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Source: Theranostics
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Total 110 results found since Jan 2013.
Flow-dependent epigenetic regulation of IGFBP5 expression by H3K27me3 contributes to endothelial anti-inflammatory effects
Conclusion: Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis.
Source: Theranostics - June 20, 2018 Category: Molecular Biology Authors: Suowen Xu, Yanni Xu, Meimei Yin, Shuya Zhang, Peng Liu, Marina Koroleva, Shuyi Si, Peter J. Little, Jaroslav Pelisek, Zheng Gen Jin Tags: Research Paper Source Type: research
Tumor Hypoxia Regulates Forkhead Box C1 to Promote Lung Cancer Progression
Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain. Increasing evidence indicates that FOXC1 is involved in tumor progression. However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans. Hypoxic stresses significantly induced FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsi...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh Tags: Research Paper Source Type: research
SiRNA Delivery with PEGylated Graphene Oxide Nanosheets for Combined Photothermal and Genetherapy for Pancreatic Cancer
In this study, we utilized multi-functionalized monolayer GO as a gene delivery system to efficiently co-deliver HDAC1 and K-Ras siRNAs (small interfering RNAs targeting the HDAC1 gene and the G12C mutant K-Ras gene, respectively) to specifically target pancreatic cancer cells MIA PaCa-2. The systematic mechanistic elucidation of the dual gene silencing effects indicated the inactivation of both the HDAC1 and the K-Ras gene, thereby causing apoptosis, proliferation inhibition and cell cycle arrest in treated MIA PaCa-2 cells. The synergistic combination of gene silencing and NIR light thermotherapy showed significant antic...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Feng Yin, Kuan Hu, Yangzi Chen, Mengying Yu, Dongyuan Wang, Qianqian Wang, Ken-Tye Yong, Fei Lu, Yongye Liang, Zigang Li Tags: Research Paper Source Type: research
Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis
Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS). ROS increased the stability and activity of ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yang Jiang, Yuan Cao, Yongbin Wang, Wei Li, Xinyi Liu, Yixuan Lv, Xiaoling Li, Jun Mi Tags: Research Paper Source Type: research
Systemic siRNA Delivery with a Dual pH-Responsive and Tumor-targeted Nanovector for Inhibiting Tumor Growth and Spontaneous Metastasis in Orthotopic Murine Model of Breast Carcinoma
Phenylboronic acid (PBA)-mediated tumor targeting nanovector is an attractive strategy for enhancing siRNA delivery and treatment of metastatic cancers. However, its nonspecific binding with various biological membranes containing cis-diol moieties restricts its potential application by systematic administration. Herein, we constructed a novel pH-activated “sheddable” PEG-coated nanoparticle for effective treatment of primary tumors and metastases, which was based on the conjugation of catechol group modified poly(ethylene glycol) (PEG-Cat) and PBA-terminated polyethylenimine (PEI-PBA) via the borate ester form...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Bo Fan, Lin Kang, Liqing Chen, Ping Sun, Mingji Jin, Qiming Wang, You Han Bae, Wei Huang, Zhonggao Gao Tags: Research Paper Source Type: research
Antitumor therapeutic application of self-assembled RNAi-AuNP nanoconstructs: Combination of VEGF-RNAi and photothermal ablation
In this study, exquisite RNAi-AuNP nanoconstructs with various geometries were developed by utilizing anti-VEGF siRNA molecules as RNAi-based therapeutics in addition to their role as building blocks for programmed self-assembly. In particular, the anti-VEGF siRNA-functionalized AuNP nanoconstructs can take additional advantage of gold-nanoclusters for photothermal cancer therapeutic agent. A noticeable technical aspect of self-assembled RNAi-AuNP nanoconstructs in this study is the precise conjugation and separation of designated numbers of therapeutic siRNA onto AuNP to develop highly sophisticated RNA-based building blo...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Sejin Son, Namho Kim, Dong Gil You, Hong Yeol Yoon, Ji Young Yhee, Kwangmeyung Kim, Ick Chan Kwon, Sun Hwa Kim Tags: Research Paper Source Type: research
Discovery of Aptamer Ligands for Hepatic Stellate Cells Using SELEX
In this study, we aim to discover an IGFIIR-specific aptamer that can be potentially used as a targeting ligand for the treatment and diagnosis of liver fibrosis. Systematic evolution of ligands by exponential enrichment (SELEX) was conducted on recombinant human IGFIIR to identify IGFIIR-specific aptamers. The binding affinity and specificity of the discovered aptamers to IGFIIR and hepatic stellate cells were studied using flow cytometry and Surface Plasmon Resonance (SPR). Aptamer-20 showed the highest affinity to recombinant human IGFIIR protein with a Kd of 35.5 nM, as determined by SPR. Aptamer-20 also has a high aff...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zhijin Chen, Hao Liu, Akshay Jain, Li Zhang, Chang Liu, Kun Cheng Tags: Research Paper Source Type: research
