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      • Development of ligustrazine-loaded lipid emulsion: Formulation optimizatiom, characterization and biodistribution

        ( Lijun Wei ),( Nirmal Marasini ),( Gao Li ),( Chul Soon Yong ),( Jong Oh Kim ),( Qizhe Quan ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

        Ligustrazine is a traditional Chinese medicine used to treat various cardiovascular and neurovascular complications. However, this compound exhibits rapid first-pass metabolism, a short biological half-life, low stability and potential vascular irritation that restrict its use for long-term therapy. The use of a lipid emulsion as a carrier for intravenous administration of ligustrazine might provide sustained and prolonged release, thereby reducing the frequency of administration and improving patient compliance. The main purpose of our study was to develop a highly stable and sterile optimal formulation of a ligustrazine lipid emulsion (LLE) and to evaluate its pharmacokinetic behavior and tissue distribution in rats. The final optimal formulation consisted of soybean oil (12.0%), oleic acid (0.6%), lecithin (1.0%), poloxamer 188 (0.6%) and glycerol (2.25%). The average particle size, polydispersity index (PDI), zeta-potential and pH of the final product were 215.0±2.5 nm, 0.076±0.033, -40.4±5.3 mV and 7.25±0.05, respectively. The LLE was stable for at least three months at room temperature. In vitro drug release studies of the LLE suggested a sustained release profile, which was further confirmed by in vivo pharmacokinetic studies in rats. The area under the drug concentration-time curve from 0 h to 10 h (AUC(0-10h)) for LLE was increased by 1.6-fold compared with that of the commercially available ligustrazine injection (LI), suggesting enhanced bioavailability from the lipid-based emulsion. Furthermore, a tissue distribution study showed significant improvement in the distribution pattern of ligustrazine with a higher AUC(0-180 min) observed in all tissues for LLE than for LI. In conclusion, LLE, with excellent stability, improved pharmacokinetics and tissue distribution, demonstrates great potential for the delivery of ligustrazine for clinical applications.ⓒ2012 Elsevier B.V.All rights reserved.

      • SCISCIESCOPUS

        NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4

        Liu, Xiaojun,Jiang, Yanan,Wu, Jianfu,Zhang, Wenjuan,Liang, Yupei,Jia, Lijun,Yu, Jinha,Jeong, L.S.,Li, Lihui Elsevier 2017 Biochemical and biophysical research communication Vol. No.

        <P><B>Abstract</B></P> <P>It has been reported that MLN4924 can inhibit cell growth and metastasis in various kinds of cancer. We have reported that MLN4924 is able to inhibit angiogenesis through the induction of cell apoptosis both in vitro and in vivo models. Moreover, Neddylation inhibition using MLN4924 triggered the accumulation of pro-apoptotic protein NOXA in Human umbilical vein endothelial cells (HUVECs). However, the mechanism of MLN4924-induced NOXA up-regulation has not been addressed in HUVECs yet. In this study, we investigated how MLN4924 induced NOXA expression and cellular apoptosis in HUVECs treated with MLN4924 at indicated concentrations. MLN4924-induced apoptosis was evaluated by Annexin V-FITC/PI analysis and expression of genes associated with apoptosis was assessed by Quantitative RT-PCR and western blotting. As a result, MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. Mechanistically, inactivation of Neddylation pathway caused up-regulation of activating transcription factor 4 (ATF-4), a substrate of Cullin-Ring E3 ubiquitin ligases (CRL). NOXA was subsequently transactivated by ATF-4 and further induced apoptosis. More importantly, knockdown of ATF-4 by siRNA significantly decreased NOXA expression and apoptotic induction in HUVECs. In summary, our study reveals a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs, which may help extend further study of MLN4924 for angiogenesis inhibition treatment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. </LI> <LI> Inactivation of neddylation caused up-regulation of ATF4, a substrate of CRL. </LI> <LI> NOXA was transactivated by ATF4 and further induced apoptosis. </LI> <LI> Knockdown of ATF-4 significantly decreased NOXA expression and apoptotic induction. </LI> <LI> We revealed a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs. </LI> </UL> </P>

      • KCI등재

        TNF-α-Induced SOX5 Upregulation Is Involved in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Through KLF4 Signal Pathway

        Lijun Xu,Lili Zheng,Zhifang Wang,Chong Li,Shan Li,Xuedi Xia,Pengyan Zhang,Li Li,Lixia Zhang 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.6

