Use of Zebrafish in Drug Discovery Toxicology

Chemical Research in Toxicology, Journal Year: 2019, Volume and Issue: 33(1), P. 95 - 118

Published: Oct. 18, 2019

Unpredicted human safety events in clinical trials for new drugs are costly terms of health and money. The drug discovery industry attempts to minimize those with diligent preclinical testing. Current standard practices good at preventing toxic compounds from being tested the clinic; however, false negative toxicity results still a reality. Continual improvement must be pursued realm. Higher-quality therapies can brought forward more information about potential toxicities associated mechanisms. zebrafish model is bridge between vitro assays mammalian vivo studies. This powerful its breadth application tractability research. In past two decades, our understanding disease biology has grown significantly owing thousands studies on this tiny vertebrate. Review summarizes challenges strengths model, discusses 3Rs value that it deliver, highlights translatable untranslatable biology, brings together reports recent focusing toxicology.

Language: Английский

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The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116160 - 116160

Published: Jan. 21, 2024

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human other biotic members. In last few decades, understanding toxicity these been given the centre stage research using many vitro vivo models. Zebrafish (Danio rerio), a freshwater fish member minnow family garnered much attention due to its distinct features, which make it an important frequently used animal model various fields embryology toxicological studies. Given that fertilization development zebrafish eggs take place externally, they serve as excellent organism for studying early developmental stages. Moreover, possess comparable genetic composition humans share almost 70% genes mammals. This particular become increasingly popular, especially research. serves link between studies analysis It is appealing choice vertebrate research, when employing high-throughput methods, small size, swift development, relatively affordable laboratory setup. enhanced comprehension pathobiology drug toxicity. review emphasizes recent developments screening assays, new insights gained about drugs through assays. Specifically, cardio, neural, and, hepatic toxicology inferred by applications nanoparticles have highlighted.

Language: Английский

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Manipulating Myc for reparative regeneration

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 21, 2024

The Myc family of proto-oncogenes is a key node for the signal transduction external pro-proliferative signals to cellular processes required development, tissue homoeostasis maintenance, and regeneration across evolution. tight regulation synthesis activity essential restricting its oncogenic potential. In this review, we highlight central role that plays in animal kingdom (from Cnidaria echinoderms Chordata) how could be employed unlock regenerative potential non-regenerative tissues humans therapeutic purposes. Mastering fine balance harnessing ability promote transcription without triggering oncogenesis may open door many exciting opportunities development wide array diseases.

Language: Английский

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Toward a Unified Theory of Aging and Regeneration

Regenerative Medicine, Journal Year: 2019, Volume and Issue: 14(9), P. 867 - 886

Published: Aug. 28, 2019

Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following pluripotency transition, and subsequent transitions such as embryonic–fetal while providing tumor suppressive antiviral survival benefits also result a loss regenerative potential leading to age-related fibrosis degenerative diseases. However, reprogramming somatic cells demonstrates possibility restoring telomerase embryonic regeneration pathways thus reversing decline capacity. A unified model aging is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue modulation embryo-onco phenotype cancer.

Language: Английский

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Evolution of Regeneration in Animals: A Tangled Story

Frontiers in Ecology and Evolution, Journal Year: 2021, Volume and Issue: 9

Published: March 5, 2021

The evolution of regenerative capacity in multicellular animals represents one the most complex and intriguing problems biology. How could such a seemingly advantageous trait as self-repair become consistently attenuated by evolution? This review article examines concept origin nature regeneration, its connection with processes embryonic development asexual reproduction, well mechanisms tissue homeostasis. presents variety classical modern hypotheses explaining different trends which is not always beneficial for individual notably species. Mechanistically, these are driven signaling pathways progressive restriction differentiation plasticity concomitant advances adaptive immunity. Examples phylogenetically enhanced considered well, appropriate evolutionary reasoning enhancement discussion molecular mechanisms.

