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Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to Gd . The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β-gal.
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http://dx.doi.org/10.1002/anie.201909933 | DOI Listing |
Stroke
September 2025
Departments of Radiology and Neurology, Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston (E.L., R.M.P., K.H., E.H.L., E.E.).
Background: Despite promising preclinical results, remote limb ischemic postconditioning efficacy in human stroke treatment remains unclear, with mixed clinical trial outcomes. A potential reason for translational difficulties could be differences in circadian rhythms between nocturnal rodent models and diurnal humans.
Methods: Male C57BL/6J mice were subjected to transient focal cerebral ischemia and then exposed to remote postconditioning during their active or inactive phase and euthanized at 24 hours and 3 days.
J Exp Biol
September 2025
Institute of Environmental Sciences, Faculty of Biology, Jagiellonian University, Kraków, Poland.
The adverse effects of Western diets (WD), high in both fat and simple sugars, which contribute to obesity and related disorders, have been extensively studied in laboratory rodents, but not in non-laboratory animals, which limits the scope of conclusions. Unlike laboratory mice or rats, non-laboratory rodents that reduce body mass for winter do not become obese when fed a high-fat diet. However, it is not known whether these rodents are also resistant to the adverse effects of WD.
View Article and Find Full Text PDFHypertension
September 2025
Department of Obstetrics and Gynecology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu (Z.W.).
Background: Early-onset preeclampsia poses significant risks to maternal and fetal health, necessitating a deeper understanding of its molecular mechanisms and effective therapeutic strategies.
Methods: Utilizing data from genome-wide association study and Mendelian randomization analysis, we investigated the relationship between mitochondrial DNA copy number and preeclampsia. Transcriptome sequencing, in vitro experiments, and animal studies were conducted to explore the roles of SENP3 and SETD7 in preeclampsia pathogenesis.
Microb Drug Resist
September 2025
Drug Discovery Research, Wockhardt Research Centre, Wockhardt Ltd., Chhatrapati Sambhajinagar, India.
Cefepime (FEP), a fourth-generation cephalosporin combined with tazobactam (TAZ), a β-lactamase inhibitor, is being developed by Wockhardt as a pharmacodynamically optimized fixed dose combination (FEP-2 g + TAZ-2 g) for the treatment of multidrug-resistant Gram-negative infections. To undertake an exposure-response analysis for establishing pharmacokinetic (PK)/pharmacodynamic (PD) targets, it is crucial to characterize the PK profile of compounds in surrogate compartments, such as plasma and lung, in clinically relevant animal infection models used to evaluate efficacy. In the current study, PKs of FEP and TAZ were assessed in plasma and in epithelial lining fluid (ELF) of neutropenic noninfected, lung-infected, and thigh-infected mice.
View Article and Find Full Text PDFCephalalgia
September 2025
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics.
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