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Synthetic transcriptional factor

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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28205555/rapid-differentiation-of-human-pluripotent-stem-cells-into-functional-neurons-by-mrnas-encoding-transcription-factors
#2
Sravan Kumar Goparaju, Kazuhisa Kohda, Keiji Ibata, Atsumi Soma, Yukhi Nakatake, Tomohiko Akiyama, Shunichi Wakabayashi, Misako Matsushita, Miki Sakota, Hiromi Kimura, Michisuke Yuzaki, Shigeru B H Ko, Minoru S H Ko
Efficient differentiation of human pluripotent stem cells (hPSCs) into neurons is paramount for disease modeling, drug screening, and cell transplantation therapy in regenerative medicine. In this manuscript, we report the capability of five transcription factors (TFs) toward this aim: NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. In contrast to previous methods that have shortcomings in their speed and efficiency, a cocktail of these TFs as synthetic mRNAs can differentiate hPSCs into neurons in 7 days, judged by calcium imaging and electrophysiology...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28190465/butein-in-health-and-disease-a-comprehensive-review
#3
REVIEW
Ganesan Padmavathi, Nand Kishor Roy, Devivasha Bordoloi, Frank Arfuso, Srishti Mishra, Gautam Sethi, Anupam Bishayee, Ajaikumar B Kunnumakkara
BACKGROUND: The risk of suffering from many chronic diseases seems to have made no improvement despite the advancement in medications available in the modern world. Moreover, the use of synthetic chemicals as medications has proved to worsen the scenario due to the various adverse side effects associated with them. PURPOSE: Extensive research on natural medicines provides ample evidence on the safety and efficacy of phytochemicals and nutraceuticals against diverse chronic ailments...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28174120/xenobiotics-and-the-glucocorticoid-receptor
#4
REVIEW
Linda S M Gulliver
Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28166537/synthetic-essentiality-of-chromatin-remodelling-factor-chd1-in-pten-deficient-cancer
#5
Di Zhao, Xin Lu, Guocan Wang, Zhengdao Lan, Wenting Liao, Jun Li, Xin Liang, Jasper Robin Chen, Sagar Shah, Xiaoying Shang, Ming Tang, Pingna Deng, Prasenjit Dey, Deepavali Chakravarti, Peiwen Chen, Denise J Spring, Nora M Navone, Patricia Troncoso, Jianhua Zhang, Y Alan Wang, Ronald A DePinho
Synthetic lethality and collateral lethality are two well-validated conceptual strategies for identifying therapeutic targets in cancers with tumour-suppressor gene deletions. Here, we explore an approach to identify potential synthetic-lethal interactions by screening mutually exclusive deletion patterns in cancer genomes. We sought to identify 'synthetic-essential' genes: those that are occasionally deleted in some cancers but are almost always retained in the context of a specific tumour-suppressor deficiency...
February 6, 2017: Nature
https://www.readbyqxmd.com/read/28165726/synthetic-protein-mimics-for-functional-protein-delivery
#6
Arife Ozgul Tezgel, Paejonette Jacobs, Coralie M Backlund, Janice C Telfer, Gregory N Tew
The use of proteins as biological tools and therapeutic agents is limited due to the fact that proteins do not effectively cross the plasma membrane of cells. Here, we report a novel class of protein transporter molecules based on protein transduction domain mimics (PTDMs) synthesized via ring opening metathesis polymerization (ROMP). The PTDMs reported here were specifically inspired by amphiphilic peptides known to deliver functional proteins into cells via non-covalent interactions between the peptide and cargo...
February 6, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28163684/the-new-synthetic-h2s-releasing-sdss-protects-mc3t3-e1-osteoblasts-against-h2o2-induced-apoptosis-by-suppressing-oxidative-stress-inhibiting-mapks-and-activating-the-pi3k-akt-pathway
#7
Xiaofei Yan, Haixia Wu, Zhiyuan Wu, Fei Hua, Dong Liang, Hong Sun, Yong Yang, Dejian Huang, Jin-Song Bian
Reactive oxygen species (ROS) are important in osteoporosis development. Oxidative stress induces apoptosis of osteoblasts and arrest of their differentiation. Both Danshensu (DSS) and hydrogen sulfide (H2S) produce significant antioxidant effect in various systems. In this study, we synthesized SDSS, a novel H2S-releasing compound derived from DSS, and studied its antioxidant effect in an H2O2-induced MC3T3-E1 osteoblastic cell injury model. We first characterized the H2S releasing property of SDSS in both in vivo and in vitro models...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28163017/small-molecule-inhibitors-of-the-sox18-transcription-factor
#8
Frank Fontaine, Jeroen Overman, Mehdi Moustaqil, Sreeman Mamidyala, Angela Salim, Kamesh Narasimhan, Nina Prokoph, Avril A B Robertson, Linda Lua, Kirill Alexandrov, Peter Koopman, Robert J Capon, Emma Sierecki, Yann Gambin, Ralf Jauch, Matthew A Cooper, Johannes Zuegg, Mathias Francois
Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors...
