• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.3
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• pp.26-36
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• 2005

Objectives: Maier symptoms of allergic rhinitis are nasal obstructions, sneezing and watery rhinorrhea. When exposed to certain allergens, the IgE covered mast cells degranulate and release inflammatory mediators and cytokines which result in a local inflammatory reaction. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of allergic rhinitis. This experimental study was done to reveal the effects of the Bojungikgi-tang on the allergic rhinitis. We have studied effect of mice on OVA-induced production of IL-4, IL-5, $INF-{\gamma}$ by murine splenocytes and effect of OVA-induced Total IgE and OVA-specific IgE Meterial and Metheds: 21 BALB/c rats were divided into three groups: normal group, control group, experimental group. To induce the allergic rhinitis in control group and experimental group, rats were sentitized intraperitioneally with 0.1% ovalbumin solution 3 times at intervals of 2 weeks. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin solution 3 times at intervals of 2 days for a week. After that time, rats in experimental group were oral administration treated by the Bojuogikgi-tang fer 28 days. We observed changes of IL-4, IL-5, $INF-{\gamma}$, Total IgE and OVA-specific IgE. We used independent-test statistically. Results: 1. In IL-4 study, Bojungikgi-tang treated group didn't show significant differences. 2. In IL-5 study, Bojungikgi-tang treated group shows significant differences. 3. In $INF-{\gamma}$ study, Bojungikgi-tang treated group shows significant differences. 4. In Total IgE, Bojungikgi-tang treated group shows significant differences. 5. In OVA-specific IgE, Bojungikgi-tang treated group didn't show significant differences. According to this result, Bojungikgi-tang was concluded to be effective on lowering the total IgE. Through this. Bojungikgi tang seems to reduce the symptoms of allergic rhinitis. More studies are required to know exact mechanism of Bojungikgi tang to show the anti allergenic effect.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.171-183
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• 1989

A general effect for cell proliferation has been incorporated into Roesch's survival equation (Accumulation Model). From this an isoeffect formula for the low dose-rate regimen is obtained. The prediction for total doses equivalent to 60Gy delivered at the constant dose-rate over 7 days agrees well with the dose-time data of Paterson and of Green, when the parameter ratio A/B (${\approx}{\alpha{\mu}}/2{\beta}\;where\;{\mu}$ is the repair rate) is chosen to be 0.7Gy/h. When a constant proliferation rate and known facts of division delay are assumed, an isoeffect relation between low dose-rate treatment and acute dose-rate treatment can be derived. This formula in the regimens where proliferation is negligible predicts exactly the data of Ellis that 8 fractions of 5 Gy/day for 7 days are equivalent to continuously applied 60Gy over 7days, provided the A/B ratio is 0.7 Gy/h and the $\alpha/\beta$ ratio is 4Gy. Overall agreement between the clinical data and the predictions made by the formula at the above parameter values suggests that the biologcal end points used as the tolerance level in the studies by Paterson, Green, and Ellis all agree and they are not entirely the early effects as generally assumed. The absence of dose-rate effects observed in the mouse KHT sarcoma can better be explained in terms of a large value for the A/B ratio. Similarly, the same total dose used independently of the dose-rate to treat head and neck tumors by Pierquin can be justified.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.212-227
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• 2009

Objective : Membranous nephropathy (MN) is one of the most commonest forms of glomerular disease in man and the most frequent cause of the adult idiopathic nephrotic syndrome. Some investigators recommend no treatment, while others propose aggressive therapy, including prednisolone plus an immunosupressant such as chlorambucil or cyclophosphamide. But a more effective way to treat MN is not defined yet. This study was to evaluate the effects of Patriniae Radix extract (PRE) on the MN induced by cBSA in mice. Methods : Mice were divided into 4 groups. The first group (normal) was injected with saline. The second group (control) was treated with cBSA (10 mg/kg i.p) only. The third group, named PRE-2S0, was treated with cBSA (10 mg/kg i.p) and PRE (250 mg/kg, p.o). The fourth group, PRE-500, was treated with cBSA (10mg/kg i.p) and PRE (500mg/kg, p.o). After cBSA and PRE treatment for 4 weeks, we measured change of body weight, 24hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, IgG, IgA, IgM, $TNF-\alpha$, $IL-1\beta$, and $IFN-\gamma$ levels and the mRNA expression of $IFN-\gamma$, IL-6, and IL-10. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results : The levels of 24 hrs proteinuria and serum triglyceride. BUN. IgG. $TNF-\alpha$, and $IL-1\beta$ significantly decreased in both PRE groups, while the level of serum albumin significantly increased in both PRE groups. The mRNA expression of IL-10 in splenocytes considerably increased in both PRE groups. The mRNA expression of $IFN-\gamma$ and IL-6 in splenocytes considerably increased in both PRE group. In histological findings of kidney tissue, thickening of GBM decreased in both PRE groups. Conclusions : The present study suggests that PRE is effective when treating mice with MN induced by cBSA. More clinical data and studies are to be done for efficient application.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.413-417
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• 2006

