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Zebrafish drug screen

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https://www.readbyqxmd.com/read/28748473/evaluation-of-embryotoxicity-using-the-zebrafish-model
#1
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
#2
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 on function as well as 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
#3
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...
July 15, 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
#4
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
#5
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
#6
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...
July 6, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/28621412/the-not-so-long-history-of-zebrafish-research-in-israel
#9
Janna Blechman, Gil Levkowitz, Yoav Gothilf
The zebrafish has become a model of choice in fundamental and applied life sciences and is widely used in various fields of biomedical research as a human disease model for cancer, metabolic and neurodegenerative diseases, and regenerative medicine. The transparency of the zebrafish embryo allows real-time visualization of the development and morphogenesis of practically all of its tissues and organs. Zebrafish are amenable to genetic manipulation, for which innovative genetic and molecular techniques are constantly being introduced...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28614822/drug-discovery-to-halt-the-progression-of-acute-kidney-injury-to-chronic-kidney-disease-a-case-for-phenotypic-drug-discovery-in-acute-kidney-injury
#10
Neil Hukriede, Andreas Vogt, Mark de Caestecker
The cellular responses that occur following acute kidney injury (AKI) are complex and dynamic, involving multiple cells types and molecular pathways. For this reason, early selection of defined molecular targets for therapeutic intervention is unlikely to be effective in complex in vivo models of AKI, let alone Phase 3 clinical trials in patients with even more complex AKI pathobiology. Phenotypic screening using zebrafish provides an attractive alternative that does not require prior knowledge of molecular targets and may identify compounds that modify multiple targets that might be missed in more traditional target-based screens...
June 15, 2017: Nephron
https://www.readbyqxmd.com/read/28600565/action-sequencing-in-the-spontaneous-swimming-behavior-of-zebrafish-larvae-implications-for-drug-development
#11
Tobias Palmér, Fredrik Ek, Olof Enqvist, Roger Olsson, Kalle Åström, Per Petersson
All motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locomotion pattern of 10 days old zebrafish larvae we have here characterized the basic organizational principles governing the swimming behavior...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598490/development-of-a-zebrafish-sepsis-model-for-high-throughput-drug-discovery
#12
Anju Mary Philip, Youdong Wang, Antonio Mauro, Suzan El-Rass, John C Marshall, Warren L Lee, Arthur S Slutsky, Claudia C dosSantos, Xiao-Yan Wen
Sepsis is a leading cause of death worldwide. Current treatment modalities remain largely supportive. Intervention strategies focused on inhibiting specific mediators of the inflammatory host response have been largely unsuccessful, a consequence of an inadequate understanding of the complexity and heterogeneity of the innate immune response. Moreover, the conventional drug development pipeline is time consuming and expensive and the low success rates associated with cell-based screens underline the need for whole organism screening strategies, especially for complex pathological processes...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28596596/optical-mapping-of-neuronal-activity-during-seizures-in-zebrafish
#13
L Turrini, C Fornetto, G Marchetto, M C Müllenbroich, N Tiso, A Vettori, F Resta, A Masi, G Mannaioni, F S Pavone, F Vanzi
Mapping neuronal activity during the onset and propagation of epileptic seizures can provide a better understanding of the mechanisms underlying this pathology and improve our approaches to the development of new drugs. Recently, zebrafish has become an important model for studying epilepsy both in basic research and in drug discovery. Here, we employed a transgenic line with pan-neuronal expression of the genetically-encoded calcium indicator GCaMP6s to measure neuronal activity in zebrafish larvae during seizures induced by pentylenetretrazole (PTZ)...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596290/yeast-genetic-interaction-screen-of-human-genes-associated-with-amyotrophic-lateral-sclerosis-identification-of-map2k5-kinase-as-a-potential-drug-target
#14
Myungjin Jo, Ah Young Chung, Nozomu Yachie, Minchul Seo, Hyejin Jeon, Youngpyo Nam, Yeojin Seo, Eunmi Kim, Quan Zhong, Marc Vidal, Hae Chul Park, Frederick P Roth, Kyoungho Suk
To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport...