Regulation on Toll-like Receptor 4 and Cell Barrier Function by Rab26 siRNA-loaded DNA Nanovector in Pulmonary Microvascular Endothelial Cells
In this study, we thoroughly investigated the role and novel mechanism of Rab26 in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose-dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4) signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partiall...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Hongli Li, Binfeng He, Xueping Liu, Jingtong Li, Qian Liu, Weijie Dong, Zhi Xu, Guisheng Qian, Hua Zuo, Changhua Hu, Hang Qian, Chengde Mao, Guansong Wang Tags: Research Paper Source Type: research
High-Yield Synthesis of Monomeric LMWP(CPP)-siRNA Covalent Conjugate for Effective Cytosolic Delivery of siRNA
Because of the unparalleled efficiency and universal utility in treating a variety of disease types, siRNA agents have evolved as the future drug-of-choice. Yet, the inability of the polyanionic siRNA macromolecules to cross the cell membrane remains as the bottleneck of possible clinical applications. With the cell penetrating peptides (CPP) being discovered lately, the most effective tactic to achieve the highest intracellular siRNA delivery deems to be by covalently conjugating the drug to a CPP; for instance, the arginine-rich Tat or low molecular weight protamine (LMWP) peptides. However, construction of such a chemic...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Junxiao Ye, Ergang Liu, Junbo Gong, Jianxin Wang, Yongzhuo Huang, Huining He, Victor C. Yang Tags: Research Paper Source Type: research
Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery In Vitro and In Vivo
The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveal...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C. Farokhzad, Jinjun Shi Tags: Research Paper Source Type: research
Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1
Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in N...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Teng-Jian Zhou, Shi-Li Zhang, Cheng-Yong He, Qun-Ying Zhuang, Pei-Yu Han, Sheng-Wei Jiang, Huan Yao, Yi-Jun Huang, Wen-Hua Ling, Yu-Chun Lin, Zhong-Ning Lin Tags: Research Paper Source Type: research
Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cel...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang Tags: Research Paper Source Type: research
Preclinical activity of DCZ3301, a novel aryl-guanidino compound in the therapy of multiple myeloma
We synthesized a novel aryl-guanidino compound, DCZ3301, and found that it has potent cytotoxicity against multiple human cancer cell lines. The anticancer activity was most potent against multiple myeloma (MM). DCZ3301 induced cytotoxicity in MM cell lines, as well as patient myeloma cells, in part by decreasing mitochondrial membrane potential to induce apoptosis. In contrast, DCZ3301 had no cytotoxic effect on normal cells. DCZ3301 also inhibited cell cycling and caused a G2/M accumulation that corresponded with downregulation of Cdc25C, CDK1, and Cyclin B1. DCZ3301 retained its activity against MM cells in the presence...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Minjie Gao, Bo Li, Xi Sun, Yunfei Zhou, Yingcong Wang, Van S. Tompkins, Zhijian Xu, Nekitsing Indima, Houcai Wang, Wenqin Xiao, Lu Gao, Gege Chen, Huiqun Wu, Xiaosong Wu, Yuanyuan Kong, Bingqian Xie, Yiwen Zhang, Gaomei Chang, Liangning Hu, Guang Yang, Bo Tags: Research Paper Source Type: research
The pH-Triggered Triblock Nanocarrier Enabled Highly Efficient siRNA Delivery for Cancer Therapy
Small interfering RNA (siRNA) therapies have been hampered by lack of delivery systems in the past decades. Nowadays, a few promising vehicles for siRNA delivery have been developed and it is gradually revealed that enhancing siRNA release from endosomes into cytosol is a very important factor for successful delivery. Here, we designed a novel pH-sensitive nanomicelle, PEG-PTTMA-P(GMA-S-DMA) (PTMS), for siRNA delivery. Owing to rapid hydrolysis in acidic environment, PTMS NPs underwent hydrophobic-to-hydrophilic transition in endosomes that enabled combination of proton sponge effect and raised osmotic pressure in endosome...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Lili Du, Junhui Zhou, Lingwei Meng, Xiaoxia Wang, Changrong Wang, Yuanyu Huang, Shuquan Zheng, Liandong Deng, Huiqing Cao, Zicai Liang, Anjie Dong, Qiang Cheng Tags: Research Paper Source Type: research
Brusatol-Mediated Inhibition of c-Myc Increases HIF-1 α Degradation and Causes Cell Death in Colorectal Cancer under Hypoxia
HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (0.5% O2). Under hypoxia, pretreatment of cancer cells with brusatol increased HIF-1α degradation and cancer cell death in a dose-dependent manner. This effect was mediated by activation of prolyl hydroxylases (PHDs), a...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Eun-Taex Oh, Chan Woo Kim, Ha Gyeong Kim, Jae-Seon Lee, Heon Joo Park Tags: Research Paper Source Type: research
