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Zebrafish drug screen

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https://www.readbyqxmd.com/read/29115578/characterization-of-prostate-cancer-cell-progression-in-zebrafish-xenograft-model
#1
Wei Xu, Brittany A Foster, Mackenzie Richards, Kenneth R Bondioli, Girish Shah, Christopher C Green
Early diagnosis of prostate cancer (PCa) is critical for the application of efficient treatment to PCa patients. However, the majority of PCas remains indolent from several months to several years before malignancy. Current diagnosis methods have limitations in their reliability and are inefficient in time cost. Thus, an efficient in vivo PCa cell xenograft model is highly desired for diagnostic studies in PCas. In the present study we present a standardized procedure to create a PCa cell xenograft model using zebrafish (Danio rerio) as the host...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29083959/screencube-a-3d-printed-system-for-rapid-and-cost-effective-chemical-screening-in-adult-zebrafish
#2
Adrian T Monstad-Rios, Claire J Watson, Ronald Y Kwon
Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish...
October 30, 2017: Zebrafish
https://www.readbyqxmd.com/read/29081356/fishing-anti-lymph-angiogenic-drugs-with-zebrafish
#3
REVIEW
Melissa García-Caballero, Ana R Quesada, Miguel A Medina, Manuel Marí-Beffa
Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation...
October 31, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/29079063/neuroprotective-and-neuro-restorative-effects-of-minocycline-and-rasagiline-in-a-zebrafish-6-hydroxydopamine-model-of-parkinson-s-disease
#4
Aileen Cronin, Maura Grealy
Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. Zebrafish larvae at two days post fertilization were exposed to 6-OHDA for three days, with co-administration of test drugs for neuroprotection experiments, or for 32 h, with subsequent treatment with test drugs for neuro-restoration experiments...
October 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/29068019/a-microfluidic-device-for-partial-immobilization-chemical-exposure-and-behavioural-screening-of-zebrafish-larvae
#5
Asal Nady, Amir Reza Peimani, Georg Zoidl, Pouya Rezai
The zebrafish larva is an important vertebrate model for sensory-motor integration studies, genetic screening, and drug discovery because of its excellent characteristics such as optical transparency, genetic manipulability, and genetic similarity to humans. Operations such as precise manipulation of zebrafish larvae, controlled exposure to chemicals, and behavioural monitoring are of utmost importance to the abovementioned studies. In this work, a novel microfluidic device is presented to easily stabilize an individual larva's head using a microfluidic trap while leaving the majority of the body and the tail unhindered to move freely in a downstream chamber...
October 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29053747/establishment-of-pten-knockout-medaka-with-transcription-activator-like-effector-nucleases-talens-as-a-model-of-pten-deficiency-disease
#6
Yuriko Matsuzaki, Tetsushi Sakuma, Takashi Yamamoto, Hideyuki Saya
Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. The PTEN gene is a major tumor suppressor, with mutations of this gene occurring frequently in tumors of humans and mice. We have now developed mutant medaka deficient in PTEN with the use of transcription activator-like effector nuclease (TALEN) technology. Medaka possesses two pten genes, ptena and ptenb, similar to zebrafish. We established 16 ptena mutant lines and two ptenb mutant lines...
2017: PloS One
https://www.readbyqxmd.com/read/29053735/characterization-of-the-first-knock-out-aldh7a1-zebrafish-model-for-pyridoxine-dependent-epilepsy-using-crispr-cas9-technology
#7
Nikita Zabinyakov, Garrett Bullivant, Feng Cao, Matilde Fernandez Ojeda, Zheng Ping Jia, Xiao-Yan Wen, James J Dowling, Gajja S Salomons, Saadet Mercimek-Andrews
Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites...
2017: PloS One
https://www.readbyqxmd.com/read/29046299/high-content-screening-assay-based-discovery-of-paullones-as-novel-podocyte-protective-agents
#8
Ha Won Lee, Ehtesham Arif, Mehmet Mete Altintas, Kevin Quick, Shrey Maheshwari, Alexandra Plezia, Aqsa Mahmood, Jochen Reiser, Deepak Nihalani, Vineet Gupta
Podocyte dysfunction and loss is an early event and a hallmark of proteinuric kidney diseases. Podocyte's normal function is maintained via its unique cellular architecture that relies on an intracellular network of filaments, including filamentous actin (F-actin) and microtubules, that provides mechanical support. Damage to this filamentous network leads to changes in cellular morphology and results in podocyte injury, dysfunction, and death. Conversely, stabilization of this network protects podocytes and ameliorates proteinuria...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29035434/zebrafish-larvae-model-of-dilated-cardiomyopathy-induced-by-terfenadine
#9
Gyojeong Gu, Yirang Na, Hyewon Chung, Seung Hyeok Seok, Hae Young Lee
BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy can be the end-stage of severe cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly and heart failure (HF). Although a wide variety of animal models are available to study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy with non-invasive, simple, and large screening methods. METHODS: We developed a dilated cardiomyopathy model in zebrafish larvae using short duration terfenadine, a known cardiotoxic drug that induces ventricular size dilation...
