[99m]Tc-세스타미비 심근 SPECT에서 180도와 360도 데이터 집적의 비교

학위논문(석사)--서울대학교 대학원 :의학과 내과학전공,1996.Maste

Quantification of brain PET images using statistical probabilistic anatomical map

학위논문(박사)--서울대학교 대학원 :의학과 핵의학전공,2001.Docto

Effect of mercaptopyrazine on the inducible Nitric Oxide Synthase in rat and mouse endotoxemia and its mechanism of action

학위논문(박사)--서울대학교 대학원 :약학과 약물학전공,1999.Docto

Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells

Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs. AUDA significantly inhibited PDGF-induced rat VSMC proliferation, which coincided with Pin1 suppression and heme oxygenase-1 (HO-1) upregulation. However, exogenous 8,9-EET, 11,12-EET, and 14,15-EET treatments did not alter Pin1 or HO-1 levels and had little effect on the proliferation of rat VSMCs. On the other hand, AUDA enhanced the PDGF-stimulated cell migration of rat VSMCs. Furthermore, AUDA-induced activation of cyclooxygenase-2 (COX-2) and subsequent thromboxane A2 (TXA2) production were required for the enhanced migration. Additionally, EETs increased COX-2 expression but inhibited the migration of rat VSMCs. In conclusion, the present study showed that AUDA exerted differential effects on the proliferation and migration of PDGF-stimulated rat VSMCs and that these results may not depend on EET stabilization.OAIID:RECH_ACHV_DSTSH_NO:T201738673RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078837CITE_RATE:3.687DEPT_NM:약학과EMAIL:[email protected]_YN:YY

Composition for antifatique or exercise performance comprising mixed extract of Atractylodes macrocephala and Agastache rugosa

본 발명은 백출 및 배초향 혼합 추출물을 포함하는 피로개선 또는 운동수행능력 증진용 조성물에 관한 것이다. 본 발명에 따라 백출 및 배초향 혼합 추출물을 유효성분으로 포함하는 조성물은 PGC-1알파의 발현을 증가시키고, 물리적 운동 수행 후 혈청 및 근육 내 젖산과 혈청 내 젖산탈수소효소 감소를 통해 운동수행능력을 증진하여, 누적된 피로를 효과적으로 개선하고 운동수행능력을 증진시킬 수 있으므로, 피로개선 또는 운동수행능력 증진용 식품 조성물, 약학 조성물, 화장료 조성물 및 피로 또는 운동수행능력 관련 질환의 예방 또는 치료용 약학 조성물로 적용할 수 있다

Inhibition of tumor growth and angiogenesis of tamoxifen-resistant breast cancer cells by ruxolitinib, a selective JAK2 inhibitor

Tamoxifen (TAM) is the most widely used treatment for estrogen receptor-positive breast cancer patients. Unfortunately, the majority of these patients exhibit TAM resistance following treatment. We previously reported that proliferation and migration were greater in TAM-resistant MCF-7 (TAMR-MCF-7) cells than in parental MCF-7 cells. Janus kinases (JAKs) are cytosolic tyrosine kinases that transduce signals from plasma membrane cytokines and growth factor receptors. JAK2 selectively phosphorylates signal transducer and activator of transcription (STAT)-3, and the JAK2-STAT3 signaling pathway is known as a crucial signaling pathway for the regulation of cancer progression and metastasis. In the present study, basal phosphorylation of STAT3 was revealed to be greater in TAMR-MCF-7 cells than in control MCF-7 cells. Ruxolitinib, a potent JAK2 inhibitor, was demonstrated to attenuate STAT3 phosphorylation and the proliferation of TAMR-MCF-7 cells. Ruxolitinib also suppressed the enhanced cell migration of TAMR-MCF-7 cells through the inhibition of epithelial mesenchymal transition. Vascular endothelial growth factor (VEGF), a representative target gene of the JAK2-STAT3 pathway, functions as a key regulator of invasion and angiogenesis. Ruxolitinib significantly inhibited VEGF mRNA expression and transcriptional activity. The present study also performed a chick embryo chorioallantoic membrane assay to assess tumor growth and angiogenesis in TAMR-MCF-7 cells. Ruxolitinib reduced tumor weight and the number of blood vessels produced by TAMR-MCF-7 cells in a concentration-dependent manner. These results indicated that JAK2 could be a new therapeutic target for TAM-resistant breast cancer.OAIID:RECH_ACHV_DSTSH_NO:T201905080RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078837CITE_RATE:1.664DEPT_NM:약학과EMAIL:[email protected]_YN:YY

