. One gram of 2-DDG Per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantion was $250mm^3$. Growth rate of Fsall tumor was measured by tumor doubling time and slope on semilog plot. After 2-DDG injection, growth rate slowed down. Tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo $^{31}P$-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and $G_2+M$ phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect of 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.425-433
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• 2004

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.128-137
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• 2006

Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.

• Korean Journal of Poultry Science
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• v.40 no.4
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• pp.299-304
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• 2013

Tracheal epithelial cells (TECs) are an important tool for studies of viral respiratory diseases. Primary TECs have been cultured from human, mouse and hamster. It is also necessary to diagnose viral respiratory disease and reveal infection mechanisms in chicken. In this study, we isolated tracheal epithelial layers from tracheal of 20-day-old chicks and cultured primary TECs from the isolated layers. Ciliated cells which were a typical morphology of TECs were observed in cultured primary TECs and maintained until cell passage 5 (15 to 20 days). When we analyzed expression patterns of epithelial marker genes (retinoic acid responder, FGF-binding protein, virus activating protease (VAP) in TECs compared to immortalized chicken embryonic fibroblast cell line (DF-1), all the marker genes are highly expressed in TECs than in DF-1. When TECs were cultured with 0.1 and 1 MOI of ND virus (rNDV-GFP strain) to test the susceptibility of TECs for ND virus, 12.6% and 48.2% of the incubated TECs were infected respectively. In addition, when DF-1 was incubated with 1 MOI of ND virus, the virus infection rate of DF-1 was three times lower than the virus infection rate of TECs. These data could contribute to study infection mechanisms of viral respiratory diseases and control them in chicken.