Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth

Lyu, Junfang,Yang, Eun Ju,Head, Sarah A.,Ai, Nana,Zhang, Baoyuan,Wu, Changjie,Li, Ruo-Jing,Liu, Yifan,Yang, Chen,Dang, Yongjun,Kwon, Ho Jeong,Ge, Wei,Liu, Jun O.,Shim, Joong Sup Elsevier 2017 Cancer letters Vol.409 No.-

<P><B>Abstract</B></P> <P>Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A phenotypic screen identified 13 existing drugs, including cepharanthine, as cholesterol trafficking inhibitors. </LI> <LI> Cepharanthine inhibited lysosomal cholesterol trafficking by binding to NPC1 protein and increasing the lysosomal pH. </LI> <LI> The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes. </LI> <LI> Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. </LI> <LI> Cepharanthine treatment enhanced the antitumor activity of cisplatin in lung and breast cancer xenografts in mice. </LI> </UL> </P>

SERS study of surface plasmon resonance induced carrier movement in Au@Cu₂O core-shell nanoparticles

Chen, Lei,Zhang, Fan,Deng, Xin-Yu,Xue, Xiangxin,Wang, Li,Sun, Yantao,Feng, Jing-Dong,Zhang, Yongjun,Wang, Yaxin,Jung, Young Mee Elsevier 2018 Spectrochimica acta. Part A, Molecular and biomole Vol.189 No.-

<P><B>Abstract</B></P> <P>A plasmon induced carrier movement enhanced mechanism of surface-enhanced Raman scattering (SERS) was investigated using a charge-transfer (CT) enhancement mechanism. Here, we designed a strategy to study SERS in Au@Cu<SUB>2</SUB>O nanoshell nanoparticles with different shell thicknesses. Among the plasmonically coupled nanostructures, Au spheres with Cu<SUB>2</SUB>O shells have been of special interest due to their ultrastrong electromagnetic fields and controllable carrier transfer properties, which are useful for SERS. Au@Cu<SUB>2</SUB>O nanoshell nanoparticles (NPs) with shell thicknesses of 48–56nm are synthesized that exhibit high SERS activity. This high activity originates from plasmonic-induced carrier transfer from Au@Cu<SUB>2</SUB>O to 4-mercaptobenzoic acid (MBA). The CT transition from the valence band (VB) of Cu<SUB>2</SUB>O to the second excited π-π* transition of MBA, and is of b<SUB>2</SUB> electronic symmetry, which was enhanced significantly. The Herzberg-Teller selection rules were employed to predict the observed enhanced b<SUB>2</SUB> symmetry modes. The system constructed in this study combines the long-range electromagnetic effect of Au NPs, localized surface plasmon resonance (LSPR) of the Au@Cu<SUB>2</SUB>O nanoshell, and the CT contribution to assist in understanding the SERS mechanism based on LSPR-induced carrier movement in metal/semiconductor nanocomposites.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We designed a shell-dependent Au@Cu<SUB>2</SUB>O nanoshell for SERS study. </LI> <LI> SERS contribution enables us to understand the possible enhancement of hybrid nanostructures. </LI> <LI> LSPR-induced carrier movement in Au@Cu<SUB>2</SUB>O nanocomposites. </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>We designed the shell-dependent Au@Cu<SUB>2</SUB>O core-shell nanoparticles (NPs) for SERS study. For the electron-hole pairs in the Cu<SUB>2</SUB>O, the plasmon induced resonant energy transfer from Au to the Cu<SUB>2</SUB>O and the direct electron transfer simultaneously which can be observed from the SERS intensity.</P> <P>[DISPLAY OMISSION]</P>

Vacuum metrological behaviors of ionization gauge with carbon nanotube cathode

Yongjun CHENG,Detian LI,Yongjun WANG,Huzhong ZHANG,Jian SUN,Kang JI 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

An ultra-high vacuum ionization gauge with carbon nanotube cathode

Detian LI,Yongjun CHENG,Yongjun WANG,Huzhong ZHANG,Jian SUN,Kang JI 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

Vacuum metrology technology and its application in aerospace

Detian LI,Yongjun CHENG,Wenjun SUN,Yongjun WANG 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

An Integrated Artificial Neural Network-based Precipitation Revision Model

( Tao Li ),( Wenduo Xu ),( Li Na Wang ),( Ningpeng Li ),( Yongjun Ren ),( Jinyue Xia ) 한국인터넷정보학회 2021 KSII Transactions on Internet and Information Syst Vol.15 No.5

Precipitation prediction during flood season has been a key task of climate prediction for a long time. This type of prediction is linked with the national economy and people's livelihood, and is also one of the difficult problems in climatology. At present, there are some precipitation forecast models for the flood season, but there are also some deviations from these models, which makes it difficult to forecast accurately. In this paper, based on the measured precipitation data from the flood season from 1993 to 2019 and the precipitation return data of CWRF, ANN cycle modeling and a weighted integration method is used to correct the CWRF used in today’s operational systems. The MAE and TCC of the precipitation forecast in the flood season are used to check the prediction performance of the proposed algorithm model. The results demonstrate a good correction effect for the proposed algorithm. In particular, the MAE error of the new algorithm is reduced by about 50%, while the time correlation TCC is improved by about 40%. Therefore, both the generalization of the correction results and the prediction performance are improved.