Therapeutic application of GPR119

GPR119 belongs to the G protein-coupled receptor family and exhibits dual modes of action upon ligand-dependent activation: pancreatic secretion of insulin in a glucose-dependent manner and intestinal secretion of incretins. Hence, GPR119 has emerged as a promising target for treating type 2 diabetes mellitus without causing hypoglycaemia. However, despite continuous efforts by many major pharmaceutical companies, no synthetic GPR119 ligand has been approved as a new class of anti-diabetic agents thus far, nor has any passed beyond phase II clinical studies. Herein, we summarize recent advances in research concerning the physiological/pharmacological effects of GPR119 and its synthetic ligands on the regulation of energy metabolism, and we speculate on future applications of GPR119 ligands for the treatment of metabolic diseases, focusing on non-alcoholic fatty liver disease.OAIID:RECH_ACHV_DSTSH_NO:T201814298RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078837CITE_RATE:5.98DEPT_NM:약학과EMAIL:[email protected]_YN:YN

Therapeutic application of GPR119 ligands in metabolic disorders

GPR119 belongs to the G protein-coupled receptor family and exhibits dual modes of action upon ligand-dependent activation: pancreatic secretion of insulin in a glucose-dependent manner and intestinal secretion of incretins. Hence, GPR119 has emerged as a promising target for treating type 2 diabetes mellitus without causing hypoglycaemia. However, despite continuous efforts by many major pharmaceutical companies, no synthetic GPR119 ligand has been approved as a new class of anti-diabetic agents thus far, nor has any passed beyond phase II clinical studies. Herein, we summarize recent advances in research concerning the physiological/pharmacological effects of GPR119 and its synthetic ligands on the regulation of energy metabolism, and we speculate on future applications of GPR119 ligands for the treatment of metabolic diseases, focusing on non-alcoholic fatty liver disease.OAIID:RECH_ACHV_DSTSH_NO:T201814298RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078837CITE_RATE:5.98DEPT_NM:약학과EMAIL:[email protected]_YN:YN

Discovery of rubiarbonone C as a selective inhibitor of cytochrome P450 4F enzymes

Cytochrome P450 (CYP) enzymes, particularly CYP4A/4F, are the major -hydroxylases of arachidonic acid (AA) that can produce 20-hydroxyeicosatetraenoic acid (20-HETE). Although there are dissimilarities in substrate specificity, tissue distribution, and gene regulation between CYP4A and CYP4F, selective CYP4A or 4F inhibitors are currently unavailable. Therefore, this study was designed to develop CYP4F selective inhibitors using a novel inhibitory assay of 20-HETE formation. The assay was established using pooled human kidney microsomes (HKMs) and human recombinant CYP4 enzymes incubated with 1,2,3,4,5-C-13 AA (C-13(5) AA) as a substrate to minimize interference by endogenous AA. The intrinsic clearance (V-max/K-m) values were 9.5 mu L/min/mg for HKMs and 0.02, 0.9, and 10.1 mu L/min/pmol for CYP4A11, CYP4F2, and CYP4F3B, respectively, which suggests a major role for CYP4F in -hydroxylation of AA. To validate the assay, we tested well-known pan-CYP4 inhibitor HET0016 along with 50 compounds derived from natural products. Of the screened compounds, rubiarbonone C showed the most potent inhibitory activity. The 50% inhibitory concentrations of rubiarbonone C against CYP4A11, CYP4F2, and 4F3B were >50, 4.2, and 4.2 mu M, respectively. Moreover, epoxyeicosatrienoic acid formation from C-13(5) AA was not inhibited by up to 30 mu M rubiarbonone C. Meanwhile, in pooled human liver microsomes, CYP1, 2, and 3 family enzymes involved in drug metabolism were not substantially inhibited by rubiarbonone C. Thus, rubiarbonone C is a selective inhibitor of CYP4F and can be used to discriminate among CYP4 family enzymes and evaluate their roles in physiological and pathophysiological conditions.OAIID:RECH_ACHV_DSTSH_NO:T201814247RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A078837CITE_RATE:5.728DEPT_NM:약학과EMAIL:[email protected]_YN:YN