• Clinical and Experimental Pediatrics
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• 제51권7호
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• pp.747-753
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• 2008

목 적 : 제1형 당뇨병은 동맥경화증의 주요 위험인자 중의 하나로 이러한 동맥경화증의 초기 변화가 소아청소년기부터 시작된다는 것은 잘 알려진 사실이다. 성인에서는 초음파를 이용한 경동맥 내중막 두께가 동맥경화증의 독립적인 대리 표식자로 널리 이용되고 있으나, 소아청소년기에 관한 연구는 흔하지 않다. 이에 저자들은 제1형 당뇨병을 가진 소아들을 대상으로 경동맥 내막-중막 두께 및 경동맥 혈관 탄성 지수 측정을 통해 혈관의 동맥경화 상태를 조기에 평가하고, 이러한 혈관의 변화와 여러 동맥경화 위험인자들과의 관련성을 파악하여 조기 동맥경화의 선별 검사로 경동맥 내막-중막 두께의 유용성 등에 대해 알아보고자 본 연구를 시행하였다. 방 법 : 대구지역 3차 병원 소아과에서 제1형 당뇨병으로 진단받고 치료 중인 환자 23명과 동일 연령 및 성별의 건강한 소아, 청소년 19명을 대상으로 신체계측을 하고 공복상태에서 혈청콜레스테롤 및 당화혈색소를 측정하였다. 또한 고해상도 초음파를 이용하여 심장 주기에 따른 우측 경동맥의 내경 및 내중막 두께를 측정하였으며 공식에 따라 경동맥 유순도 및 신전도를 구하였다. 결 과 : 두 군 간의 성별, 연령, 혈압과 혈청콜레스테롤 등은 차이가 없었다. 경동맥 초음파 소견에서 당뇨군의 경동맥 내막-중막 두께는 의미 있게 증가되었으나 유순도와 신전도의 차이는 없었다. 당화혈색소와 고밀도혈청콜레스테롤은 다른 동맥경화의 위험인자와 독립적으로 경동맥 내막-중막 두께에 영향을 미치는 것으로 나타났다. 결 론 : 제1형 소아 당뇨 환아의 경우 정상 환아에 비해 경동맥 내막-중막 두께가 의미 있게 증가되어 있고, 이것이 혈당 조절 정도나 혈청 지질치와 같은 심혈관계의 위험인자와 깊은 상관관계를 나타내는 것으로 보아 소아 당뇨 환아에서 동맥경화의 발생을 조기에 파악하는 선별 검사로서 경동맥 내막-증막 두께는 유용하다고 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권8호
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• pp.1190-1197
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• 2017

Objective: Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods: An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha ($TNF-{\alpha}$), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce's correlation analysis. Results: Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and $TNF-{\alpha}$ showed no difference, while the values of $TNF-{\alpha}$ in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion: AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

• Toxicological Research
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• 제23권1호
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• pp.79-86
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• 2007

The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

• 생약학회지
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• 제25권3호
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• pp.238-248
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• 1994

The hypoglycemic and metabolic effects of Commelina communis L. extract were investigated in alloxan induced diabetic rats. The increased blood glucose level in the diabetic rats was significantly reduced and the loss of body weight was recovered with the treatment of the plant protein fractions($30{\sim}70%$ ammonium sulfate precipitates). Administration of the plant protein fractions elicited the significant increase of glucose-6-phosphate dehydrogenase (G-6-P DH) activity and liver weight which were decreased in the diabetic rat liver. G-6-P DH was partially purified from extract- or insulin-treated diabetics, diabetic control, and normal rat liver and studied for the biochemical properties. The $K_m$ value(9.002 mM) of diabetic rat liver enzyme was greatly higher than that (0.033 mM) of normal enzyme indicating the affinity of enzyme for the substrate was significantly reduced in the diabetic rat liver. This reduced affinity of enzyme for the substrate in the diabetic rat was recovered in the extract- or insulin-treated rat liver enzyme having 0.164 or 0.208 mM of their $K_m$ values, respectively. Although there was no significant difference in the optimum pH(6.0) and optimum temperature($37^{\circ}C$) of enzyme among the experimental groups, the dependence of their activities on pH appeared to be slightly resistant in the extract- or insulin-treated group compared to the diabetic group. In order to investigate the antigenicity of rat liver enzyme among experimental groups, enzyme-linked immunosorbent assay was carried out by using anti-G-6-P DH anti-serum. Absorbance(0.102) shown in the normal rat liver was reduced even below zero in the alloxan-diabetic rat liver, but increased again in the extract- or insulin-treated rat liver(0.096 or 0.118, respectively). The result of this study suggested that G-6-P DH may be used as a marker enzyme to diagnose and to indicate the progress of the diabetics, and the hypoglycemic effect of the extracts of Commelina communis L. was certainly associated with action or mode of G-6-P DH on the rat liver.

