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Zebrafish drug screen

Peter M Eimon, Mostafa Ghannad-Rezaie, Gianluca De Rienzo, Amin Allalou, Yuelong Wu, Mu Gao, Ambrish Roy, Jeffrey Skolnick, Mehmet Fatih Yanik
Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease...
January 15, 2018: Nature Communications
Kai-Di Hsu, Yu-Hin Chan, Hong-Jhang Chen, Shi-Ping Lin, Kuan-Chen Cheng
Tyrosinase-based TLC (thin layer chromatography) was developed for screening of anti-melanogenic drugs. In particular, this technique enables researchers to identify melanogenic inhibitor(s) in tested mixtures with the naked eye. In comparison with traditional colorimetric screening assays for tyrosinase inhibitor(s), not only is tyrosinase-based TLC a more cost-effective option (nearly one-tenth the enzyme cost of colorimetric methods) but also is a more sensitive detection approach for kojic acid (KA), a standard anti-melanogenic drug...
January 10, 2018: Scientific Reports
Wenjuan Zhang, Jingjin Xu, Juhui Qiu, Cencan Xing, Xiumin Li, Bo Leng, Yi Su, Jinmei Lin, Jiaofen Lin, Xuqiao Mei, Yiqun Huang, Anming Meng, Yutian Pan, Yu Xue
Osteoporosis is a global public health concern and, it can result from numerous pathogenic mechanisms, many of which are closely related with age, nutritional disorders, endocrine imbalance, or adverse drug side effects presented by glucocorticoids, heparin, and anti-epileptics. Given its wide range etiologies, it is crucial to establish an animal model of osteoporosis for use in screening potential drugs quickly and effectively. Previous research has reported that an accumulation of elevated iron in the body is an independent risk factor for osteoporosis...
January 3, 2018: Biochemical and Biophysical Research Communications
Lifeng Liu, Guang Yang, Shoupeng Liu, Linbo Wang, Xibin Yang, Huiming Qu, Xiaofen Liu, Le Cao, Weijun Pan, Hui Li
High-throughput imaging and screening is essential for biomedical research and drug discovery using miniature model organisms such as zebrafish. This study introduces a high-speed imaging system which illuminates zebrafish embryos flowing through a capillary tube with a sheet of light and captures them using a linear charge-coupled device (CCD). This system can image dozens of zebrafish embryos per second. An image algorithm was developed to recognize each embryo and to perform automatic analysis. We distinguished dead and living embryos according to the gray level distribution and conducted statistics of morphological characteristics of embryos at different growing stages...
December 1, 2017: Biomedical Optics Express
Lilian B Romero-Sánchez, Manuel Marí-Beffa, Paloma Carrillo, Miguel Ángel Medina, Aránzazu Díaz-Cuenca
The osteogenic and angiogenic responses of organisms to the ionic products of degradation of bioactive glasses (BGs) are being intensively investigated. The promotion of angiogenesis by copper (Cu) has been known for more than three decades. This element can be incorporated to delivery carriers, such as BGs, and the materials used in biological assays. In this work, Cu-containing mesoporous bioactive glass (MBG) in the SiO2-CaO-P2O5 compositional system was prepared incorporating 5% mol Cu (MBG-5Cu) by replacement of the corresponding amount of Ca...
December 27, 2017: Acta Biomaterialia
A C Berrun, D L Stachura
Hematopoiesis is an essential cellular process in which hematopoietic stem and progenitor cells (HSPCs) differentiate into the multitude of different cell lineages that comprise mature blood. Isolation and identification of these HSPCs is difficult because they are defined ex post facto; they can only be defined after their differentiation into specific cell lineages. Over the past few decades, the zebrafish (Danio rerio) has become a model organism to study hematopoiesis. Zebrafish embryos develop ex utero, and by 48 h post-fertilization (hpf) have generated definitive HSPCs...
