• Nutrition Research and Practice
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• 제4권2호
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• pp.99-105
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• 2010

Obesity is considered a mild inflammatory state, and the secretion of inflammation-related cytokines rises as adipose tissue expands. Inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interlukin 6 (IL-6) and monocyte-chemoattractant protein 1 (MCP-1), are modulated by adipose tissue and known to play an important role in insulin resistance which is the common characteristics of obesity related disorders. In this study we analyzed the effects of Sasa borealis leaves extract on inflammatory cytokines and insulin resistance in diet induced obese C57/BL6J mice. The obese state was induced by a high fat diet for 20 weeks and then the mice were divided into two groups; obese control group (OBC, n = 7) and experimental group (OB-SBE, n = 7). The OBC group was fed a high fat diet and the OB-SBE group was fed a high fat diet containing 5% Sasa borealis leaves extract (SBE) for 12 weeks. We also used mice fed a standard diet as a normal control (NC, n = 7). The body weight and adipose tissue weight in the OB group were significantly higher than those in the NC group. The effects of the high fat diet were reduced by SBE treatments, and the body weight and adipose tissue deposition in the OB-SBE group were significantly decreased compared to the OBC group. The OBC group showed higher serum glucose and insulin levels which resulted in a significant increase of incremental area under the curve (IAUC) and HOMA-IR than the NC group. Also, serum leptin, TNF-${\alpha}$, and IL-6 levels were significantly higher in the OBC group than in the NC group. In contrast, the OB-SBE group showed a reversal in the metabolic defects, including a decrease in glucose, insulin, IAUC, HOMA-IR, TNF-${\alpha}$, IL-6 and leptin levels. These results suggest that BSE can suppress increased weight gain and/or fat deposition induced by a high fat diet and theses effects are accompanied by modulation of the inflammatory cytokines, TNF-${\alpha}$ and IL-6 secretion resulting in improved insulin resistance.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.23-25
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• 2008

Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권1호
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• pp.44-51
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• 2012

Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.

• Clinical and Experimental Reproductive Medicine
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• 제36권4호
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• pp.293-300
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• 2009

목 적: 본 연구는 배아이식일의 자궁동맥혈류가 인간 체외수정술에서 임신예후의 예측인자가 될 수 있는지 알아보기 위해 시행되었다. 연구방법: 51회의 체외수정술 주기에 대해 전향적인 임상 관찰로 시행되었으며 혈청 estradiol 농도는 hCG 투여일에 측정되었고, 자궁동맥 박동율 (PI)과 저항율 (RI)은 배아이식 3일째에 측정되었다. 결 과: 51회의 주기 중 22주기에서 임상적으로 임신이 확인되었고 (43.1%), 착상률은 14.7%였다. 자궁동맥 PI와 RI는 혈청 estradiol 농도과 의미 있는 음의 상관관계 (p<0.05)를 보였으며 자궁혈류량은 임신된 그룹과 임신 되지 않은 그룹에서 차이가 없었다. 임신율은 PI가 3.0 이상인 군에서 PI가 3.0 이하인 군보다 조금 높게 측정되었으나 통계학적인 유의성은 없었다. 결 론: 배아이식일의 자궁동맥 PI와 RI는 체외수정술에서 임신의 예측인자로는 효용성이 떨어지지만 estradiol 농도와는 음의 상관관계를 보여 자궁혈류와 estradiol 농도가 상관관계가 있음을 알 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.

• 한국식품영양과학회지
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• 제46권2호
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• pp.153-160
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• 2017

