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161.
Synthesis and cell transfection properties of guanidinium-functionalized uracil morpholino tetramer have been reported for the first time. Due to the basic nature of guanidinium groups they remain protonated under physiological conditions. Such cationic tetramer exhibits efficient cellular uptake properties as visualized by microscopy imaging using fluorescent dye BODIPY. 7′-End of this morpholino tetramer was functionalized with an azide group for conjugation with various types of biomolecules or drugs for cellular delivery. 相似文献
162.
BackgroundBiomarkers are important in the study of tumor processes for early detection and precise treatment. The biomarkers that have been previously detected are not useful for clinical application for primary colorectal carcinoma (PCRC). The aim of this study was to explore clinically valuable biomarkers of PCRC based on integrated bioinformatic analysis.Material and methodsGene expression data were acquired from the GSE41258 dataset, and the differentially expressed genes were determined between PCRC and normal colorectal samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were implemented via Gene Set Enrichment Analysis. A protein-protein interaction (PPI) network was constructed. The significant modules and hub genes were screened and identified in the PPI network.ResultsA total of 202 DEGs were identified, including 58 upregulated and 144 downregulated genes in PCRC samples compared to those in normal colorectal samples. Enrichment analysis demonstrated that the gene sets enriched in PCRC were significantly related to bicarbonate transport, regulation of sodium ion transport, potassium ion homeostasis, regulation of telomere maintenance, and other processes. A total of 10 hub genes was identified by cytoHubba: PYY, CXCL3, CXCL11, CXCL8, CXCL12, CCL20, MMP3, P2RY14, NPY1R, and CXCL1.ConclusionThe hub genes, such as NPY1R, P2RY14, and CXCL12, and the electrolyte disequilibrium resulting from the differential expression of genes, especially bicarbonate imbalance, may provide novel insights and evidence for the future diagnosis and targeted therapy of PCRC. 相似文献
163.
Identifying significant protein groups is of great importance for further understanding protein functions. This paper introduces a novel three-phase heuristic method for identifying such groups in weighted PPI networks. In the first phase a variable neighborhood search (VNS) algorithm is applied on a weighted PPI network, in order to support protein complexes by adding a minimum number of new PPIs. In the second phase proteins from different complexes are merged into larger protein groups. In the third phase these groups are expanded by a number of 2-level neighbor proteins, favoring proteins that have higher average gene co-expression with the base group proteins. Experimental results show that: (i) the proposed VNS algorithm outperforms the existing approach described in literature and (ii) the above-mentioned three-phase method identifies protein groups with very high statistical significance. 相似文献
164.
Many human diseases occur due to the over or under-expression of genes which can be corrected either by silencing or over-expression, respectively by transforming with specific nucleic acid (NA). NA transformation for medical purposes to alter the cellular gene expression is challenging because NA cannot cross efficiently the cellular biomembrane. One option, the viral vectors, is risky for patients and, the non-viral vectors have lower transformation efficiency. From the past few years, nanoparticles (NPs) are being studied extensively for their use as a vector to deliver NA. They are of a sub-micron size, have a large surface area, rapid absorption ability and can reach inside of the cells. These properties make them a suitable gene carrier. NPs types - organic, inorganic, organic/inorganic hybrid and polymeric NPs, having different properties that can be used to deliver the NA. They possess various properties like biocompatibility, targeted delivery of gene, controlled release of NA which makes them suitable for different uses. In this review, we are describing and comparing various methods to synthesize various kinds of NPs and how they can be conjugated with NA. A series of modifications in NPs to form the polyplex are also discussed along with the varying outcomes in terms of changes in the gene expression and its cytotoxicity towards different cell lines. This review is helpful for nano-scientists to decide which method to be followed for a specific need via controlling gene expression. 相似文献
165.
H. Jia Y. Yang M. Li Y. Li X. Han J. Li X. Zhang C. Fan T. Wu C. Cui X. Wei W. Liu 《Materials Today Chemistry》2020
Inflammation represents a real micromilieu of many diseases as well as the actual application environment of nanocarriers. However, few studies have focused on the influence of the inflammatory environment on the effects of nanoparticle delivery. Herein, a novel inflammation self-adaptive nanocarrier is designed and fabricated by attaching the ascorbyl palmitate (AP) onto the surface of gene-entrapped polymeric nanocomplexes through the formation of phenylboronate bond. In vitro and in vivo studies demonstrate that the introduction of AP enhances considerably the accumulation of entrapped gene in inflammation and facilitates the intracellular uptake of gene-loading nanoparticles. Meanwhile, the gene transfection efficiency of DNA and in vivo gene therapy of nanocomplexes under an inflammation stimulus is significantly enhanced. Hence, our delicate design concept opens up a new pathway to develop an inflammation self-adaptive drug delivery system for precise drug/gene delivery and therapy. 相似文献
166.
