• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.153-159
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• 2009

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-${\beta}$ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-${\beta}$ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

• Environmental Analysis Health and Toxicology
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• 제19권2호
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• pp.191-200
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• 2004

Zinc (Zn) is an essential element in biological process, however inadequate Zn status in general population have been recognized. To update the knowledge for Zn-cadmium (Cd) interaction, we studied the intestinal uptake and transport, and the expression of metal transporter proteins (divalent metal transporter 1, DMT1 ; metal transporter protein 1, MTP1 ; zinc transporter 1, ZnTl ; metallothionein 1 , MT1) in duodenum after Cd exposure using Zn deficient animal model. Rats were led Zn deficient (ZnD, 0.5-1.0 mgZn/kg) or Zn supplemented (ZnS, 50mg Zn/kg) diet for 4 weeks, and followed single administration of $^{109}$ CdCl$_2$orally. The body Zn flatus and tissue Cd concentration were determined at 24 hrs after Cd administration. Total body burden of Cd and Cd absorption index (AI, %) were estimated based on the tissue Cd analyzed. DMT1, MTP1, ZnTl and MT1 mRNA were analyzed by using RT-PCR method. Feeding of Zn deficient diet for 4 weeks produced a reduced body weight gain and a depletion of body Zn. Tissue Cd concentration, body burden of Cd and Cd absorption index were higher in the ZnD diet fed rats than the ZnS diet red rats. Especially, Cd concentration in the small intestine (duodenum, jejunum and ileum) and the colon of FeD diet fed rats were higher markedly than in the FeS diet group. The expression levels of DMT1, MTP1 and ZnT1 mRNA in FeD diet fed rats were similar to the FeS diet. The level of MT1 mRNA expression was significantly lower in the FeD than the FeS diet fed rats. Taken together, theses results indicate that Zn deficiency in diet induce an increased intestinal absorption and tissue retention of Cd, and down -regulate the MT1 expression in the intestine which might be play a part of role in Cd absorption and transport in mammalian. These findings suggest that deficiency of essential metal could be enhanced the toxicity of toxic, non-esstial metals through the metal-metal interaction.

• Journal of Nutrition and Health
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• 제36권5호
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• pp.491-499
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• 2003

Selenium is a strong antioxidant trace mineral, scavenging free radicals. The prevalence of chronic degenerative diseases is increasing in Korean adults with increasing age. The increased cell damage from free radicals has been implicated in the etiology of these diseases, and evidence is accumulating that the low selenium status that comes with advanced aged is involved in the prevalence of age-associated diseases. However, little is known about the selenium status of Koreans, its age-related change and its relationship to dietary nutrient intake. In this study, the serum selenium levels of healthy adult females according to life cycle and its association with blood albumin levels and nutrient intake were examined. Serum selenium level was measured with the Huwo research reactor using the neutron activation analysis method (NAA). The overall proportion of women with selenium deficiency, serum selenium concentrations below 7.0 $\mu\textrm{g}$/dl, was 9.4%. The average serum selenium levels were 12.39 $\mu\textrm{g}$/dl, 9.45 $\mu\textrm{g}$/dl and 9.16 $\mu\textrm{g}$/dl in the young adult, middle-aged and elderly groups, respectively, showing a reduction of selenium status with advancing age. Selenium deficiency was seen only in the elderly group. Generally, serum selenium levels positively or negatively correlated with nutrient intake, but these association patterns differed depending on the age. The nutrients that showed positive correlations with selenium levels were proteins and phosphate in the young adult group (p < 0.05, p < 0.05), and total calcium, potassium and vegetable-origin calcium in the middle-aged group. Vitamin C and fiber were the negative correlated nutrients with serum selenium levels in the elderly group (p < 0.05, p < 0.05). Multiple stepwise regression analysis of the determining factors responsible for selenium status showed that age and serum albumin levels were important factors which explained up to 26.9% variances in serum selenium levels. The average selenium concentrations of Korean adult female subjects were above the deficiency levels in all three age groups. There was a tendency toward decreasing selenium levels as the age of the subjects increased. The factors with the strongest in-fluence on selenium status in healthy adult Korean females were age and serum protein status. (Korean J Nutrition 36(5): 491~499, 2003)

• 대한핵의학회지
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• 제32권1호
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• pp.114-119
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• 1998

반복적인 수혈을 받은 급성전격성간염 환자에서 Ga-67 체내분포의 양상을 추적하였다. 급성기에 시행한 갈륨스캔에서 간의 악성종양을 의심하게 하는 간섭취증가와 신장, 뼈섭취증가가 관찰되었다. 간섭취증가는 철운반단백질에 결합하지 않은 Ga-67이 염증이 일어난 간세포에 섭취되었기 때문으로 해석되었다. 신장과 뼈섭취증가는 반복적인 수혈에 의한 철운반단백질의 포화에 따른 Ga-67의 세포내운반저하에 의한 것으로 생각되었다. 10개월 후에 다시 시행한 갈륨스캔에서 간섭취는 더욱 증가되었으며 골수섭취의 증가가 관찰되었다. 반면 신장섭취는 정상화되었다. 이러한 소견은 철결핍성 빈혈에 의한 것으로 해석되었다. 이 증례는 체내 철의 양과 이에 따른 철운반단백질 포화도의 변화에 의한 Ga-67의 체내분포의 변화를 예시해 준다.

