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https://www.readbyqxmd.com/read/27926654/neonatal-abstinence-syndrome-and-ethical-approaches-to-the-identification-of-pregnant-women-who-use-drugs
#1
Mishka Terplan, Howard Minkoff
The United States is experiencing an epidemic of opioid use, addiction, and neonatal abstinence syndrome. Consequentially, a great deal of public, and public health, attention has turned toward the timely recognition of pregnant women who use drugs. We explore the clinical efficacy and ethical acceptability of different methods of identification-contrasting drug testing (using biologic samples such as urine) with screening (using an instrument or questionnaire) under both universal and selective approaches within the current legal and social landscape, which is fraught with potential adverse consequences for both the woman and her child...
December 2, 2016: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/27926534/irna-ai-identifying-the-adenosine-to-inosine-editing-sites-in-rna-sequences
#2
Wei Chen, Pengmian Feng, Hui Yang, Hui Ding, Hao Lin, Kuo-Chen Chou
Catalyzed by adenosine deaminase (ADAR), the adenosine to inosine (A-to-I) editing in RNA is not only involved in various important biological processes, but also closely associated with a series of major diseases. Therefore, knowledge about the A-to-I editing sites in RNA is crucially important for both basic research and drug development. Given an uncharacterized RNA sequence that contains many adenosine (A) residues, can we identify which one of them can be of A-to-I editing, and which one cannot? Unfortunately, so far no computational method whatsoever has been developed to address such an important problem based on the RNA sequence information alone...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925398/cell-based-biohybrid-drug-delivery-systems-the-best-of-the-synthetic-and-natural-worlds
#3
Samagya Banskota, Parisa Yousefpour, Ashutosh Chilkoti
The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles...
December 7, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27925266/marine-mollusk-derived-agents-with-antiproliferative-activity-as-promising-anticancer-agents-to-overcome-chemotherapy-resistance
#4
REVIEW
Maria Letizia Ciavatta, Florence Lefranc, Marianna Carbone, Ernesto Mollo, Margherita Gavagnin, Tania Betancourt, Ramesh Dasari, Alexander Kornienko, Robert Kiss
The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as "chemotaxonomic markers" for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy...
December 7, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27924826/iron-chelators-target-both-proliferating-and-quiescent-cancer-cells
#5
Mårten Fryknäs, Xiaonan Zhang, Ulf Bremberg, Wojciech Senkowski, Maria Hägg Olofsson, Peter Brandt, Ingmar Persson, Padraig D'Arcy, Joachim Gullbo, Peter Nygren, Leoni Kunz Schughart, Stig Linder, Rolf Larsson
Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924725/anticancer-drug-targets-of-salvia-phytometabolites-chemistry-biology-and-omics
#6
Da-Cheng Hao, Guang-Bo Ge, Pei-Gen Xiao
Salvia displays diverse anticancer properties, which are attributable to their diterpene and phenolic contents. There is no comprehensive review on the anticancer diversity and molecular targets of Salvia components. We investigate the diversity and molecular targets of Salvia phytometabolites responsible for the prevention and treatment of cancer and sarcoma. Traditional therapeutic knowledge suggests that Salvia species can be used to develop anticancer drugs. Lots of concerns have been raised for tanshinone (Tan) IIA and cryptotanshinone...
December 7, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27924687/the-fluad-case-in-italy-could-it-have-been-dealt-differently
#7
Miriam Levi, Ersilia Sinisgalli, Chiara Lorini, Francesca Santomauro, Martina Chellini, Paolo Bonanni
During the influenza vaccination campaign 2014-2015, the reporting of three deaths within 48 hours of vaccination with Fluad brought the Italian Medicines Agency (AIFA) to pronounce the withdrawal of two batches of vaccine, based on the precautionary principle. Investigations by the Istituto Superiore di Sanità, the National Institute of Health, and by the Pharmacovigilance Risk Assessment Committee (PRAC), the committee at the European Medicines Agency (EMA) responsible for monitoring and assessing the safety profiles of human drugs, concluded that there was a lack of causality between the reported deaths and the vaccines administered...