September 20, 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/29030288/in-vitro-characterization-of-zebrafish-danio-rerio-organic-anion-transporters-oat2a-e
#10
Jelena Dragojević, Ivan Mihaljević, Marta Popović, Roko Zaja, Tvrtko Smital
OATS/Oats are transmembrane proteins that transport a variety of drugs, environmental toxins and endogenous metabolites into the cell. Zebrafish (Danio rerio) has seven OAT orthologs: Oat1, Oat2a-e and Oat3. In this study we specifically address Oat2 (Slc22a7) family. Conserved synteny analysis showed localization of zebrafish oat2 genes on two chromosomes, 11 and 17. All five zebrafish Oats were localized by live cell imaging in membranes of transiently transfected HEK293-T cells, and Oat2a, b, d, and e were confirmed using western blot analysis...
October 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28987462/the-developing-utility-of-zebrafish-models-of-neurological-and-neuropsychiatric-disorders-a-critical-review
#11
REVIEW
Barbara D Fontana, Nathana J Mezzomo, Allan V Kalueff, Denis B Rosemberg
Zebrafish (Danio rerio) have become a powerful tool in neuroscience research due to their genetic tractability, molecular/physiological conservation, small body size, ease of experimental manipulations in vivo, and rich behavioral repertoire. Zebrafish models and tests are particularly useful in genetics research, neurophenotyping, CNS drug screening, as well as in modeling complex neurological and psychiatric disorders. Here, we discuss selected examples of successful application of zebrafish models to mimicking various aspects of brain pathology, and emphasize their developing utility for studying the underlying molecular and genetic mechanisms...
October 5, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28984854/adult-zebrafish-in-cns-disease-modeling-a-tank-that-s-half-full-not-half-empty-and-still-filling
#12
Darya A Meshalkina, Elana V Kysil, Jason E Warnick, Konstantin A Demin, Allan V Kalueff
The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits...
October 6, 2017: Lab Animal
https://www.readbyqxmd.com/read/28975691/gut-feelings-studying-enteric-nervous-system-development-function-and-disease-in-the-zebrafish-model-system
#13
REVIEW
Julia Ganz
The enteric nervous system (ENS) is the largest part of the peripheral nervous system and is entirely neural crest-derived. It provides the intrinsic innervation of the gut, controlling different aspects of gut function, such as motility. In this review, we will discuss key points of Zebrafish ENS development, genes, and signaling pathways regulating ENS development, as well as contributions of the Zebrafish model system to better understand ENS disorders. During their migration, enteric progenitor cells (EPCs) display a gradient of developmental states based on their proliferative and migratory characteristics, and show spatiotemporal heterogeneity based on gene expression patterns...
October 4, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28943320/purinergic-and-adenosine-receptors-contribute-to-hypoxic-hyperventilation-in-zebrafish-danio-rerio
#14
Alisha J Coe, Alexina J Picard, Michael G Jonz
The chemoreceptors involved in oxygen sensing in teleost fish are neuroepithelial cells (NECs) in the gills, and are analogous to glomus cells in the mammalian carotid body. Purinergic signalling mechanisms involving the neurotransmitters, ATP and adenosine, have been identified in mediating hypoxic signalling in the carotid body, but these pathways are not well understood in the fish gill. The present study used a behavioural assay to screen for the effects of drugs, that target purinergic and adenosine receptors, on the hyperventilatory response to hypoxia in larval zebrafish (Danio rerio) in order to determine if the receptors on which these drugs act may be involved in hypoxic signalling...
September 21, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28938553/homocysteine-induced-peripheral-microcirculation-dysfunction-in-zebrafish-and-its-attenuation-by-l-arginine
#15
Sang Joon Lee, Sung Ho Park, Jinhyuk Fred Chung, Woorak Choi, Hyung Kyu Huh
Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter [Formula: see text], where [Formula: see text] and [Formula: see text] represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935902/targeting-neph1-and-zo-1-protein-protein-interaction-in-podocytes-prevents-podocyte-injury-and-preserves-glomerular-filtration-function
#16
Amin Sagar, Ehtesham Arif, Ashish Kumar Solanki, Pankaj Srivastava, Michael G Janech, Seok-Hyung Kim, Joshua H Lipschutz, Sang-Ho Kwon, Ashish, Deepak Nihalani
Targeting protein-protein interaction (PPI) is rapidly becoming an attractive alternative for drug development. While drug development commonly involves inhibiting a PPI, in this study, we show that stabilizing PPI may also be therapeutically beneficial. Junctional proteins Neph1 and ZO-1 and their interaction is an important determinant of the structural integrity of slit diaphragm, which is a critical component of kidney's filtration system. Since injury induces loss of this interaction, we hypothesized that strengthening this interaction may protect kidney's filtration barrier and preserve kidney function...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923401/pharmacological-blockade-of-cholesterol-trafficking-by-cepharanthine-in-endothelial-cells-suppresses-angiogenesis-and-tumor-growth
#17
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...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28916270/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#18
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
#19
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
#20
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
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