• 동의생리병리학회지
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• 제18권1호
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• pp.93-100
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• 2004

This study was carried out for analyzing pathological and epidemiological factors of osteoporosis and doing pilot test using trial compounds of tuna bone and oriental herbs based on the factors. Osteoporosis is originated from osteoblast, osteoclast, organic and inorganic factors etc. Therefore the pathology of osteoporosis is not simple because the cytokine, growth factors and hormones of the components are various a lot. Taking a view of epidemiological factors of type I osteoporosis, ageㆍmenarcheㆍcholesterolㆍBMI etc. have definite relation to them. So we can approach to aging or consumptive disease in oriental medicine, specifically differential diagnosis of blood depletion with deficiency of qi, deficiency of kidney, deficiency of yin, bony weakness etc. And it should be considered together with rules for maintaining good health or habit concomitantly. Therefore IL1ㆍ6 or TNF αㆍβ are generally used as molecular biological index for osteoblast and osteoclast because the most important index is bone mineral density and strength, but the factors like collagen and noncollagen protein must be accounted as biomarkers. Trial compounds generally showed favorable effects on accompanying subjective symptoms of osteoporosis in the pilot test for menopausal woman. But if she didn't have specific symptoms of osteoporosis there wasn't any specific change. And osteocalcin was increased in case of being under standard level, but wasn't changed in case of normal level. Therefore these trial compounds can be used as a funcdonal diet for type I osteoporotic patients or preventive measures.

• 한국식품영양과학회지
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• 제27권1호
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• pp.191-199
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• 1998

This paper has studied the nutritional iron status of adults in the city of Taegu. The subjects of the experiment were twenty six men and women living in the city of Taegu. The iron intake was 26.1mg for men and 17.1mg for women, which were respectively 217.5% and 95% of RDA. For men heme iron was 5% and nonheme iron, 95% for women heme iron was 5.8% and nonheme iron, 94.2%. The absorption rate of dietary iron was 6.2% for men and 9.1% for women. The hemoglobin was 14.5g/dl for men and 11.9g/dl for women, and the rate of developing anemia was 8.3% in men and 57.1% in women. The serum ferritin was 57.8ng/ml with men, which was found to be normal, and 14.7ng/ml with women, which showed that 57.1% of women were in the condition of iron depletion or iron deficiency anemia. The rate of developing anemia resulting from the deficiency of serum ferritin was as high as that from the deficiency of hemoglobin. The correlation between iron intake based on the dietary record, and energy intake, vegetable protein intake and dietary fiber intake was found to be positive. So was the correlation between the iron intake, and hemoglobin, serum ferritin and urinary iron excretion. There was also a positive correlation between hemoglobin, and hematocrit and serum ferritin. The correlation between fecal iron excretion and serum ferritin was positive. Fecal iron excretion and urinary iron excretion can be complemented by iron intake but the fact should be considered that 95% of iron intake is nonheme iron, which is difficult to absorb. Based on the above-mentioned things, serum ferritin and hemoglobin can be used as the standards of measuring anemia. As women in their child bearing years show the high rate of 57.1% of developing anemia, the more thorough nutritional education of iron is required.

• 동국한의학연구소논문집
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• 제8권1호
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• pp.145-158
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• 1999

본 실험은 사군자탕합창출지유탕(四君子湯合蒼朮地楡湯)의 만성설사(慢性泄瀉)에 미치는 영향을 조사하기 위해 시행되었다. 실험을 위해 흰쥐에 3주일간 castor oil과 대황(大黃)분말을 병행 투여하여 1주일후부터 지속적인 설사를 보인쥐를 선정, 만성설사의 모델로 삼았다. 이를 대조군과 실험군으로 구분하여 위장관 기능과 영양상태를 비교하였고, 개선여부를 알아보기 위해 아무런 처치를 받지 않은 정상군을 검체 체취에 사용하였다. 실험군과 대조군에서 검액 투여전 모두 위장관 기능과 영양상태가 감소한 상태였으며, 검액을 투여한 후 실험군에서 대조군에 비해 위장관 기능과 영양상태가 개선된 경향을 보였는데, 특히 gastrin과 total lipid, 그리고 hematocrit 수치가 유의성 있게 나타나 사군자탕합창출지유탕(四君子湯合蒼朮地楡湯)이 만성설사(慢性泄瀉)에 효과가 있는 것으로 사료된다.

