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>

Effects of Ga-doping on the microstructure and magnetic properties of MnBi alloys

Yang, Yang,Kim, Jong-Woo,Si, Ping-Zhan,Qian, Hui-Dong,Shin, Yongho,Wang, Xinyou,Park, Jihoon,Li, Oi Lun,Wu, Qiong,Ge, Hongliang,Choi, Chul-Jin Elsevier 2018 JOURNAL OF ALLOYS AND COMPOUNDS Vol.769 No.-

<P><B>Abstract</B></P> <P>The low temperature phase Mn<SUB>55</SUB>Bi<SUB>45-<I>x</I> </SUB>Ga<SUB> <I>x</I> </SUB> (<I>x</I> = 0, 1, 3, 5, and 10) alloys were prepared by induction melting process with subsequent low temperature annealing. The effects of Ga-doping on the crystal structure and magnetic properties of the alloys were systematically studied. The room temperature coercivities of Mn<SUB>55</SUB>Bi<SUB>45-<I>x</I> </SUB>Ga<SUB> <I>x</I> </SUB> after ball milling increased from 1.43 T for <I>x</I> = 0 to 1.66 T for <I>x</I> = 5, while the saturation magnetization decreased from 60.7 Am<SUP>2</SUP>/kg (<I>x</I> = 0) to 45.1 Am<SUP>2</SUP>/kg (<I>x</I> = 5). The maximum energy product (<I>BH</I>)<SUB>max</SUB> of Mn<SUB>55</SUB>Bi<SUB>44</SUB>Ga powders reached 7.87 MGOe. The Curie temperature of the Mn<SUB>55</SUB>Bi<SUB>45-<I>x</I> </SUB>Ga<SUB> <I>x</I> </SUB> alloys increased from 633 K to 658 K with increasing Ga concentration in the range of 0 ≤ <I>x</I> ≤ 5.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Effects of doping Ga on the microstructural and magnetic properties of MnBi alloy. </LI> <LI> The MnBi-Ga powders are achieved by surfactant assisted high energy ball milling. </LI> <LI> The maximum energy produce (<I>BH</I>)<SUB>max</SUB> shows 7.87 MGOe for Mn<SUB>55</SUB>Bi<SUB>44</SUB>Ga sample. </LI> <LI> The coercivity of Mn<SUB>55</SUB>Bi<SUB>40</SUB>Ga<SUB>5</SUB> after ball milling reached 1.66 T at room temperature. </LI> <LI> The elevated curie temperature (<I>T</I> <SUB>c</SUB>) by doping Ga makes it a possible candidate for high temperature applications. </LI> </UL> </P>

Gyral net: A new representation of cortical folding organization

Chen, Hanbo,Li, Yujie,Ge, Fangfei,Li, Gang,Shen, Dinggang,Liu, Tianming Elsevier 2017 Medical image analysis Vol.42 No.-

<P><B>Abstract</B></P> <P>One distinct feature of the cerebral cortex is its convex (gyri) and concave (sulci) folding patterns. Due to the remarkable complexity and variability of gyral/sulcal shapes, it has been challenging to quantitatively model their organization patterns. Inspired by the observation that the lines of gyral crests can form a connected graph on each brain hemisphere, we propose a new representation of cortical gyri/sulci organization pattern – gyral net, which models cortical architecture from a graph perspective, starting with nodes and edges obtained from the reconstructed cortical surfaces. A novel computational framework is developed to efficiently and automatically construct gyral nets from surface meshes, and four measurements are devised to quantify the folding patterns. Using an MRI dataset for autism study as a test bed, we identified reduced local connectivity cost and increased curviness of gyral net bilaterally on the parietal lobe, occipital lobe, and temporal lobe in autistic patients. Additionally, we found that the cortical thickness and the gyral straightness of gyral joints are higher than the rest of gyral crest regions. The proposed representation offers a new tool for a comprehensive and reliable characterization of the cortical folding organization. This novel computational framework will enable large-scale analyses of cortical folding patterns in the future.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new representation of cortical gyri/sulci organization pattern. </LI> <LI> A novel framework to efficiently and automatically construct gyral net from mesh surface. </LI> <LI> A new tool for a comprehensive and reliable characterization of the cortical folding organization. </LI> <LI> Enable large-scale cortical folding pattern analyses in the future. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Illustration of the concept of gyral net and gyral joint. (a) Reconstructed cortical surface color-coded by gyral altitude. (b) Extracted gyral net. (c) Zoom in view of the circled area in (b). In this paper, we propose a new representation of cortical gyri/sulci organization pattern – gyral net, which models cortical architecture from a graph perspective, starting with nodes and edges obtained from the surface reconstructions.</P> <P>[DISPLAY OMISSION]</P>

Excellent microwave absorption of FeCo/ZnO composites with defects in ZnO for regulating the impedance matching

Bao, Xiukun,Wang, Xiaolei,Zhou, Xinao,Shi, Guimei,Xu, Ge,Yu, Jin,Guan, Yinyan,Zhang, Yajing,Li, Da,Choi, Chuijin Elsevier 2018 JOURNAL OF ALLOYS AND COMPOUNDS Vol.769 No.-

