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https://www.readbyqxmd.com/read/28340487/microrna-4739-regulates-osteogenic-and-adipocytic-differentiation-of-immortalized-human-bone-marrow-stromal-cells-via-targeting-lrp3
#1
Mona Elsafadi, Muthurangan Manikandan, Nehad M Alajez, Rimi Hamam, Raed Abu Dawud, Abdullah Aldahmash, Zafar Iqbal, Musaad Alfayez, Moustapha Kassem, Amer Mahmood
Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone...
March 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#2
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340435/optimization-of-hydrogen-dispersion-in-thermophilic-up-flow-reactors-for-ex-situ-biogas-upgrading
#3
Ilaria Bassani, Panagiotis G Kougias, Laura Treu, Hugo Porté, Stefano Campanaro, Irini Angelidaki
This study evaluates the efficiency of four novel up-flow reactors for ex situ biogas upgrading converting externally provided CO2 and H2 to CH4, via hydrogenotrophic methanogenesis. The gases were injected through stainless steel diffusers combined with alumina ceramic sponge or through alumina ceramic membranes. Pore size, input gas loading and gas recirculation flow rate were modulated to optimize gas-liquid mass transfer, and thus methanation efficiency. Results showed that larger pore size diffusion devices achieved the best kinetics and output-gas quality converting all the injected H2 and CO2, up to 3...
March 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28340379/knockdown-of-ska1-gene-inhibits-cell-proliferation-and-metastasis-in-human-adenoid-cystic-carcinoma
#4
Li-Juan Zhao, Hong-Li Yang, Ke-Yi Li, Yue-Hua Gao, Kai Dong, Zhong-Hao Liu, Le-Xin Wang, Bin Zhang
The spindle and kinetochore-associated complex subunit 1(SKA1) is a newly discovered gene, which has been associated with mitosis and tumorigenesis. However, its role insalivary adenoid cystic carcinoma (SACC) is still unknown, and the invasive and metastatic mechanism in SACC is still unclear. To explore the molecular mechanism of SKA1 in the process of malignant proliferation and metastasis in adenoid cystic cancer (ACC) cells, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in SACC-83 cells...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#5
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340220/her2-neu-status-determination-in-breast-cancer-a-single-institutional-experience-using-a-dual-testing-approach-with-immunohistochemistry-and-fluorescence-in-situ-hybridization
#6
James P Solomon, Marie Dell'Aquila, Oluwole Fadare, Farnaz Hasteh
Objectives: According to current guidelines, either immunohistochemistry (IHC) or in situ hybridization (ISH) can be used to determine human epidermal growth factor receptor 2 (Her2/neu) status in breast carcinoma. While the guidelines explicitly delineate result interpretation, there is no consensus on the most appropriate testing algorithm. Methods: The Her2/neu statuses of 369 consecutive cases of invasive breast cancer (from 351 patients) were assessed in a dual-testing algorithm that uses both IHC and fluorescence ISH (FISH)...
March 11, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340175/funresdb-a-web-resource-for-genotypic-susceptibility-testing-of-aspergillus-fumigatus
#7
Michael Weber, Jonas Schaer, Grit Walther, Kerstin Kaerger, Jörg Steinmann, Peter-Michael Rath, Birgit Spiess, Dieter Buchheidt, Axel Hamprecht, Oliver Kurzai
Therapy of invasive aspergillosis is becoming more difficult due to the emergence of azole resistance in Aspergillus fumigatus. A majority of resistant strains carries mutations in the CYP51A gene. Due to a lack of sensitivity of culture-based methods, molecular detection of A. fumigatus has become an important diagnostic tool. We set up the database FunResDB (www.nrz-myk.de/funresdb) to gather all available information about CYP51A-dependent azole resistance from published literature. In summary, the screening resulted in 79 CYP51A variants, which are linked to 59 nonsynonymous mutations...
March 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28339995/long-term-flecainide-therapy-in-type-3-long-qt-syndrome
#8
Ehud Chorin, Rivki Taub, Aron Medina, Nir Flint, Sami Viskin, Jesaia Benhorin
Aims: Type 3 long QT syndrome (LQT3) is caused by gain-of-function mutations in the cardiac sodium channel gene (SCN5A). Previous reports on the long-term use of sodium channel blockers in LQT3 are sparse. The objective of the current study was to evaluate the long-term safety and efficacy of flecainide therapy in patients with LQT3 who carry the D1790G SCN5A mutation. Methods and results: The study population comprised 30 D1790G carriers who were treated with flecainide and followed for 1-215 months (mean 145 ± 54 months, median 140 months)...
February 28, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339926/study-on-the-expression-of-human-lysozyme-in-oviduct-bioreactor-mediated-by-recombinant-avian-adeno-associated-virus1
#9
A P Wang, Y J Wang, S Wu, W Y Zuo, C M Guo, W M Hong, S Y Zhu
Due to its antimicrobial properties and low toxicity, human lysozyme (hLYZ) has broad application in the medical field and as a preservative used by the food industry. However, limited availability hinders its widespread use. Hence, we constructed a recombinant avian adeno-associated virus (rAAAV) that would specifically express hLYZ in the chicken oviduct and harvested hLYZ from the egg whites of laying hens. The oviduct-specific human lysozyme expression cassette flanked by avian adeno-associated virus (AAAV) inverted terminal repeats (ITRs) was subcloned into the modified baculovirus transfer vector pFBX, and then the recombinant baculovirus rBac-ITRLYZ was generated...
