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https://www.readbyqxmd.com/read/29775757/molecular-characterization-of-physis-tissue-by-rna-sequencing
#1
Christopher R Paradise, Catalina Galeano-Garces, Daniela Galeano-Garces, Amel Dudakovic, Todd A Milbrandt, Daniel B F Saris, Aaron J Krych, Marcel Karperien, Gabriel B Ferguson, Denis Evseenko, Scott M Riester, Andre J van Wijnen, A Noelle Larson
The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775756/pkm2-a-potential-target-for-regulating-cancer
#2
REVIEW
Yu-Huan Li, Xiao-Feng Li, Jia-Tao Liu, Hua Wang, Lu-Lu Fan, Jun Li, Guo-Ping Sun
Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#3
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29775685/phenotypic-and-genetic-resistance-traits-in-pseudomonas-aeruginosa-strains-infecting-cystic-fibrosis-patients-a-french-cohort-study
#4
Nathalie Courtois, Yvan Caspar, Max Maurin
Pseudomonas aeruginosa is responsible for chronic respiratory tract colonisation and acute exacerbations in cystic fibrosis (CF) patients. This Gram-negative bacterium often develops multidrug resistance, which represents a therapeutic challenge. Our objective was to characterize the phenotypic and genetic β-lactam resistance traits of P. aeruginosa strains isolated from CF patients followed at Grenoble Alpes university hospital. The susceptibility to β-lactam compounds of 123 P. aeruginosa strains collected from the lower respiratory tract of 45 CF patients, between 2010 and 2014, was evaluated...
May 15, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29775627/acquisition-of-tumorigenic-potential-and-therapeutic-resistance-in-cd133-subpopulation-of-prostate-cancer-cells-exhibiting-stem-cell-like-characteristics
#5
Rajnee Kanwal, Sanjeev Shukla, Ethan Walker, Sanjay Gupta
The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice...
May 15, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29775572/gene-therapy-with-antisense-oligonucleotides-silencing-c-myc-reduces-neointima-formation-and-vessel-wall-thickness-in-a-mouse-model-of-vein-graft-disease
#6
Christina Maria Steger, Nikolaos Bonaros, Ralf Joachim Rieker, Johannes Bonatti, Thomas Schachner
Gene therapy for avoiding intimal hyperplasia of vein grafts after coronary artery bypass grafting is still discussed controversially. A promising application of gene therapy in vein grafts is the use of antisense oligonucleotides to block the expression of genes encoding cell cycle regulatory proteins in vascular smooth muscle cells. C-myc, either directly or by regulating the expression of other proteins, controls cell proliferation, apoptosis and cell survival, tissue remodeling, angiogenesis, cell metabolism, production of inflammatory and anti-inflammatory cytokines, and also participates in cell transformation...
May 15, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29775460/genus-wide-comparison-of-pseudovibrio-bacterial-genomes-reveal-diverse-adaptations-to-different-marine-invertebrate-hosts
#7
Anoop Alex, Agostinho Antunes
Bacteria belonging to the genus Pseudovibrio have been frequently found in association with a wide variety of marine eukaryotic invertebrate hosts, indicative of their versatile and symbiotic lifestyle. A recent comparison of the sponge-associated Pseudovibrio genomes has shed light on the mechanisms influencing a successful symbiotic association with sponges. In contrast, the genomic architecture of Pseudovibrio bacteria associated with other marine hosts has received less attention. Here, we performed genus-wide comparative analyses of 18 Pseudovibrio isolated from sponges, coral, tunicates, flatworm, and seawater...
2018: PloS One
https://www.readbyqxmd.com/read/29775441/-the-biological-function-and-significance-of-il-35-in-the-pathogenesis-of-atherosclerosis
#8
EDITORIAL
Mateusz Staciwa, Marlena Broncel
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29774792/hypofractionated-radiotherapy-is-superior-to-conventional-fractionation-in-an-orthotopic-model-of-anaplastic-thyroid-cancer
#9
Ayman J Oweida, Andy Phan, Benjamin Vancourt, Tyler Robin, Mohammad K Hararah, Shilpa Bhatia, Dallin Milner, Shelby Lennon, Laura Pike, David Raben, Bryan R Haugen, Nikita Pozdeyev, Rebecca E Schweppe, Sana D Karam
Anaplastic thyroid cancer is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment including radiation therapy and chemotherapy, response rates remain below 15% with a median time to progression of less than 3 months. Recent advances in radiotherapy delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative radiotherapy fractionation schedules for overcoming radioresistance...