• The Plant Pathology Journal
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• 제30권4호
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• pp.343-354
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• 2014

Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

• 대한두경부종양학회지
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• 제17권2호
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• pp.169-173
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• 2001

Objectives: The p53 tumor suppressor gene encodes a nuclear transcription factor that is critical regulator of cell growth and proliferation through its action in cell-cycle checkpoint control. The wide variety of stressful stmuli which include DNA damage, hypoxia, heat shock, metabolic changes activate the p53 protein, which in turn drives a series of events that culminate either in cell cycle arrest or apoptosis. Mutations of the p53 gene is the most common genetic alteration in human cancer. This gene is altered in approximately 40-60% of head and neck cancers. Whereas the wild-type form of the p53 protein plays a central role in cell-cycle control in response to DNA damage, most of the mutant forms are unable to do so. The high levels of p53 protein expression in tissues are related to the increased cellular proliferative activity and may be associated with the poor clinical outcome. To determine whether the expression of the p53 protein has prognostic significance and is associated with patterns of treatment failure in head and neck squamous cell carcinoma (HNSCC), We analyzed p53 overexpression in 40 cases of HNSCC. Materials and Methods: Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 40 HNSCC. We evaluated p53 protein expression and analyzed the relationship between the p53 overexpression and age, sex, primary tumor site, stage, survival rate, recurrence. All reported P values resulted from two-sided statistical tests. Results: Overexpression of p53 was detected in 20 cases(50%) among 40 cases of HNSCC. The p53 overexpression was not associated with age, sex, primary tumor site, stage, recurrence and survival rate. Conclusions: In our results, p53 was not significant prognostic factor in HNSCC. Based on many previous studies, It is evident that p53 has a certain role in tumorigenesis of HNSCC. So, the further study is needed to evaluate the prognostic significance of p53 in HNSCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2699-2705
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• 2014

This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.

• 생명과학회지
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• 제27권3호
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• pp.361-369
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• 2017

미토콘드리아의 항상성은 미토콘드리아 생합성과 마이토파지(자가포식에 의한 미토콘드리아 분해)로 불리는 2가지 주요 과정들에 의해 정교하게 조절되고 있다. 지구성 운동 훈련에 반응하여 골격근에서 미토콘드리아 생합성에 관한 기전들은 잘 정립되어 있는 반면 지구성 운동 훈련 후 골격근의 마이토파지 조절 기전과 마이토파지와 미토콘드리아 생합성의 협응을 조절하는 기전은 아직 명확히 밝혀져 있지 않다. 최근 연구들에 의하면 지구성 운동 훈련은 골격근에서 미토콘드리아 생합성, 미토콘드리아 역동성, 미토콘드리아 분해와 관련된 유전인자들의 발현을 증가시킨다고 하였다. 하지만 골격근에서 자가포식이 억제되었을 경우, 지구성 운동 훈련에 의한 미토콘드리아 생합성과 관련된 지표들인 Cox IV와 citrate synthase의 증가는 상쇄되었다. 따라서 자가포식과 마이토파지는 골격근의 미토콘드리아 생합성에 중요한 역할을 하며 정반대되는 이 두 과정(이화 또는 동화작용)의 협응 과정이 지구성 운동 훈련에 반응하여 대사적 기능과 지구력 운동 수행능력을 향상시키는 것과 같은 골격근의 적응에 중요한 듯하다. 지구성 운동은 미토콘드리아의 일정한 숫자를 유지시키기 위해 미토콘드리아 생합성, 미토콘드리아의 융합과 분열, 자가포식/마이토 파지들의 각각의 과정들을 조절하는 것으로 여겨진다. 지구성 운동 훈련은 골격근에서 마이토파지를 활성화시켜 미토콘드리아 양과 질을 조절하여 늙고 건강하지 않은 미토콘드리아를 젊고 건강한 미토콘드리아로 교체시킬 수 있다. 이 총론에서 미토콘드리아 생합성과 마이토파지의 분자학적 기전과 서로 상반되는 이 두 과정간의 협응이 골격근의 지구성 훈련에 대한 세포적 적응에 관련한다는 내용이 논의될 것이다.

