• Molecules and Cells
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• 제38권6호
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• 약학회지
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• 제48권6호
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• pp.379-383
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• 2004

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of chronic viral hepatitis B and drug-induced hepatitis through the inhibition of lipid peroxidation and c ovalent binding of drug metabolites to lipids of microsomes. The bioequivalence of two DDB products was evaluated according to the guidelines of KFDA. The test product was Hepaphil soft capsule(R) made by KMS Pharm. Co. Containing 3 mg DDB and the reference product was Nissel tablet(R) made by Taerim Pharm. Co. Containing 25 mg DDB. Twenty healthy male subjects, 25.4(22~30) years old and 66.7(54~77)kg, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets or two capsules were orally administered, blood was taken at predetermined time intervals and the concentration of DDB in plasma was determined using a validated HPLC method with UV detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.91~log1.00 and log 1.05~log 1.15, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hepaphil soft capsule is bioequivalent to Nissel tablet.

• 대한화장품학회지
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• 제27권1호
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• pp.73-81
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• 2001

For an attempt to develop safe materials protecting UV-induced skin damage, plant extracts were evaluated for their antioxidative and free radical scavenging activities. From the results of these screening procedures, the ethanol extract of the flowers of Prunus persica was selected for further study. It was found that Prunus persica (50-200 $\mu\textrm{g}$/㎖) inhibited UVB-induced DNA damage measured by tail moment in the Single Cell Gel Electrophoresis(COMET assay) and inhibited UV-induced lipid peroxidation, expecially against UVB-induced peroxidation at higher than 10 $\mu\textrm{g}$/㎖. Also P.persica(100∼1,000 $\mu\textrm{g}$/㎖) inhibited the amount of $\^$14/C-arachidonic acid metabolites release from UVB-irradiated keratinocytes and it possessed the protective activity against UV-induced cytotoxicity of keratinocytes. All these results indicate that the flowers of P. persica extract may be beneficial for protection UV-induced skin damage when topically applied.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.267-282
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• 2000

Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

• 대한화장품학회지
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• 제30권3호
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• pp.345-352
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• 2004

아토피 피부염을 설명하는 데는 두 가지 패러다임이 있는데, 첫 번째는 outside-inside paradigm이고 두 번째는 inside-ouside paradigm이다. Outside-inside paradigm에 의하면 아토피 피부염을 치료하기 위한 가장 좋은 방법은 피부 장벽 기능을 회복시키는 것이다. 장벽 기능은 각질층의 특징적인 구조에 의해 유지되는데, 각질층은 층상구조의 inter-cellular lipids와 corneocyte로 구성되어 있다. 아토피 피부염 환자, 층판상 어린선 환자의 각질층 내 층상구조는 hexagonal 구조가 많이 존재하고 있음을 보였으며, 이는 Ceramide 1 타입과 long chain fatty acid의 감소 때문이라고 보여진다. 이러한 이유에서 라멜라구조를 가지며 intercellular long periodicity phase 기능을 복원할 수 있는 보습제는 각질층의 intercellular lipid의 층상구조를 복원시킬 수 있을 것이다. 또한 세라마이드와 유사세라마이드를 함유한 보습제는 손상된 피부장벽, 피부질환, 아토피 피부염을 위한 유용한 치료제로 사용할 수 있다. Inside-outside paradigm에 따르면, 아토피 피부염 등이 보조 T cell, lg E, eosinophil 등을 포함한 면역반응과 관계되는데, 특히 Th1/Th2 imbalance의 복원이 아토피 피부염을 치료하는데 효과적일 것이다. 현재 여러 종류의 면역억제제가 소개되고 있지만, 이들은 고유 면역기능을 감소시킬 우려를 가지고 있다. 따라서, 세라마이드 대사산물인 SPC와 S1P는 면역조절 기능 및 상처치유의 기능을 가짐으로써 향후 관심이 집중될 것이다.

• 생명과학회지
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• 제32권3호
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• pp.256-262
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• 2022

옥시스테롤은 담즙산 합성 동안 일련의 효소 반응에 의해 생성된 콜레스테롤의 산화물로써, 콜레스테롤과 유사하게 세포내 영역으로 빠르게 이동하여 면역 세포 반응, 지질 대사 및 콜레스테롤 항상성과 같은 다양한 세포 과정을 조절한다. 글루코코르티코이드 수용체(GR), 에스트로겐 수용체(ER) 및 간 X 수용체(LXR)와 같은 종류의 핵 수용체는 여러 조직에서 옥시스테롤에 의해 조절될 수 있다. 가장 풍부한 옥시스테롤인 27-하이드록시콜레스테롤(27-OHC)은 조직 특이적 방식에 의해 에스트로겐 수용체 활성을 활성화하거나 억제하기 때문에 선택적 에스트로겐 수용체 조절자로 규명되었다. 특히 27-하이드록시콜레스테롤이 동맥 경화증 플라크에서 많이 발견되고 대식세포가 거품 세포로 변형되는 것을 가속화하기 때문에 동맥 경화증 발병에 기여하는 것이 분명해 보이나, 다른 연구들에서는 27-하이드록시콜레스테롤이 간 및 지방 조직을 포함한 다양한 대사 기관에 미치는 영향에 대해 반대 의견이 존재한다. 따라서 본 총설을 통해 대사 조직에서의 27-하이드록시콜레스테롤 역할에 대한 논의와 함께, 죽상 동맥 경화증 및 대사 증후군에 영향을 주는 27-하이드록시콜레스테롤의 세부 기전에 대해 논의하고자 한다.

