• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1102-1111
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• 2008

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and $30{\mu}g/mL$) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

• Applied Microscopy
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• v.37 no.4
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• pp.271-280
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• 2007

Tonicity-responsive enhancer binding protein(TonEBP) is a transcriptional factor essential in the function and development of the renal medulla. TonEBP plays a critical role in protecting renal medullary cells from the deleterious effect of hypertonicity. TonEBP is a key regulator of urinary concentration via stimulation of transcription of urea transporter(UT) in a manner independent of vasopressin. UT in the renal inner medulla is important for the conservation of body water due to its role in the urine concentrating mechanism. Mongolian gerbil(Meriones unguiculatus) has been as an model animal for studying the neurological disease such as stroke and epilepsy because of the congenital incomplete in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animal. In this study, we divide 3 groups of which each group include the 5 animals. In the study of 7 or 14 days water restricted condition, we investigated the TonEBP and UT-A by using a immunohistochemistry in the kidney. In the normal kidney, the distribution of TonEBP is generally localized on nuclei of inner medullary cells. Nuclear distribution of TonEBP is generally increased throughout the medulla in 7 and 14 days dehydrated group compared with control group. Increased nuclear localization was particularly dramatic in thin limbs. In control groups, UT-A was expressed in inner stripe of outer medulla(ISOM) and inner medulla(IM). UT-A was present in the terminal part of the short-loop of descending thin limbs (DTL) in ISOM and also present in the inner medullary collecting duct(IMCD), where the intensity of it gradually increased toward the papillary tip. In the dehydrated kidney, UT-A immunoreactivity was increased in the short-loop of DTL in ISOM and in the long-loop of DTL in the initial part of IM, where was expressed moderate positive reaction in the normal kidney. Also it was up regulated in the IMCD in initial & middle part of IM. However UT-A down regulated in the IMCD, where the intensity of it gradually decreased toward the papillary tip. These findings suggest that increased levels of TonEBP in medulla and UT-A in shot-loop of DTL and IMCD play a important role for maintain fluid balance in the water-deprived mongolian gerbil kidney.

• Progress in Medical Physics
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• v.9 no.4
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• pp.227-245
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• 1998

A most appropriate model of 3-D conformal radiotherapy has been induced by clinical evaluation and animal study, and therapeutic gains were evaluated by numerical equation of tumor control probability(TCP) and normal tissue complication probability (NTCP). The radiation dose to the tumor and the adjacent normal organs was accurately evaluated and compared using the dose volume histogram(DVH). The TCP and NTCP was derived from the distribution of given dosage and irradiated volume, and these numbers were used as the biological index for the assessment of the treatment effects. Ten patients with liver disease have been evaluated and 3 dogs were sacrificed for this study. Based on the 3-D images of the tumor and adjacent organs, the optimum radiation dose and the projection direction which could maximize the radiation effect while minimizing the effects to the adjacent organs could be decided. 3). The most effective collimation for the normal adjacent organs was made through the beams eye view with the use of multileaf collimator. When the dose was increased from 50Gy to 70Gy, the TCP for the conventional 2-port radiation and the 5-port multidimensional therapy was 0.982 and 0.995 respectively, while the NTCP was 0.725 and 0.142 respectively, suggesting that the 3-D conformal radiotherapy might be the appropriate therapy to apply sufficient radiation dose to the tumor while minimizing the damages to the normal areas of the liver. Positive correlation was observed between the NTCP and the actual complication of the normal liver in the animal study. The present study suggest that the use of 3-D conformal radiotherapy and the application of the mathematical models of TCP and NTCP may provide the improvements in the treatment of hepatoma with enhanced results.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.1
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• pp.42-45
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• 1999

Our previous studies have demonstrated the biological effects of alginic acid as a brown algae (Undaria pinnatifida) component on inhibitory action of obesity using animal model. Sprague-Dawely (SD) male rats were fed experimental diets ($10\%,\;20\%$ and $40\%$ brown algae noodle: BA-noodles) for 4 weeks. Effects of BA-noodles on triglyceride (TG), total cholesterol. LDL and HDL-cholesterol, and atherogenic ($10\%\~15\%$ and $15\%\~18%$, respectively) by administration of $10\%,\;20\%$and $40\%$ BA-noodles compared with control group. HDL-cholesterol contents in serum of SD rats for 4 weeks significantly increased in ranges of 7 to $16\%$ by administration of $10\%,\;20\%$ and $40\%$ BA-noodles compared with control group. Atherogenic index (AI) in serum of SD rats as a initial attack markers of chronic degenerative disease for 4 weeks remarkably decreased in ranges of 14 to $28\%$ by the adminstration of $10\%,\;20\%$ and $40\%$ BA-noodles compared with control group. These results suggest that administration of BA-noodle can not only effectively inhibit chronic degenerative disease, but also may be intervent the aging process.