• Nutrition Research and Practice
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• 제7권4호
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• pp.281-286
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• 2013

We examined the effect of parental folate deficiency on the folate content, global DNA methylation, folate receptor-alpha (FR${\alpha}$), insulin-like-growth factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in the postnatal rat. Male and female rats were randomly fed a folic acid-deficient (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid-supplemented diet (paternal folate-supplemented, PS and maternal-folate-supplemented, MS) for four weeks. They were mated and grouped accordingly: $PS{\times}MS$, $PS{\times}MD$, $PD{\times}MS$, and $PD{\times}MD$. Pups were killed on day 21 of lactation. The hepatic folate content was markedly reduced in the $PD{\times}MD$ and $PS{\times}MD$ and $PD{\times}MS$ as compared with the $PS{\times}MS$ group. The hepatic global DNA methylation was decreased in the $PD{\times}MS$ and $PS{\times}MD$ groups as much as in the $PD{\times}MD$ group, and all the three groups were significantly lower as compared to the $PS{\times}MS$ group. There were no significant differences in the hepatic FR${\alpha}$, IGF-2 and IGF-1R expressions among the groups. Positive correlations were found between the hepatic folate content and global DNA methylation and protein expressions of FR${\alpha}$, IGF-2 and IGF-1R, whereas an inverse correlation was found between hepatic folate content and plasma homocysteine level in the 3-week-old rat pup. The results of this study show that both paternal and maternal folate deficiency at mating can influence the folate content and global DNA methylation in the postnatal rat liver.

• Preventive Nutrition and Food Science
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• 제1권1호
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• pp.75-79
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• 1996

The purpose of this study was to investigate the effect of vitamin {TEX}$B_{6}${/TEX} deficiency on the utilization and recuperation of stored fuel in exercising rats. Thirty six rats were fed either a vitamin {TEX}$B_{6}${/TEX} deficient diet(-{TEX}$B_{6}${/TEX}) or a control diet(+{TEX}$B_{6}${/TEX}) for 5 weeks, then subdivided into 3 group: non-exercise group(NE), exercise group(EX), exercise and recuperation group(EX). EX group were exercised in treadmill({TEX}$10^{o}${/TEX}, 0.5~0.8km/h)for 2 hours and ER group were recuperated three days with the respective diet after exercise. Glucose(GLU), glycogen(GLY), protein(PRO), trigyceride(TG) and free fatty acid(FFA) were compared in plasma(P), liver(L) and skeletal muscle(M) of rats. Compared to +{TEX}$B_{6}${/TEX} rats, in NE group, the level of L-GLY of -{TEX}$B_{6}${/TEX} rats was higher, M-TG, L-PRO of -{TEX}$B_{6}${/TEX} rats were lower and there were no differences in P-PRO, P-FFA, P-TG, M-GLY, M-PRO and L-TG. In EX group, the levels of P-FFA, L-PRO of -{TEX}$B_{6}${/TEX} rats were higher. P-TG, L-TG of -{TEX}$B_{6}${/TEX} rats were lower and there was no difference in L-GLY. In EG group, the levels of P-GLU, P-PRO, P-RG, L-PRO of -{TEX}$B_{6}${/TEX} rats were lower and there were no differences in L-GLY, L-TG, M-TG and M-GLY. these results suggest that a lowered intake of vitamin {TEX}$B_{6}${/TEX} may impair the recuperation of aminals after exercise related to exercise fuel stores although there is a compensation among stored fuel utilization during exercise.

• Molecules and Cells
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• 제45권6호
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• pp.413-424
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• 2022

Suppressor of mothers against decapentaplegic homolog (SMAD) 4 is a pluripotent signaling mediator that regulates myriad cellular functions, including cell growth, cell division, angiogenesis, apoptosis, cell invasion, and metastasis, through transforming growth factor β (TGF-β)-dependent and -independent pathways. SMAD4 is a critical modulator in signal transduction and functions primarily as a transcription factor or cofactor. Apart from being a DNA-binding factor, the additional SMAD4 mechanisms in tumor suppression remain elusive. We previously identified methyl malonyl aciduria cobalamin deficiency B type (MMAB) as a critical SMAD4 binding protein using a proto array analysis. This study confirmed the interaction between SMAD4 and MMAB using bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and conventional immunoprecipitation. We found that transient SMAD4 overexpression down-regulates MMAB expression via a proteasome-dependent pathway. SMAD4-MMAB interaction was independent of TGF-β signaling. Finally, we determined the effect of MMAB downregulation on cancer cells. siRNA-mediated knockdown of MMAB affected cancer cell metabolism in HeLa cells by decreasing ATP production and glucose consumption as well as inducing apoptosis. These findings suggest that SMAD4 controls cancer cell metabolism by regulating MMAB.