Dissecting the Enantioselective Neurotoxicity of Isocarbophos: Chiral Insight from Cellular, Molecular, and Computational Investigations DOI
Jiaqi Wang,

Zhi-Cong He,

Wei Peng

et al.

Chemical Research in Toxicology, Journal Year: 2023, Volume and Issue: 36(3), P. 535 - 551

Published: Feb. 17, 2023

Chiral organophosphorus pollutants are found abundantly in the environment, but neurotoxicity risks of these asymmetric chemicals to human health have not been fully assessed. Using cellular, molecular, and computational toxicology methods, this story is explore static dynamic toxic actions its stereoselective differences chiral isocarbophos toward SH-SY5Y nerve cells mediated by acetylcholinesterase (AChE) further dissect microscopic basis enantioselective neurotoxicity. Cell-based assays indicate that exhibits strong enantioselectivity inhibition survival rates intracellular AChE activity, cytotoxicity (S)-isocarbophos significantly greater than (R)-isocarbophos. The inhibitory effects enantiomers on activity dose-dependent, half-maximal concentrations (IC50) (R)-/(S)-isocarbophos 6.179/1.753 μM, respectively. Molecular experiments explain results cellular assays, namely, stemmed from bioaffinities between neuronal AChE. In meantime, modes neurotoxic display key amino acid residues formed noncovalent interactions obviously different, which related closely molecular structural rigidity conformational dynamics flexibility substrate binding domain Still, we observed stable "sandwich-type π–π stacking" fashioned aromatic Trp-86 Tyr-337 crucial, notably reduces van der Waals' contribution (ΔGvdW) AChE–(S)-isocarbophos complexes induces disparities free energies during conjugations thus elucidating synaptic has a effect cells. Clearly, effort can provide experimental insights for evaluating exposure organophosphates macroscopic levels.

Language: Английский

The uses of zebrafish (Danio rerio) as an in vivo model for toxicological studies: A review based on bibliometrics DOI Creative Commons
Weichao Zhao,

Y.-W. Chen,

Nan Hu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 272, P. 116023 - 116023

Published: Jan. 30, 2024

An in vivo model is necessary for toxicology. This review analyzed the uses of zebrafish (Danio rerio) toxicology based on bibliometrics. Totally 56,816 publications about from 2002 to 2023 were found Web Science Core Collection, with Toxicology as top 6 among all disciplines. Accordingly, bibliometric map reveals that "toxicity" has become a hot keyword. It further most common exposure types include acute, chronic, and combined exposure. The toxicological effects behavioral, intestinal, cardiovascular, hepatic, endocrine toxicity, neurotoxicity, immunotoxicity, genotoxicity, reproductive transgenerational toxicity. mechanisms oxidative stress, inflammation, autophagy, dysbiosis gut microbiota. toxicants commonly evaluated by using nanomaterials, arsenic, metals, bisphenol, dioxin. Overall, provide unique well-accepted investigate mechanisms. We also discussed possible ways address some limitations model, such combination human organoids avoid species differences.

Language: Английский

Citations

33
The technology, opportunities, and challenges of Synthetic Biological Intelligence DOI Creative Commons
Brett J. Kagan, Christopher Gyngell, Tamra Lysaght

et al.

Biotechnology Advances, Journal Year: 2023, Volume and Issue: 68, P. 108233 - 108233

Published: Aug. 7, 2023

Integrating neural cultures developed through synthetic biology methods with digital computing has enabled the early development of Synthetic Biological Intelligence (SBI). Recently, key studies have emphasized advantages biological systems in some information processing tasks. However, neither technology behind this development, nor potential ethical opportunities or challenges, been explored detail yet. Here, we review aspects that facilitate SBI and explore applications. Considering these foreseeable use cases, various implications are proposed. Ultimately, work aims to provide a robust framework structure considerations ensure can be both researched applied responsibly.