January 27, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28137873/systematic-dissection-of-genomic-features-determining-transcription-factor-binding-and-enhancer-function
#9
Sharon R Grossman, Xiaolan Zhang, Li Wang, Jesse Engreitz, Alexandre Melnikov, Peter Rogov, Ryan Tewhey, Alina Isakova, Bart Deplancke, Bradley E Bernstein, Tarjei S Mikkelsen, Eric S Lander
Enhancers regulate gene expression through the binding of sequence-specific transcription factors (TFs) to cognate motifs. Various features influence TF binding and enhancer function-including the chromatin state of the genomic locus, the affinities of the binding site, the activity of the bound TFs, and interactions among TFs. However, the precise nature and relative contributions of these features remain unclear. Here, we used massively parallel reporter assays (MPRAs) involving 32,115 natural and synthetic enhancers, together with high-throughput in vivo binding assays, to systematically dissect the contribution of each of these features to the binding and activity of genomic regulatory elements that contain motifs for PPARγ, a TF that serves as a key regulator of adipogenesis...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28136159/crispr-cas-type-ii-based-synthetic-biology-applications-in-eukaryotic-cells
#10
Mario Andrea Marchisio, Zhiwei Huang
The CRISPR-Cas system has rapidly reached a huge popularity as a new, powerful method for precise DNA editing and genome reengineering. In Synthetic Biology, the CRISPR-Cas type II system has inspired the construction of a novel class of RNA-based transcription factors. In their simplest form, they are made of a CRISPR RNA molecule, which targets a promoter sequence, and a deficient Cas9 (i.e. deprived of any nuclease activity) that has been fused to an activation or a repression domain. Up- and down-regulation of single genes in mammalian and yeast cells have been achieved with satisfactory results...
January 31, 2017: RNA Biology
https://www.readbyqxmd.com/read/28131904/potential-therapeutic-targets-of-epithelial-mesenchymal-transition-in-melanoma
#11
Ross L Pearlman, Mary Katherine Montes de Oca, Harish Chandra Pal, Farrukh Afaq
Melanoma is a cutaneous neoplastic growth of melanocytes with great potential to invade and metastasize, especially when not treated early and effectively. Epithelial-mesenchymal transition (EMT) is the process by which melanocytes lose their epithelial characteristics and acquire mesenchymal phenotypes. Mesenchymal protein expression increases the motility, invasiveness, and metastatic potential of melanoma. Many pathways play a role in promotion of mesenchymal protein expression including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, and several others...
January 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28131009/relocation-sensors-to-quantify-signaling-dynamics-in-live-single-cells
#12
REVIEW
Victoria Wosika, Serge Pelet
All cells are different. Even isogenic cells can possess diverse shapes, reside in different cell-cycle stages or express various sets of proteins. These variations can modulate the cell response to environmental stimuli and thereby provide key insights into the regulation of signal transduction cascades. Fluorescence microscopy allows to visualize these differences and monitor in real-time the responses of live single cells. In order to observe key cellular events, fluorescent biosensors have been developed...
January 25, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28130383/large-scale-collection-of-full-length-cdna-and-transcriptome-analysis-in-hevea-brasiliensis
#13
Yuko Makita, Kiaw Kiaw Ng, G Veera Singham, Mika Kawashima, Hideki Hirakawa, Shusei Sato, Ahmad Sofiman Othman, Minami Matsui
Natural rubber has unique physical properties that cannot be replaced by products from other latex-producing plants or petrochemically produced synthetic rubbers. Rubber from Hevea brasiliensis is the main commercial source for this natural rubber that has a cis-polyisoprene configuration. For sustainable production of enough rubber to meet demand elucidation of the molecular mechanisms involved in the production of latex is vital. To this end, we firstly constructed rubber full-length cDNA libraries of RRIM 600 cultivar and sequenced around 20,000 clones by the Sanger method and over 15,000 contigs by Illumina sequencer...