        Postmenopausal osteoporosis (PMOP) is a common sys-temic skeletal disease characterized by reduced bone mass and microarchitecture deterioration. Although differentially expressed SOX5 has been found in bone marrow from ovariectomized mice, its role in osteogenic differentiation in human mesenchymal stem cells (hMSCs) from bone marrow in PMOP remains unknown. In this study, we investigated the biological function of SOX5 and explore its molecular mechanism in hMSCs from patients with PMOP. Our findings showed that the mRNA and protein expression levels of SOX5 were upregulated in hMSCs isolated from bone marrow samples of PMOP patients. We also found that SOX5 overexpression decreased the alkaline phosphatase (ALP) activity and the gene expression of osteoblast markers including Collagen I, Runx2 and Osterix, which were increased by SOX5 knockdown using RNA interference. Furthermore, TNF- notably upregulated the SOX5 mRNA expression level, and SOX5 knockdown reversed the effect of TNF- on osteogenic differentiation of hMSCs. In addition, SOX5 overexpression increased Kruppel-like factor 4 (KLF4) gene expression, which was decreased by SOX5 silencing. KLF4 knockdown abrogated the suppressive effect of SOX5 overexpression on osteogenic differentiation of hMSCs. Taken together, our results indicated that TNF--induced SOX5 upregulation inhibited osteogenic differentiation of hMSCs through KLF4 signal pathway, suggesting that SOX5 might be a novel therapeutic target for PMOP treatment.

      • KCI등재

        TNF-α-Induced SOX5 Upregulation Is Involved in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Through KLF4 Signal Pathway

        Xu, Lijun,Zheng, Lili,Wang, Zhifang,Li, Chong,Li, Shan,Xia, Xuedi,Zhang, Pengyan,Li, Li,Zhang, Lixia Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.6

        Postmenopausal osteoporosis (PMOP) is a common systemic skeletal disease characterized by reduced bone mass and microarchitecture deterioration. Although differentially expressed SOX5 has been found in bone marrow from ovariectomized mice, its role in osteogenic differentiation in human mesenchymal stem cells (hMSCs) from bone marrow in PMOP remains unknown. In this study, we investigated the biological function of SOX5 and explore its molecular mechanism in hMSCs from patients with PMOP. Our findings showed that the mRNA and protein expression levels of SOX5 were upregulated in hMSCs isolated from bone marrow samples of PMOP patients. We also found that SOX5 overexpression decreased the alkaline phosphatase (ALP) activity and the gene expression of osteoblast markers including Collagen I, Runx2 and Osterix, which were increased by SOX5 knockdown using RNA interference. Furthermore, $TNF-{\alpha}$ notably upregulated the SOX5 mRNA expression level, and SOX5 knockdown reversed the effect of $TNF-{\alpha}$ on osteogenic differentiation of hMSCs. In addition, SOX5 overexpression increased Kruppel-like factor 4 (KLF4) gene expression, which was decreased by SOX5 silencing. KLF4 knockdown abrogated the suppressive effect of SOX5 overexpression on osteogenic differentiation of hMSCs. Taken together, our results indicated that $TNF-{\alpha}$-induced SOX5 upregulation inhibited osteogenic differentiation of hMSCs through KLF4 signal pathway, suggesting that SOX5 might be a novel therapeutic target for PMOP treatment.

      • KCI등재

        NiCoSe4@CFF with excellent properties prepared by microwave method for flexible supercapacitors and oxygen evolution reaction

        Lijun Du,Ning Lv,Jiashuai Li,Jiayi Zhang,Yilan Chen,Yalin Zhang,Zhen Li,Xianqiang Huang,Jujie Luo 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.120 No.-

        NiCoSe4 nanoflowers were synthesized on carbon fiber felt (CFF) by microwave method, and the effects ofmicrowave time and microwave power on the morphology, physical phase and performance ofNiCoSe4@CFF were explored. The results display that the nanostructured NiCoSe4 prepared under themicrowave irradiation of 1000 W for 120 s is uniformly loaded on the CFF. The NiCoSe4@CFF electrodeexhibits a superior specific capacity of 1653.6F g1 at 1A/g and maintains a superior cycling performanceof 87.05 % of the initial capacitance over 150,000 cycles. In addition, the flexible supercapacitor fabricatedwith NiCoSe4@CFF as the cathode exhibits excellent flexibility and flexural strength. As an effective catalystfor oxygen evolution reaction (OER), NiCoSe4@CFF demonstrates a low overpotential of 0.358 V, arelatively small Tafel slope of 115.93 mV dec1 and an excellent lifetime at 10 mA cm2.