November 30, 2017: Journal of Visualized Experiments: JoVE
Michael Lenning, Joseph Fortunato, Tai Le, Isaac Clark, Ang Sherpa, Soyeon Yi, Peter Hofsteen, Geethapriya Thamilarasu, Jingchun Yang, Xiaolei Xu, Huy-Dung Han, Tzung K Hsiai, Hung Cao
Heart disease is the leading cause of mortality in the U.S. with approximately 610,000 people dying every year. Effective therapies for many cardiac diseases are lacking, largely due to an incomplete understanding of their genetic basis and underlying molecular mechanisms. Zebrafish (Danio rerio) are an excellent model system for studying heart disease as they enable a forward genetic approach to tackle this unmet medical need. In recent years, our team has been employing electrocardiogram (ECG) as an efficient tool to study the zebrafish heart along with conventional approaches, such as immunohistochemistry, DNA and protein analyses...
December 28, 2017: Sensors
Héctor Carreño Gutiérrez, Irene Vacca, Anna Inguanzo Pons, William H J Norton
BACKGROUND: Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. The zebrafish is an ideal model for aggression research. Zebrafish are small, amenable to genetic and pharmacological manipulation, and agonistic behaviour can be measured reliably. NEW METHOD: In this study we have established a novel setup to automatically quantify aggression and locomotion in one-month old juvenile zebrafish, a stage at which fish exhibit adult-like behaviour but are small that one camera can film several animals...
December 21, 2017: Journal of Neuroscience Methods
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
Sandra Richter, Ulrike Schulze, Pavel Tomançak, Andrew C Oates
Small molecule in vivo phenotypic screening is used to identify drugs or biological activities by directly assessing effects in intact organisms. However, current screening designs may not exploit the full potential of chemical libraries due to false negatives. Here, we demonstrate a modular small molecule screen in embryonic zebrafish that varies concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column. By testing each small molecule in multiple interrelated ways, this screen recovers compounds that a standard screening design would have missed, increasing the hit frequency from the chemical library three-fold...
December 1, 2017: Nature Communications
Kyu-Seok Hwang, Jung Yoon Yang, Jooyun Lee, Yu-Ri Lee, Seong Soon Kim, Geum Ran Kim, Jin Sil Chae, Jin Hee Ahn, Dae-Seop Shin, Tae-Young Choi, Myung Ae Bae
BACKGROUND: The demand for anti-melanogenic agents is increasing due to the unwanted side effects of current treatments. To find an effective anti-melanogenic agent, we used zebrafish as a whole animal model for phenotype-based drug and cosmetic discovery screening. OBJECTIVES: The aim of this study was to identify and explore a small molecule that could be used for skin-whitening cosmetics. METHODS: Using zebrafish embryos, we examined the effects of 1000 compounds on zebrafish development and pigmentation...
November 20, 2017: Journal of Dermatological Science
Jung-Ren Chen, Yu-Heng Lai, Jhih-Jie Tsai, Chung-Der Hsiao
Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo mammalian models. The zebrafish is an ideal model that could link preclinical toxicity screening with the drug development pipeline. Taking advantage of a highly conservative genomic, rapid development, large number of offspring, low cost and easy manipulation, zebrafish has been considered an excellent animal model for disease-based drug screening...
November 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Valentin Trofimov, Joana Costa-Gouveia, Eik Hoffmann, Priscille Brodin
Tuberculosis (TB) is a global disease causing 1.8 million deaths each year. The appearance of drug-resistant strains raised the demand for new anti-mycobacterial drugs and therapies, because previously discovered antibiotics are shown to be inefficient. Moreover, the number of newly discovered drugs is not increasing in proportion to the emergence of drug resistance, which suggests that more optimized methodology and screening procedures are required including the incorporation of in vivo properties of TB infection...
November 24, 2017: Current Opinion in Microbiology
Sergey V Prykhozhij, Lucia Caceres, Jason N Berman
Genome editing using CRISPR/Cas9 has advanced very rapidly in its scope, versatility and ease of use. Zebrafish (Danio rerio) has been one of the vertebrate model species where CRISPR/Cas9 has been applied very extensively for many different purposes and with great success. In particular, disease modeling in zebrafish is useful for testing specific gene variants for pathogenicity in a preclinical setting. Here we describe multiple advances in diverse species and systems that can improve genome editing in zebrafish...
November 21, 2017: Current Gene Therapy
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...
January 2018: International Journal of Oncology
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
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
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
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...
November 21, 2017: Lab on a Chip
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
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