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.

비영리 조직의 경영 및 그 경영 범위에 관한 연구 : It's Management and Enclosure

李維安,申光龍 啓明大學校 産業經營硏究所 2002 經營經濟 Vol.35 No.1

20세기 80년대부터 전세계 범위에서 정부, 기업 및 제3부문 모두 비영리 조직의 경경에 대해서 중시하게 되었다. 그러나, 비영리 조직의 경영에 대하여 명백한 정의, 혹은 명확한 판단의 정의를 내리는 것이 쉽지 않다. 본 논문에서는 비영리 조직의 경영 및 그 경영범위의 연구를 통해 비영리 조직 경영의 가치를 파악하고 구현하는데 이해를 돕고자 한다. 비영리 조직이 사회로부터 높은 도덕적 표준을 부여 받음에 따라 약자의 입장에 처해 있는 대중을 위해 사회적 책임을 가지고 활동하며, 이러한 비영리 조직의 경영에 있어서 쉽게 발생하는 사회적 논쟁들을 경영학적 측면에서 고찰하고자 한다.

Identification of candidate odorant‐degrading enzyme genes in the antennal transcriptome of Aphidius gifuensis

Kang Zhi‐Wei,Liu Fang‐Hua,Xu Yong‐Yu,Cheng Jia‐Hui,Lin Xiao‐Li,Jing Xiang‐Feng,Tian Hong‐Gang,Liu Tong‐Xian 한국곤충학회 2021 Entomological Research Vol.51 No.1

Odorant‐degrading enzymes (ODEs) have been found in insect antennae and play a critical role in signal chemical degradation once the message is conveyed. Significant progress has been made in characterizing ODEs in a variety of pests but very little is known in their natural enemies. We have carried out an antennae‐ and sex‐specific transcriptome of Aphidius gifuensis, a natural enemy of aphid, to identify the candidate ODEs. Based on the antennae‐ and sex‐specific transcriptome, a total of 100 putative ODEs were identified including one aldehyde oxidase (AOX), four alcohol dehydrogenases (ADs), eight UDP‐glucuronosyltransferases (UGTs), 45 cytochrome P450 (P450s), nine glutathione S‐transferases (GSTs) and 40 carboxylesterases (CCEs or CXEs). Additionally, we used RT‐qPCR to determine the expression profiles of these genes in tissues of both sexes. Based on the phylogenic analysis and tissue‐expression patterns, AgifEstE4, AgifCXE3, AgifCCE4, AgifCCE7, and AgifCCE18 were suggested as key ODEs in A. gifuensis. In addition, the female or male specifically enriched genes, such as AgifCCE17, AgifEstB1, AgifCYP18a1, AgifUGT2C2, were also considered to involve in the chemosensory processing in A. gifuensis. This study not only identified the candidate ODEs in A. gifuensis but also provided source for further exploration of the molecular mechanisms of chemical signal transductions in A. gifuensis, as well as other hymenopteran species.

Catalytic synthesis and enhanced Curie temperature of ε-Fe₃N@C nanostructure synthesized in a tetraethylenepentamine solution

Li, Yong,Pan, Desheng,Li, Da,Feng, Yang,Choi, C.J.,Liu, Wei,Zhang, Zhidong Elsevier 2018 Journal of magnetism and magnetic materials Vol.465 No.-

<P><B>Abstract</B></P> <P>ε-Fe<SUB>3</SUB>N@C nanocrystals without oxidation are one-pot synthesized by using the iron(II) acetylacetonate and tetraethylenepentamine (TEPA) as Fe and N precursors under a low temperature (533 K) in the presence of a small quantity of Pt atoms as the co-catalyst. The ε-Fe<SUB>3</SUB>N@C nanoparticles with a core-shell structure are nearly spherical and have a wide particle size distribution of 100–500 nm in diameter. Fe nanoparticles obtained by reduction of Fe<SUP>2+</SUP> with TEPA are an effective catalyzer for decomposing TEPA to produce N and C atoms at a temperature much lower than the boiling point of TEPA. The diffusion of N atoms into Fe nanoparticles for the formation of ε-Fe<SUB>3</SUB>N@C is proposed, based on the results obtained by kinetically controlling the synthetic temperature and surfactants. The ε-Fe<SUB>3</SUB>N@C nanoparticles have an excellent saturation magnetization of 135.5 emu/g at room temperature. A significantly enhanced Curie temperature (T<SUB>C</SUB>) of 614 K is reached in the present ε-Fe<SUB>3</SUB>N@C nanoparticles, which is much higher than the T<SUB>C</SUB> values in the previously reported ε-Fe<SUB>3</SUB>N<SUB>x</SUB>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Tetraethylenepentamine is proposed as a new N source to synthesize Fe nitride. </LI> <LI> Core-shelled ε-Fe<SUB>3</SUB>N@C nanoparticles are one-pot synthesized at 260 °C. </LI> <LI> Curie temperature of ε-Fe<SUB>3</SUB>N is significantly enhanced to 614 K. </LI> <LI> ε-Fe<SUB>3</SUB>N@C shows a high saturation magnetization of 135.5 emu/g at 300 K. </LI> </UL> </P>

SALT-INDUCED CHLOROPLAST PROTEIN (SCP) is Involved in Plant Tolerance to Salt Stress in Arabidopsis

Yong Zhuang,Yangxuan Liu,Yuxiang Li,Ming Wei,Yuying Tang,Penghui Li,Zhijian Liu,Hui Li,Weizao Huang,Songhu Wang 한국식물학회 2019 Journal of Plant Biology Vol.62 No.6