본 연구는 7주령의 백서 40마리를 이용하여 만성 분절수면과 식이제한이 식욕조절 호르몬을 포함한 심혈관 위험지표에 미치는 영향에 대해 실험하였다. 13일 동안의 만성적인 분절수면 및 식이제한의 조건에 노출된 백서의 체중 변화와 혈중 leptin, ghrelin, adiponectin, cortisol, epinephrine, norepinephrine 등의 호르몬 농도, 심혈관 위험지표인 혈중 총콜레스테롤, LDL-cholesterol, HDL-cholesterol, 중성지방, 유리지방산의 농도를 대조군 및 3군의 실험군(만성 분절수면 군, 식이제한 군, 분절수면과 식이제한 모두를 적용한 군)에서 비교하였다. 그 결과 실험기간 동안 만성 분절수면 군에서 백서의 체중이 증가하며, 혈중 leptin 및 adiponectin 농도가 감소하고 ghrelin 농도가 증가하여 결국 혈중 LDL-cholesterol 농도가 증가하였다. 분절수면과 식이제한을 동시에 적용한 백서에서는 체중이 감소하고 adiponectin 농도는 대조군과 유의적인 차이를 보이지 않았으며 ghrelin 농도는 분절수면만 했던 백서에 비해 감소한 것으로 나타나 식이제한이 식욕을 조절하는 것으로 나타났다. 하지만 이들 백서에서 혈중 leptin 농도가 현격히 감소하고 혈중 LDL-cholesterol 농도가 증가하는 양상을 나타내 만성 분절수면 환자들의 심한 식이제한이 심혈관질환의 위험을 더욱 증가시킬 수 있다는 결과를 보여주었다.

• Preventive Nutrition and Food Science
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• 제14권1호
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• pp.1-7
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• 2009

Control of hyperglycemia and dyslipidemia is strongly correlated with decreased risk for cardiovascular disease, the most common and fatal diabetic complication. The purpose of this study is to determine the effects of garlic and aged black garlic on glycemic control and blood lipid profile in animal model of type 2 diabetes. Three week-old db/db mice (C57BL/Ks, n=21) were fed AIN-93G semipurified diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Fasting serum glucose, insulin, triglyceride, total cholesterol, and HDL-cholesterol and blood glycated hemoglobin were measured. Body weight and food intake of garlic and aged black garlic group were not significantly different from those of the control group. Fasting serum glucose and blood glycated hemoglobin levels were significantly decreased and insulin level was significantly increased in garlic group compared with control group (p<0.05). Consumption of aged black garlic significantly decreased homeostasis model assessment for insulin resistance (HOMA-IR) and tended to decrease serum glucose. Garlic consumption significantly decreased total cholesterol, while aged black garlic significantly reduced serum total cholesterol and triglyceride and increased HDL-cholesterol levels. These results suggest that garlic exerts hypoglycemic and hypocholesterolemic effect and aged black garlic improved insulin sensitivity and dyslipidemia in db/db mice.

• Nutrition Research and Practice
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• 제8권2호
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• pp.172-176
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• 2014

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1285-1292
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• 2016

Background: It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy. Purpose: The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated. Materials and Methods: Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy. Results: BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). Conclusions: The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1060-1069
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• 2002

High insulin level is known to be a risk factor of coronary heart disease. High insulin level with normal glycemic control is known to be an indicator for insulin resistance. This study was aimed to find out the influencing factors for the fasting serum insulin levels in elderly females with normal glycemic control. One hundred thirty-eight older females aged over 60 years without diabetes medication and high blood HBA1c level were examined on the serum fasting insulin concentration, anthropometry and asked about nutrient intake and exercise habits. The elderly were categorized into 3 group according to the fasting insulin level. The high insulin group was in a state of hyperinsulinemia. Except vitamin C, the nutrient intakes showed no difference according to fasting serum insulin level. But the intakes of calorie and protein per kg body weight were significantly lower in the high insulin group. The intakes of most nutrients except vitamin B$_1$, C and niacin were lower than the korean RDA in all the insulin group. Especially, the intakes of vitamin B$_1$ and Ca were below 75% of the korean RDA. Weight, BMI, body fat percent, body fat mass and fat-free mass, circumferences of waist and hip, WHR of elderly females were significantly higher in the group with the highest insulin level. The body fat percent in the highest insulin group was 35.8%. showing a state of obesity. The high insulin group showed higher proportion of low exercise frequencies per week and short exercise duration. Therefore, the mean energy expenditure for exercise were lower in this group, showing a state of very low exercise activity. Age and waist circumference in elderly females could explain to the 14.5% variances of the fasting insulin level according to multiple stepwise regression. It can be concluded that aging and central body fat deposition influence independently the serum fasting insulin level in elderly females with normal glucose level.