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https://www.readbyqxmd.com/read/28819449/self-assembly-dna-polyplex-vaccine-inside-dissolving-microneedles-for-high-potency-intradermal-vaccination
#1
Jing-Fong Liao, Jin-Ching Lee, Chun-Kuang Lin, Kuo-Chen Wei, Pin-Yuan Chen, Hung-Wei Yang
The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency...
2017: Theranostics
https://www.readbyqxmd.com/read/28818749/a-conjugate-protein-containing-hiv-tat-isg20-and-a-prrsv-polymerase-binding-inhibits-prrsv-replication-and-may-be-a-novel-therapeutic-platform
#2
Ke Liu, Yuming Li, Bin Zhou, Feifei Wang, Beili Huan, Donghua Shao, Jianchao Wei, Yafeng Qiu, Beibei Li, Yingjuan Qian, Yong-Sam Jung, Denian Miao, Guangzhi Tong, Zhiyong Ma
Porcine Reproductive and Respiratory Syndrome (PRRS), which is caused by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection, has caused substantial economic losses for the global swine industry. To date, there are limited commercially available measures to control the spread of PRRSV. The available vaccines are unstable and there is no anti-PRRSV therapeutic available. Therefore, this study designed a novel recombinant antiviral protein that included a novel polypeptide that binds to the PRRSV polymerase (p9), the transduction ability of the HIV TAT, and the nucleotide degradation activity of interferon stimulated gene 20 (ISG20)...
August 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28815481/gene-delivery-approaches-for-mesenchymal-stem-cell-therapy-strategies-to-increase-efficiency-and-specificity
#3
REVIEW
Gopi Suresh Oggu, Shyama Sasikumar, Nirosha Reddy, Kranthi Kiran Reddy Ella, Ch Mohan Rao, Kiran Kumar Bokara
A significant number of clinical trials have been undertaken to explore the use of mesenchymal stem cells (MSCs) for the treatment of several diseases such as Crohn's disease, diabetes, bone defects, myocardial infarction, stroke etc., Due to their efficiency in homing to the tissue injury sites, their differentiation potential, the capability to secrete a large amount of trophic factors and their immunomodulatory effects, MSCs are becoming increasingly popular and expected to be one of the promising therapeutic approaches...
August 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28809098/interfacially-engineered-pyridinium-pseudo-gemini-surfactants-as-versatile-and-efficient-supramolecular-delivery-systems-for-dna-sirna-and-mrna
#4
Uttam Satyal, Bogdan Draghici, Lisa L Dragic, Qiangnan Zhang, Kyle Norris, Muniswamy Madesh, Eugen Brailoiu, Marc A Ilies
The article presents the synthesis, self-assembling and biological activity as transfection agents for pDNA, siRNA and mRNA of novel pyridinium pseudo-gemini surfactants, interfacially-engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to gemini surfactants, despite their lipid-like charge/mass ratio. This dual character was found to also enhance endosomal escape and significantly increase the transfection efficiency...
August 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28808446/neuron-specific-fluorescence-reporter-based-live-cell-tracing-for-transdifferentiation-of-mesenchymal-stem-cells-into-neurons-by-chemical-compound
#5
Do Won Hwang, Hyun Woo Kwon, Jaeho Jang, Hee Jung Jung, Kwang Rok Kim, Dong Soo Lee
Although transdifferentiation of mesenchymal stem cells (MSCs) into neurons increases the possibility of therapeutic use of MSCs for neurodevelopmental disorders, the use of MSCs has the limitation on differentiation efficiency to neuronal lineage and lack of an easy method to monitor the transdifferentiation. In this study, using time-lapse live cell imaging, we assessed the neuronal differentiation of MSCs induced by a small molecule "NHPDQC (N-hydroxy-2-oxo-3-(3-phenylprophyl)-1,2-dihydroquinoxaline-6-carboxamide, C18H17N3O3)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28801282/-sost-knockdown-promotes-differentiation-of-osteoblasts-mg63-and-mesenchymal-stem-cells-c3h10-in-an-in-vitro-model-of-bone-metastasis-of-breast-cancer
#6
Jia-Yi Huang, Dan Guo
OBJECTIVE: To investigate whether SOST is involved in breast cancer MDA-MB-231 cells-induced suppression of differentiation of osteoblast MG63 cells and mesenchymal stem C3H10 cells. METHODS: SOST-specific small interfering RNA (siRNA) was transfected into breast cancer MDA-MB-231 cells, and the interfering efficiency was verified by RT-PCR. The supernatants were collected from MDA-MB-231 cells in routine culture, cells transfected with SOST siRNA via adenovirus, and cells transfected with empty adenoviral vectors and added in MG63 or C3H10 cell cultures...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28796245/dioscin-induces-prostate-cancer-cell-apoptosis-through-activation-of-estrogen-receptor-%C3%AE
#7
Xufeng Tao, Lina Xu, Lianhong Yin, Xu Han, Yan Qi, Youwei Xu, Shasha Song, Yanyan Zhao, Jinyong Peng
Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133(+)/CD44(+) cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794626/folic-acid-functionalized-polyethylenimine-superparamagnetic-iron-oxide-nanoparticles-as-theranostic-agents-for-magnetic-resonance-imaging-and-pd-l1-sirna-delivery-for-gastric-cancer
#8
Xin Luo, Xia Peng, Jingying Hou, Shuyun Wu, Jun Shen, Lingyun Wang
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28789965/application-of-polyploid-adeno-associated-virus-vectors-for-transduction-enhancement-and-neutralizing-antibody-evasion
#9
Zheng Chai, Junjiang Sun, Kelly Michelle Rigsbee, Mei Wang, R Jude Samulski, Chengwen Li
Adeno-associated virus (AAV) vectors have been used successfully in clinical trials for patients with hemophilia or blindness, but pre-existing neutralizing antibodies (Nab) are common in the general population and exclude many patients from clinical trials. Exploration of effective strategies to enhance AAV transduction and escape from Nab activity is still imperative. Previous studies have shown the compatibility of capsids from AAV serotypes and homology of recognition sites of AAV Nab located on different capsid subunits from one virion...
