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Aquatic Organisms as Disease Models, Sources of Therapeutics, and Pollution Markers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 9618

Special Issue Editors


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Guest Editor
Dynamics and Mechanics of Epithelia Group, Faculty of Medicine, Institute of Genetics and Development of Rennes, University of Rennes, CNRS, UMR 6290, 35043 Rennes, France
Interests: embryo development; cell cycle; gene regulation; cancer; stem cells; gonads; genetic diseases
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Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; stem cells; Xenopus laevis; development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aquatic organisms are an irreplaceable source of medicinal drugs and therapeutics, a perfect model system and indicator for many human diseases, and often also a source of remedy for environmental pollutants. To mention a few examples: for several decades the African-clawed frog Xenopus laevis has been used for human pregnancy tests. Between the 1940s and 1960s, thousands of frogs were imported to the USA by pharmaceutical companies and injected with pregnant women’s urine. Xenopus frogs are the perfect human ciliary-based model for kidney disease, and the Xenopus sex reversal is an excellent indicator of water contamination with endocrine disruptors that mimic human sex hormones and are present in the majority of cosmetics and everyday products. Zebrafish and squid eyes are a model for human ocular diseases, such as glaucoma, cataracts, photoreceptor degeneration, and cornea and retina disorders. The Atlantic horseshoe crab (Limulus polyphemus) blue blood has been the source of Limulus amebocyte lysate (LAL) used to test bacterial contamination of vaccines and medical equipment. Over the past 30 years, scientists have identified over 20,000 new biochemical compounds from aquatic organisms, and dozens have been tested in clinical trials. Cytarabine and Vidarabine, isolated from the Caribbean sponges, are used for the treatment of leukemia and lymphoma, and systematic herpes virus infection, respectively. Ziconotide, a powerful analgesic drug, was isolated from the cone snail and Trabectedin (Yondelis); a marine alkaloid, isolated from the tunicate, is used for the treatment of advanced soft-tissue sarcoma and ovarian cancer. GoJelly, a European Union project, investigates the properties of the jellyfish, including its mucus, which can be used as a biofilter to adsorb and remove micro and nano plastics from the water.

For this Special Issue, we invite research and review articles on the recent progress in aquatic organisms as a source of medication, models for human diseases, markers of environmental pollutants, and, finally, as a source of anti-pollutant compounds.

Prof. Dr. Jacek Z Kubiak
Prof. Dr. Malgorzata Kloc
Guest Editors

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Keywords

  • aquatic organism
  • human disease model
  • environmental pollutants
  • novel drugs

Published Papers (4 papers)