The purpose of this study was to investigate the hypoglycemic effect of Saururus chinensis Baill in vitro and in vivo. Methanol extract of S. chinensis Baill inhibited yeast ${\alpha}$-glucosidase activity by 49.8%, which was twice as strong as that of acarbose at a concentration of 0.5 mg/mL in vitro. The effect of S. chinensis Baill methanol extract on the postprandial increase in blood glucose levels was studied in streptozotocin-induced diabetic rats using a carbohydrate load test. Oral administration of S. chinensis Baill extract (500 mg/kg) significantly decreased incremental blood glucose levels at 60 and 90 min (p<0.05) after oral ingestion of starch (1 g/kg). The area under the glucose response curve of the S. chinensis Baill group was significantly decreased compared to that of the control group (p<0.05). The effect of prolonged feeding of S. chinensis Baill was studied in an animal model of type 2 diabetes. Three-week-old db/db mice were fed an AIN-93G diet or a diet containing 0.5% S. chinensis Baill extract for 7 weeks after 1 week of adaptation. Plasma glucose, insulin, and blood glycated hemoglobin levels of the mice fed S. chinensis Baill extract were significantly lower than those of the control group (p<0.05). Therefore, we conclude that S. chinensis Baill is effective in controlling hyperglycemia in animal models of diabetes mellitus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.1
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• pp.32-42
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• 2007

This study was conducted on the immunoregulatory effect of Saengshik on gut-associated lymphoid tissue with inflammatory bowel disease. Although the contents of IgA increased in mesenteric lymph node, IgE content was suppressed by Saengshik. The same results were found in spleen, but IgA and IgE responses were very weak. Concentration of fecal IgA was high from the first day through the third day in Saengshik group. In DSS + Saengshik group, concentration of IgA was high till the 2nd day and it maintained the highest level among the test groups on 5th day. Concentration of IFN-gamma and IL-2 was the highest in the Saengshik group, but the concentration of TNF-alpha was lower in DSS + Saengshik compared to DSS. The expressions of STAT1 in Saengshik group were high, while those of STAT6 were low According to these findings, Saengshik exhibited effectiveness via increasing the IgA production, suppressing the IgE production, followed by inhibiting the production of IL-4 and IL-10. Saengshik also strengthened the immune system and alleviated injury in DSS -induced inflammation.

• Journal of The Korean Dental Society of Anesthesiology
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• v.14 no.2
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• pp.101-106
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• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.4
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• pp.1-13
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• 2019

Objective: This study is aimed to investigate the anti-tumor metastasis by innate immunomodulating effects of crude polysaccharide isolated from Polygonati Rhizoma (CP-PR) on 4T1 breast cancer cells. Methods: CP-PR was isolated from Polygonati Rhizoma. Antimetastatic experiments were conducted in vivo mouse model by using 4T1 breast cancer cells. The cell viability of CP-PR was tested with normal spleen and 4T1 breast cancer cells. To observe the activation of macrophages with/without 4T1 breast cancer cells, production of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), IL-10 and IL-12 were measured with enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the lysis of YAC-1 cells and the production of granzymes were measured to observe the activation of natural killer (NK) cell. Results: Intravenous administration of CP-PR significantly inhibited metastasis of 4T1 breast cancer cells. In an in vitro cytotoxicity analysis, CP-PR affected the growth of normal spleen and 4T1 breast cancer cells above specific concentration. The production of $TNF-{\alpha}$, IL-6, IL-10 and IL-12 were significantly increased in macrophages with CP-PR. As compared with control, CP-PR showed significantly higher production of $TNF-{\alpha}$, IL-10 and IL-12 in macrophages co-cultured with 4T1 breast cancer cells. The lysis of YAC-1 cells and the production of granzymes were significantly up regulated by CP-PR. Conclusion: CP-PR appears to have considerable activity on the anti-metastasis by activation of innate immune system.

• Development and Reproduction
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• v.23 no.3
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• pp.223-229
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• 2019

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic $BKS.Cg-m+/+Lepr^{db}$ mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.