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https://www.readbyqxmd.com/read/28534661/characterization-of-human-fetal-brain-endothelial-cells-reveals-barrier-properties-suitable-for-in%C3%A2-vitro-modeling-of-the-bbb-with-syngenic-co-cultures
#1
Allison M Andrews, Evan M Lutton, Lee A Cannella, Nancy Reichenbach, Roshanak Razmpour, Matthew J Seasock, Steven J Kaspin, Steven F Merkel, Dianne Langford, Yuri Persidsky, Servio H Ramirez
Endothelial cells (ECs) form the basis of the blood-brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28534658/dynamic-brain-glucose-metabolism-identifies-anti-correlated-cortical-cerebellar-networks-at-rest
#2
Dardo G Tomasi, Ehsan Shokri-Kojori, Corinde E Wiers, Sunny W Kim, Şukru B Demiral, Elizabeth A Cabrera, Elsa Lindgren, Gregg Miller, Gene-Jack Wang, Nora D Volkow
It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[(18)F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28534452/the-recurrent-domestication-of-viruses-major-evolutionary-transitions-in-parasitic-wasps
#3
Jérémy Gauthier, Jean-Michel Drezen, Elisabeth A Herniou
Several lineages of endoparasitoid wasps, which develop inside the body of other insects, have domesticated viruses, used as delivery tools of essential virulence factors for the successful development of their progeny. Virus domestications are major evolutionary transitions in highly diverse parasitoid wasps. Much progress has recently been made to characterize the nature of these ancestrally captured endogenous viruses that have evolved within the wasp genomes. Virus domestication from different viral families occurred at least three times in parasitoid wasps...
May 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28533388/selective-lowering-of-synapsins-induced-by-oligomeric-%C3%AE-synuclein-exacerbates-memory-deficits
#4
Megan E Larson, Susan J Greimel, Fatou Amar, Michael LaCroix, Gabriel Boyle, Mathew A Sherman, Hallie Schley, Camille Miel, Julie A Schneider, Rakez Kayed, Fabio Benfenati, Michael K Lee, David A Bennett, Sylvain E Lesné
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533386/metabolic-basis-to-sherpa-altitude-adaptation
#5
James A Horscroft, Aleksandra O Kotwica, Verena Laner, James A West, Philip J Hennis, Denny Z H Levett, David J Howard, Bernadette O Fernandez, Sarah L Burgess, Zsuzsanna Ament, Edward T Gilbert-Kawai, André Vercueil, Blaine D Landis, Kay Mitchell, Monty G Mythen, Cristina Branco, Randall S Johnson, Martin Feelisch, Hugh E Montgomery, Julian L Griffin, Michael P W Grocott, Erich Gnaiger, Daniel S Martin, Andrew J Murray
The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m)...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533089/synergistic-anti-tumor-effects-of-bevacizumab-and-tumor-targeted-polymerized-vegf-sirna-nanoparticles
#6
Myung Goo Kim, Sung Duk Jo, Ji Young Yhee, Beom Suk Lee, So Jin Lee, Sung Gurl Park, Sun-Woong Kang, Sun Hwa Kim, Ji Hoon Jeong
A variety of VEGF inhibitors have been reported to treat cancers by suppressing tumor angiogenesis. Bevacizumab, a monoclonal VEGF antibody, was the first FDA approved anti-angiogenic agent for cancer treatments. However, bevacizumab shows modest therapeutic efficiency and often cause resistant problem in significant populations of cancer patients. To solve these problem, we investigated the therapeutic efficacy of siRNA drugs targeting VEGF and combination of the RNAi drug with bevacizumab for cancer treatments...
May 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28532899/nanodiamond-based-injectable-hydrogel-for-sustained-growth-factor-release-preparation-characterization-and-in-vitro-analysis
#7
Settimio Pacelli, Francisca Acosta, Aparna R Chakravarti, Saheli G Samanta, Jonathan Whitlow, Saman Modaresi, Rafeeq P H Ahmed, Johnson Rajasingh, Arghya Paul
Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications...