• 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.

• Journal of Applied Biological Chemistry
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• v.64 no.2
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• pp.185-192
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• 2021

Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

• Progress in Medical Physics
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• v.21 no.1
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• pp.35-41
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• 2010

The purpose of this study is to quantitate regional neurochemical profile of regional normal adult mice brain and assess regional metabolic differences by using ex vivo $^1H$ high-resolution magic angle spinning nuclear magnetic resonance spectroscopy ($^1H$ HR-MAS NMRS). The animals were matched in sex and age. The collected brain tissue included frontal cortex, temporal cortex, thalamus, and hippocampus. Quantitative 1D spectra were acquired on 40 samples with the CPMG pulse sequence (8 kHz spectral window, TR/TE = 5500/2.2 ms, NEX = 128, scan time: 17 min 20 sec). The mass of brain tissue and $D_2O$+TSP solvent were 8~14 mg and 7~13 mg. A total of 16 metabolites were quantified as follow: Acet, NAA, NAAG, tCr, Cr, tCho, Cho, GPC + PC, mIns, Lac, GABA, Glu, Gln, Tau and Ala. As a results, Acet, Cho, NAA, NAAG and mIns were showed significantly different aspects on frontal cortex, hippocampus, temporal cortex and thalamus respectively. The present study demonstrated that absolute metabolite concentrations were significantly different among four brain regions of adult mice. Our finding might be helpful to investigate brain metabolism of neuro-disease in animal model.

• Korean Journal of Microbiology
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• v.48 no.2
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• pp.109-115
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• 2012

Helicobacter pylori is an important factor of chronic gastritis, digestive ulcer, and stomach cancer. CagL, a virulence factor of H. pylori, is well-known as a pilus protein which acts as adhesion to host cell and a component of Type 4 secretion system. In this study, we evaluated the protective response of recombinant CagL protein (rCagL) using Mongolian gerbil animal model for H. pylori infection. The cagL gene was cloned from 26695 H. pylori followed by over-expression and purification of the protein in E. coli. Mongolian gerbils were immunized with rCagL protein mixed with aluminum adjuvant via intramuscular injections once a week during 4 weeks. At a week after the last immunization, the Mongolian gerbils were administrated with H. pylori 7.13 strain into the stomach and sacrificed to measure antibody titer on rCagL by ELISA and bacterial colonization in the stomach, and to examine the histopathological changes and cytokine expression at 6 week after challenge. Antibody titers on recombinant protein were significantly increased from a week after the first immunization. There was no significant change of the number of bacterial colony between control group and immunized group. The relative stomach weight was significantly decreased in immunized group, but the significant change of histopathological assessment was not observed in the stomach. Cytokine expression such as IL-$1{\beta}$ and KC also was not significantly different between control and immunized groups. These results indicate that rCagL could effectively induce the formation of the specific IgG antibodies. However, bacterial colonization and histopathological lesions could not be inhibited by the immunization in the stomach, indicating not enough protection against H. pylori infection. We consider that along with CagL other adequate antigens could be needed stimulating immune response and inducing protective effects against gastric disease, and also a better adjuvant could be considered.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.108-121
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• 2001

Background : The $p16^{INK4a}$ (p16) twnor suppressor gene is frequently inactivated in hwnan non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon $\gamma$-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. Methods : This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. Results : Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57. $8{\pm}10.5$ years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I (1 IA, 10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III (9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. Conclusion: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.

• The Korean Journal of Food And Nutrition
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• v.24 no.3
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• pp.442-450
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• 2011

Numerous studies have suggested that dietary flavonoids contribute to prevent cardiovascular disease. Onion contains many functional phytochemicals such as quercetin. The aim of this study was to examine whether onion peel extracts supplementation affect blood lipid profiles and blood coagulation in animal model. Total 48 Sprague-Dawley male rats at 5 weeks old were divided into 6 groups with different diets(C: control, HF: high fat diet, HFOE 0.01%: high fat+onion peel extract 0.01% diet, HFOE 0.02%, HFOE 0.05%, HFOE 0.1%) for 8 weeks. Onion peel extract supplementation significantly decreased serum levels of LDL-cholesterol and increased HDL-cholesterol, while total cholesterol and triglyceride levels were not affected. Hematological parameters(hematocrit, white blood cell, red blood cell, and platelet count) and blood coagulation parameters(prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen) were not significantly different among 6 groups. However, activated partial thromboplastin time of HFOE 0.05% group was significantly longer than that of HF group. These results indicate that onion peel extract supplementation displays hypocholestrolemic effects but does not seem to have anti-coagulation effects in high fat fed SD rats.