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Zebrafish drug screen

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https://www.readbyqxmd.com/read/28923401/pharmacological-blockade-of-cholesterol-trafficking-by-cepharanthine-in-endothelial-cells-suppresses-angiogenesis-and-tumor-growth
#1
Junfang Lyu, Eun Ju Yang, Sarah A Head, Nana Ai, Baoyuan Zhang, Changjie Wu, Ruo-Jing Li, Yifan Liu, Chen Yang, Yongjun Dang, Ho Jeong Kwon, Wei Ge, Jun O Liu, Joong Sup Shim
Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28916270/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#2
REVIEW
Nathana J Mezzomo, Barbara D Fontana, Allan V Kalueff, Leonardo J G Barcellos, Denis B Rosemberg
Taurine is a highly abundant "amino acid" in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action...
September 12, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28903500/intrinsic-xenobiotic-metabolizing-enzyme-activities-in-early-life-stages-of-zebrafish-danio-rerio
#3
Jens C Otte, Bernadette Schultz, Daniela Fruth, Eric Fabian, Bennard van Ravenzwaay, Björn Hidding, Edward R Salinas
Early life stages of zebrafish (Danio rerio, zf) are gaining attention as an alternative invivo test system for drug discovery, early developmental toxicity screenings and chemical testing in ecotoxicological and toxicological testing strategies. Previous studies have demonstrated transcriptional evidence for xenobiotic metabolizing enzymes (XME) during early zf development. However, elaborate experiments on XME activities during development are incomplete. In this work, the intrinsic activities of representative phase I and II XME were monitored by transformation of putative zf model substrates analyzed using photometry and high pressure liquid chromatography techniques...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28890736/the-psychoactive-drug-25b-nbome-recapitulates-rhabdomyolysis-in-zebrafish-larvae
#4
Genri Kawahara, Hideyuki Maeda, Ruri Kikura-Hanajiri, Ken-Ichi Yoshida, Yukiko K Hayashi
N-Benzyl-substituted 2C class phenethylamines (NBOMes) are psychoactive designer drugs, with strong hallucinogenic and stimulant effects, even at low doses. The designer drug, 2-(4-bromo-2, 5-dimethoxyphenyl)-N-(2-methoxybenzyl) ethanamine (25B-NBOMe) is considered to be one of the most potent agonists of the serotonin-2A (5-HT2A) receptor. Recently, we reported the first lethal case of 25B-NBOMe intoxication with severe rhabdomyolysis, concluded by clinical, pathological and toxicological analyses. There are currently no good animal models that closely recapitulate serotonin receptor-dependent rhabdomyolysis...
2017: Forensic Toxicology
https://www.readbyqxmd.com/read/28888214/catching-new-targets-in-metabolic-disease-with-a-zebrafish
#5
REVIEW
Margrit Kamel, Nikolay Ninov
Traditionally, the development of novel therapeutics for metabolic diseases has relied mainly on high-throughput screening using biochemical or cell-based assays. While this approach represents a driving force in drug discovery, there is also a need to perform large-scale screens without disrupting inter-organ communication and tissue architecture, essential components for understanding the complexity of metabolic regulation and the identification of small molecules with appropriate biological activities in vivo...
September 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28887224/the-zebrafish-as-a-promising-tool-for-modeling-human-brain-disorders-a-review-based-upon-an-ibns-symposium
#6
REVIEW
Soaleha Shams, Jason Rihel, Jose G Ortiz, Robert Gerlai
The zebrafish represents an excellent compromise between system complexity and practical simplicity, features that make it useful for modeling and mechanistic analysis of complex brain disorders. Also promising are screens for psychoactive drugs with effects on larval and adult zebrafish behavior. This review, based upon a recent symposium held at the 2016 IBNS Congress, provides different perspectives on how the zebrafish may be utilized to advance research into human central nervous system disorders. It starts with a discussion on an important bottleneck in zebrafish research, measuring the behavior of this species (specifically shoaling), and continues with examples on research on autism spectrum disorder in larval zebrafish, on screening natural products for compounds with psychoactive properties in adult zebrafish, and on the development of a zebrafish model of fetal alcohol spectrum disorders...