May 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28532763/nanomaterial-enabled-cancer-therapy
#8
REVIEW
Sabina Quader, Kazunori Kataoka
While cancer remains the major cause of death worldwide, nanomaterial (NM)-based diagnosis and treatment modalities are showing remarkable potential to better tackle clinical oncology by effectively targeting therapeutic agents to tumors. NMs can selectively accumulate in solid tumors, and they can improve the bioavailability and reduce the toxicity of encapsulated cytotoxic agents. Additional noteworthy functions of NMs in cancer treatment include the delivery of contrast agents to image tumor sites, delivery of genetic materials for gene therapy, and co-delivery of multiple agents to achieve combination therapy or simultaneous diagnostic and therapeutic outcomes...
May 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28532300/engineered-polymeric-amphiphiles-self-assembling-into-nanostructures-and-acting-as-efficient-gene-and-drug-carriers
#9
Ruby Bansal, Pradeep Kumar
Nonviral gene delivery systems are finding widespread use due to their safety, rapid and economical production, and ease of modification. In this work, series of N-alkyl-substituted linear polyethylenimine (CP) polymers have been synthesized, characterized, and investigated about how degree of substitution (hydrophobic-hydrophilic balance) (i.e. N-alkylation) influenced the transfection efficiency. Mobility shift assay demonstrated efficient binding of plasmid DNA (pDNA). Transfection efficiency and cytotoxicity of CP polymers were assessed in vitro, which revealed that all the formulations exhibited higher transfection activity than linear polyethylenimine (lPEI) and commercial transfection reagents, Lipofectamine and Superfect, with negligible toxicity (MTT assay)...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28532005/non-viral-strategies-for-ocular-gene-delivery
#10
REVIEW
Ana V Oliveira, Ana M Rosa da Costa, Gabriela A Silva
The success of gene therapy relies on efficient gene transfer and stable transgene expression. The in vivo efficiency is determined by the delivery vector, route of administration, therapeutic gene, and target cells. While some requirements are common to several strategies, others depend on the target disease and transgene product. Consequently, it is unlikely that a single system is suitable for all applications. This review examines current gene therapy strategies, focusing on non-viral approaches and the use of natural polymers with the eye, and particularly the retina, as their gene delivery target...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531220/highly-conserved-type-1-pili-promote-enterotoxigenic-e-coli-pathogen-host-interactions
#11
Alaullah Sheikh, Rasheduzzaman Rashu, Yasmin Ara Begum, F Matthew Kuhlman, Matthew A Ciorba, Scott J Hultgren, Firdausi Qadri, James M Fleckenstein
Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host...
May 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28530287/microfluidic-self-assembly-of-folate-targeted-monomolecular-sirna-lipid-nanoparticles
#12
R Krzysztoń, B Salem, D J Lee, G Schwake, E Wagner, J O Rädler
Non-viral delivery of nucleic acids for therapies based on RNA interference requires a rational design and optimal self-assembly strategies. Nucleic acid particles need to be small, stable and functional in terms of selective cell uptake and controlled release of encapsulated nucleic acids. Here we report on small (∼38 nm) monomolecular nucleic acid/lipid particles (mNALPs) that contain single molecules of short double-stranded oligonucleotides covered by a tight, highly curved lipid bilayer. The particles consist of DOPE, DOTAP, DOPC and DSPE-PEG(2000) and are assembled with 21 bp double-stranded DNA or small interfering RNA by solvent exchange on a hydrodynamic-focusing microfluidic chip...
May 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28530135/prolonged-expression-of-secreted-enzymes-in-dogs-after-liver-directed-delivery-of-i-sleeping-beauty-i-transposons-implications-for-non-viral-gene-therapy-of-systemic-disease
#13
Elena L Aronovich, Kendra Anne Hyland, Bryan C Hall, Jason B Bell, Erik R Olson, Myra Urness Rusten, David W Hunter, N Matthew Ellinwood, R Scott McIvor, Perry B Hackett
The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice including hemophilias A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis (MPS) types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. We recently reported modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), we demonstrated transgenic protein in the plasma for up to six weeks post-infusion...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28529641/multifunctional-nucleus-targeting-nanoparticles-with-ultra-high-gene-transfection-efficiency-for-in-vivo-gene-therapy
#14
Ling Li, Xia Li, Yuzhe Wu, Linjiang Song, Xi Yang, Tao He, Ning Wang, Suleixin Yang, Yan Zeng, Qinjie Wu, Zhiyong Qian, Yuquan Wei, Changyang Gong
Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy). Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based gene delivery system which is capable of targeting and eradicating CSCL. These nanoparticles can facilitate efficient endosomal escape and spontaneously penetrate into nucleus without additional nuclear localization signal. They also induced extremely high gene transfection efficiency (>95%) even in culture medium containing 30% serum, which significantly surpassed that of some commercial transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc...
