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https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#1
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785479/ngspanpipe-a-pipeline-for-pan-genome-identification-in-microbial-strains-from-experimental-reads
#2
Umay Kulsum, Arti Kapil, Harpreet Singh, Punit Kaur
Recent advancements in sequencing technologies have decreased both time span and cost for sequencing the whole bacterial genome. High-throughput Next-Generation Sequencing (NGS) technology has led to the generation of enormous data concerning microbial populations publically available across various repositories. As a consequence, it has become possible to study and compare the genomes of different bacterial strains within a species or genus in terms of evolution, ecology and diversity. Studying the pan-genome provides insights into deciphering microevolution, global composition and diversity in virulence and pathogenesis of a species...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29784598/a-novel-digital-method-to-assess-air-space-loss-associated-with-acute-lung-injury-in-experimental-acute-pancreatitis
#3
R Mukherjee, L Wen, X Zhang, P Bhattacharya, W Huang, R Sutton
BACKGROUND/OBJECTIVES: Respiratory dysfunction and/or failure from acute lung injury (ALI) are common in acute pancreatitis (AP), but assessment of ALI in experimental AP has lacked standardisation. METHODS: A range of experimental AP models induced in C57BL/6 mice with corresponding controls (n = 6/group). Full double lung or right lung specimens were taken for histopathological assessment and slides analysed by a pre-set pipeline using Aperio Scanner (Leica), ImageJ software and CellProfiler software...
May 4, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29777871/pain-therapeutics-from-cone-snail-venoms-from-ziconotide-to-novel-non-opioid-pathways
#4
Helena Safavi-Hemami, Shane E Brogan, Baldomero M Olivera
There have been numerous attempts to develop non-opioid drugs for severe pain, but the vast majority of these efforts have failed. A notable exception is Ziconotide (Prialt®), approved by the FDA in 2004. In this review, we summarize the present status of Ziconotide as a therapeutic drug and introduce a wider framework: the potential of venom peptides from cone snails as a resource providing a continuous pipeline for the discovery of non-opioid pain therapeutics. An auxiliary theme that we hope to develop is that these venoms, already a validated starting point for non-opioid drug leads, should also provide an opportunity for identifying novel molecular targets for future pain drugs...
May 16, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29776602/blurring-boundaries-receptor-tyrosine-kinases-as-functional-g-protein-coupled-receptors
#5
Caitrin Crudden, Takashi Shibano, Dawei Song, Naida Suleymanova, Ada Girnita, Leonard Girnita
Receptor tyrosine kinases (RTKs) such as the insulin-like growth factor type 1 receptor (IGF-1R) control important biological activities as well as being involved in pathological processes. Due to their supportive nature in many human cancers they have long been considered attractive therapeutic targets. However, lessons learnt from early targeting trials highlight that a simple "active versus inactive" state model with classical kinase-only signaling is overly simplistic and does not describe reality...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29774062/-in-vivo-imaging-biomarkers-of-neuroinflammation-in-the-development-and-assessment-of-stroke-therapies-towards-clinical-translation
#6
REVIEW
Bastian Zinnhardt, Maximilian Wiesmann, Lisa Honold, Cristina Barca, Michael Schäfers, Amanda J Kiliaan, Andreas H Jacobs
Modulation of the inflammatory microenvironment after stroke opens a new avenue for the development of novel neurorestorative therapies in stroke. Understanding the spatio-temporal profile of (neuro-)inflammatory imaging biomarkers in detail thereby represents a crucial factor in the development and application of immunomodulatory therapies. The early integration of quantitative molecular imaging biomarkers in stroke drug development may provide key information about (i) early diagnosis and follow-up, (ii) spatio-temporal drug-target engagement (pharmacodynamic biomarker), (iii) differentiation of responders and non-responders in the patient cohort (inclusion/exclusion criteria; predictive biomarkers), and (iv) the mechanism of action...
2018: Theranostics
https://www.readbyqxmd.com/read/29771109/the-therapeutic-pipeline-for-pseudomonas-aeruginosa-infections
#7
Lori L Burrows
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen, designated by the World Health Organization as a critical priority for development of new therapeutics due to high levels of intrinsic and acquired antibiotic resistance. Other challenges include its versatility (it can persist in the environment and most strains are capable of causing disease in compromised hosts), robust efflux mechanisms that limit drug penetration, and the propensity to form antimicrobial-tolerant biofilms. Novel therapeutics in development to prevent or treat P...