August 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28773087/improved-gene-transfer-with-functionalized-hollow-mesoporous-silica-nanoparticles-of-reduced-cytotoxicity
#10
Zhengwen Zhan, Xiaoxu Zhang, Jiayuan Huang, Ying Huang, Zhengwei Huang, Xin Pan, Guilan Quan, Hu Liu, Lili Wang, And Chuanbin Wu
Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene delivery carriers. However, 25 kD PEI could significantly reduce the safety of the modified MSNs although it is efficient for intracellular delivery of nucleic acids. In addition, limited drug loading remains a challenge for conventional MSNs drug carriers...
June 30, 2017: Materials
https://www.readbyqxmd.com/read/28765933/gene-therapy-for-human-ovarian-cancer-cells-using-efficient-expression-of-fas-gene-combined-with-%C3%AE-%C3%AE-t-cells
#11
Jiajing Lin, Dingyuan Zeng, Hongying He, Guangping Tan, Ying Lan, Fuyan Jiang, Shuting Sheng
Low tissue specificity and efficiency of exogenous gene expression are the two major obstacles in tumor‑targeted gene therapy. The Fas cell surface death receptor (Fas)/Fas ligand pathway is one of the primary pathways responsible for the regulation of cell apoptosis. The aim of the present study was to explore whether the regulation of tumor specific promoters and a two‑step transcriptional amplification system (TSTA) assured efficient, targeted expression of their downstream Fas gene in human ovarian cancer cells, and to assess the killing effect of γδT cells on these cells with high Fas expression...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765880/microrna%C3%A2-494-inhibits-nerve-growth-factor%C3%A2-induced-cell-proliferation-by-targeting-cyclin-d1-in-human-corneal-epithelial-cells
#12
Dan Wu, Tingting Qian, Jiaxu Hong, Gang Li, Weiyun Shi, Jianjiang Xu
Nerve growth factor (NGF) is expressed in the human corneal epithelium and stroma. It is an efficient therapy for human corneal ulcers caused by neurotropic disease. However, little is known about the molecular mechanism of NGF in healing human corneal epithelial diseases. Numerous microRNAs (miRNAs) are expressed in the cornea and miRNAs have important roles in regulating corneal development. In the present study, novel miRNA regulators were demonstrated to be involved in NGF‑induced human corneal epithelial cell (hCEC) proliferation...
July 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28759195/photoacoustic-imaging-of-human-mesenchymal-stem-cells-labeled-with-prussian-blue-poly-l-lysine-nanocomplexes
#13
Taeho Kim, Jeanne E Lemaster, Fang Chen, Jin Li, Jesse V Jokerst
Acoustic imaging is affordable and accessible without ionizing radiation. Photoacoustic imaging increases the contrast of traditional ultrasound and can offer good spatial resolution when used at high frequencies with excellent temporal resolution. Prussian blue nanoparticles (PBNPs) are an emerging photoacoustic contrast agent with strong optical absorption in the near-infrared region. In this study, we developed a simple and efficient method to label human mesenchymal stem cells (hMSCs) with PBNPs and imaged them with photoacoustic imaging...
August 4, 2017: ACS Nano
https://www.readbyqxmd.com/read/28758979/suppression-of-mrna-nanoparticle-transfection-in-human-fibroblasts-by-selected-interferon-inhibiting-small-molecule-compounds
#14
Yang Liu, Manoj N Krishnan, Kyle K L Phua
In vitro transcribed (IVT) mRNA is increasingly applied in lieu of DNA to deliver reprogramming genes to fibroblasts for stem cell derivation. However, IVT mRNA induces interferon (IFN) responses from mammalian cells that reduces transfection efficiency. It has been previously suggested that small molecule inhibitors of IFN are a viable strategy to enhance mRNA transfection efficiency. Herein, we screen a list of commercially available small molecules, including published IFN inhibitors, for their potential to enhance mRNA transfection in BJ fibroblasts...
