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https://www.readbyqxmd.com/read/28454355/what-is-known-about-melatonin-chemotherapy-and-altered-gene-expression-in-breast-cancer
#1
Carlos Martínez-Campa, Javier Menéndez-Menéndez, Carolina Alonso-González, Alicia González, Virginia Álvarez-García, Samuel Cos
Melatonin, synthesized in and released from the pineal gland, has been demonstrated by multiple in vivo and in vitro studies to have an oncostatic role in hormone-dependent tumors. Furthermore, several clinical trials point to melatonin as a promising adjuvant molecule to be considered for cancer treatment. In the past few years, evidence of a broader spectrum of action of melatonin as an antitumor agent has arisen; thus, melatonin appears to also have therapeutic effects in several types of hormone-independent cancer, including ovarian, leukemic, pancreatic, gastric and non-small cell lung carcinoma...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453775/deconvoluting-kinase-inhibitor-induced-cardiotoxicity
#2
Sarah D Lamore, Ernst Ahlberg, Scott Boyer, Michelle L Lamb, Maria P Hortigon-Vinagre, Victor Rodriguez, Godfrey L Smith, Johanna Sagemark, Lars Carlsson, Stephanie M Bates, Allison L Choy, Jonna Stålring, Clay W Scott, Matthew F Peters
Many drugs designed to inhibit kinases have their clinical utility limited by cardiotoxicity-related label warnings or prescribing restrictions. While this liability is widely recognized, designing safer kinase inhibitors (KI) requires knowledge of the causative kinase(s). Efforts to unravel the kinases have encountered pharmacology with nearly prohibitive complexity. At therapeutically relevant concentrations, KIs show promiscuity distributed across the kinome. Here, to overcome this complexity, 65 KIs with known kinome-scale polypharmacology profiles were assessed for effects on cardiomyocyte beating...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28453255/characterization-and-identification-of-dityrosine-cross-linked-peptides-using-tandem-mass-spectrometry
#3
Soumya Mukherjee, Eugene A Kapp, Amber Lothian, Anne M Roberts, Yury Vasilev, Berin Boughton, Kevin Jeffrey Barnham, W Mei Kok, Craig A Hutton, Colin L Masters, Ashley Bush, Joseph S Beckman, Somdatta Ghosh Dey, Blaine R Roberts
The use of mass spectrometry coupled with chemical cross-linking of proteins has become a powerful tool for proteins structure and interactions studies. Unlike structural analysis of proteins using chemical reagents specific for lysine or cysteine residues, identification of gas-phase fragmentation patterns of endogenous dityrosine cross-linked peptides have not been investigated. Dityrosine cross-linking in proteins and peptides are clinical markers of oxidative stress, ageing and neurodegenerative diseases including Alzheimer's disease and Parkinson's disease...
April 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28449096/two-ribosome-recruitment-sites-direct-multiple-translation-events-within-hiv1-gag-open-reading-frame
#4
Jules Deforges, Sylvain de Breyne, Melissa Ameur, Nathalie Ulryck, Nathalie Chamond, Afaf Saadi, Yann Ponty, Theophile Ohlmann, Bruno Sargueil
In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported to the cytoplasm for the necessary translation of the Gag and Gag-pol polyproteins. Three distinct translation initiation mechanisms ensuring Gag production have been described with little rationale for their multiplicity. The Gag-IRES has the singularity to be located within Gag ORF and to directly interact with ribosomal 40S. Aiming at elucidating the specificity and the relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed an innovative integrative modelling strategy to take into account all the gathered information...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#5
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447979/reconstitution-of-nucleosomes-with-differentially-isotope-labeled-sister-histones
#6
Stamatios Liokatis
Asymmetrically modified nucleosomes contain the two copies of a histone (sister histones) decorated with distinct sets of Post-translational Modifications (PTMs). They are newly identified species with unknown means of establishment and functional implications. Current analytical methods are inadequate to detect the copy-specific occurrence of PTMs on the nucleosomal sister histones. This protocol presents a biochemical method for the in vitro reconstitution of nucleosomes containing differentially isotope-labeled sister histones...
