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https://www.readbyqxmd.com/read/29451775/fluorescence-imaging-of-huntingtin-mrna-knockdown
#1
Eunseon Oh, Yuhong Liu, Mahesh V Sonar, Diane Merry, Eric Wickstrom
Huntington's disease (HD) is an autosomal-dominant neurodegenerative genetic disorder caused by CAG repeat expansion in exon 1 of the HTT gene. Expression of the mutant gene results in the production of a neurotoxic polyglutamine (polyQ)-expanded huntingtin (Htt) protein. Clinical trials of knockdown therapy of mutant polyglutamine-encoding HTT mRNA in Huntington's disease (HD) have begun. To measure HTT mRNA knockdown effectiveness in human cells, we utilized a fluorescent hybridization imaging agent specific to the region encompassing the human HTT mRNA initiation codon...
February 16, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29451210/intravenous-morphine-self-administration-alters-accumbal-microrna-profiles-in-the-mouse-brain
#2
Juhwan Kim, Heh-In Im, Changjong Moon
A significant amount of evidence indicates that microRNAs (miRNAs) play an important role in drug addiction. The nucleus accumbens (NAc) is a critical part of the brain's reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine (0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and showed inverted U-shaped response...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29448633/copolymeric-micelles-loading-curcumin-preparation-characterization-and-in-vitro-evaluation
#3
Min Li, Li Lv, Aijie Guo, Yuanyuan Shen, Shengrong Guo
Curcumin (Cur) has potent antitumor activity; however, its clinical use is limited due to its hydrophobicity and instability at physiological pH. In this work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur-loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having excellent water-solubility and good stability at pH 7...
March 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29447443/inhibitor-bound-dengue-ns2b-ns3pro-reveals-multiple-dynamic-binding-modes
#4
Alan C Gibbs, Ruth Steele, Gaohua Liu, Brett A Tounge, Gaetano Montelione
Dengue virus poses a significant global health threat as the source of increasingly deleterious dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. As no specific antiviral treatment exists for dengue infection, considerable effort is being applied to discover therapies and drugs for maintenance and prevention of these afflictions. The virus is primarily transmitted by mosquitoes, and infection occurs following viral endocytosis by host cells. Upon entering the cell, viral RNA is translated into a large multi-subunit polyprotein which is post-translationally cleaved into mature, structural and non-structural (NS) proteins...
February 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/29447276/mesenchymal-stem-cell-derived-exosomes-have-altered-microrna-profiles-and-induce-osteogenic-differentiation-depending-on-the-stage-of-differentiation
#5
Xiaoqin Wang, Omar Omar, Forugh Vazirisani, Peter Thomsen, Karin Ekström
Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation...
2018: PloS One
https://www.readbyqxmd.com/read/29446631/mechanistic-investigation-and-multiplexing-of-liposome-assisted-metabolic-glycan-labeling
#6
Yuting Sun, Senlian Hong, Ran Xie, Rongbing Huang, Ruoxing Lei, Bo Cheng, Deen Sun, Yifei Du, Corwin M Nycholat, James C Paulson, Xing Chen
Metabolic labeling of glycans with bioorthogonal reporters has been widely used for glycan imaging and glycoproteomic profiling. One of the intrinsic limitations of metabolic glycan labeling is the lack of cell-type selectivity. The recently developed liposome-assisted bioorthogonal reporter (LABOR) strategy provides a promising means to overcome this limitation, but the mechanism of LABOR has not been investigated in detail. In this work, we performed a mechanistic study on LABOR and explored its multiplexing capability...
February 15, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29446616/new-mechanism-for-release-of-endosomal-contents-osmotic-lysis-via-nigericin-mediated-k-h-exchange
#7
Loganathan Rangasamy, Venkatesh Chelvam, Ananda Kumar Kanduluru, Madduri Srinivasarao, Achini N Bandara, Fei You, Esteban Orellana, Andrea L Kasinski, Philip S Low
Although peptides, antibodies/antibody fragments, siRNAs, antisense DNAs, enzymes and aptamers are all under development as possible therapeutic agents, the breadth of their applications has been severely compromised by their inability to reach intracellular targets. Thus, while macromolecules can often enter cells by receptor-mediated endocytosis, their missions frequently fail due to an inability to escape their entrapping endosomes. In this paper, we describe a general method for promoting release of any biologic material from any entrapping endosome...
