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Choi, Woon-Seok,Lee, Jung-Jin,Kim, Yo-Han,Kim, In-Su,Zhang, Wei-Yun,Myung, Chang-Seon 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4
Peroxisome proliferator-activated receptor (PPAR) ${\alpha}$, which is abundant in the liver, increases lipoprotein lipase activity, resulting in a decrease of triglyceride (TG) levels. $PPAR{\gamma}$, which is abundant in adipose tissue, stimulates adipocyte differentiation and adipogenesis, and results in an increase in insulin sensitivity. Fenofibrate, a $PPAR{\alpha}$ agonist, is commonly used to treat dyslipidemia, and rosiglitazone, a $PPAR{\gamma}$ agonist, is effective in improving glycemic control. To examine the synergistic effects of rosiglitazone in combination with fenofibrate, an obese type 2 diabetes mellitus (DM) mouse model was established by the combined administration of streptozotocin and nicotinamide and fed on a high-fat diet (35% of energy as fat) for 3 weeks. The mice had significantly higher plasma glucose concentrations and insulin resistance, as examined by an oral glucose tolerance test and insulin challenge test compared with normal mice. After establishing a dose-response curve for each drug, the drugs were orally administered for 3 weeks either alone or in combination. After individual administration of fenofibrate, HDL cholesterol levels significantly increased, and plasma glucose and TG levels decreased in obese type 2 DM mice. The individual administration of rosiglitazone showed increased insulin resistance (QUICKI). However, HDL cholesterol and TG levels were not significantly changed. In a combination of fenofibrate at 25 mg/kg and rosiglitazone at 1.25 mg/kg there was a decrease in plasma glucose and TG levels, and a combination of fenofibrate at 50 mg/kg and rosiglitazone at 2.5 mg/kg showed an increase in plasma HDL cholesterol levels. Moreover, parameters related to insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were improved significantly. Thus, our results show that combination therapy with lower doses of fenofibrate and rosiglitazone ameliorates the type 2 DM condition to a greater extent than high doses of either individual monotherapy.
Chang-Yun Liu,Ji-Lan Lin,Shu-Yan Feng,Chun-Hui Che,Hua-Pin Huang,Zhang-Yu Zou 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.1
Background and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. Methods All 23 exons of FIG4 were sequenced using targeted next-generation sequencing. An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. Results No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. Conclusions Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.
APPLICATION OF FUZZY LOGIC IN THE CLASSICAL CELLULAR AUTOMATA MODEL
Chang, Chun-Ling,Zhang, Yun-Jie,Dong, Yun-Ying 한국전산응용수학회 2006 Journal of applied mathematics & informatics Vol.20 No.1
In [1], they build two populations' cellular automata model with predation based on the Penna model. In this paper, uncertain aspects and problems of imprecise and vague data are considered in this model. A fuzzy cellular automata model containing movable wolves and sheep has been built. The results show that the fuzzy cellular automata can simulate the classical CA model and can deal with imprecise and vague data.
Water-soluble inclusion complex of fullerene with γ-cyclodextrin polymer for photodynamic therapy
Zhang, Wang,Gong, Xiangdong,Liu, Chang,Piao, Yuanzhe,Sun, Yun,Diao, Guowang The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.31
<P>A stable aqueous inclusion complex of fullerene (C60) with macromolecules (C60 concentration as high as 3 × 10<SUP>−4</SUP> mol L<SUP>−1</SUP>) was achieved by a one-step strategy using γ-cyclodextrin polymer (γ-CDP). The inclusion complex of C60 with γ-CDP (C60-γ-CDP) was characterized by ultraviolet-visible, Raman and <SUP>1</SUP>H-NMR spectroscopies, powder X-ray diffraction analysis, and thermogravimetric analysis. The supramolecular interactions and the equilibrium constant for a 1 : 2 (C60 : CD unit in γ-CDP) complex of C60 with γ-CDP were studied. Under ultraviolet A (UVA) irradiation C60-γ-CDP in water could generate singlet oxygen, which was detected by electron paramagnetic resonance spectroscopy. We also evaluated the cytotoxicities of C60-γ-CDP, and investigated the phototoxicity of C60-γ-CDP and pristine C60 toward B16-F10 melanoma cells. The cell viability test showed that C60-γ-CDP had a significantly higher photodynamic ability than that of the pristine C60 under UVA irradiation. This work demonstrated both a CDP-functionalized strategy for enhancing the water-solubility and phototoxicity of fullerenes for applications in cancer photodynamic therapy, as well as remediating the negative biological effects of pristine fullerenes.</P>
Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin
Zhang, Wei Yun,Lee, Jung-Jin,Kim, In-Su,Kim, Yohan,Myung, Chang-Seon S. Karger AG 2011 Pharmacology Vol. No.