March 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447936/ppp1r15a-mediated-dephosphorylation-of-eif2%C3%AE-is-unaffected-by-sephin1-or-guanabenz
#7
Ana Crespillo-Casado, Joseph E Chambers, Peter M Fischer, Stefan J Marciniak, David Ron
Dephosphorylation of translation initiation factor 2 (eIF2α) terminates signalling in the mammalian integrated stress response (ISR) and has emerged as a promising target for modifying the course of protein misfolding diseases. The [(o-chlorobenzylidene)amino]guanidines (Guanabenz and Sephin1) have been proposed to exert protective effects against misfolding by interfering with eIF2α-P dephosphorylation through selective disruption of a PP1-PPP1R15A holophosphatase complex. Surprisingly, they proved inert in vitro affecting neither stability of the PP1-PPP1R15A complex nor substrate-specific dephosphorylation...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28446677/variable-inhibition-of-zika-virus-replication-by-different-wolbachia-strains-in-mosquito-cell-cultures
#8
Michaela J Schultz, Sharon Isern, Scott F Michael, Ronald B Corley, John Connor, Horacio M Frydman
Mosquito-borne arboviruses are a major source of human disease. One strategy to reduce arbovirus disease is to reduce the mosquito's ability to transmit virus. Mosquito infection with bacterial endosymbiont, Wolbachia pipientis wMel, is a novel strategy to reduce Aedes mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of wMel potentially weakening the integration of this strain into a mosquito population relative to other Wolbachia strains...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446530/long-non-coding-rnas-and-their-role-in-metastasis
#9
REVIEW
Ulrich H Weidle, Fabian Birzele, Gwen Kollmorgen, Rüdiger Rüger
The perception of long non-coding RNAs as chunk RNA and transcriptional noise has been steadily replaced by their role as validated targets for a diverse set of physiological processes in the past few years. However, for the vast majority of lncRNAs their precise mode of action and physiological function remain to be uncovered. A large body of evidence has revealed their essential role in all stages of cancirogenesis and metastasis. In this review we focus on the role of lncRNAs in metastasis. We grouped selected lncRNAs into three categories based on in vitro and in vivo mode of action-related studies and clinical relevance for metastasis...
May 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#10
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28446248/the-therapeutic-potential-of-three-dimensional-multipotent-mesenchymal-stromal-cell-spheroids
#11
REVIEW
Yuriy Petrenko, Eva Syková, Šárka Kubinová
The efficiency of clinical trials involving transplantation of multipotent mesenchymal stromal cells (MSCs) is often insufficient due to harsh conditions present within the target tissue including hypoxia, low nutrient supply as well as inflammatory reactions. This indicates the necessity for optimization of cell-based therapy approaches which might include either modification of the cell manufacturing process or specific cell pretreatment procedures prior to transplantation. Recent reports confirm evidence that the aggregation of MSCs into three-dimensional (3D) multicellular spheroids results in enhancement of the overall therapeutic potential of cells, by improving the anti-inflammatory and angiogenic properties, stemness and survival of MSCs after transplantation...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#12
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445803/jetvalve-rapid-manufacturing-of-biohybrid-scaffolds-for-biomimetic-heart-valve-replacement
#13
Andrew K Capulli, Maximillian Y Emmert, Francesco S Pasqualini, Debora Kehl, Etem Caliskan, Johan U Lind, Sean P Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Weber, Josue A Goss, Simon P Hoerstrup, Kevin Kit Parker
Tissue engineered scaffolds have emerged as a promising solution for heart valve replacement because of their potential for regeneration. However, traditional heart valve tissue engineering has relied on resource-intensive, cell-based manufacturing, which increases cost and hinders clinical translation. To overcome these limitations, in situ tissue engineering approaches aim to develop scaffold materials and manufacturing processes that elicit endogenous tissue remodeling and repair. Yet despite recent advances in synthetic materials manufacturing, there remains a lack of cell-free, automated approaches for rapidly producing biomimetic heart valve scaffolds...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28445416/structure-function-model-for-kissing-loop-interactions-that-initiate-dimerization-of-ty1-rna
#14
Eric R Gamache, Jung H Doh, Justin Ritz, Alain Laederach, Stanislav Bellaousov, David H Mathews, M Joan Curcio
The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5' terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT). To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1), a 1-nucleotide interhelical loop and an 8-bp stem (S2) that delineate two long, structured loops...