Soil salinization threats the agricultural productionand food security worldwide. Salt stress induced plantsenescence and chloroplast degradation. However, it remainslargely unknown how the chloroplast-localized proteins affectplant response to salt stress. Here, we characterized a novelgene (At5g39520) in Arabidopsis, which is induced by saltstress and encodes a chloroplast-localized protein. Thus, thisgene was named SALT-INDUCED CHLOROPLAST PROTEIN(SCP). A T-DNA insertion mutant of SCP gene (scp-1)showed the enhanced tolerance to salt stress, as indicated bythe increased survival rates, fresh weights and chlorophyllcontents compared with wild type plants under salt treatment. Salt-induced leaf senescence was also delayed in scp-1 mutant. The scp-1 complementation line and SCP overexpressionlines displayed the hypersensitivity to salt stress. The qRTPCRanalysis indicated that the transcripts of CHLOROPLASTVESICULATION (CV), which mediates stress-inducedchloroplast degradation, were altered in scp-1 mutant andSCP overexpression lines. Taken together, our results suggestthat SCP gene plays a negative role in response to salt stress andhas potential application for genetic modification of improvingplant tolerance to salt stress.

Anti-androgen-independent Prostate Cancer Effects of Ginsenoside Metabolites In Vitro: Mechanism and Possible Structure-Activity Relationship Investigation

Wei Li,Yong Liu,Jiang-Wei Zhang,Chun-Zhi Ai,Nan Xiang,Hui-Xin Liu,Ling Yang 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

Treatment of androgen-independent prostate cancer (AIPC) remains unsatisfactory. In our present experiment, natural occurring ginsenosides (NOGs) and intestinal bacterial metabolites (IBMs) were employed to investigate their anti-AIPC cell growth activity using PC-3 cells. Our results showed that the IBMs exerted more portent anti-AIPC activity than NOGs, by decreasing survival rate, inhibiting proliferation, inducing apoptosis, and leading to cell cycle arrest in AIPC PC-3 cells. The increase of LogP and decrease of C-6 steric hindrance, which were caused by deglycosylation by intestinal bacteria, may be the reason for the higher anti-AIPC activity of IBMs.

Occurrence and Source Effect of Novel Brominated Flame Retardants (NBFRs) in Soils from Five Asian Countries and Their Relationship with PBDEs

Li, Wen-Long,Ma, Wan-Li,Zhang, Zi-Feng,Liu, Li-Yan,Song, Wei-Wei,Jia, Hong-Liang,Ding, Yong-Sheng,Nakata, Haruhiko,Minh, Nguyen Hung,Sinha, Ravindra Kumar,Moon, Hyo-Bang,Kannan, Kurunthachalam,Sverko, American Chemical Society 2017 Environmental science & technology Vol.51 No.19

<P>This paper presents the first comprehensive survey of 19 novel brominated flame retardants (NBFRs) in soil samples collected among five Asian countries. High variability in concentrations of all NBFRs was found in soils with the geometric mean (GM) values ranging from 0.50 ng/g dry weight (dw) in Vietnam to 540 ng/g dw in the vicinity of a BFR manufacturer in China. In urban, rural, and background locations, the GM concentrations of Sigma(19)NBFRs decreased in the order of Japan > South Korea > China > India > Vietnam. Correlations among different NBFR compounds were positive and statistically significant (p < 0.05), suggesting that they originate from similar sources. Evidence for simultaneous application between polybrominated diphenyl ethers (PBDEs) and NBFRs were also noted. Principal component analysis of NBFR concentrations revealed specific pollution sources for different NBFRs coming from urban, BFR-related industrial, and e-waste sites. For the first time, this study demonstrates a 'point source fractionation effect' for NBFRs and PBDEs. The concentrations of all NBFRs and PBDEs were negatively and significantly correlated with the distance from BFR-related industrial and e-waste regions. Positive and significant correlation between population density and NBFR concentrations in soils was identified. Our study revealed that the primary sources effects were stronger than the secondary sources effects in controlling the levels and distribution of NBFRs and PBDEs in soils in these five Asian countries.</P>

Chemical Constituents from the Aerial Parts of Isodon coetsa and their Cytotoxicity

Wei Zhao,Jian Xin Pu,Xue Du,Yong Zhao,Fei He,Hai Bo Zhang,Yong Bo Xue,Wei Lie Xiao,Han Dong Sun,Ying Li Wu,Guo Qiang Chen 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.12

Three new compounds (1-3), including a neolignan, a triterpenoid, and a diterpenoid, together with twenty known compounds (4-23), were isolated from the aerial parts of Isodon coetsa. Their structures and relative configurations were elucidated on the basis of spectroscopic data. Compounds 1, 3, 5-9, 11-13, 16-17, and 19-23 were evaluated for their cytotoxicity against HT-29, BEL-7402, and SK-OV-3 human tumor cell lines. Compound 7 showed significant inhibitory effects on all three types of cells, with IC50 values of 2.52, 3.06, 2.14 μM, respectively.

Application of Joint Detection of AFP, CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Li, Yong,Li, Da-Jiang,Chen, Jian,Liu, Wei,Li, Jian-Wei,Jiang, Peng,Zhao, Xin,Guo, Fei,Li, Xiao-Wu,Wang, Shu-Guang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identification and diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125 and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and joint detection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEA in CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s. The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84 and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly, and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combined AFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99). Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity, the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEA are highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosis of CC.

Concurrent Weekly Docetaxel Chemotherapy in Combination with Radiotherapy for Stage III and IVA-B Nasopharyngeal Carcinoma

Wei, Wei-Hong,Cai, Xiu-Yu,Xu, Tao,Zhang, Guo-Yi,Wu, Yong-Feng,Feng, Wei-Neng,Lin, Li,Deng, Yan-Ming,Lu, Qiu-Xia,Huang, Zhe-Li Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Background and Purpose: Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Methods and Materials: Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Results: Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Conclusions: Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.