May 18, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29774579/integrative-epigenetic-analysis-reveals-therapeutic-targets-to-the-dna-methyltransferase-inhibitor-sgi-110-in-hepatocellular-carcinoma
#10
Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff, Qianjin Lu, Daniel J Weisenberger, Gangning Liang
There is an urgent need for developing more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles and its clinical relevance by comparisons to TCGA HCC clinical data...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774543/human-monocyte-transciptional-profiling-identifies-interleukin-18-receptor-accessory-protein-and-lactoferrin-as-novel-immune-targets-in-hypertension
#11
Matthew R Alexander, Allison E Norlander, Fernando Elijovich, Ravi V Atreya, Amadou Gaye, Juan S Gnecco, Cheryl L Laffer, Cristi L Galindo, Meena S Madhur
BACKGROUND AND PURPOSE: Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach to determine whether hypertensive individuals on conventional therapy exhibit an altered monocyte gene expression profile and to perform validation studies of select genes to identify novel therapeutic targets for hypertension. EXPERIMENTAL APPROACH: Next-generation RNA sequencing identified differentially expressed genes in a small discovery cohort of normotensive and hypertensive individuals...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29774125/the-critical-role-that-stat3-plays-in-glioma-initiating-cells-stat3-addiction-in-glioma
#12
Debolina Ganguly, Meiyun Fan, Chuan He Yang, Blazej Zbytek, David Finkelstein, Martine F Roussel, Lawrence M Pfeffer
Glioma-Initiating Cells (GICs) are thought to be responsible for tumor initiation, progression and recurrence in glioblastoma (GBM). In previous studies, we reported the constitutive phosphorylation of the STAT3 transcription factor in GICs derived from GBM patient-derived xenografts, and that STAT3 played a critical role in GBM tumorigenesis. In this study, we show that CRISPR/Cas9-mediated deletion of STAT3 in an established GBM cell line markedly inhibited tumorigenesis by intracranial injection but had little effect on cell proliferation in vitro ...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#13
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774076/the-human-somatostatin-receptor-type-2-as-an-imaging-and-suicide-reporter-gene-for-pluripotent-stem-cell-derived-therapy-of-myocardial-infarction
#14
Katrien Neyrinck, Natacha Breuls, Bryan Holvoet, Wouter Oosterlinck, Esther Wolfs, Hubert Vanbilloen, Olivier Gheysens, Robin Duelen, Willy Gsell, Ivo Lambrichts, Uwe Himmelreich, Catherine M Verfaillie, Maurilio Sampaolesi, Christophe M Deroose
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation...
2018: Theranostics
https://www.readbyqxmd.com/read/29774063/dual-target-gene-therapy-to-eml4-alk-nsclc-by-a-gold-nanoshell-based-system
#15
Siwen Li, Yuxi Liu, Yalan Rui, Liping Tang, Samuel Achilefu, Yueqing Gu
Although EML4-ALK transforming fusion gene is represented in only 8% of non-small cell lung cancer (NSCLC) cases, its expression is partly responsive for the failure of current NSCLC treatments. Preventing secondary mutation of the ALK protein through direct gene manipulation could overcome NSCLC drug resistance. Method: In this study, we developed a gold nanoshell (HAuNs) drug carrier for delivery and selective photo-thermal release of genes that target ALK and microRNA-301 in NSCLC. Additionally, the densely-coated nanoshell adsorbed high amounts of the positively-charged anticancer drug doxorubicin (DOX), generating an exciting multidimensional treatment strategy that includes gene-, thermal- and chemo- therapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29774056/epigenetic-regulation-of-inflammation-in-stroke
#16
REVIEW
Gavin Yong-Quan Ng, Lim Yun-An, Christopher G Sobey, Thameem Dheen, David Yang-Wei Fann, Thiruma V Arumugam
Despite extensive research, treatments for clinical stroke are still limited only to the administration of tissue plasminogen activator and the recent introduction of mechanical thrombectomy, which can be used in only a limited proportion of patients due to time constraints. A plethora of inflammatory events occur during stroke, arising in part due to the body's immune response to brain injury. Neuroinflammation contributes significantly to neuronal cell death and the development of functional impairment and death in stroke patients...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#17
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773851/modeling-transcriptional-rewiring-in-neutrophils-through-the-course-of-treated-juvenile-idiopathic-arthritis
#18
Zihua Hu, Kaiyu Jiang, Mark Barton Frank, Yanmin Chen, James N Jarvis
Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773850/comparative-genomic-analysis-of-acinetobacter-spp-plasmids-originating-from-clinical-settings-and-environmental-habitats
#19
Ileana P Salto, Gonzalo Torres Tejerizo, Daniel Wibberg, Alfred Pühler, Andreas Schlüter, Mariano Pistorio
Bacteria belonging to the genus Acinetobacter have become of clinical importance over the last decade due to the development of a multi-resistant phenotype and their ability to survive under multiple environmental conditions. The development of these traits among Acinetobacter strains occurs frequently as a result of plasmid-mediated horizontal gene transfer. In this work, plasmids from nosocomial and environmental Acinetobacter spp. collections were separately sequenced and characterized. Assembly of the sequenced data resulted in 19 complete replicons in the nosocomial collection and 77 plasmid contigs in the environmental collection...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773788/immunogene-therapy-with-fusogenic-nanoparticles-modulates-macrophage-response-to-staphylococcus-aureus
#20
Byungji Kim, Hong-Bo Pang, Jinyoung Kang, Ji-Ho Park, Erkki Ruoslahti, Michael J Sailor
The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy...
May 17, 2018: Nature Communications
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