September 5, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28851572/zebrafish-as-an-early-stage-screening-tool-to-study-the-systemic-circulation-of-nanoparticulate-drug-delivery-systems-in-vivo
#7
Sandro Sieber, Philip Grossen, Pascal Detampel, Salome Siegfried, Dominik Witzigmann, Jörg Huwyler
Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessment, and first in vivo experiments using rodent animal models...
August 26, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28840558/the-power-of-zebrafish-in-personalised-medicine
#8
Sarah Baxendale, Freek van Eeden, Robert Wilkinson
The goal of personalised medicine is to develop tailor-made therapies for patients in whom currently available therapeutics fail. This approach requires correlating individual patient genotype data to specific disease phenotype data and using these stratified data sets to identify bespoke therapeutics. Applications for personalised medicine include common complex diseases which may have multiple targets, as well as rare monogenic disorders, for which the target may be unknown. In both cases, whole genome sequence analysis (WGS) is discovering large numbers of disease associated mutations in new candidate genes and potential modifier genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28811180/development-of-an-opioid-self-administration-assay-to-study-drug-seeking-in-zebrafish
#9
Gabriel D Bossé, Randall T Peterson
The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways...
August 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28805098/assessment-of-the-permeability-and-toxicity-of-polymeric-nanocapsules-using-the-zebrafish-model
#10
Carmen Teijeiro-Valiño, Elena Yebra-Pimentel, Jorge Guerra-Varela, Noemi Csaba, María J Alonso, Laura Sánchez
AIM: To assess the capacity of a new drug delivery nanocapsule (NC) with a double shell of hyaluronic acid and protamine to overcome biological barriers using the zebrafish model. MATERIALS & METHODS: NCs were prepared by the solvent displacement method, tagged with fluorescent makers and physicochemically characterized. Toxicity was evaluated according to the Fish Embryo Acute Toxicity test, and permeability was tested by exposing zebrafish, with and without chorion, to the fluorescent NCs...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28801043/rapid-identification-of-herbal-compounds-derived-metabolites-using-zebrafish-larvae-as-the-biotransformation-system
#11
Chen Wang, Ying-Hao Yin, Ying-Jie Wei, Zi-Qi Shi, Jian-Qun Liu, Li-Fang Liu, Gui-Zhong Xin
Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds. Two pivotal steps involved in this strategy are to differentiate metabolites from herbal compounds and match metabolites with their parent compounds...
July 29, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28800244/exploiting-analysis-of-heterogeneity-to-increase-the-information-content-extracted-from-fluorescence-micrographs-of-transgenic-zebrafish-embryos
#12
Tongying Shun, Albert H Gough, Subramaniam Sanker, Neil A Hukriede, Andreas Vogt
Zebrafish embryos are a near-ideal animal model for drug discovery because of their high genetic and physiological similarity to mammals, small size, high fecundity, and optical transparency. The latter properties make zebrafish at larval stages especially suited for high-content analysis and high throughput screening (HTS). However, inherent biological complexity and the inability to screen multiple specimens in a single well present a challenge for HTS because limiting replicates and high variability often prevent assays from reaching the stringent performance criteria demanded of large-scale screening assays...