Formulation of nimodipine nanocrystals for oral administration

Jianwen Li,Qiang Fu,Xiaohong Liu,Mo Li,Yongjun Wang 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.2

The aim of this paper is to optimize nimodipine (NMD) nanocrystals (NCs) for oral administration. The effects of independent process variables (microprecipitation temperature, shearing speed, shearing time, homogenization pressure and number of cycles) on the particle size have been studied. Experiments were conducted to optimize the formulation composition. A single factor exploration was used to screen the primary stabilizers. Then, the selected polymers/surfactants were further optimized using an L9 (34) orthogonal design. The optimal formulation was composed of NMD (0.7 %, w/v), F127 (0.4 %, w/v), HPMC-E5 (0.1 %, w/v), and sodium deoxycholate (0.05 %, w/v) and was rod-shaped as shown by SEM observations, and it had a particle size of 833.3 ± 20.6 nm, determined by laser diffraction. These aqueous NCs were physically stable for 15 days. To further improve the stability, the NCs were freeze-dried. The powder obtained exhibited acceptable flowability and was physically stable for at least 24 months. Additionally, the NMD NCs displayed much higher dissolution profiles than the bulk drug. The pharmacokinetic results showed that the relative bioavailability was 397 % in comparison with Nimotop, suggesting that NCs are an efficient strategy for improving the oral bioavailability of poorly water-soluble drugs.

Effect of additives on structure and corrosion resistance of ceramic coatings on Mg–Li alloy by micro-arc oxidation

Shi Lingling,Xu Yongjun,Li Kang,Yao Zhongping,Wu Songquan 한국물리학회 2010 Current Applied Physics Vol.10 No.3

In order to improve the corrosion resistance of ceramic coatings formed on Mg–5mass%Li substrate by micro-arc oxidation (MAO) method, two kinds of additives (Na2B4O7 and EDTA) were doped in Na2SiO3–Na3PO4 solution system. The surface and cross-section morphology feature, phase composition and elemental composition were examined by SEM, XRD and EDX, respectively. Corrosion resistance of ceramic coating was tested by electrochemical methods. It was revealed that all coatings were composed of MgO and Mg2SiO4, and had porous surface structure. Doping of additives had little effect on the elemental composition, while it influenced the morphological feature of the coating. The results of electrochemical tests showed that the coatings prepared in the solutions with additive had good corrosion resistance. The addition of EDTA to the solution made coatings thinner and more uniform which resulted in better general corrosion resistance. The addition of Na2B4O7 to the solution made coatings much thicker and compacter, which improved the pitting corrosion resistance.

A New Direction of Cancer Classification: Positive Effect of Low-Ranking MicroRNAs

Feifei Li,Minghao Piao,Yongjun Piao,Meijing Li,류근호 질병관리본부 2014 Osong Public Health and Research Persptectives Vol.5 No.5

Objectives: Many studies based on microRNA (miRNA) expression profiles showed a new aspect of cancer classification. Because one characteristic of miRNA expression data is the high dimensionality, feature selection methods have been used to facilitate dimensionality reduction. The feature selection methods have one shortcoming thus far: they just consider the problem of where feature to class is 1:1 or n:1. However, because one miRNA may influence more than one type of cancer, human miRNA is considered to be ranked low in traditional feature selection methods and are removed most of the time. In view of the limitation of the miRNA number, low-ranking miRNAs are also important to cancer classification. Methods: We considered both high- and low-ranking features to cover all problems (1:1, n:1, 1:n, and m:n) in cancer classification. First, we used the correlation-based feature selection method to select the high-ranking miRNAs, and chose the support vector machine, Bayes network, decision tree, k-nearestneighbor, and logistic classifier to construct cancer classification. Then, we chose Chi-square test, information gain, gain ratio, and Pearson’s correlation feature selection methods to build the m:n feature subset, and used the selected miRNAs to determine cancer classification. Results: The low-ranking miRNA expression profiles achieved higher classification accuracy compared with just using high-ranking miRNAs in traditional feature selection methods. Conclusion: Our results demonstrate that the m:n feature subset made a positive impression of low-ranking miRNAs in cancer classification.

RAPD Variation and Genetic Distances among Tibetan, Inner Mongolia and Liaoning Cashmere Goats

Chen, Shilin,Li, Menghua,Li, Yongjun,Zhao, Shuhong,Yu, Chuanzhou,Yu, Mei,Fan, Bin,Li, Kui Asian Australasian Association of Animal Productio 2001 Animal Bioscience Vol.14 No.11

Relationship among Tibetan cashmere goats, Inner Mongolia cashmere goats and Liaoning cashmere goats was studied using the technique of random amplified polymorphic DNA (RAPD). One primer and four primer combinations were screened. With the five primers and primer combinations, DNA fragments were amplified from the three breeds. Each breed has 28 samples. According to their RAPD fingerprint maps, the Nei's (1972) standard genetic distance was: 0.0876 between Tibetan cashmere goats and Inner Mongolia cashmere goats, 0.1601 between Tibetan cashmere goats and Liaoning cashmere goats, 0.0803 between the Inner Mongolia cashmere goats and Liaoning cashmere goats. It coincides with their geographic location. The genetic heterogeneity of Tibetan cashmere goats, Inner Mongolia cashmere goats and Liaoning cashmere goats is 0.3266, 0.2622 and 0.2475 respectively. It is also consistent with their development history.