May 17, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29770249/snorkel-rapid-training-data-creation-with-weak-supervision
#8
Alexander Ratner, Stephen H Bach, Henry Ehrenberg, Jason Fries, Sen Wu, Christopher Ré
Labeling training data is increasingly the largest bottleneck in deploying machine learning systems. We present Snorkel, a first-of-its-kind system that enables users to train state-of- the-art models without hand labeling any training data. Instead, users write labeling functions that express arbitrary heuristics, which can have unknown accuracies and correlations. Snorkel denoises their outputs without access to ground truth by incorporating the first end-to-end implementation of our recently proposed machine learning paradigm, data programming...
November 2017: Proceedings of the VLDB Endowment
https://www.readbyqxmd.com/read/29761645/redox-guided-small-molecule-antimycobacterials
#9
REVIEW
Amogh Kulkarni, Ajay Kumar Sharma, Harinath Chakrapani
The emergence of drug resistance has posed a major challenge to treatment of tuberculosis worldwide. The new drug candidates in the pipeline are few and therefore there is an urgent need to develop antimycobacterials with novel mechanisms of action. Maintenance of redox homeostasis is integral to mycobacterial survival and growth. Therefore, perturbation of this equilibrium can result in irreversible stress induction and inhibition of growth. Herein, we review a number of small molecules that have either been designed to induce redox stress or were found to do so after their discovery...
May 14, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29758235/innovation-and-trends-in-the-development-and-approval-of-antiviral-medicines-1987-2017-and-beyond
#10
REVIEW
Shuvam Chaudhuri, Julian A Symons, Jerome Deval
2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV infection. Here, we provide a retrospective analysis of approved antiviral drugs, including therapeutics against other major chronic infections such as hepatitis B and C, and herpes viruses, over the last thirty years. During this time, only a few drugs were approved to treat acute viral infections, mainly influenza...
May 15, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29758049/user-evaluations-offer-promise-for-pod-intravaginal-ring-as-a-drug-delivery-platform-a-mixed-methods-study-of-acceptability-and-use-experiences
#11
Kate M Guthrie, Rochelle K Rosen, Sara E Vargas, Melissa L Getz, Lauren Dawson, Melissa Guillen, Jaime J Ramirez, Marc M Baum, Kathleen L Vincent
BACKGROUND: Effective HIV prevention requires efficient delivery of safe and efficacious drugs and optimization of user adherence. The user's experiences with the drug, delivery system, and use parameters are critical to product acceptability and adherence. Prevention product developers have the opportunity to directly control a drug delivery system and its impact on acceptability and adherence, as well as product efficacy. Involvement of potential users during preclinical design and development can facilitate this process...
2018: PloS One
https://www.readbyqxmd.com/read/29750902/machine-learning-in-chemoinformatics-and-drug-discovery
#12
REVIEW
Yu-Chen Lo, Stefano E Rensi, Wen Torng, Russ B Altman
Chemoinformatics is an established discipline focusing on extracting, processing and extrapolating meaningful data from chemical structures. With the rapid explosion of chemical 'big' data from HTS and combinatorial synthesis, machine learning has become an indispensable tool for drug designers to mine chemical information from large compound databases to design drugs with important biological properties. To process the chemical data, we first reviewed multiple processing layers in the chemoinformatics pipeline followed by the introduction of commonly used machine learning models in drug discovery and QSAR analysis...
May 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29740351/pain-therapy-guided-by-purpose-and-perspective-in-light-of-the-opioid-epidemic
#13
REVIEW
Amie L Severino, Arash Shadfar, Joshua K Hakimian, Oliver Crane, Ganeev Singh, Keith Heinzerling, Wendy M Walwyn
Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29736708/phenotypic-screening-of-small-molecules-with-antimalarial-activity-for-three-different-parasitic-life-stages
#14
Nobutaka Kato, Sandra March, Sangeeta N Bhatia, Matthias Marti
Malaria remains one of the deadliest infectious diseases globally. Available therapeutic agents are already limited in their efficacy, and drug resistance threatens to diminish further our ability to prevent and treat the disease. Despite a renewed effort to identify compounds with antimalarial activity, the drug discovery and development pipeline lacks target diversity and availability of compounds that target liver- and gametocyte-stage parasites. Phenotypic screens are a powerful and valuable tool for identifying new chemical compounds with antimalarial activity...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29734307/drug-pipeline-1q18
#15
Laura DeFrancesco
No abstract text is available yet for this article.