February 15, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29445792/understanding-receptor-mediated-endocytosis-of-elastic-nanoparticles-through-coarse-grained-molecular-dynamic-simulation
#8
Zhiqiang Shen, Huilin Ye, Ying Li
For nanoparticle (NP)-based drug delivery platforms, the elasticity of the NPs has a significant influence on their blood circulation time and cellular uptake efficiency. However, due to the complexity of the endocytosis process and the inconsistency in the definition of elasticity for NPs in experiments, the understanding about the receptor-mediated endocytosis process of elastic NPs is still limited. In this work, we developed a coarse-grained molecular dynamics (CGMD) model for elastic NPs. The energy change of the elastic NPs can be precisely controlled by the bond, area, volume and bending potentials of this CGMD model...
February 15, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29445787/nanoparticles-based-on-glycyrrhetinic-acid-modified-porphyrin-for-photodynamic-therapy-of-cancer
#9
Xin Wang, Peisong Wang, Shuai Xue, Xiaohua Zheng, Zhigang Xie, Guang Chen, Tingting Sun
Self-assembled small molecules, as a novel form of drug presentation, have splendid capabilities for water stability and cell endocytosis. Photodynamic therapy (PDT) is regarded as a promising cancer treatment because it is less invasive and has fewer side effects. In this work, an amphiphilic glycyrrhetinic acid-porphyrin conjugate (TPP-GA) was designed and synthesized, and this could self-assemble into nanoparticles (TPP-GA NPs) in water. The morphology of the TPP-GA NPs was observed using transmission electron microscopy (TEM) and their stability in water was revealed by dynamic light scattering (DLS)...
February 15, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29442621/construction-of-fluorescein-isothiocyanate-labeled-msns-peg-lycorine-antibody-as-drug-carrier-for-targeting-prostate-cancer-cells
#10
Xiaoning Liu, Jingjing Kang, Hui Wang, Tao Huang, Chun Li
Lycorine possesses various pharmacological effects, including anti-tumor, antiviral, anti-malarial and anti-inflammatory properties, as well as a potential therapeutic against prostate cancer cells. Therefore, a drug carrier of lycorine with good biocompatibility, high drug loading capacity and good release ability is required to develop to gain maximum benefit from lycorine to target cancer cells. In this study, MSNs labeled with FITC and PEG were synthesized. These FITC-labeled MSNs/PEG/Lycorine/Antibody were loaded with lycorine and anti-EpCAM antibody, and analyzed for endocytosis, biocompatibility, drug loading and release ability...
July 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#11
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29439726/a-novel-cav-derived-cell-penetrating-peptide-efficiently-delivers-exogenous-molecules-through-caveolae-mediated-endocytosis
#12
Gaowei Hu, Wenlv Zheng, Ao Li, Yaru Mu, Mingyu Shi, Tuofan Li, Haitao Zou, Hongxia Shao, Aijian Qin, Jianqiang Ye
Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity...
February 13, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29438268/endocytosis-of-red-blood-cell-microparticles-by-pulmonary-endothelial-cells-is-mediated-by-rab5
#13
Young Kim, William A Abplanalp, Andrew D Jung, Rebecca M Schuster, Alex B Lentsch, Erich Gulbins, Charles C Caldwell, Timothy A Pritts
Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6...
March 2018: Shock
https://www.readbyqxmd.com/read/29437275/intersection-of-endocytic-and-exocytic-systems-in-toxoplasma-gondii
#14
Olivia L McGovern, Yolanda Rivera-Cuevas, Geetha Kannan, Andrew Narwold, Vern B Carruthers
Host cytosolic proteins are endocytosed by Toxoplasma gondii and degraded in its lysosome-like compartment, the VAC, but the dynamics and route of endocytic trafficking remain undefined. Conserved endocytic components and plant-like features suggest T. gondii endocytic trafficking involves transit through early and late endosome-like compartments (ELCs) and potentially the trans-Golgi network (TGN) as in plants. However, exocytic trafficking to regulated secretory organelles, micronemes and rhoptries, also proceeds through ELCs and requires classical endocytic components including a dynamin-related protein, DrpB...