Language: Английский

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Sustained induction of autophagy enhances survival during prolonged starvation in newt cells

Life Science Alliance, Journal Year: 2025, Volume and Issue: 8(4), P. e202402772 - e202402772

Published: Feb. 4, 2025

Salamanders demonstrate exceptional resistance to starvation, allowing them endure extended periods without food in their natural habitats. Although autophagy, a process involving evolutionarily conserved proteins, promotes survival during scarcity, the specific mechanism by which it contributes extreme starvation newt cells remains unexplored. Our study, using species Pleurodeles waltl , reveals that primary fibroblasts maintain constant autophagy activation prolonged cellular starvation. Unlike normal mammalian fibroblasts, where autophagosome formation increases acute but returns baseline levels after periods, elevated numbers even 4 d initiation, surpassing observed nutrient-rich conditions. Unique P. mTOR orthologs show reduced lysosomal localization compared with both and starved states. However, exhibit dephosphorylation of substrates under conditions, similar cells. These observations suggest newts may have evolved distinctive system balance seemingly conflicting factors: high regenerative capacity autophagy-mediated

Language: Английский

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Cell Reprogramming, Transdifferentiation, and Dedifferentiation Approaches for Heart Repair

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3063 - 3063

Published: March 27, 2025

Cardiovascular disease (CVD) remains the leading cause of death globally, with myocardial infarction (MI) being a major contributor. The current therapeutic approaches are limited in effectively regenerating damaged cardiac tissue. Up-to-date strategies for heart regeneration/reconstitution aim at remodeling through repairing tissue an external cell source or by stimulating existing cells to proliferate and repopulate compromised area. Cell reprogramming is addressed this challenge as promising solution, converting fibroblasts other types into functional cardiomyocytes, either reverting pluripotent state directly switching lineage. Several such gene editing application miRNA small molecules have been explored their potential enhance regeneration. Those take advantage plasticity introducing factors that regress maturity vitro, allowing later differentiation thus endorsing transplantation, promote situ proliferation, leveraged scaffolds embedded pro-regenerative promoting efficient restoration. Despite notable advancements, important challenges persist, including low efficiency, maturation limitations, safety concerns clinical applications. Nonetheless, integrating these innovative offers alternative restoring function reducing dependency on full transplants.

Language: Английский

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Genetic Reprogramming of Positional Memory in a Regenerating Appendage

Current Biology, Journal Year: 2019, Volume and Issue: 29(24), P. 4193 - 4207.e4

Published: Nov. 27, 2019

Language: Английский

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Hippo signaling: bridging the gap between cancer and neurodegenerative disorders

Neural Regeneration Research, Journal Year: 2020, Volume and Issue: 16(4), P. 643 - 643

Published: Oct. 9, 2020

During development, regulation of organ size requires a balance between cell proliferation, growth and death. Dysregulation these fundamental processes can cause variety diseases. Excessive proliferation results in cancer whereas excessive death neurodegenerative disorders. Many signaling pathways known-to-date have role regulation. Among them, evolutionarily conserved Hippo pathway is unique as it controls both by mechanisms during sculpture development. Neurodegeneration, complex process progressive neuronal population, fatal disorders with no available cure to date. normal required for sculpting an organ. However, aberrant population result has gathered major attention its cancer, however, other functions like neurodegeneration are also emerging rapidly. This review highlights the diseases provide information on chemical inhibitors employed block pathway. Understanding mediated will aid development reliable effective therapeutic strategies future.

Language: Английский

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Developmental toxicity of pre-production plastic pellets affects a large swathe of invertebrate taxa

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Abstract Microplastics pose risks to marine organisms through ingestion, entanglement, and as carriers of toxic additives environmental pollutants. Plastic pre-production pellet leachates have been shown affect the development sea urchins and, some extent, mussels. The extent those developmental effects on other animal phyla remains unknown. Here, we test toxicity mixed nurdle samples new PVC pellets for embryonic or asexual reproduction by regeneration animals from all major superphyla (Lophotrochozoa, Ecdysozoa, Deuterostomia Cnidaria). Our results show diverse, concentration-dependent impacts in species sampled pellets, molluscs deuterostomes samples. Embryo axial formation, cell specification specially, morphogenesis seem be main processes affected plastic leachate exposure. study serves a proof principle potentially catastrophic that increasing concentrations oceans ecosystems can across populations superphyla.

Language: Английский

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