<P><B>Abstract</B></P> <P>FeCo/ZnO composites have been successfully prepared through liquid-phase reduction process for the formation of FeCo polyhedrons and sequentially thermal decomposition of colloidal mixture of FeCo and Zn(Ac)<SUB>2</SUB>·2H<SUB>2</SUB>O under nitrogen atmospheres. ZnO nanoparticles are homogeneously deposited on the surface of FeCo polyhedrons and the level of oxygen-vacancy defects in ZnO can be elevated with the increase of ZnO content. By comparison with FeCo polyhedrons, FeCo/ZnO composites exhibit excellent microwave absorption. The optimal RL value can reach −34.8 dB at 14.8 GHz and effective bandwidth (RL < −10 dB) is 5.1 GHz in the frequency range of 12.4–17.5 GHz with a matching thickness of 1.5 mm. The integrated bandwidth with RL < −10 dB can reach 14.1 GHz covering 3.4–17.5 GHz. Theory analysis demonstrates the interfacial polarization, dipole polarization and high conductivity due to oxygen-vacancy defects in FeCo/ZnO composites contribute to enhancement of dielectric loss capacity, which is more favorable for impedance matching.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The preferable impedance matching of FeCo/ZnO composites can be achieved by regulating the ZnO content. </LI> <LI> The optimal reflection loss (RL) can reach −34.8 dB with a matching thickness of 1.5 mm. </LI> <LI> The effective bandwidth with RL < −10 dB achieve 14.1 GHz covering 3.4–17.5 GHz with integrated thickness of 1.5–5 mm. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Design of ultralong single-crystal nanowire-based bifunctional electrodes for efficient oxygen and hydrogen evolution in a mild alkaline electrolyte

Li, Ge,Wang, Xiaolei,Seo, Min Ho,Hemmati, Sahar,Yu, Aiping,Chen, Zhongwei The Royal Society of Chemistry 2017 Journal of Materials Chemistry A Vol.5 No.22

Diacylglycerol Acyltransferase-inhibitory Prenylated Flavonoids from Maackia amurensis Rupr

Li, Na,Lee, Hyun Sun,Tuo, Zhen Dong,Li, Jia Lin,Du, Pei Ge,Cui, Long Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.10

Influence of Lighting Schedule and Nutrient Density in Broiler Chickens: Effect on Growth Performance, Carcass Traits and Meat Quality

Li, Wen-Bin,Guo, Yan-Li,Chen, Ji-Lan,Wang, Rong,He, Yao,Su, Dong-Ge Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.11

The study was conducted to evaluate the effect of lighting schedule and nutrient density on growth performance, carcass traits and meat quality of broiler chickens. A total of 576 day old Arbor Acre male chickens was used with a $4{\times}2$ factorial arrangement. The four lighting schedules were continuous (23 L:1 D, CL), 20 L:4 D (12 L:2 D:8 L:2 D), 16 L:8 D (12 L:3 D:2 L:3 D: 2 L:2 D) and 12 L:12 D (9 L:3 D:1 L:3 D:1 L:3 D:1 L:3 D) and provided by incandescent bulbs. The two nutrient densities were high (H, starter diet: 13.39 MJ/kg apparent metabolisable energy (AME), 23.00% crude protein (CP); finisher diet: 13.39 MJ AME/kg, 19.70% CP) and low energy and protein level (L, starter diet: 12.03 MJ AME/kg, 20.80% CP; finisher diet: 12.14 MJ AME/kg, 18.30% CP). Houses with dark curtains and solid sidewalls were used. Chickens were randomly allocated to the 8 treatments with each treatment comprising 6 replicates of 12 chickens. Feed and water were available ad libitum. Lighting schedules showed no difference (p>0.05) in growth performance at the end of the experiment. 12 L:12 D significantly reduced (p<0.05) the concentration of malondialdehyde (MDA) compared to 23 L:1 D treatment. Intermittent lighting (IL) schedules produced higher protein content (p<0.001) in breast meat. Birds on high density diets had higher body weight (BW), feed intake (FI) (p<0.001), and feed conversion ratio (FCR) (p<0.001) throughout the experiment with the exception of 36 to 42 d. High nutrient density increased (p<0.05) abdominal fat, decreased (p<0.05) the moisture loss of meat, and reduced percentage of wings and legs. There was a significant lighting schedule${\times}$diet interaction (p<0.001) on FCR for days 8 to 14 and 15 to 21. Results indicated that IL can give similar growth performance in comparison with CL, meanwhile with positive effects on meat quality by increasing protein content and decreasing the concentration of MDA. High nutrient density resulted in greater growth performance.

GSTP1, ERCC1 and ERCC2 Polymorphisms, Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Li, Hui-Yan,Ge, Xin,Huang, Guang-Ming,Li, Kai-Yu,Zhao, Jing-Quan,Yu, Xi-Miao,Bi, Wen-Si,Wang, Yu-Lin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients.

Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the Management of Solitary Plasmacytoma

Li, Qi-Wen,Niu, Shao-Qing,Wang, Han-Yu,Wen, Ge,Li, Yi-Yang,Xia, Yun-Fei,Zhang, Yu-Jing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Materials and Methods: Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. Results: The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Conclusions: Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

MicroRNA-3200-5p Promotes Osteosarcoma Cell Invasion via Suppression of BRMS1

Li, Gen,Li, Li,Sun, Qi,Wu, Jiezhou,Ge, Wei,Lu, Guanghua,Cai, Ming Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.6

Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.