April 26, 2017: Viruses
https://www.readbyqxmd.com/read/28445239/aldosterone-and-vascular-mineralocorticoid-receptors-in-murine-endotoxic-and-human-septic-shock
#15
Fouad Fadel, Gwennan André-Grégoire, Basile Gravez, Brigitte Bauvois, Sandrine Bouchet, Catalina Sierra-Ramos, Andrea Polito, Arnaud Mansart, Diego Alvarez de la Rosa, Djillali Annane, Frédéric Jaisser
OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients...
April 25, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28443280/in-vivo-reprogramming-of-cancer-metabolism-by-myc
#16
REVIEW
Roman Camarda, Jeremy Williams, Andrei Goga
The past few decades have welcomed tremendous advancements toward understanding the functional significance of altered metabolism during tumorigenesis. However, many conclusions drawn from studies of cancer cells in a dish (i.e., in vitro) have been put into question as multiple lines of evidence have demonstrated that the metabolism of cells can differ significantly from that of primary tumors (in vivo). This realization, along with the need to identify tissue-specific vulnerabilities of driver oncogenes, has led to an increased focus on oncogene-dependent metabolic programming in vivo...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28443091/natural-killer-group-2d-ligand-depletion-reconstitutes-natural-killer-cell-immunosurveillance-of-head-and-neck-squamous-cell-carcinoma
#17
Sandra Weil, Stefanie Memmer, Axel Lechner, Volker Huppert, Ariane Giannattasio, Tamara Becker, Andreas Müller-Runte, Karen Lampe, Dirk Beutner, Alexander Quaas, Ralf Schubert, Eva Herrmann, Alexander Steinle, Ulrike Koehl, Lutz Walter, Michael S von Bergwelt-Baildon, Joachim Koch
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442428/rapamycin-modulation-of-p70-s6-kinase-signaling-inhibits-rift-valley-fever-virus-pathogenesis
#18
Todd M Bell, Virginia Espina, Svetlana Senina, Caitlin Woodson, Ashwini Brahms, Brian Carey, Shih-Chao Lin, Lindsay Lundberg, Chelsea Pinkham, Alan Baer, Claudius Mueller, Elizabeth A Chlipala, Faye Sharman, Cynthia de la Fuente, Lance Liotta, Kylene Kehn-Hall
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA)...
April 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28441382/hedgehog-signalling-pathway-orchestrates-angiogenesis-in-triple-negative-breast-cancers
#19
Concetta Di Mauro, Roberta Rosa, Valentina D'Amato, Paola Ciciola, Alberto Servetto, Roberta Marciano, Roberta Clara Orsini, Luigi Formisano, Sandro De Falco, Valeria Cicatiello, Maurizio Di Bonito, Monica Cantile, Francesca Collina, Angela Chambery, Bianca Maria Veneziani, Sabino De Placido, Roberto Bianco
BACKGROUND: Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated. METHODS: Expression and regulation of the Hh pathway transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC-initiated angiogenesis...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28440708/towards-in-vitro-to-in-vivo-translation-of-monoclonal-antibody-pharmacokinetics-application-of-a-neonatal-fc-receptor-mediated-transcytosis-assay-to-understand-the-interplaying-clearance-mechanisms
#20
Claudia A Castro Jaramillo, Sara Belli, Anne-Christine Cascais, Sherri Dudal, Martin R Edelmann, Markus Haak, Marie-Elise Brun, Michael B Otteneder, Mohammed Ullah, Christoph Funk, Franz Schuler, Silke Simon
Monoclonal antibodies (mAbs) are a rapidly growing drug class for which great efforts have been made to optimize certain molecular features in order to achieve the desired pharmacokinetic (PK) properties. One approach is to engineer the interactions of the mAb with the neonatal Fc receptor (FcRn) by introducing specific amino acid sequence mutations, and to assess their effect on the PK profile with in vivo studies. Indeed, FcRn protects mAbs from intracellular degradation, thereby prolongs antibody circulation time in plasma and modulates its systemic clearance...
April 25, 2017: MAbs
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