Background: Circulating lipid metabolites are associated with many physiological and biological processes in the body, and therefore could be used as biomarkers for evaluating drug efficacy and safety in preclinical studies. However, differences in circulating lipid profiles among humans and animals often used in preclinical studies have not been fully investigated.
Methods: We performed lipidomic analysis to obtain circulating lipid profiles of fasted humans (Caucasian, n = 15) and three animal species used in preclinical studies (mice [BALB/c, n = 5], rats [Sprague-Dawley, n = 5], and rabbits [New Zealand White, n = 5]) by using liquid chromatography-mass spectrometry.
Results: Our data showed marked differences in lipid profiles among humans and these animal species. Furthermore, we observed that the levels of many lipid metabolites, such as poly-unsaturated fatty acid-containing cholesteryl esters, ether-type phosphoglycerolipids, and sulfatides, were significantly different (p < 0.05) by more than 10-fold in these animals (depending on the animal species) from humans.
Conclusion: Our data could be useful while extrapolating the data on the biomarker candidates identified in preclinical studies into clinical studies.
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http://dx.doi.org/10.1186/s12944-015-0104-4 | DOI Listing |
Chronic wounds, due to their high prevalence, are a serious global health concern. Effective therapeutic strategies can significantly accelerate healing, thereby reducing the risk of complications and alleviating the economic burden on healthcare systems. Although numerous experimental studies have investigated wound healing, most rely on qualitative observations or quantitative direct measurements.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Departments of Radiology and Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
Purpose: Trophoblast cell-surface antigen 2 (Trop2) is overexpressed in various solid tumors and contributes to tumor progression, while its expression remains low in normal tissues. Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan-hziy (Trodelvy), has shown efficacy in targeting this antigen. Leveraging the enhanced specificity of ADCs, we conducted the first immunoPET imaging study of Trop2 expression in gastric cancer (GC) and triple-negative breast cancer (TNBC) models using Zr-labeled Trodelvy ([Zr]Zr-DFO-Trodelvy).
View Article and Find Full Text PDFCurr Cardiol Rep
January 2025
Cardiovascular Division, University of Minnesota, 420 Delaware Street SE, MMC 508, Minneapolis, MN, 55455, USA.
Purpose Of Review: We aim to summarize the available literature guiding tailored sedation practices for specific conditions encountered in the Cardiovascular Intensive Care Unit (CICU).
Recent Findings: Data specific for the CICU population is lacking. Preclinical data and observational studies guide sedation approaches for specific pathologies that we have used to generate a guideline for sedative choice for various scenarios.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Leste Universitario, 240th Street, Corner of 5th Avenue, Goiania, GO, 74605-170, Brazil.
The CCl-induced hepatotoxicity model is a traditional preclinical assay applied to evaluate potential hepatoprotective compounds. However, several studies have used it with inappropriate dose and exposure time, generating both weak response or irreversible liver injury, as well as lack of representative liver and plasma biomarkers. Therefore, this study aims to determine the best dose and exposure time of CCl in Wistar rats, permitting a proper evaluation of potential hepatoprotective effect.
View Article and Find Full Text PDFTransl Vis Sci Technol
January 2025
STZ eyetrial at the Centre for Ophthalmology, Tuebingen, Germany.
Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).
Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.
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