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Biphasic Release Characteristics of Dual Drug-loaded Alginate Beads

  • Lee, Beom-Jin;Cui, Jing-Hao;Kim, Tae-Wan;Heo, Min-Young;Kim, Chong-Kook
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.645-650
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    • 1998
  • The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into $CaCl_2$ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorlv water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329mcm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate bead, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing $Eudragit^{\circledR}$ polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with $Eudragit^{\circledR}$ RS1OO polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of druc released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.

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Preparation and Characterization of Paclitaxel-loaded PLGA Nanoparticles Coated with Cationic SM5-1 Single-chain Antibody

  • Kou, Geng;Gao, Jie;Wang, Hao;Chen, Huaiwen;Li, Bohua;Zhang, Dapeng;Wang, Shuhui;Hou, Sheng;Qian, Weizhu;Dai, Jianxin;Zhong, Yanqiang;Guo, Yajun
    • BMB Reports
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    • v.40 no.5
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    • pp.731-739
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    • 2007
  • The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.

A Novel Polyclonal Antiserum against Toxoplasma gondii Sodium Hydrogen Exchanger 1

  • Xiao, Bin;Kuang, Zhenzhan;Zhan, Yanli;Chen, Daxiang;Gao, Yang;Li, Ming;Luo, Shuhong;Hao, Wenbo
    • Parasites, Hosts and Diseases
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    • v.54 no.1
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    • pp.21-29
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    • 2016
  • The sodium hydrogen exchanger 1 (NHE1), which functions in maintaining the ratio of $Na^+$ and $H^+$ ions, is widely distributed in cell plasma membranes. It plays a prominent role in pH balancing, cell proliferation, differentiation, adhesion, and migration. However, its exact subcellular location and biological functions in Toxoplasma gondii are largely unclear. In this study, we cloned the C-terminal sequence of T. gondii NHE1 (TgNHE1) incorporating the C-terminal peptide of NHE1 (C-NHE1) into the pGEX4T-1 expression plasmid. The peptide sequence was predicted to have good antigenicity based on the information obtained from an immune epitope database. After induction of heterologous gene expression with isopropyl-b-D-thiogalactoside, the recombinant C-NHE1 protein successfully expressed in a soluble form was purified by glutathione sepharose beads as an immunogen for production of a rabbit polyclonal antiserum. The specificity of this antiserum was confirmed by western blotting and immunofluorescence. The antiserum could reduce T. gondii invasion into host cells, indicated by the decreased TgNHE1 expression in T. gondii parasites that were pre-incubated with antiserum in the process of cell entry. Furthermore, the antiserum reduced the virulence of T. gondii parasites to host cells in vitro, possibly by blocking the release of $Ca^{2+}$. In this regard, this antiserum has potential to be a valuable tool for further studies of TgNHE1.

Design of Low-Noise and High-Reliability Differential Paired eFuse OTP Memory (저잡음 · 고신뢰성 Differential Paired eFuse OTP 메모리 설계)

  • Kim, Min-Sung;Jin, Liyan;Hao, Wenchao;Ha, Pan-Bong;Kim, Young-Hee
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.17 no.10
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    • pp.2359-2368
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    • 2013
  • In this paper, an IRD (internal read data) circuit preventing the reentry into the read mode while keeping the read-out DOUT datum at power-up even if noise such as glitches occurs at signal ports such as an input signal port RD (read) when a power IC is on, is proposed. Also, a pulsed WL (word line) driving method is used to prevent a DC current of several tens of micro amperes from flowing into the read transistor of a differential paired eFuse OTP cell. Thus, reliability is secured by preventing non-blown eFuse links from being blown by the EM (electro-migration). Furthermore, a compared output between a programmed datum and a read-out datum is outputted to the PFb (pass fail bar) pin while performing a sensing margin test with a variable pull-up load in consideration of resistance variation of a programmed eFuse in the program-verify-read mode. The layout size of the 8-bit eFuse OTP IP with a $0.18{\mu}m$ process is $189.625{\mu}m{\times}138.850{\mu}m(=0.0263mm^2)$.

Design of eFuse OTP Memory with Wide Operating Voltage Range for PMICs (PMIC용 넓은 동작전압 영역을 갖는 eFuse OTP 설계)

  • Jeong, Woo-Young;Hao, Wen-Chao;Ha, Pan-Bong;Kim, Young-Hee
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.18 no.1
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    • pp.115-122
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    • 2014
  • In this paper, reliability is secured by sensing a post-program resistance of several tens of kilo ohms and restricting a read current flowing over an unblown eFuse within $100{\mu}A$ since RWL driver and BL pull-up load circuits using a regulated voltage of V2V ($=2V{\pm}10%$) are proposed to have a wide operating voltage range for eFuse OTP memory. Also, when a comparison of a cell array of 1 row ${\times}$ 32 columns with that of 4 rows ${\times}$ 8 columns is done, the layout size of 4 rows ${\times}$ 8 columns is smaller with $187.065{\mu}m{\times}94.525{\mu}m$ ($=0.01768mm^2$) than that of 1 row ${\times}$ 32 columns with $735.96{\mu}m{\times}61.605{\mu}m$ ($=0.04534mm^2$).

Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid Stimulation

  • Wang, Jiying;Wang, Yanping;Wang, Huaizhong;Hao, Xiaojing;Wu, Ying;Guo, Jianfeng
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.4
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    • pp.471-478
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    • 2014
  • Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation.

Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs

  • Bao, Yinghui;Gao, Chunqi;Hao, Wenbo;Ji, Cheng;Zhao, Lihong;Zhang, Jianyun;Liu, Tao;Ma, Qiugang
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.10
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    • pp.1465-1470
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    • 2015
  • The present study was conducted to determine the effects of L-carnosine (LC) and/or alpha-lipoic acid (ALA) supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 ($Landrace{\times}Yorkshire$) pigs with an initial body weight of $57.93{\pm}3.14kg$ were randomly allocated to 4 experimental diets using a $2{\times}2$ factorial arrangement with 2 LC supplemental levels (0 or 0.1%) and 2 ALA supplemental levels (0 or 0.03%) in basal diets. The results showed that pigs fed LC-supplemented diets increased final live weight, average daily gain, and average daily feed intake compared to those of pigs fed without LC-supplemented diets (p<0.05). Dietary supplementation with ALA did not affect the growth performance and carcass traits of pigs (p>0.05). Additionally, LC supplementation increased serum triiodothyronine, thyroxine levels, and ALA supplementation increased serum triiodothyronine levels (p<0.05). Serum total cholesterol and triglycerides levels were significantly decreased in LC and ALA supplemented groups, respectively (p<0.05). Moreover, serum low density lipoprotein cholesterol levels were lower in the ALA-supplemented groups than those of pigs fed without ALA-supplemented diets (p<0.05). However, no significant $LC{\times}ALA$ interaction effect on growth performance, blood thyroid hormones and lipid profiles was found. This study suggested that dietary supplementation of LC resulted in better growth performance compared to that of ALA supplementation. L-carnosine and/or ALA supplementation positively modified blood lipid profiles, which may have the potential to prevent cardiovascular diseases.

Hydrogen Bonding Dynamics of Phenol-(H2O)2 Cluster in the Electronic Excited State: a DFT/TDDFT Study (전자 여기상태에서 phenol-(H2O)2 크러스터의 수소결합 동력학: DFT/TDDFT 연구)

  • Wang, Se;Hao, Ce;Wang, Dandan;Dong, Hong;Qiu, Jieshan
    • Journal of the Korean Chemical Society
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    • v.55 no.3
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    • pp.385-391
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    • 2011
  • The time-dependent density functional theory (TDDFT) method has been carried out to investigate the excitedstate hydrogen-bonding dynamics of phenol-$(H_2O)_2$ complex. The geometric structures and infrared (IR) spectra in ground state and different electronically excited states ($S_1$ and $T_1$) of the hydrogen-bonded complex have been calculated using the density functional theory (DFT) and TDDFT method. A ring of three hydrogen bonds is formed between phenol and two water molecules. We have demonstrated that the intermolecular hydrogen bond $O_1-H_2{\cdots}O_3-H$ of the three hydrogen bonds is strengthened in $S_1$ and $T_1$ states. In contrast, the hydrogen bond $O_5-H_6{\cdots}O_1-H$ is weakened in $S_1$ and $T_1$ states. These results are obtained by theoretically monitoring the changes of the bond lengths of the hydrogen bonds and hydrogen-bonding groups in different electronic states. The hydrogen bond $O_1-H_2{\cdots}O_3-H$ strengthening in both the $S_1$ and $T_1$ states is confirmed by the calculated stretching vibrational mode of O-H (phenol) being red-shifted upon photoexcitation. The hydrogen bond strengthening and weakening behavior in electronically excited states may exist in other ring structures of phenol-$(H_2O)_n$.

Design and Implementation of Low-power Neuromodulation S/W based on MSP430 (MSP430 기반 저전력 뇌 신경자극기 S/W 설계 및 구현)

  • Hong, Sangpyo;Quan, Cheng-Hao;Shim, Hyun-Min;Lee, Sangmin
    • Journal of the Institute of Electronics and Information Engineers
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    • v.53 no.7
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    • pp.110-120
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    • 2016
  • A power-efficient neuromodulator is needed for implantable systems. In spite of their stimulation signal's simplicity of wave shape and waiting time of MCU(micro controller unit) much longer than execution time, there is no consideration for low-power design. In this paper, we propose a novel of low-power algorithm based on the characteristics of stimulation signals. Then, we designed and implement a neuromodulation software that we call NMS(neuro modulation simulation). In order to implement low-power algorithm, first, we analyze running time of every function in existing NMS. Then, we calculate execution time and waiting time for these functions. Subsequently, we estimate the transition time between active mode (AM) and low-power mode (LPM). By using these results, we redesign the architecture of NMS in the proposed low-power algorithm: a stimulation signal divided into a number of segments by using characteristics of the signal from which AM or LPM segments are defined for determining the MCU power reduces to turn off or not. Our experimental results indicate that NMS with low-power algorithm reducing current consumption of MCU by 76.31 percent compared to NMS without low-power algorithm.

Anti-tumor Activity and Apoptosis-regulation Mechanisms of Bufalin in Various Cancers: New Hope for Cancer Patients

  • Yin, Pei-Hao;Liu, Xuan;Qiu, Yan-Yan;Cai, Jian-Feng;Qin, Jian-Min;Zhu, Hui-Rong;Li, Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5339-5343
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    • 2012
  • The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.