Cross‐Species Extrapolation of Biological Data to Guide the Environmental Safety Assessment of Pharmaceuticals—The State of the Art and Future Priorities

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Cross-Species Extrapolation of Biological Data to Guide the Environmental Safety Assessment of Pharmaceuticals—The State of the Art and Future Priorities

Enhancing chemical safety assessment with high-precision ecotoxicology predictions.


Abstract

The extrapolation of biological data across species is a key aspect of biomedical research and drug development. In this context, comparative biology considerations are applied with the goal of understanding human disease and guiding the development of effective and safe medicines. However, the widespread occurrence of pharmaceuticals in the environment and the need to assess the risk posed to wildlife have prompted a renewed interest in the extrapolation of pharmacological and toxicological data across the entire tree of life. To address this challenge, a biological “read-across” approach, based on the use of mammalian data to inform toxicity predictions in wildlife species, has been proposed as an effective way to streamline the environmental safety assessment of pharmaceuticals. Yet, how effective has this approach been, and are we any closer to being able to accurately predict environmental risk based on known human risk? We discuss the main theoretical and experimental advancements achieved in the last 10 years of research in this field. We propose that a better understanding of the functional conservation of drug targets across species and of the quantitative relationship between target modulation and adverse effects should be considered as future research priorities. This pharmacodynamic focus should be complemented with the application of higher-throughput experimental and computational approaches to accelerate the prediction of internal exposure dynamics. The translation of comparative (eco)toxicology research into real-world applications, however, relies on the (limited) availability of experts with the skill set needed to navigate the complexity of the problem; hence, we also call for synergistic multistakeholder efforts to support and strengthen comparative toxicology research and education at a global level. Environ Toxicol Chem 2023;00:1–13. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Regulating Intermediate Concentration to Synthesize Highly Crystalline g‐C3N4 under Spontaneous Ultrahigh Pressure

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Regulating Intermediate Concentration to Synthesize Highly Crystalline g-C3N4 under Spontaneous Ultrahigh Pressure

The effects of the concentration of gaseous intermediates on the polymerization, crystallization, and hydrogen production properties of graphitic carbon nitride synthesized under spontaneous ultrahigh atmospheric pressure are explored.


Abstract

Improving polymerization and crystallization properties has become a key point to maximize the intrinsic photocatalytic performance of graphitic carbon nitride (g-C3N4), however, the critical roles of intermediates in the polymerization and crystallization process are not clear. Herein, highly crystalline g-C3N4 is obtained by calcinating different amount of dicyandiamide in a closed environment. Ultrahigh atmospheric pressure up to 6.2 MPa can be spontaneously formed due to the produced gaseous intermediates. The best crystallization properties were achieved when 1.8 g of dicyandiamide was used. The photocatalytic hydrogen production rate reaches 9241.3 μmol ⋅ g−1 ⋅ h−1, which is improved by about 12.5 times by comparison. The crystallization and hydrogen production activities cannot be enhanced only by adding an initial gas pressure meanwhile keeping the quality of dicyandiamide constant, confirming that the intermediate concentration determines the polymerization and hydrogen production performance of g-C3N4. This study is important to improve the intrinsic photocatalytic performance of g-C3N4 and the composites.

Possible Approaches to Drug Delivery via Glutathione Transferase Proteins and Chitosan

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Possible Approaches to Drug Delivery via Glutathione Transferase Proteins and Chitosan


Abstract

Novel means of drug delivery are in great demand in particular for the administration of macromolecules. Glutathione transferase proteins can undergo cellular uptake and thereby deliver pharmaceutical cargo to intracellular sites. The proteins are soluble and can be produced in large quantities by facile bacterial expression. Molecular engineering may endow the proteins with signal sequences directing the delivery to specific intracellular targets and escape domains that facilitate cargo release from endosomes. Sequences providing high affinity for nucleic acids may find use in vaccines based on DNA or RNA. The combination of chitosan and glutathione transferase synergistically enhances the cellular uptake of the protein. Engineered glutathione transferase proteins offer great potential in the area of drug delivery research.