August 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28748473/evaluation-of-embryotoxicity-using-the-zebrafish-model
#13
Lisa Truong, Robert L Tanguay
The embryonic zebrafish model offers the power of whole-animal investigations (e.g., intact organism, functional homeostatic feedback mechanisms, and intercellular signaling) with the convenience of cell culture (e.g., cost- and time-efficient, minimal infrastructure, small quantities of solutions required). The model system overcomes many of the current limitations in rapid to high-throughput screening of drugs/compounds and casts a broad net to rapidly evaluate integrated system effects. Additionally, it is an ideal platform to follow up with targeted studies aimed at the mechanisms of toxic action...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28732770/pharmacologic-modeling-of-primary-mitochondrial-respiratory-chain-dysfunction-in-zebrafish
#14
James Byrnes, Rebecca Ganetzky, Richard Lightfoot, Michael Tzeng, Eiko Nakamaru-Ogiso, Christoph Seiler, Marni J Falk
Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28720487/pdms-b-pmoxa-polymersomes-for-hepatocyte-targeting-and-assessment-of-toxicity
#15
Klara Kiene, Susanne H Schenk, Fabiola Porta, Alexandra Ernst, Dominik Witzigmann, Philip Grossen, Jörg Huwyler
Nanoparticles, such as polymersomes, can be directed to the hepatic asialoglycoprotein receptor to achieve targeted drug delivery. In this study, we prepared asialofetuin conjugated polymersomes based on the amphiphilic di-block copolymer poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-b-PMOXA). They had an average diameter of 150nm and formed monodisperse vesicles. Drug encapsulation and sustained release was monitored using the hydrophilic model compound carboxyfluorescein. Asialoglycoprotein receptor specific uptake by HepG2 cells in vitro was energy dependent and could be competitively inhibited by the free targeting ligand...
October 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28718799/zebrafish-as-a-model-organism-for-the-development-of-drugs-for-skin-cancer
#16
REVIEW
Fatemeh Bootorabi, Hamed Manouchehri, Reza Changizi, Harlan Barker, Elisabetta Palazzo, Annalisa Saltari, Mataleena Parikka, Carlo Pincelli, Ashok Aspatwar
Skin cancer, which includes melanoma and squamous cell carcinoma, represents the most common type of cutaneous malignancy worldwide, and its incidence is expected to rise in the near future. This condition derives from acquired genetic dysregulation of signaling pathways involved in the proliferation and apoptosis of skin cells. The development of animal models has allowed a better understanding of these pathomechanisms, with the possibility of carrying out toxicological screening and drug development. In particular, the zebrafish (Danio rerio) has been established as one of the most important model organisms for cancer research...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28683849/large-scale-human-yeast-genetic-interaction-for-construction-of-disease-network-systematic-discovery-of-multiple-drug-targets
#17
Kyoungho Suk
A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by firstly searching for candidate human disease genes that confer toxicity in yeast, and secondly identifying modulators of this toxicity. The study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for instance...
July 7, 2017: BMB Reports
https://www.readbyqxmd.com/read/28682135/using-zebrafish-as-a-model-to-study-the-role-of-epigenetics-in-hearing-loss
#18
REVIEW
Yingzi He, Beier Bao, Huawei Li
The rapid progress of bioinformatics and high-throughput screening techniques in recent years has led to the identification of many candidate genes and small-molecule drugs that have the potential to make significant contributions to our understanding of the developmental and pathological processes of hearing, but it remains unclear how these genes and regulatory factors are coordinated. Increasing evidence suggests that epigenetic mechanisms are essential for establishing gene expression profiles and likely play an important role in the development of inner ear and in the pathology of hearing-associated diseases...
September 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28632848/effect-of-gabapentin-memantine-on-the-infantile-nystagmus-syndrome-in-the-zebrafish-model-implications-for-the-therapy-of-ocular-motor-diseases
#19
Stefan Yu Bögli, Maresa Afthinos, Melody Ying-Yu Huang
Purpose: Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28629306/%C3%AE-ca-specific-inhibitor-dithiocarbamate-fc14-584b-a-novel-antimycobacterial-agent-with-potential-to-treat-drug-resistant-tuberculosis
#20
Ashok Aspatwar, Milka Hammarén, Sanni Koskinen, Bruno Luukinen, Harlan Barker, Fabrizio Carta, Claudiu T Supuran, Mataleena Parikka, Seppo Parkkila
Inhibition of novel biological pathways in Mycobacterium tuberculosis (Mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. In vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-CA) inhibitors Fc14-594 A and Fc14-584B effectively inhibit the activity of Mtb β-CA enzymes. We screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on M. marinum in a zebrafish model. In our toxicity screening, Fc14-584B emerged as the least toxic and showed minimal toxicity in 5-day-old larvae at 300 µM concentration...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
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