June 8, 2017: Genome Research
https://www.readbyqxmd.com/read/28577986/automated-analysis-of-brain-activity-for-seizure-detection-in-zebrafish-models-of-epilepsy
#15
Borbála Hunyadi, Aleksandra Siekierska, Jo Sourbron, Daniëlle Copmans, Peter A M de Witte
BACKGROUND: Epilepsy is a chronic neurological condition, with over 30% of cases unresponsive to treatment. Zebrafish larvae show great potential to serve as an animal model of epilepsy in drug discovery. Thanks to their high fecundity and relatively low cost, they are amenable to high-throughput screening. However, the assessment of seizure occurrences in zebrafish larvae remains a bottleneck, as visual analysis is subjective and time-consuming. NEW METHOD: For the first time, we present an automated algorithm to detect epileptic discharges in single-channel local field potential (LFP) recordings in zebrafish...
June 1, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28574477/utilizing-zebrafish-visual-behaviors-in-drug-screening-for-retinal-degeneration
#16
REVIEW
Logan Ganzen, Prahatha Venkatraman, Chi Pui Pang, Yuk Fai Leung, Mingzhi Zhang
Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo...
June 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28570545/transplantation-of-zebrafish-pediatric-brain-tumors-into-immune-competent-hosts-for-long-term-study-of-tumor-cell-behavior-and-drug-response
#17
Mattie J Casey, Katarzyna Modzelewska, Daniela Anderson, James Goodman, Elena F Boer, Laura Jimenez, Douglas Grossman, Rodney A Stewart
Tumor cell transplantation is an important technique to define the mechanisms controlling cancer cell growth, migration, and host response, as well as to assess potential patient response to therapy. Current methods largely depend on using syngeneic or immune-compromised animals to avoid rejection of the tumor graft. Such methods require the use of specific genetic strains that often prevent the analysis of immune-tumor cell interactions and/or are limited to specific genetic backgrounds. An alternative method in zebrafish takes advantage of an incompletely developed immune system in the embryonic brain before 3 days, where tumor cells are transplanted for use in short-term assays (i...
May 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28554163/the-influence-of-temperature-on-adult-zebrafish-sensitivity-to-pentylenetetrazole
#18
Fabiano Peres Menezes, Rosane Souza Da Silva
Pentylenetetrazole (PTZ) is one of the most valuable drugs used to induce seizure-like state in zebrafish especially considering the pharmacological screening for anticonvulsants and the study of basic mechanisms of epilepsy. Here, the effect of gender, weight and changes in temperature on latency to adult zebrafish reach classical seizure states induced by PTZ (10mM) was evaluated. Gender and weight (200-250mg versus 400-500mg) did not affect the profile of response to PTZ. When water temperature was changed from 22 to 30°C the lower temperature increased the latency time to reach seizure states and the higher temperature significantly decreased it, in comparison to the control group maintained at 26°C...
May 22, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28547797/vitamin-d-receptor-agonists-regulate-ocular-developmental-angiogenesis-and-modulate-expression-of-dre-mir-21-and-vegf
#19
Stephanie L Merrigan, Breandán N Kennedy
BACKGROUND AND PURPOSE: Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype-based screening in zebrafish. EXPERIMENTAL APPROACH: A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28544957/zebrafish-as-a-visual-and-dynamic-model-to-study-the-transport-of-nanosized-drug-delivery-systems-across-the-biological-barriers
#20
Ye Li, Xiaoqing Miao, Tongkai Chen, Xiang Yi, Ruibing Wang, Haitao Zhao, Simon Ming-Yuen Lee, Xueqing Wang, Ying Zheng
With the wide application of nanotechnology to drug delivery systems, a simple, dynamic and visual in vivo model for high-throughput screening of novel formulations with fluorescence markers across biological barriers is desperately needed. In vitro cell culture models have been widely used, although they are far from a complimentary in vivo system. Mammalian animal models are common predictive models to study transport, but they are costly and time consuming. Zebrafish (Danio rerio), a small vertebrate model, have the potential to be developed as an "intermediate" model for quick evaluations...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
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