Language: Английский

Citations

20
Neurobehavioral toxic effects and mechanisms of 2-aminobenzothiazole exposure on zebrafish DOI Creative Commons
Jie Gu,

Liguo Guo,

Chen Chen

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 913, P. 169495 - 169495

Published: Dec. 22, 2023

2-Aminobenzothiazole (NTH), a benzothiazole derivative, exhibits potent biochemical activities and plays significant role in modern industry. Widespread intensive utilization of NTH has led to its detection aquatic environments, encompassing both groundwater surface water. Despite wide usage, the effect on developmental neurotoxicity organisms remains uncharted. Therefore, aim this investigation was create exposure models for short- long-term studies order analyze neurobehavioral toxic impact (0, 50, 500, 5000 μg/L) zebrafish, which includes motor function, anxiety, memory performance, as well examine mechanism neurotoxicity. The results revealed suppression initial embryonic mobility by NTH. However, during short-term experiments, it did not significantly functions zebrafish. In addition, effects zebrafish were observed after 50 500 μg/L NTH, mainly impacting locomotion, social behavior, cognitive functions. Moreover, caused oxidative damage adult brain tissue, accompanied abnormal expression damage-related genes. Furthermore, Real-Time PCR indicated genes related specifically those GABA synthesis pathway (gabrg2, gad2, gad1b, abat) 5-HT (tph2, tph1b, pet1, htr1aa). Taken together, study demonstrates first time that chronic decreases associated with pathway. This is damage, ultimately resulting changes ability, performance.

Language: Английский

Citations

11
High-throughput screening paradigms in ecotoxicity testing: Emerging prospects and ongoing challenges DOI
Donald Włodkowic, Marcus Jansen

Chemosphere, Journal Year: 2022, Volume and Issue: 307, P. 135929 - 135929

Published: Aug. 6, 2022

Language: Английский

Citations

13
Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research DOI Creative Commons
Wenjie Xiao,

Peile Li,

Fujiao Kong

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: March 6, 2024

Abstract Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, thorough understanding intricate neural circuits vital development targeted therapies enhancement clinical outcomes. This review begins with an exploration historical evolution techniques used in studying related to epilepsy. It then provides extensive overview diverse employed this domain, discussing their fundamental principles, strengths, limitations, as well application. Additionally, synthesis multiple unveil complexity summarized. Finally, also presents associated epileptic circuits. By providing critical assessment methodologies study circuits, seeks enhance these techniques, stimulate innovative approaches unraveling epilepsy's complexities, ultimately facilitate improved treatment translation Graphical

Language: Английский

Citations

2
Dissecting the Enantioselective Neurotoxicity of Isocarbophos: Chiral Insight from Cellular, Molecular, and Computational Investigations DOI
Jiaqi Wang,

Zhi-Cong He,

Wei Peng

et al.

Chemical Research in Toxicology, Journal Year: 2023, Volume and Issue: 36(3), P. 535 - 551

Published: Feb. 17, 2023

Chiral organophosphorus pollutants are found abundantly in the environment, but neurotoxicity risks of these asymmetric chemicals to human health have not been fully assessed. Using cellular, molecular, and computational toxicology methods, this story is explore static dynamic toxic actions its stereoselective differences chiral isocarbophos toward SH-SY5Y nerve cells mediated by acetylcholinesterase (AChE) further dissect microscopic basis enantioselective neurotoxicity. Cell-based assays indicate that exhibits strong enantioselectivity inhibition survival rates intracellular AChE activity, cytotoxicity (S)-isocarbophos significantly greater than (R)-isocarbophos. The inhibitory effects enantiomers on activity dose-dependent, half-maximal concentrations (IC50) (R)-/(S)-isocarbophos 6.179/1.753 μM, respectively. Molecular experiments explain results cellular assays, namely, stemmed from bioaffinities between neuronal AChE. In meantime, modes neurotoxic display key amino acid residues formed noncovalent interactions obviously different, which related closely molecular structural rigidity conformational dynamics flexibility substrate binding domain Still, we observed stable "sandwich-type π–π stacking" fashioned aromatic Trp-86 Tyr-337 crucial, notably reduces van der Waals' contribution (ΔGvdW) AChE–(S)-isocarbophos complexes induces disparities free energies during conjugations thus elucidating synaptic has a effect cells. Clearly, effort can provide experimental insights for evaluating exposure organophosphates macroscopic levels.

Language: Английский

Citations

2