December 7, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27924646/influence-of-anti-tnf-immunogenicity-on-safety-in-rheumatic-disease-a-narrative-review
#8
Andrea Matucci, Daniele Cammelli, Fabrizio Cantini, Delia Goletti, Valentina Marino, Giuseppe Maria Milano, Raffaele Scarpa, Giuliano Tocci, Enrico Maggi, Alessandra Vultaggio
Tumor necrosis factor-alpha (TNF-α) antagonists have been shown to be effective in the treatment of chronic inflammatory rheumatic conditions. The use of anti-TNF agents, combined with improved diagnosis, aggressive regimens and regular monitoring, have substantially improved patient outcomes. However, all biological agents are immunogenic, resulting in the formation of anti-drug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27924488/elucidating-mechanisms-of-molecular-recognition-between-human-argonaute-and-mirna-using-computational-approaches
#9
Hanlun Jiang, Lizhe Zhu, Amélie Héliou, Xin Gao, Julie Bernauer, Xuhui Huang
MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924481/machine-learning-approaches-toward-building-predictive-models-for-small-molecule-modulators-of-mirna-and-its-utility-in-virtual-screening-of-molecular-databases
#10
Vinita Periwal, Vinod Scaria
The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924480/design-of-multimodal-small-molecules-targeting-mirnas-biogenesis-synthesis-and-in-vitro-evaluation
#11
Duc D Vo, Maria Duca
microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924477/assessing-anti-mir-pharmacology-with-mirna-polysome-shift-assay
#12
John R Androsavich
Target engagement measurements are critical for evaluating developmental drug candidates and their pharmacological activity. microRNA (miRNA) Polysome Shift Assay enables measurement of anti-miR drug target engagement (i.e. extent of miRNA inhibition) without the need to pre-identify or pre-validate downstream miRNA-regulated genes. This makes it useful for assessing anti-miR activity in target tissues or cells where biology of the inhibited miRNAs may not be well understood. In addition, miRNA Polysome Shift Assay can be multiplexed to assess inhibition of multiple miRNAs by a single anti-miR, thus guiding drug optimization for enhancing or avoiding these activities as desired...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924468/whether-a-novel-drug-delivery-system-can-overcome-the-problem-of-biofilms-in-respiratory-diseases
#13
REVIEW
Kamal Dua, Shakti D Shukla, Rakesh K Tekade, Philip M Hansbro
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches...
December 6, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27924426/preditor-a-synthetic-biology-approach-to-removing-heterochromatin-from-cells
#14
Oscar Molina, Mar Carmena, Isabella E Maudlin, William C Earnshaw
It is widely accepted that heterochromatin is necessary to maintain genomic stability. However, direct experimental evidence supporting this is slim. Previous studies using either enzyme inhibitors, gene knockout or knockdown studies all are subject to the caveat that drugs may have off-target effects and enzymes that modify chromatin proteins to support heterochromatin formation may also have numerous other cellular targets as well. Here, we describe PREditOR (protein reading and editing of residues), a synthetic biology approach that allows us to directly remove heterochromatin from cells without either drugs or global interference with gene function...
December 6, 2016: Chromosome Research
https://www.readbyqxmd.com/read/27924262/mass-spectrometric-analysis-of-protein-ligand-interactions
#15
Kentaro Ishii, Masanori Noda, Susumu Uchiyama
The interactions of small molecules with proteins (protein-ligand interactions) mediate various biological phenomena including signal transduction and protein transcription and translation. Synthetic compounds such as drugs can also bind to target proteins, leading to the inhibition of protein-ligand interactions. These interactions typically accompany association-dissociation equilibrium according to the free energy difference between free and bound states; therefore, the quantitative biophysical analysis of the interactions, which uncovers the stoichiometry and dissociation constant, is important for understanding biological reactions as well as for rational drug development...
2016: Biophysics and Physicobiology
https://www.readbyqxmd.com/read/27923918/identification-of-bicarbonate-as-a-trigger-and-genes-involved-with-extracellular-dna-export-in-mycobacterial-biofilms
#16
Sasha J Rose, Luiz E Bermudez
: Extracellular DNA (eDNA) is an integral biofilm matrix component of numerous pathogens, including nontuberculous mycobacteria (NTM). Cell lysis is the source of eDNA in certain bacteria, but the source of eDNA remains unidentified for NTM, as well as for other eDNA-containing bacterial species. In this study, conditions affecting eDNA export were examined, and genes involved with the eDNA export mechanism were identified. After a method for monitoring eDNA in real time in undisturbed biofilms was established, different conditions affecting eDNA were investigated...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27923679/evolutionary-scalpels-for-dissecting-tumor-ecosystems
#17
Daniel I S Rosenbloom, Pablo G Camara, Tim Chu, Raul Rabadan
Amidst the growing literature on cancer genomics and intratumor heterogeneity, essential principles in evolutionary biology recur time and time again. Here we use these principles to guide the reader through major advances in cancer research, highlighting issues of "hit hard, hit early" treatment strategies, drug resistance, and metastasis. We distinguish between two frameworks for understanding heterogeneous tumors, both of which can inform treatment strategies: (1) The tumor as diverse ecosystem, a Darwinian population of sometimes-competing, sometimes-cooperating cells; (2) The tumor as tightly integrated, self-regulating organ, which may hijack developmental signals to restore functional heterogeneity after treatment...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923476/establishment-of-quantitative-retention-activity-model-by-optimized-microemulsion-liquid-chromatography
#18
Liyuan Xu, Haoshi Gao, Liangxing Li, Yinnong Li, Liuyun Wang, Chongkai Gao, Ning Li
The effective permeability coefficient is of theoretical and practical importance in evaluation of the bioavailability of drug candidates. However, most methods currently used to measure this coefficient are expensive and time-consuming. In this paper, we addressed these problems by proposing a new measurement method which is based on the microemulsion liquid chromatography. First, the parallel artificial membrane permeability assays model was used to determine the effective permeability of drug so that quantitative retention-activity relationships could be established, which were used to optimize the microemulsion liquid chromatography...
November 4, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#19
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#20
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
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