February 13, 2018: Traffic
https://www.readbyqxmd.com/read/29435600/the-role-of-unfolded-protein-response-and-er-phagy-in-quantum-dots-induced-nephrotoxicity-an-in-vitro-and-in-vivo-study
#15
Shengwei Jiang, Yuchun Lin, Huan Yao, Chuanli Yang, Liyin Zhang, Bing Luo, Zhao Lei, Liwei Cao, Naibo Lin, Xiangyang Liu, Zhongning Lin, Chengyong He
Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h...
February 12, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29434374/reactive-oxygen-species-regulate-axonal-regeneration-through-the-release-of-exosomal-nadph-oxidase-2-complexes-into-injured-axons
#16
Arnau Hervera, Francesco De Virgiliis, Ilaria Palmisano, Luming Zhou, Elena Tantardini, Guiping Kong, Thomas Hutson, Matt C Danzi, Rotem Ben-Tov Perry, Celio X C Santos, Alexander N Kapustin, Roland A Fleck, José Antonio Del Río, Thomas Carroll, Vance Lemmon, John L Bixby, Ajay M Shah, Mike Fainzilber, Simone Di Giovanni
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis...
February 12, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29433754/noncovalent-tagging-of-sirna-with-steroids-for-transmembrane-delivery
#17
Wanyi Tai, Xiaohu Gao
Short interfering RNA (siRNA) has broad applications in biology and medicine, and holds tremendous potential to become a new class of therapeutics for many diseases. As a highly anionic macrobiomolecule, its cytosolic delivery, however, has been a major roadblock in translation. Here, we report the development of small, bifunctional chemical tags capable of transporting siRNA directly into the cytosol. The bifunctional tags consist of a siRNA-binding moiety that interacts with siRNA non-covalently, and a steroid domain that readily fuses with the mammalian cell membrane...
February 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29433357/transferrin-and-octaarginine-modified-dual-functional-liposomes-with-improved-cancer-cell-targeting-and-enhanced-intracellular-delivery-for-the-treatment-of-ovarian-cancer
#18
Pranali Deshpande, Aditi Jhaveri, Bhushan Pattni, Swati Biswas, Vladimir Torchilin
Off-target effects of drugs severely limit cancer therapy. Targeted nanocarriers are promising to enhance the delivery of therapeutics to tumors. Among many approaches for active tumor-targeting, arginine-rich cell penetrating peptides (AR-CPP) and ligands specific to target over-expressed receptors on cancer-cell surfaces, are popular. Earlier, we showed that the attachment of an AR-CPP octaarginine (R8) to the surface of DOXIL® (Doxorubicin encapsulated PEGylated liposomes) improved cytoplasmic and nuclear DOX delivery that enhanced the cytotoxic effect in vitro and improved therapeutic efficacy in vivo...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29433060/dual-tumor-targeted-multifunctional-magnetic-hyaluronic-acid-micelles-for-enhanced-mr-imaging-and-combined-photothermal-chemotherapy
#19
Shaohui Zheng, Jiwon Han, Zhen Jin, Chang-Sei Kim, Sukho Park, Kyu-Pyo Kim, Jong-Oh Park, Eunpyo Choi
Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C16 copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29432720/exosomes-and-regenerative-medicine-state-of-the-art-and-perspectives
#20
REVIEW
Hui Jing, Xiaomin He, Jinghao Zheng
Exosomes have attracted the attention of the scientific community in recent years due to their widespread distribution, their possible functions as biomarkers of disease, and their great potential to be applied as therapeutic agents. Exosomes carry proteins and nucleic acids that can facilitate their uptake by distant target cells through endocytosis, such that exosomes could be targeted to a specific cell or cells to enhance or interfere with specific biological processes. This review will mainly focus on their roles in tissue repair and regenerative processes...
January 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
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