<P>Agents that stimulate glucose uptake and improve insulin resistance may be useful in the management of type 2 diabetes mellitus (DM). Thus, the aims of this study were to assess the effects of aromadendrin, a flavonoid from <I>Gleditsia sinensis</I> Lam., on stimulation of glucose uptake and improvement of insulin resistance and to characterize the molecular mechanisms underlying these activities. Insulin-stimulated glucose uptake was measured in HepG2 cells and in differentiated 3T3-L1 adipocytes using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-<I>D</I>-glucose (2-NBDG), a fluorescent <I>D</I>-glucose analog. Expression of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) and adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARγ2 protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively. Insulin-stimulated protein kinase B (Akt/PKB) phosphorylation was measured in high glucose-induced, insulin-resistant HepG2 cells. Similar to 30 μmol/l rosiglitazone, treatment with 30 μmol/l aromadendrin significantly stimulated insulin-sensitive glucose uptake in both HepG2 cells and 3T3-L1 adipocytes. Aromadendrin treatment also enhanced adipogenesis and caused increases in the expression of PPARγ2 and aP2 mRNAs and the PPARγ2 protein in differentiated 3T3-L1 adipocytes. In high glucose-induced, insulin-resistant HepG2 cells, aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to insulin, which could be abrogated by pretreatment with LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Aromadendrin treatment induced adipogenesis by increases in PPARγ2 expression, resulting in stimulation of glucose uptake and ameliorated insulin resistance. These findings suggest that aromadendrin may represent a potential therapeutic candidate for the management of type 2 DM.</P><P>Copyright © 2011 S. Karger AG, Basel</P>
포도주스 침지 제조 흑삼의 Ginsenoside Rg<sub>3</sub> 함량 변화와 Acetylcholinesterase 억제효과
이미라,윤범식,손백신,류뢰,장동량,왕춘년,왕젠,이선영,모은경,성창근,Lee, Mi-Ra,Yun, Beom-Sik,Sun, Bai-Shen,Liu, Lei,Zhang, Dong-Liang,Wang, Chun-Yan,Wang, Zhen,Ly, Sun-Young,Mo, Eun-Kyung,Sung, Chang-Keun 고려인삼학회 2009 Journal of Ginseng Research Vol.33 No.4
흑삼의 속성제조와 ginsenoside $Rg_3$ 함량을 극대화하고자 흑삼 제조시 포도주스에 24시간 침지한 후 $120^{\circ}C$에서 30분간 3회 반복 증숙하여 흑삼을 제조한 후 HPLC 방법을 이용하여 ginsenosides를 분석하였다. 포도주스에 침지하여 제조한 흑삼의 ginsenoside $Rg_3$ 함량은 10.91 mg/g으로 구증구포 방법으로 제조한 흑삼보다 약 2배 가량 함량이 증가되었다. 총 사포닌 함량은 14.97 mg/g으로 전통적인 구증구포 방식으로 제조한 흑삼 (12.79 mg)보다 그 함량이 높았다. 흑삼의 단회투여 (200 mg/kg, p.o.)에 의한 뇌조직 AChE 활성은 투여 24시간 후에 유의적으로 억제되는 효과를 보여주었다. 따라서 본 연구에 적용한 새로운 제조방법은 ginsenoside $Rg_3$를 강화하는 흑삼의 속성제조에 효과적인 방법으로 판단된다. 또한, AChE 활성억제를 통해 흑삼이 뇌기능 개선에 대한 잠재적인 효능을 가지고 있는 것으로 사료된다. This study was conducted to develop a new method for enhancing ginsenoside $Rg_3$, which is abundant in black ginseng. The cognition-enhancing effect of black ginseng extract was investigated via the assay of acetylcholinesterase (AChE) activity. Black ginseng I was prepared through the traditional method (by steaming and drying nine times repetitions). Black ginseng II, on the other hand, was prepared by steaming the ginseng three times at $120^{\circ}C$ for 30 min after soaking it in grape juice for 24 h. The ginsenosides of white, red, and black ginseng I, and II were investigated using the HPLC method, respectively. In black ginseng II, the ginsenoside $Rg_3$ contents, which cannot be found in white ginseng, amounted to 10.91 mg/g, approximately 18 times more than that in red ginseng. In the in-vivo study, black ginseng extract (200 mg/kg, p.o.) inhibited the AChE activity after 24 h by a single administration in the brain. Thus, the new manufacturing method for black ginseng was found to more effective in the conversion of ginsenoside $Rg_3$ compared to the traditional method. Black ginseng may also have the effect of preventing the cognitive impairment induced by cholinergic dysfunction.
Chang, Sung-A,Lee, Eun Ju,Kang, Hyun-Jae,Zhang, Shu-Ying,Kim, Ji-Hyun,Li, Lian,Youn, Seock-Won,Lee, Choon-Soo,Kim, Keum-Hyun,Won, Joo-Yun,Sohn, Jong-Woo,Park, Kyung-Woo,Cho, Hyun-Jai,Yang, Sung-Eun,Oh Wiley (John WileySons) 2008 Stem Cells Vol.26 No.7
<P>Stem cell transplantation in acute myocardial infarction (AMI) has emerged as a promising therapeutic option. We evaluated the impact of AMI on mesenchymal stem cell (MSC) differentiation into cardiomyocyte lineage. Cord blood-derived human MSCs were exposed to in vitro conditions simulating in vivo environments of the beating heart with acute ischemia, as follows: (a) myocardial proteins or serum obtained from sham-operated rats, and (b) myocardial proteins or serum from AMI rats, with or without application of oscillating pressure. Expression of cardiac-specific markers on MSCs was greatly induced by the infarcted myocardial proteins, compared with the normal proteins. It was also induced by application of oscillating pressure to MSCs. Treatment of MSCs with infarcted myocardial proteins and oscillating pressure greatly augmented expression of cardiac-specific genes. Such expression was blocked by inhibitor of transforming growth factor beta(1) (TGF-beta(1)) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocyte-specific markers were able to make a coupling with cardiomyocytes but not to selfbeat. The pathophysiologic significance of in vitro results was confirmed using the rat AMI model. The protein amount of TGF-beta(1) and BMP-2 in myocardium of AMI was significantly higher than that in normal myocardium. When MSCs were transplanted to the heart and analyzed 8 weeks later, they expressed cardiomyocyte-specific markers, leading to improved cardiac function. These in vitro and in vivo results suggest that infarct-related biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-beta/BMP-2 pathways.</P>