July 31, 2017: Biomolecules
https://www.readbyqxmd.com/read/28750082/enhanced-generation-of-ipscs-from-older-adult-human-cells-by-a-synthetic-five-factor-self-replicative-rna
#15
Naohisa Yoshioka, Steven F Dowdy
We previously devised a polycistronic, synthetic self-replicating RNA (srRNA) to generate human induced Pluripotent Stem Cells (iPSCs) that simultaneously expresses four reprogramming factors (4F). However, while the best 4F srRNA efficiently generated iPSCs from young fibroblasts, it was inefficient on adult human fibroblasts (>50 years). To increase the iPSC generation efficiency, we included additional reprogramming factors. We found that a single transfection of a five factor (5F) srRNA, containing OCT4, KLF4, SOX2, GLIS1 and c-MYC, robustly generated iPSCs from adult human fibroblasts aged 54 to 77 and from a 24 year old cardiomyopathy patient donor...
2017: PloS One
https://www.readbyqxmd.com/read/28748694/bilayered-nanoparticles-with-sequential-release-of-vegf-gene-and-paclitaxel-for-restenosis-inhibition-in-atherosclerosis
#16
Xiaowei Zhu, Hongzhi Xie, Xiaoyu Liang, Xuanling Li, Jianwei Duan, Yongxia Chen, Ziying Yang, Chao Liu, Cuiwei Wang, Hailing Zhang, Quan Fang, Hongfan Sun, Chen Li, Yongjun Li, Chun Wang, Cunxian Song, Yong Zeng, Jing Yang
Complete reendothelialization followed by inhibition of smooth muscle cell (SMC) proliferation is considered as an effective therapeutic option to prevent restenosis. We have designed poly(lactide-co-glycolide)-loaded bilayered nanoparticles (NPs) with the ability to sequentially release vascular endothelial growth factor (VEGF)-encoding plasmids from the outer layer and paclitaxel (PTX) from the core to promote endothelial regeneration as well as prevent restenosis. Comparing with conventional NPs, which release VEGF plasmid and PTX simultaneously, we expect that the bilayered NPs could release the VEGF plasmid more rapidly, followed by a delayed release of PTX, resulting in an efficient VEGF gene transfection, which ideally could promote reendothelialization and inhibit excessive SMC growth...
August 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28745625/a-protocol-for-multiple-gene-knockout-in-mouse-small-intestinal-organoids-using-a-crispr-concatemer
#17
Alessandra Merenda, Amanda Andersson-Rolf, Roxana C Mustata, Taibo Li, Hyunki Kim, Bon-Kyoung Koo
CRISPR/Cas9 technology has greatly improved the feasibility and speed of loss-of-function studies that are essential in understanding gene function. In higher eukaryotes, paralogous genes can mask a potential phenotype by compensating the loss of a gene, thus limiting the information that can be obtained from genetic studies relying on single gene knockouts. We have developed a novel, rapid cloning method for guide RNA (gRNA) concatemers in order to create multi-gene knockouts following a single round of transfection in mouse small intestinal organoids...
July 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28743275/block-copolymer-conjugated-au-coated-fe3o4-nanoparticles-as-vectors-for-enhancing-colloidal-stability-and-cellular-uptake
#18
Junbo Li, Sheng Zou, Jiayu Gao, Ju Liang, Huiyun Zhou, Lijuan Liang, Wenlan Wu
BACKGROUND: Polymer surface-modified inorganic nanoparticles (NPs) provide a multifunctional platform for assisting gene delivery. Rational structure design for enhancing colloidal stability and cellular uptake is an important strategy in the development of safe and highly efficient gene vectors. RESULTS: Heterogeneous Au-coated Fe3O4 (Fe3O4@Au) NPs capped by polyethylene glycol-b-poly1-(3-aminopropyl)-3-(2-methacryloyloxy propylimidazolium bromine) (PEG-b-PAMPImB-Fe3O4@Au) were prepared for DNA loading and magnetofection assays...
July 25, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28717157/cellular-uptake-pathways-of-sepiolite-nanofibers-and-dna-transfection-improvement
#19
Fidel Antonio Castro-Smirnov, Jeanne Ayache, Jean-Rémi Bertrand, Elodie Dardillac, Eric Le Cam, Olivier Piétrement, Pilar Aranda, Eduardo Ruiz-Hitzky, Bernard S Lopez
Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier because it can be naturally internalized into mammalian cells, due to its nano-size dimension. Therefore, deciphering the mechanisms of sepiolite cell internalization constitutes a question interesting biotechnology, for the use of sepiolite as nanocarrier, as well as environmental and public health concerns. Though it is low, the perfectly stable and natural intrinsic fluorescence of sepiolite nanofibers allows to follow their fate into cells by specifically sensitive technics...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714224/codelivery-for-paclitaxel-and-bcl-2-conversion-gene-by-phb-pdmaema-amphiphilic-cationic-copolymer-for-effective-drug-resistant-cancer-therapy
#20
Xiaoyuan Wang, Sing Shy Liow, Qiaoqiong Wu, Chuang Li, Cally Owh, Zibiao Li, Xian Jun Loh, Yun-Long Wu
Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment...
July 17, 2017: Macromolecular Bioscience
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