January 27, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28122947/functional-analysis-of-kinases-and-transcription-factors-in-saccharomyces-cerevisiae-using-an-integrated-overexpression-library
#14
Ji-Young Youn, Helena Friesen, Alex N Nguyen Ba, Wendy Liang, Vincent Messier, Mike J Cox, Alan M Moses, Brenda Andrews
Kinases and transcription factors (TFs) are key modulators of important signaling pathways and their activities underlie the proper function of many basic cellular processes such as cell division, differentiation and development. Changes in kinase and TF dosage are often associated with disease, yet a systematic assessment of the cellular phenotypes caused by the combined perturbation of kinases and TFs has not been undertaken. We used a reverse-genetics approach to study the phenotypic consequences of kinase and TF overexpression in the budding yeast, Saccharomyces cerevisiae We constructed a collection of strains expressing stably integrated inducible alleles of kinases and TFs and used a variety of assays to characterize the phenotypes caused by TF and kinase overexpression...
January 25, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28120892/antimicrobial-nanoplexes-meet-model-bacterial-membranes-the-key-role-of-cardiolipin
#15
Alejandro Marín-Menéndez, Costanza Montis, Teresa Díaz-Calvo, Davide Carta, Kostas Hatzixanthis, Christopher J Morris, Michael McArthur, Debora Berti
Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes)...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115518/tmed10-interferes-with-tgf-%C3%AE-signaling-by-disrupting-tgf-%C3%AE-receptor-complex-formation
#16
Naoko Nakano, Yuki Tsuchiya, Kenro Kako, Kenryu Umezaki, Keigo Sano, Souichi Ikeno, Eri Otsuka, Masashi Shigeta, Ai Nakagawa, Nobuo Sakata, Fumiko Itoh, Yota Nakano, Shun-Ichiro Iemura, Maarten van Dinther, Tohru Natsume, Peter Ten Dijke, Susumu Itoh
The intensity and duration of transforming growth factor (TGF)-βsignaling determine the cellular biological response. How this is negatively regulated is not well understood. Here, we identified a novel negative regulator of TGF-β signaling, transmembrane p24 trafficking protein10 (TMED10). TMED10 disrupts the complex formation between TGF-β type I (also termed ALK5) and type II receptors (TβRII). Misexpression studies revealed that TMED10 attenuated TGF-β-mediated signaling. A 20 amino acid-long region from Thr91 to Glu110 within the extracellular region of TMED10 was found to be crucial for TMED10 interaction with both ALK5 and TβRII...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28113043/activation-of-gga-mir-155-by-reticuloendotheliosis-virus-t-strain-and-its-contribution-to-transformation
#17
Yongxiu Yao, Deepali Vasoya, Lydia Kgosana, Lorraine Smith, Yulong Gao, Xiaomei Wang, Michael Watson, Venugopal Nair
The v-rel oncoprotein encoded by reticuloendotheliosis virus T strain (Rev-T) is a member of the rel/NF-κB family of transcription factors capable of transformation of primary chicken spleen and bone marrow cells. Rapid transformation of avian haematopoietic cells by v-rel occurs through a process of deregulation of multiple protein-encoding genes through its direct effect on their promoters. More recently, upregulation of oncogenic miR-155 and its precursor pre-miR-155 were demonstrated in Rev-T-infected chicken embryo fibroblast cultures as well as Rev-T-induced B-cell lymphomas...
January 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28109147/-co-culture-with-umbilical-cord-mesenchymal-stem-cells-promotes-the-synthesis-and-mechnism-of-milk-protein-in-bovine-mammary-epithelial-cells
#18
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28105147/fgfr3-silencing-by-sirna-inhibits-invasion-of-a549-cells
#19
Yuhua Li, Xiguang Liu, Hongjun Zhang, Tao Jiang, Wenjing Xiao, Shufen Zhao, Xiaoyun Yu, Fanjie Han
The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101336/regulatory-elements-and-transcriptional-control-of-chicken-vasa-homologue-cvh-promoter-in-chicken-primordial-germ-cells
#20
So Dam Jin, Bo Ram Lee, Young Sun Hwang, Hong Jo Lee, Jong Seop Rim, Jae Yong Han
BACKGROUND: Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis- and trans-regulatory elements. Studies on gene structures of chicken vasa homologue (CVH), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells...
2017: Journal of Animal Science and Biotechnology
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