BackgroundExogenous microRNAs (miRNAs) enter the human body through food, and their effects on metabolic processes can be considerable. It is important to determine which miRNAs from plants affect the expression of human genes and the extent of their influence.MethodThe binding sites of 738Oryza sativa miRNAs (osa-miRNAs) that interact with 17 508 mRNAs of human genes were determined using the MirTarget program.ResultThe characteristics of the binding of 46 single osa-miRNAs to 86 mRNAs of human genes with a value of free energy (ΔG) interaction equal 94%–100% from maximum ΔG were established. The findings showed that osa-miR2102-5p, osa-miR5075-3p, osa-miR2097-5p, osa-miR2919 targeted the largest number of genes at 38, 36, 23, 19 sites, respectively. mRNAs of 86 human genes were identified as targets for 93 osa-miRNAs of all family osa-miRNAs with ΔG values equal 94%–98% from maximum ΔG. Each miRNA of the osa-miR156-5p, osa-miR164-5p, osa-miR168-5p, osa-miR395-3p, osa-miR396-3p, osa-miR396-5p, osa-miR444-3p, osa-miR529-3p, osa-miR1846-3p, osa-miR2907-3p families had binding sites in mRNAs of several human target genes. The binding sites of osa-miRNAs in mRNAs of the target genes for each family of osa-miRNAs were conserved when compared to flanking nucleotide sequences.ConclusionTarget mRNA human genes of osa-miRNAs are also candidate genes of cancer, cardiovascular and neurodegenerative diseases. 相似文献
167.
Bazoly Rasolonjatovo Nicolas Illy Vronique Bennevault Jrme Math Patrick Midoux Tony Le Gall Thomas Haudebourg Tristan Montier Pierre Lehn Bruno Pitard Herve Cheradame Ccile Huin Philippe Gugan 《Macromolecular bioscience》2020,20(3)
It is reported that low concentration of amphiphilic triblock copolymers of pMeOx‐b‐pTHF‐b‐pMeOx structure (TBCPs) improves gene expression in skeletal muscle upon intramuscular co‐injection with plasmid DNA. Physicochemical studies carried out to understand the involved mechanism show that a phase transition of TBCPs under their unimer state is induced when the temperature is elevated from 25 to 37 °C, the body temperature. Several lines of evidences suggest that TBCP insertion in a lipid bilayer causes enough lipid bilayer destabilization and even pore formation, a phenomenon heightened during the phase transition of TBCPs. Interestingly, this property allows DNA translocation across the lipid bilayer model. Overall, the results indicate that TBCPs exhibiting a phase transition at the body temperature is promising to favor in vivo pDNA translocation in skeletal muscle cells for gene therapy applications. 相似文献
168.
Vanessa Loczenski Rose G. Sebastiaan Winkler Stephanie Allen Sanyogitta Puri Giuseppe Mantovani 《European Polymer Journal》2013
Oligonucleotide therapeutics such as antisense RNA, micro RNA, mRNA and small interfering RNA have great potential to generate a novel therapeutic portfolio within the pharmaceutical market. The promising outlook of oligonucleotide therapeutics lies in their ability to knockdown genes responsible for disease progression. However, the efficient delivery of RNA medicines without causing toxicity remains a major challenge. With growing interest in siRNA therapeutics, a number of synthetic polymers have been developed to facilitate efficient in vitro and in vivo delivery. With the advent of controlled radical polymerisation (CRP) techniques – such as RAFT polymerisation and ATRP – new families of well-defined polymers with narrow molecular weight distribution and predictable molecular architecture potentially suitable to generate siRNA delivery devices are becoming available. In this review article we will describe and discuss how CRP can be utilised to generate siRNA delivery nanodevices. 相似文献
169.
Jessica D. Townsend Angela R. Williams April J. Angel Anne E. Finefrock Charles F. Beam 《合成通讯》2013,43(4):689-699
Dilithiated 2-indanone was prepared with excess lithium diisopropylamide, and the resulting intermediate was condensed with several lithiated methyl salicylates or lithiated methyl thiosalicylate, which was followed by acid cyclization to benz[b]indeno[1,2-e]pyran-11(6H)-ones 3--9 or benz[b]indeno[1,2-e]thiopyran-11(6H)-one 10, which are rare fused-ring indeno-chromones and a new indeno-thiochromone, respectively. 相似文献
170.
高聚物基因载体的功能化研究 总被引:1,自引:0,他引:1
寻找安全、高效的基因载体是基因治疗的关键问题之一,聚合物基因载体具有低毒、低成本、可设计性强等优良的性质,是未来基因载体发展的方向。传统的高聚物作为基因载体时,功能单一,不能完全满足基因治疗的需要,因此对载体进行功能化修饰是十分必要的。本文在分析基因治疗过程的基础上,详述了基因载体应具有的四种基本功能——在细胞外保持稳定的功能、进入细胞的功能、逃离溶酶体的功能、进入细胞核的功能,并详细介绍了有关基因载体功能化修饰的方法和目前国际上的进展情况,最后本文总结了高聚物载体目前存在的主要问题及未来的发展方向。 相似文献