• Journal of Dairy Science and Biotechnology
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• 제34권2호
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• pp.137-144
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• 2016

본 시험은 GMP 내 기본적으로 7%로 결합되어 있는 sialic acid의 함유량을 그대로 보유하도록 제조한 유청단백가수분말(시험물질명: 7%-GNANA)을 기능성 식품 원료 개발함에 최종 연구목표를 두었다. 시험물질은 GMP(7% sialic acid 함유)를 원료로 하고, 여기에 식품첨가물로 허용된 효소인 Alcalase를 사용하여 지표성분인 sialic acid를 100% 효율로 분리시킨 후, 동결 건조한 7%-GNANA(7% sialic acid와 GMP 단백질로 구성, 제품명: HELICOBACTROL-7)을 (주)한일바이오메드사(한국)에서 공여 받아 GLP 가이드라인에 따라 미생물복귀돌연변이시험을 실시하였다. 미생물에 대한 돌연변이 유발성 유무를 검색하기 위해 히스티딘 요구성 균주인 Sal. typhimurium TA98, TA100, TA1535 및 TA1537과 트립토판 요구성 균주인 E. coli WP2uvrA를 이용하였다. 미생물복귀돌연변이시험은 시험물질을 5단계의 농도군(0, 61.7, 185, 556, 1,670, $5,000{\mu}g/plate$)으로 하여 평가하였다. 본 시험을 통한 평가결과, 대사활성계 존재 유무와 관계없이 모든 균주에서 시험물질의 각 농도에 의한 복귀돌연변이 유발원 양성기준인 콜로니 생성수치가 재현성 있는 증가를 나타내지 않았으며, 용량의존성도 확인되지 않았다. 결론적으로, 시험물질인 7% G-NANA의 식품첨가물로서 등록을 위하여 수행한 미생물돌연변이시험에서 안전성이 확인되었다.

• Journal of Dairy Science and Biotechnology
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• 제34권2호
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• pp.91-98
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• 2016

본 시험은 안전식품인 우유단백질에서 분리되어 영유아 식품 등에 세계적으로 사용되고 있는 GMP 내 기본적으로 7%로 결합되어 있는 지표성분인 sialic acid의 함유량이 높게 제조한 23%-GNANA를 기능성 식품 원료 개발함에 최종 연구 목표를 두었다. 시험물질은 23% sialic acid와 GMP 단백질로 구성(제품명: HELICOBACTROL-23)되어 있으며, (주)한일바이오메드사(한국)에서 공여 받아 미생물복귀돌연변이시험을 실시하였다. 미생물에 대한 돌연변이 유발성 유무를 검색하기 위해 히스티딘 요구성 균주인 Salmonella typhimurium TA98, TA100, TA1535 및 TA1537과 트립토판 요구성 균주인 Escherichia coli WP2uvrA를 이용하였다. 미생물복귀돌연변이시험은 시험물질을 5단계의 농도군(0, 61.7, 185, 556, 1,670, $5,000{\mu}g/plate$)으로 하여 평가하였다. 평가결과로서, 대사활성계 존재 유무와 관계없이 5균주 모두에서 시험물질의 각 농도에 의한 복귀돌연변이 유발원 양성기준인 콜로니 생성수치가 재현성있는 증가를 나타내지 않았으며, 용량의존성도 확인되지 않았다. 결론적으로, 시험물질인 23%-GNANA의 식품첨가물로서 등록을 위하여 수행한 미생물돌연변이시험에서 안전성이 확인되었다.