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>

Understanding Spatial Divisions of Innovation in Urban Regions

Li Nana 대한지리학회 2011 대한지리학회 컨퍼런스 자료집 Vol.- No.6

Plate column adsorption of Pb(II) from industrial wastewater on sponge-type composite adsorbent: Optimization and application

Nana Wang,Xingjian Xu,Li Yang,Lizhu Yuan,Tangfu Xiao,Haiyan Li,Hongwen Yu 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.66 No.-

A sponge-type composite adsorbent xanthate-modified chitosan @ titanate nanotubes (XCTS@TNTs) was prepared via a simple and low-cost procedure, and its adsorption capacity was evaluated in batch and continuous plate column systems. The three-dimensional network macroporous structure made it easy to separate from the solution and suitable for the column-based treatment. The excellent adsorption capacity of Pb(II) was as high as 342.47 mg/g and could be obtained in wide ranges of pH and temperature. Interestingly, XCTS@TNTs exhibited outstanding selectivity for Pb(II) rather than other divalent heavy metal ions. Adsorption mechanism was elucidated by the FTIR and XPS analyses. The column adsorption results indicated that the treatment effect was proportional to bed height and inversely to flow rate and influent concentration. XCTS@TNTs was remarkably effective in the removal of Pb(II) from actual industrial effluents to meet the discharge requirements and contributed to the recovery of Pb(II). The treatment volumes of simulated actual battery wastewater and smelting effluent by 2.40 g XCTS@TNTs were as high as 6360 and 49584 mL for Pb(II) with the concentration of 30.55 and 4.49 mg/L, respectively. This work developed a highly practical process for removing heavy metal ions from practical wastewaters.

BMB Reports : Nutlin-3 downregulates p53 phosphorylation on serine and induces apoptosis in hepatocellular carcinoma cells

( Xin Li Shi ),( Jing Li Liu ),( Lai Feng Ren ),( Nan Mao ),( Fang Tan ),( Nana Ding ),( Jing Yang ),( Ming Yuan Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.4

Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-Ser392-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-Ser392-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-Ser392-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on Ser392 presents an alternative for HCC chemotherapy. [BMB Reports 2014; 47(4): 221-226]

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

Liang Li,Zhang Fengmei,Feng Naibo,Kuang Biao,Fan Mengtian,Chen Cheng,Pan Yiming,Zhou Pengfei,Geng Nana,Li Xingyue,Xian Menglin,Deng Lin,Li Xiaoli,Kuang Liang,Luo Fengtao,Tan Qiaoyan,Xie Yangli,Guo Fen 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Anthocyanin Extracted from Purple Sweet Potato Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Suppressing Pyroptosis and Altering Intestinal Flora Structure

Rongpeng Li,Cong Li,Jing Chen,Fei Jiang,Nana Xu,Guokai Dong,Jiebang Jiang,Meng Wang 한국식품영양과학회 2024 Journal of medicinal food Vol.27 No.2

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS)in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group):DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. TheDSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefullymonitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessmentwas conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels ofIL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-a, N-GSDMS, and cleaved-IL-1b proteins were evaluated by Western blotanalysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gutmicrobiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-inducedUC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, andsignificantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1b, and TNF-a, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria andDeferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviatedDSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gutmicrobiota.

ZmFKBP20-1 improves the drought and salt tolerance of transformed Arabidopsis

Yanli Yu,Yanjiao Li,Fengjuan Jia,Meng Zhao,Wencai Li,Qi Sun,Nana Li,Wenlan Li,Zhaodong Meng 한국식물학회 2017 Journal of Plant Biology Vol.60 No.6

FK506-binding proteins (FKBPs), which belongto the peptidyl-prolyl cis/trans isomerase superfamily, areinvolved in plant response to abiotic stresses. A number ofFKBP family genes have been isolated in plants, but littlehas been reported of FKBP genes in maize. In this study, adrought-induced FKBP gene, ZmFKBP20-1, was isolated frommaize and was characterized for its role in stress responsesusing gene expression, protein subcellular localization,transformation in Arabidopsis, expression patterns of thestress-responsive genes, and physiological parameter analysis. During drought and salt stresses, ZmFKBP20-1 transgenicArabidopsis plants exhibited enhanced tolerance, which wasconcomitant with the altered expression of stress/ABAresponsivegenes, such as COR15a, COR47, ERD10, RD22,KIN1, ABI1, and ABI2. The resistance characteristics ofZmFKBP20-1 overexpression were associated with a significantincrease in survival rate. These results suggested thatZmFKBP20-1 plays a positive role in drought and salt stressresponses in Arabidopsis and provided new insights into themechanisms of FKBP in response to abiotic stresses inplants.

Some Manifestations of Antioxidation Coating for Hot Precision Forging Gears

Li, Dongcheng,Han, Nana,Quagliato, Luca,Kim, Naksoo,Yu, Ge Hindawi Publishing Corporation 2019 Advances In Materials Science And Engineering Vol.2019 No.-

<P>A high temperature protective coating was prepared onto the surface of 20CrMnTi steel by brushing technique, and the heated billet was subjected to hot forging. Compared with an uncoated sample, the effect of coating on high-temperature oxidation behavior of steel was investigated by scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction. Before hot forging, an oxide layer of 153 <I>μ</I>m was formed on the surface of the uncoated sample; however, no oxide layer was formed on the surface of the coated sample. After hot forging, the thickness of scale on the surface of uncoated gear forging is 89 <I>μ</I>m while the thickness of coating on the surface of coated gear forging is 39 <I>μ</I>m. It is concluded that such a coating material not only enhances the dimensional accuracy but also improves the surface quality of the gear.</P>

False-Negative Results of Real-Time ReverseTranscriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus 2: Role of Deep-Learning-Based CT Diagnosis and Insights from Two Cases

Dasheng Li,Dawei Wang,Jianping Dong,Nana Wang,He Huang,Haiwang Xu,Chen Xia 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.4

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

Microstructure and Wear Properties of Cu–La2O3 Composites Prepared by Spark Plasma Sintering

Runguo Zheng,Nana Li 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.5

The Cu–La2O3 composite was prepared by internal oxidation method. The friction and wear behavior was examined underdifferent applied load and sliding velocity according to ASTM G99 standard. The results showed the size of La2O3particleswas about 150 nm, which were homogeneous distributed in the Cu matrix. The mean size of Cu grains in the Cu–1.32 wt%La2O3composite decreased by 60% compared with that of pure Cu. The ultimate tensile strength of the Cu–1.32 wt% La2O3composite was 328 MPa. The dominant strengthening mechanisms were the grain size strengthening and thermal mismatchstrengthening. The wear rate of Cu–1.32 wt% La2O3composites was lower than that of pure copper and it increased withthe increase of applied load and sliding velocity. The mild to severe wear transition appeared at different load and velocity.The wear mechanisms were abrasive wear and oxidative wear in mild wear. However, it changed to plastic deformation anddelamination wear in severe wear.