      • SCISCIESCOPUS

        Spin diffusion and non-local spin-valve effect in an exfoliated multilayer graphene with a Co electrode

        Li, Lijun,Lee, Inyeal,Lim, Dongsuk,Rathi, Servin,Kang, Moonshik,Uemura, Tetsuya,Kim, Gil-Ho IOP 2016 Nanotechnology Vol.27 No.33

        <P>We fabricated a non-local spin valve with a thin layer of graphite with Co transparent electrodes. The spin-valve effect and spin precession were observed at room temperature. The magnitude of the mangetoresistance increases when temperature decreases. The spin-relaxation time, <img ALIGN='MIDDLE' ALT='${\tau }_{s}$' SRC='http://ej.iop.org/images/0957-4484/27/33/335201/nanoaa2bccieqn1.gif'/>, obtained from the fitting of the Hanle curves increases with decreasing temperature with a weak dependence <img ALIGN='MIDDLE' ALT='$\sim {T}^{-0.065}$' SRC='http://ej.iop.org/images/0957-4484/27/33/335201/nanoaa2bccieqn2.gif'/> while the spin-diffusion constant <I>D</I> decreases. At room temperature, <img ALIGN='MIDDLE' ALT='${\tau }_{s}$' SRC='http://ej.iop.org/images/0957-4484/27/33/335201/nanoaa2bccieqn3.gif'/> exceeds 100 ps and the spin-diffusion length, <img ALIGN='MIDDLE' ALT='${\lambda }_{s}$' SRC='http://ej.iop.org/images/0957-4484/27/33/335201/nanoaa2bccieqn4.gif'/>, is ∼2 <I>μ</I>m. The temperature dependence of <img ALIGN='MIDDLE' ALT='${\lambda }_{s}$' SRC='http://ej.iop.org/images/0957-4484/27/33/335201/nanoaa2bccieqn5.gif'/> is not monotonic, and it has the largest value at room temperature. Our results show that multilayer graphene is a suitable material for spintronic devices.</P>

      • KCI등재

        Dominant genera of cyanobacteria in Lake Taihu and their relationships with environmental factors

        Lijun Feng,Shiyou Liu,Wenxian Wu,Jiawen Ma,Pei Li,Hailing Xu,Na Li,Yaoyu Feng 한국미생물학회 2016 The journal of microbiology Vol.54 No.7

        Cyanobacterial blooms in freshwaters have become one of the most widespread of environmental problems and threaten water resources worldwide. Previous studies on cyanobacteria in Lake Taihu often collected samples from one site (like Meiliang Bay or Zhushan Bay) and focused on the variation in patterns or abundance of Microcystis during the blooming season. However, the distribution of cyanobacteria in Lake Taihu shows differing pattern in various seasons. In this study, water samples were collected monthly for one year at five sites in Lake Taihu with different trophic status and a physicochemical analysis and denaturing gradient gel electrophoresis (DGGE) were conducted. DGGE fingerprint analysis showed that Microcystis (7/35 bands) and Synechococcus (12/35 bands) were the two most dominant genera present during the study period at all five sites. Cyanobium (3/35 bands) was the third most common genus which has seldom been previously reported in Lake Taihu. Redundancy analysis (RDA) indicated that the cyanobacterial community structure was significantly correlated with NO3 --N, CODMn, and NH4 +-N in the winter and spring, whereas it was correlated with water temperature in the summer and autumn. Limiting the nutrient input (especially of N and C loading) in Lake Taihu would be a key factor in controlling the growth of different genera of cyanobacteria.

      • KCI등재

        Maternal betaine supplementation ameliorates fatty liver disease in offspring mice by inhibiting hepatic NLRP3 inflammasome activation

        Li Lun,Sun Liuqiao,Liang Xiaoping,Ou Qian,Tan Xuying,Li Fangyuan,Lai Zhiwei,Ding Chenghe,Chen Hangjun,Yu Xinxue,Wu Qiongmei,Wei Jun,Wu Feng,Wang Lijun 한국영양학회 2023 Nutrition Research and Practice Vol.17 No.6

        BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

      • KCI등재

        Action Recognition with deep network features and dimension reduction

        ( Lijun Li ),( Shuling Dai ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.2

        Action recognition has been studied in computer vision field for years. We present an effective approach to recognize actions using a dimension reduction method, which is applied as a crucial step to reduce the dimensionality of feature descriptors after extracting features. We propose to use sparse matrix and randomized kd-tree to modify it and then propose modified Local Fisher Discriminant Analysis (mLFDA) method which greatly reduces the required memory and accelerate the standard Local Fisher Discriminant Analysis. For feature encoding, we propose a useful encoding method called mix encoding which combines Fisher vector encoding and locality-constrained linear coding to get the final video representations. In order to add more meaningful features to the process of action recognition, the convolutional neural network is utilized and combined with mix encoding to produce the deep network feature. Experimental results show that our algorithm is a competitive method on KTH dataset, HMDB51 dataset and UCF101 dataset when combining all these methods.

      • KCI등재

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