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>

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>

Cloning and Sequence Analysis of Glyceraldehyde-3-Phosphate Dehydrogenase Gene in Yak

Li, Sheng-Wei,Jiang, Ming-Feng,Liu, Yong-Tao,Yang, Tu-Feng,Wang, Yong,Zhong, Jin-Cheng Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.11

In order to study the biological function of gapdh gene in yak, and prove whether the gapdh gene was a useful intra-reference gene that can be given an important role in molecular biology research of yak, the cDNA sequence encoding glyceraldehyde-3-phosphate dehydrogenase from yak was cloned by the RT-PCR method using gene specific PCR primers. The sequence results indicated that the cloned cDNA fragment (1,008 bp) contained a 1,002 bp open reading frame, encoding 333 amino acids (AAs) with a molecular mass of 35.753 kDa. The deduced amino acids sequence showed a high level of sequence identity to Bos Taurus (99.70%), Xenopus laevis (94.29%), Homo sapiens (97.01%), Mus musculus (97.90%) and Sus scrofa (98.20%). The expression of yak's gapdh gene in heart, spleen, kidney and brain tissues was also detected; the results showed that the gapdh gene was expressed in all these tissues. Further analysis of yak GAPDH amino acid sequence implied that it contained a complete glyceraldehyde-3-phosphate dehydrogenase active site (ASCTTNCL) which ranged from 148 to 155 amino acid residues. It also contained two conserved domains, a NAD binding domain in its N-terminal and a complete catalytic domain of sugar transport in its C-terminal. The phylogenetic analysis showed that yak and Bos taurus were the closest species. The prediction of secondary structures indicated that GAPDH of yak had a similar secondary structure to other isolated GAPDH. The results of this study suggested that the gapdh gene of yak was similar to other species and could be used as the intra-reference to analyze the expression of other genes in yak.

Expression of Lamininγ2 in Extrahepatic Cholangiocarcinoma Tissues and its Influence on Tumor Invasion and Metastasis

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.5

Objective: To explore the expression of $laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of $laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results: $Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of $laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$, P=0.0065; ${\chi}^2=4.0077$, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of $laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of $laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of $laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of $laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.

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.

Protective Effects of Decursin and Decursinol Angelate against Amyloid β-Protein-Induced Oxidative Stress in the PC12 Cell Line: The Role of Nrf2 and Antioxidant Enzymes

LI, Li,LI, Wei,JUNG, Sang-Won,LEE, Yong-Woo,KIM, Yong-Ho Japan Society for Bioscience, Biotechnology, and A 2011 Bioscience, biotechnology, and biochemistry Vol.75 No.3

<P>The protective effects of decursin (D) and decursinol angelate (DA) purified from <I>Angelica gigas</I> Nakai on amyloid β-protein (Aβ)-induced neurotoxicity and the underlying mechanisms were investigated. Aβ plays a major role in the pathogenesis of Alzheimer’s disease (AD) by eliciting oxidative stress. It significantly increased cytotoxicity and lipid peroxidation, but decreased glutathione contents and antioxidant enzyme activities. All of these results were markedly reversed by pretreatment with D or DA. Nuclear transcription factor Nrf2, which regulates the expression of antioxidant enzymes, was significantly increased by D or DA pretreatment. Furthermore, D and DA suppressed Aβ aggregation. These results suggest that D and DA increase cellular resistance to Aβ-induced oxidative injury in the rat pheochromocytoma (PC12) cells, presumably through not only the induction of Nrf2 and related antioxidant enzymes, but also the anti-aggregation of Aβ. Thus D and DA have therapeutic potential in treating AD and other oxidative stress-related diseases.</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.