Elsevier eBooks, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Human Genomics, Год журнала: 2024, Номер 18(1)
Опубликована: Ноя. 21, 2024
Abstract The merging of physiology and toxicokinetics, or pharmacokinetics, with computational modeling to characterize dosimetry has led major advances for both the chemical pharmaceutical research arenas. Driven by mutual need estimate internal exposures where in vivo data generation was simply not possible, application toxicokinetic grown exponentially past 30 years. In toxicology been derivation quantitative estimates toxicodynamic variability evaluate suitability tenfold uncertainty factor employed risk assessment decision-making. Consideration a host physiologic, ontogenetic, genetic, exposure factors are all required comprehensive characterization. Fortunately, underlying framework physiologically based models can accommodate these inputs, addition being amenable capturing time-varying dynamics. Meanwhile, international interest advancing new approach methodologies fueled vitro toxicity that be applied vitro-in extrapolation approaches provide human-specific risk-based information historically data-poor chemicals. This review will brief introduction structure evolution as they advanced incorporate wide range complex scenarios. followed state science update describing current emerging experimental strategies population life-stage variability, including increasing safety research. conclude case study examples demonstrating novel applications an on its regulatory Physiologically provides sound evaluation assessment.
Язык: Английский
Процитировано
4
Journal of Hazardous Materials, Год журнала: 2023, Номер 465, С. 133233 - 133233
Опубликована: Дек. 14, 2023
Язык: Английский
Процитировано
6
Metabolites, Год журнала: 2024, Номер 14(2), С. 84 - 84
Опубликована: Янв. 24, 2024
The role of the sodium citrate transporter (NaCT) SLC13A5 is multifaceted and context-dependent. While aberrant dysfunction leads to neonatal epilepsy, its therapeutic inhibition protects against metabolic disease. Notably, insights regarding cellular molecular mechanisms underlying these phenomena are limited due intricacy complexity latent human physiology, which poorly captured by existing animal models. This review explores innovative technologies aimed at bridging such a knowledge gap. First, I provide an overview variants in context disease specific cell types where expression has been observed. Next, discuss current for generating patient-specific induced pluripotent stem cells (iPSCs) their inherent advantages limitations, followed summary methods differentiating iPSCs into neurons, hepatocytes, organoids. Finally, explore relevance models as platforms delving intricate SLC13A5-related disorders.
Язык: Английский
Процитировано
2
Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11
Опубликована: Авг. 21, 2023
Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, integration between BD hepatocytes is basis liver function. However, lack a source cholangiocytes limits vitro research. aim present study was to establish three-dimensional BDs combined with human mature (hMHs) using chemically induced progenitor cells (hCLiPs) derived from hMHs. Methods: In this study, we formed functional hCLiPs hepatocyte growth factor extracellular matrix. expressed typical biliary markers CK-7, GGT1, CFTR EpCAM were able bile-like substance rhodamine 123 into lumen. established cocultured These bind BDs, acid analog CLF transported culture medium through hMHs accumulated lumen BDs. generated showed function physiological system (e.g., within liver) when they connected Conclusion: We novel for drug screening therapeutic modulation cholangiocyte
Язык: Английский
Процитировано
2
Elsevier eBooks, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0