March 2, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339768/the-transcription-factor-olig2-is-important-for-the-biology-of-diffuse-intrinsic-pontine-gliomas
#10
Jane L Anderson, Ranjithmenon Muraleedharan, Nicole Oatman, Amanda Klotter, Satarupa Sengupta, Ronald R Waclaw, Jianqiang Wu, Rachid Drissi, Lili Miles, Eric H Raabe, Matthew L Weirauch, Maryam Fouladi, Lionel M Chow, Lindsey Hoffman, Mariko DeWire, Biplab Dasgupta
Background.: Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons...
February 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339564/emerging-molecular-therapies-targeting-myocardial-infarction-related-arrhythmias
#11
Helen E Driessen, Toon A B van Veen, Gerard J J Boink
Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate...
October 6, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339517/omics-studies-their-use-in-diagnosis-and-reclassification-of-sle-and-other-systemic-autoimmune-diseases
#12
Maria Teruel, Chris Chamberlain, Marta E Alarcón-Riquelme
Omics studies of systemic autoimmune diseases (SADs) in general, and SLE in particular, have delivered isolated information from transcriptome, epigenome, genome, cytokine and metabolome analyses. Such analyses have resulted in the identification of disease susceptibility genes and the description of IFN expression signatures, allowing extensive insight into the mechanisms of disease and the development of new therapies. Access to such technologies allows the recognition of patterns of disease at a pathway level, thereby, to reclassify SLE and other SADs and to develop new therapeutics from a personalized perspective...
October 19, 2016: Rheumatology
https://www.readbyqxmd.com/read/28339498/enhancement-of-osteogenic-differentiation-of-rat-adipose-tissue-derived-mesenchymal-stem-cells-by-zinc-sulphate-under-electromagnetic-field-via-the-pka-erk1-2-and-wnt-%C3%AE-catenin-signaling-pathways
#13
Ezzatollah Fathi, Raheleh Farahzadi
Zinc ion as an essential trace element and electromagnetic fields (EMFs) has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4) on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP) activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF...
2017: PloS One
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#14
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#15
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335015/the-synaptic-function-of-parkin
#16
Jenny Sassone, GiuliaMaia Serratto, Flavia Valtorta, Vincenzo Silani, Maria Passafaro, Andrea Ciammola
Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334940/aav9-delivered-bispecific-nanobody-attenuates-amyloid-burden-in-the-gelsolin-amyloidosis-mouse-model
#17
Adriaan Verhelle, Nisha Nair, Inge Everaert, Wouter Van Overbeke, Lynn Supply, Olivier Zwaenepoel, Cindy Peleman, Jo Van Dorpe, Tony Lahoutte, Nick Devoogdt, Wim Derave, Marinee K Chuah, Thierry Vanden Driessche, Jan Gettemans
Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+  binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at the surface. During secretion of mutant plasma gelsolin consecutive cleavage by furin and MT1-MMP results in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies that are able to (partly) inhibit furin or MT1-MMP proteolysis have previously been reported...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334934/a-pseudaminic-acid-or-a-legionaminic-acid-derivative-transferase-is-strain-specifically-implicated-in-the-general-protein-o-glycosylation-system-of-the-periodontal-pathogen-tannerella-forsythia
#18
Markus B Tomek, Bettina Janesch, Daniel Maresch, Markus Windwarder, Friedrich Altmann, Paul Messner, Christina Schäffer
The occurrence of nonulosonic acids in bacteria is wide-spread and linked to pathogenicity. However, the knowledge of cognate nonulosonic acid transferases is scarce. In the periodontopathogen Tannerella forsythia, several proposed virulence factors carry strain-specifically either a pseudaminic or a legionaminic acid derivative as terminal sugar on an otherwise structurally identical, protein-bound oligosaccharide. This study aims to shed light on the transfer of either nonulosonic acid derivative on a proximal N-acetylmannosaminuronic acid residue within the O-glycan structure, exemplified with the bacterium's abundant S-layer glycoproteins...
March 16, 2017: Glycobiology
https://www.readbyqxmd.com/read/28334919/antibiotics-trigger-initiation-of-sccmec-transfer-by-inducing-sos-responses
#19
Pilong Liu, Zhaowei Wu, Huping Xue, Xin Zhao
The rise of antimicrobial resistance limits therapeutic options for infections by methicillin-resistant staphylococci. The staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element as the only carrier of the methicillin-resistance determinants, the mecA or mecC gene. The use of antibiotics increases the spread of antibiotic resistance, but the mechanism by which antibiotics promote horizontal dissemination of SCCmec is largely unknown. In this study, we demonstrate that many antibiotics, including β-lactams, can induce the expression of ccrC1 and SCCmec excision from the bacterial chromosome...
March 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334876/pdgfrb-gain-of-function-mutations-in-sporadic-infantile-myofibromatosis
#20
Florence A Arts, Raf Sciot, Bénédicte Brichard, Marleen Renard, Audrey de Rocca Serra, Guillaume Dachy, Laura A Noël, Amélie I Velghe, Christine Galant, Maria Debiec-Rychter, An Van Damme, Miikka Vikkula, Raphaël Helaers, Nisha Limaye, Hélène A Poirel, Jean-Baptiste Demoulin
Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma...
March 3, 2017: Human Molecular Genetics
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