• Reproductive and Developmental Biology
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• 제32권4호
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• pp.211-215
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• 2008

The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell-like cells (hSSC-like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT-PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC-like cells 2P) and spontaneous differentiated stem cells (hSSC-like cells 4P). It was overexpressed in hESC and hSSC-like cells 2P but not in hSSC-like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI-38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC-like cells. HBP2 was differently expressed in colon tissues and was related to G1-progression in WI-38 cells. It may playa role in the maintenance of an undifferentiated hSSC-like cell state and transits from G1 to S in WI-38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC-like cells and characterized its involvement to arrest during cell cycle in colon cancer.

• Nutrition Research and Practice
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• 제8권6호
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• pp.632-637
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• 2014

BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-${\alpha}$-hydroxylase (CYP7a1), and sterol 12-${\alpha}$-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.

• 한국축산식품학회지
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• 제38권2호
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• pp.350-361
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• 2018

Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

• 대한한방내과학회지
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• 제30권2호
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• pp.338-354
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• 2009

Objective : Gamijihwang-tang(GJT) has been used as a therapeutic agent for hyperlipidemia in oriental medicine for several years. This study was performed to investigate the effects of GJT on hyperlipidemia in rats using diverse biological methods. Method : Hyperlipidemia was induced by a hyper-lipidemic diet fed for 4 weeks. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, and glucose were measured in the serum after an oral administration of GJT. Lipid peroxidase, SOD, catalase, ACAT, and HMG-CoA were measured in liver after oral administration of GJT. Result: 1. GJT showed safety against cytotoxicity and toxicity in liver. 2. GJT significantly decreased rat's body and liver weight. 3. GJT significantly decreased serum total cholesterol and LDL-cholesterol, but increased serum HDL-cholesterol. 4. GJT significantly decreased serum triglyceride and glucose. 5. GJT significantly decreased lipid peroxidation and increased SOD and catalase in liver. 6. GJT significantly decreased ACAT and HMG-CoA reductase of cholesterol manifestation in liver. Conclusions : These results suggest that GJT might be effective in treatment and prevention of hyperlipidemia.

• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.171-177
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• 2016

Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme $Q_{10}$ ($CoQ_{10}$) with statins. The goal of the current research is to assess the efficacy of combined treatment of $CoQ_{10}$ with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of $CoQ_{10}$ (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin only treatment, $CoQ_{10}$ supplementation significantly reduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, $CoQ_{10}$ supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and $CoQ_{10}$ were increased in the $CoQ_{10}$ co-treated group. These results indicate that $CoQ_{10}$ treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary $CoQ_{10}$ is helpful for solving problem of obese metabolism, so the multiple prescription of $CoQ_{10}$ makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism.

• 생명과학회지
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• 제28권4호
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• pp.472-477
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• 2018

Pravastatin은 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) 환원효소 억제제이며, 혈청 콜레스테롤 농도를 낮추어 심혈 관계 위험성 및 사망률을 감소시킨다. 이번 연구는 부형제, 안정화제, 붕해제, 활택제, 착색제로 사용되는 첨가제들 및 pravastatin과의 적합성 연구를 위해 진행되었다. 모든 첨가제들과의 혼합은 PTP 포장으로 포장되어 가속시험장치($40^{\circ}C/75%$ Relative Humidity)에서 3개월 동안 진행하였다. 가시적인 시험결과로는 백색의 가루 또는 밝은 갈색으로 변화는 없었다. 모든 첨가제들과 pravastatin 혼합 시 pravastatin 함량 및 순도에 있어 아주 적은 수준으로 영향을 주었으며, 그 중 pravastatin의 lactone 함량의 변화가 조금 있는 첨가제로는 microcrystalline cellulose 및 croscamellose sodium이었다. 초기의 pravastatin의 lactone 함량과 비교 시 약 0.22% 및 0.18%로 증가하였고 모든 첨가제들과의 전체 혼합 시도 3개월에서 lactone 함량이 0.43%로 증가하는 것을 확인 하였다. 이번 연구 결과들은 복용편리성을 위한 pravastatin 정제 크기 감소 연구에 크게 기여 할 것으로 판단된다.