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Research

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24 pages, 4820 KiB  
Article
A Focal Impact Model of Traumatic Brain Injury in Xenopus Tadpoles Reveals Behavioral Alterations, Neuroinflammation, and an Astroglial Response
by Sydnee L. Spruiell Eldridge, Jonathan F. K. Teetsel, Ray A. Torres, Christina H. Ulrich, Vrutant V. Shah, Devanshi Singh, Melissa J. Zamora, Steven Zamora and Amy K. Sater
Int. J. Mol. Sci. 2022, 23(14), 7578; https://doi.org/10.3390/ijms23147578 - 08 Jul 2022
Cited by 4 | Viewed by 2217
Abstract
Traumatic Brain Injury (TBI) is a global driver of disability, and we currently lack effective therapies to promote neural repair and recovery. TBI is characterized by an initial insult, followed by a secondary injury cascade, including inflammation, excitotoxicity, and glial cellular response. This [...] Read more.
Traumatic Brain Injury (TBI) is a global driver of disability, and we currently lack effective therapies to promote neural repair and recovery. TBI is characterized by an initial insult, followed by a secondary injury cascade, including inflammation, excitotoxicity, and glial cellular response. This cascade incorporates molecular mechanisms that represent potential targets of therapeutic intervention. In this study, we investigate the response to focal impact injury to the optic tectum of Xenopus laevis tadpoles. This injury disrupts the blood-brain barrier, causing edema, and produces deficits in visually-driven behaviors which are resolved within one week. Within 3 h, injured brains show a dramatic transcriptional activation of inflammatory cytokines, upregulation of genes associated with inflammation, and recruitment of microglia to the injury site and surrounding tissue. Shortly afterward, astrocytes undergo morphological alterations and accumulate near the injury site, and these changes persist for at least 48 h following injury. Genes associated with astrocyte reactivity and neuroprotective functions also show elevated levels of expression following injury. Since our results demonstrate that the response to focal impact injury in Xenopus resembles the cellular alterations observed in rodents and other mammalian models, the Xenopus tadpole offers a new, scalable vertebrate model for TBI. Full article
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9 pages, 1381 KiB  
Communication
Short-Term Exposure Effects of the Environmental Endocrine Disruptor Benzo(a)Pyrene on Thyroid Axis Function in Zebrafish
by Giuditta Rurale, Ilaria Gentile, Camilla Carbonero, Luca Persani and Federica Marelli
Int. J. Mol. Sci. 2022, 23(10), 5833; https://doi.org/10.3390/ijms23105833 - 23 May 2022
Cited by 9 | Viewed by 1742
Abstract
Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were [...] Read more.
Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were treated with 50 nM BaP from 2.5 to 72 h post fertilization (hpf) and compared to 1.2% DMSO controls. The expression profiles of markers of thyroid primordium specification, thyroid hormone (TH) synthesis, hypothalamus-pituitary-thyroid (HPT) axis, TH transport and metabolism, and TH action were analyzed in pools of treated and control embryos at different developmental stages. BaP treatment did not affect early markers of thyroid differentiation but resulted in a significant decrease of markers of TH synthesis (tg and nis) likely secondary to defective expression of the central stimulatory hormones of thyroid axis (trh, tshba) and of TH metabolism (dio2). Consequently, immunofluorescence of BaP treated larvae showed a low number of follicles immunoreactive to T4. In conclusion, our results revealed that the short-term exposure to BaP significantly affects thyroid function in zebrafish, but the primary toxic effects would be exerted at the hypothalamic-pituitary level thus creating a model of central hypothyroidism. Full article
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15 pages, 5343 KiB  
Communication
CNPase, a 2′,3′-Cyclic-nucleotide 3′-phosphodiesterase, as a Therapeutic Target to Attenuate Cardiac Hypertrophy by Enhancing Mitochondrial Energy Production
by Keai Sinn Tan, Dongfang Wang, Ziqiang Lu, Yihan Zhang, Sixu Li, Yue Lin and Wen Tan
Int. J. Mol. Sci. 2021, 22(19), 10806; https://doi.org/10.3390/ijms221910806 - 06 Oct 2021
Cited by 3 | Viewed by 2336
Abstract
Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully [...] Read more.
Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2′-3′-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2′,3′-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity. Full article
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Review

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17 pages, 852 KiB  
Review
Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery
by Rachel E. Williams and Karen Mruk
Int. J. Mol. Sci. 2022, 23(15), 8608; https://doi.org/10.3390/ijms23158608 - 03 Aug 2022
Cited by 1 | Viewed by 2044
Abstract
Epilepsy is an international public health concern that greatly affects patients’ health and lifestyle. About 30% of patients do not respond to available therapies, making new research models important for further drug discovery. Aquatic vertebrates present a promising avenue for improved seizure drug [...] Read more.
Epilepsy is an international public health concern that greatly affects patients’ health and lifestyle. About 30% of patients do not respond to available therapies, making new research models important for further drug discovery. Aquatic vertebrates present a promising avenue for improved seizure drug screening and discovery. Zebrafish (Danio rerio) and African clawed frogs (Xenopus laevis and tropicalis) are increasing in popularity for seizure research due to their cost-effective housing and rearing, similar genome to humans, ease of genetic manipulation, and simplicity of drug dosing. These organisms have demonstrated utility in a variety of seizure-induction models including chemical and genetic methods. Past studies with these methods have produced promising data and generated questions for further applications of these models to promote discovery of drug-resistant seizure pathology and lead to effective treatments for these patients. Full article
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