May 9, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29730830/the-epidemiology-evolution-and-treatment-of-kpc-producing-organisms
#16
REVIEW
Ann Marie Porreca, Kaede V Sullivan, Jason C Gallagher
PURPOSE OF REVIEW: The purpose of this review is to investigate the evolution and epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the current and future treatment options for infections caused by KPC-producing isolates. RECENT FINDINGS: The emergence of resistance in Enterobacteriaceae producing carbapenemases globally has increased the challenges in treating infections caused by these organisms. One of the prominent mechanisms of resistance is the production of KPC enzymes...
May 5, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29726962/integrated-use-of-bioinformatic-resources-reveals-that-co-targeting-of-histone-deacetylases-ikbk-and-src-inhibits-epithelial-mesenchymal-transition-in-cancer
#17
Farnaz Barneh, Mehdi Mirzaie, Payman Nickchi, Tuan Zea Tan, Jean Paul Thiery, Mehran Piran, Mona Salimi, Fatemeh Goshadrou, Amir R Aref, Mohieddin Jafari
With the advent of high-throughput technologies leading to big data generation, increasing number of gene signatures are being published to predict various features of diseases such as prognosis and patient survival. However, to use these signatures for identifying therapeutic targets, use of additional bioinformatic tools is indispensible part of research. Here, we have generated a pipeline comprised of nearly 15 bioinformatic tools and enrichment statistical methods to propose and validate a drug combination strategy from already approved drugs and present our approach using published pan-cancer epithelial-mesenchymal transition (EMT) signatures as a case study...
May 2, 2018: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29726961/application-of-atlas-of-cancer-signalling-network-in-preclinical-studies
#18
L Cristobal Monraz Gomez, Maria Kondratova, Jean-Marie Ravel, Emmanuel Barillot, Andrei Zinovyev, Inna Kuperstein
Cancer initiation and progression are associated with multiple molecular mechanisms. The knowledge of these mechanisms is expanding and should be converted into guidelines for tackling the disease. Here, we discuss the formalization of biological knowledge into a comprehensive resource: the Atlas of Cancer Signalling Network (ACSN) and the Google Maps-based tool NaviCell, which supports map navigation. The application of ACSN for omics data visualization, in the context of signalling maps, is possible via the NaviCell Web Service module and through the NaviCom tool...
May 3, 2018: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29725729/large-scale-identification-and-visualization-of-human-liver-n-glycome-enriched-from-lo2-cells
#19
Kaijie Xiao, Yuyin Han, Zhixin Tian
Aberrant glycosylation has been commonly observed in various physiological and pathological disorders (including cancers), and quite a few glycoproteins have been approved by the US Food and Drug Administration (FDA) as markers for early diagnosis. Each glycoprotein may have multiple glycoforms, and cancer-related ones can be only some specific glycoforms which have much higher sensitivity and specificity; for example, AFP glycoform AFP-L3 with N-glycan of 01Y(61F)41Y41M(31M41Y41L41S61M41Y41L41S is of bigger diagnostic value for hepatocellular carcinoma than total AFP (i...
May 3, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29721784/subtractive-genomics-molecular-docking-and-molecular-dynamics-simulation-revealed-lpxc-as-a-potential-drug-target-against-multi-drug-resistant-klebsiella-pneumoniae
#20
Sajjad Ahmad, Afifa Navid, Amina Saleem Akhtar, Syed Sikander Azam, Abdul Wadood, Horacio Pérez-Sánchez
The emergence and dissemination of pan drug resistant clones of Klebsiella pneumoniae are great threat to public health. In this regard new therapeutic targets must be highlighted to pave the path for novel drug discovery and development. Subtractive proteomic pipeline brought forth UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase (LpxC), a Zn+2 dependent cytoplasmic metalloprotein and catalyze the rate limiting deacetylation step of lipid A biosynthesis pathway. Primary sequence analysis followed by 3-dimensional (3-D) structure elucidation of the protein led to the detection of K...
May 2, 2018: Interdisciplinary Sciences, Computational Life Sciences
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