• Clinical and Experimental Reproductive Medicine
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• 제47권3호
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• pp.207-212
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• 2020

Objective: Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is a subunit of a ligand-gated ion channel that regulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by controlling the release of gonadotropin-releasing hormone. Few studies have investigated the association between the GRIA1 gene and human infertility. This study evaluated the association of the GRIA1 rs548294 C > T and rs2195450 G > A polymorphisms with the ovarian response to human menopausal gonadotropin (HMG) in Iranian women. Methods: One hundred women with histories of at least 1 year of infertility were included. On the second day of menstruation, patients were injected with HMG; on the third day, blood samples were collected. After hormonal analysis, the GRIA1 rs548294 C > T and rs2195450 G > A genotypes of samples were identified via the restriction fragment length polymorphism method, and on day 9, the number of follicles was assessed via ultrasound. Results: For the GRIA1 rs548294 C > T and rs2195450 G > A single nucleotide polymorphisms, the subjects with CT and GG genotypes, respectively, displayed the highest mean FSH level, LH level, and number of follicles on day 9 of the menstrual cycle (p< 0.05). Significant positive correlations were observed between LH and FSH (p< 0.01), LH and follicle count (p< 0.01), FSH and age (p< 0.05), follicle count and age (p= 0.048), and FSH and follicle count (p< 0.01). Conclusion: This study showed a significant relationship between GRIA1 polymorphisms and ovarian response to the induction of ovulation. Therefore, determining patients' GRIA1 genotype may be useful for improving treatment and prescribing suitable doses of ovulation-stimulating drugs.

• 한국소음진동공학회논문집
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• 제24권3호
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• pp.180-188
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• 2014

현대자동차그룹은 HSM이라고 불리는 간략화된 차량 모델에 대하여 썬루프 버페팅 현상의 실험적인 조사를 시행하였다. 현대자동차그룹은 어떤 CFD솔버가 충분한 정확도를 가지고 썬루프 버페팅 현상을 예측하는지 조사하기 위해 상용CFD공급업체의 참여를 요청하였다. ANSYS Korea는 이번 조사에 참여하여 ANSYS fluent를 이용하여 HSM의 썬루프 버페팅에 대한 수치해석을 수행하였다. 먼저 유동장 검증을 위해 풍속 60 km/h에 대하여 썬루프가 닫힌 HSM모델에 대하여 해석을 수행하였다. HSM상부 면의 세 지점에서 속도 분포를 예측하였고, 이는 시험결과와 비교되었다. 그런 다음 고해상도 난류 모델인 DES를 이용한 해석이 전 풍속영역에 걸쳐 수행되었다. 버페팅 주파수와 버페팅 음압레벨이 예측되었고, 이는 시험결과와 비교되었다. 이를 통해 실제 차량 개발을 위한 CFD의 예측 가능성에 대하여 결론을 얻을 수 있었다.

• 대한한방내과학회지
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• 제38권3호
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• pp.367-375
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• 2017

Objective: To investigate the effect of Artemisiae Iwayomogii Herba, Curcumae Radix, and Aurantii Fructus Immaturus complex extract (ACA) on dyslipidemia-related factor expression and anti-oxidation in HepG2 cells. Method: After treatment with ACA in the HepG2 cells, DPPH, ABTS radical scavenging activity, ROS production, and glutathione (GSH) production were measured. The free fatty acid, lipid peroxidation (MDA), ACAT1, and HMG-CoA reductase mRNA expression were measured in the HepG2 cells after treatment with ACA. Results: 1. DPPH, ABTS radical scavenging activity increased in an ACA concentration-dependent manner. 2. ACA significantly decreased ROS production in comparison to the control group. 3. ACA significantly increased glutathione production. 4. ACA significantly decreased free fatty acid and lipid peroxidation (MDA) in the HepG2 cells. 5. ACA decreased the mRNA expression of ACAT1 and HMG-CoA reductase. Conclusion: These results suggest that Artemisiae Iwayomogii Herba, Curcumae Radix, and Aurantii Fructus Immaturus complex extract (ACA) inhibits dyslipidemia-related factor expression and that it is effective in anti-oxidation. A future in vivo experiment with ACA is needed to investigate the effect on anti-dyslipidemia. It is expected that ACA is effective in anti-dyslipidemia and applied to cardiovascular disease, ischemic heart disease, stroke, etc.