2017: Theranostics
https://www.readbyqxmd.com/read/28529584/anti-microrna-21-221-and-microrna-199a-transfected-by-ultrasound-microbubbles-induces-the-apoptosis-of-human-hepatoma-hepg2-cells
#15
Xinmin Guo, Shunhua Guo, Liwen Pan, Li Ruan, Yingshi Gu, Jichuang Lai
Gene therapy, particularly microRNA (miRNA), is a promising candidate in the treatment of cancer; however, it is challenging to develop gene delivery systems. Ultrasound microbubbles have been used for gene delivery with excellent results. The present study aimed to investigate the transfection efficiency of HepG2 cells using ultrasound microbubbles. The effects of three miRNAs (miR-21, miR-221 and miR-199a) on HepG2 cells were also determined by performing ultrasound microbubble-mediated gene transfection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529331/butyrylcholinesterase-regulates-central-ghrelin-signaling-and-impacts-food-intake-and-glucose-homeostasis
#16
V P Chen, Y Gao, L Geng, S Brimijoin
BACKGROUND: Ghrelin is the only orexigenic hormone known to stimulate food intake and promote obesity and insulin resistance. We recently showed that plasma ghrelin is controlled by butyrylcholinesterase (BChE), which has a strong impact on feeding and weight gain. BChE knockout (KO) mice are prone to obesity on high-fat diet but hepatic BChE gene transfer rescues normal food intake and obesity resistance. However, these mice lack brain BChE and still develop hyperinsulinemia and insulin resistance, suggesting essential interactions between BChE and ghrelin within the brain...
May 22, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28529158/evaluation-of-direct-and-cell-mediated-triple-gene-therapy-in-spinal-cord-injury-in-rats
#17
Rustem Robertovich Islamov, Andrey Alexandrovich Izmailov, Mikhail Evgenyevich Sokolov, Philip Olegovich Fadeev, Farid Vagizovich Bashirov, Anton Alexandrovich Eremeev, Gulnara Ferdinantovna Shaymardanova, Maxim Michaylovich Shmarov, Boris Savelyevich Naroditskiy, Yuri Alexandrovich Chelyshev, Igor Aleksandrovich Lavrov, András Palotás
Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs)...
May 18, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28528119/autophagy-plays-a-dual-role-during-intracellular-sirna-delivery-by-lipoplex-and-polyplex-nanoparticles
#18
Wen Song, Zhiwei Ma, Yumei Zhang, Chuanxu Yang
Growing evidence indicates that autophagy plays a vital role during the intracellular DNA delivery mediated by lipoplex and polyplex nanoparticles. However, autophagy in intracellular siRNA delivery has not been well understood. In this study, lipofectamine 2000 and chitosan were used to formulate lipoplex and polyplex with siRNA for systematically investigating the interplay between siRNA delivery and autophagy. After transfection of H1299 cells with lipoplex and polyplex, the number of autophagic vacuoles was increased significantly indicated by the accumulation of monodansylcadaverine (MDC) staining...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28527665/therapeutic-editing-of-hepatocyte-genome-in-vivo
#19
REVIEW
Marina Ruiz de Galarreta, Amaia Lujambio
The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527520/recent-advances-in-smart-biotechnology-hydrogels-and-nanocarriers-for-tailored-bioactive-molecules-depot
#20
REVIEW
Gesmi Milcovich, Stefania Lettieri, Filipe E Antunes, Bruno Medronho, Ana C Fonseca, Jorge F J Coelho, Paolo Marizza, Francesca Perrone, Rossella Farra, Barbara Dapas, Gabriele Grassi, Mario Grassi, Silvia Giordani
Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs...
May 9, 2017: Advances in Colloid and Interface Science
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