• 한국유기농업학회지
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• 제17권2호
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• pp.237-251
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• 2009

본 시험은 돼지사료에 첨가하여 사용하던 항생제를 대체하기 위한 유기산제의 효과를 평가하기 위하여 생후 79일령, $32{\sim}33kg$ 범위의 일대 잡종(Large White${\times}$Landrace) 돼지 25두에 항생제 무첨가사료(대조구)와 대조구 사료에 각각 Chlortetracycline(CTC) 100mg/kg을 첨가한 사료(T1), CTC 100mg/kg과 $Acidomix^{(R)}$ (formic acid 25%, sorbic acid 10%, fumaric acid 10%)를 0.1% 첨가한 사료(T2), $Acidomix^{(R)}$를 0.1% 첨가한 사료(T3), $Acidomix^{(R)}$를 0.3% 첨가한 사료(T4)의 5개 처리로 구분하여 급여한 다음 생산성과 혈액성상의 변화를 조사하였다. 시험 기간 동안 육성전기 돼지의 일당증체량은 생육이 진행됨에 따라 지속적으로 증가하였고 평균 일당증체 량은 T4구 > T2구 > T1구> T3구 > 대조구 순으로 낮아졌다. 특히 T4구가 대조구에 비하여 유의하게 높았고(p<0.05) 다음으로 CTC 또는 $Acidomix^{(R)}$를 첨가한 모든 처리구가 대조구에 비하여 높았다. 사료요구율의 경우에도 생육이 진행됨에 따라 높아졌고 평군 사료요구 율은 T4구 < T3구 < T2구 < T1구 < 대조구의 순서로 높아져 T4구와 T3구의 사료요구율이 낮았으나 통계적으로 유의한 차이는 나타내지 않았다. 사료 섭취량은 대조구 및 처리구 간에서 큰 차이를 보이지 않았다. 혈액내의 요소태 질소(BUN), cholesterol, triglyceride, total lipid함량은 유의한 차이가 인정되었으나 비교적 정상 수치에 근접한 결과로 개체간의 차이로 판단되며 유기산 또는 항생제의 급여가 혈액성상에는 그다지 큰 영향을 미치지 않았다. 이상의 결과를 볼 때, 유기산제의 첨가가 대조구 혹은 항생제 첨가구 보다 육성전기 돼지에 있어서 일당증체량을 증가시키고 사료요구율은 낮아져 유기산제에 의한 돼지의 성장촉진 및 사료요구율의 개선효과가 나타남으로써 항생제의 대체 가능성을 시사하였다.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.465-482
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• 2021

Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

• Investigative Magnetic Resonance Imaging
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• 제16권1호
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• pp.40-46
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• 2012

목적: 폐암의 생체 수소자기공명분광법의 실행가능성을 탐색하고자 하였다. 대상과 방법: 이 전향적 연구는 해당병원의 임상시험심사위원회로 승인을 받았고 모든 환자로부터 사전동의를 받았다. 병리적으로 폐암으로 확인된 (평균 직경, 56.8 mm; 범위, 44-77 mm) 10명의 환자들에서 (남자 7명, 여자 3명; 평균나이, 64.4세) 단일 복셀 수소자기공명분광기법으로 호흡 유발 PRESS (point-resolved spectroscopic sequence)를 사용하여 1.5 T 수소자기공명 분광법을 시행하였다. 스펙트럼 습득의 기술적 성공률을 평가하고 실패한 증례들의 이유를 고찰하였다. 결과: 10개의 폐암 중 8개 폐암에서 분석 가능한 수소자기공명 분광 스펙트럼을 획득했다 (기술적 성공률, 80%). 두 개의 수소자기공명 분광 데이터는 심각한 기준치 왜곡으로 분석할 수 없었다. 대표적인 대사물질로 choline과 lipid들이 관찰되었다. 결론: 비록 제한적 수의 환자에서의 결과이지만 폐암에서 얻어진 생체 수소 자기공명 분광 스펙트럼이 분석가능하고 높은 성공률로 획득하였기 때문에 폐암 환자에서 호흡 유발 PRESS 방법을 사용한 생체 수소자기공명분광법이 실행가능하다고 판단된다.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.100-105
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• 2008

The sphingolipid metabolites act as lipid mediator for cell proliferation and apoptosis in mammalian cells. In bacteria, sphingolipid metabolism remains unknown. The purpose of this study was to investigate whether sphingolipid metabolism is potential target for fumonisin $B_1$($FB_1$) and desipramine in Sphingomonas chungbukensis, Gram-negative bacteria, by comparing the intracellular contents of bacterial sphingolipids with ones of HIT-T15 ${\beta}$-cells, hamster pancreatic cells. The concentrations of ceramide and dihydroceramide were 18.0 ${\pm}$ 12.0 and 0.025 ${\pm}$ 0.018 nmol/mg protein, respectively, in HIT-T15 cells. However, the concentrations of ceramide and dihydroceramide in the bacterial culture were 2.0 ${\pm}$ 1.2 and 10.6 ${\pm}$ 5.5 nmol/mg protein, respectively. $FB_1$ decreased the level of ceramide from 18.0 to 3.8 nmol/mg protein in HIT-T15 ${\beta}$-cells. However, dihydroceramide content in $FB_1$-treated HIT-T15 cells was slightly decreased compared with the control culture. When S. chungbukensis was treated with either $FB_1$ or desipramine, dihydroceramide level was increased by 5- and 4-fold, respectively, compared with the control bacteria. These results indicate that $FB_1$ and desipramine may act as an activator in bacterial sphingolipid biosynthetic pathway, and bacterial sphingolipid metabolism pathway appears to be different from the pathway of mammalian cells.