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Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder that typically leads to severe pregnancy outcomes. Although genetic, endocrine, and environmental factors are involved in the etiology of ICP, the role of metabolic disorders remains unclear. Here we report an examination of the biomolecular alterations in placental tissues of women with ICP and healthy pregnant women at a molecular level. By integrating FTIR microspectroscopy with advanced multivariate statistical analysis and semiquantitative methods, including PCA, OPLS-DA and peak area ratio calculations, the biomolecular alterations were revealed. Specifically, alterations in lipid conformations and increased lipid acyl chain unsaturation in the ICP group were associated with bile acids participating in the regulation of lipid metabolism. Additionally, a reduction in the relative α-helix content of proteins compared to β-sheet structures was associated with changes in apoptosis-related proteins. Furthermore, the nucleic acid content relative to lipids and proteins was elevated in the ICP group. Our study underscores the potential of FTIR microspectroscopy as a powerful tool for investigating the underlying biochemical mechanisms related to ICP.
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http://dx.doi.org/10.1039/d4ay02072c | DOI Listing |
J Thromb Haemost
September 2025
Department of Immunology and Inflammation, Centre for Haematology, Imperial College, London, UK. Electronic address:
Background: The VWF Phe2561Tyr variant has been previously shown to exhibit gain-of-function like activity and increase the risk of repeated MI in patients below 55 years of age. It was hypothesised that altered stem dynamics enhanced the responsiveness of the molecule to shear stress. In this study we investigated the evolutionary significance of the amino acid at position 2561 and functional impacts of variants at this site.
View Article and Find Full Text PDFPLoS Genet
September 2025
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America.
MicroRNAs (miRNAs) are essential regulators of gene expression, yet few comprehensive databases exist for miRNA expression in non-model species, limiting our ability to characterize their roles in gene regulation, development, and disease. Similarly, isomiRs - length and sequence isoforms of canonical miRNAs with potentially altered regulatory targets and functions - have received even less attention in non-model species, including the horse, leaving a critical gap in our understanding of their biological significance. To address these challenges, we developed an open-source, containerized pipeline for identifying and quantifying miRNAs and isomiRs (FARmiR: Framework for Analysis and Refinement of miRNAs), and an associated interactive browser (AIMEE: Animal IsomiR and MiRNA Expression Explorer).
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.
Control of the glass transition temperature () is a major goal in polymer engineering as is a key determinant of mechanical behavior, barrier properties, and material processability. In copolymers of nonpolar monomers, the Fox equation can provide an approximate description of the dependence of on copolymer composition (monomer ratio), based on a harmonic weighted average of values for the individual homopolymers. However, the Fox equation does not consider the influence of intermonomer interactions, nor does it account for self-concentration effects.
View Article and Find Full Text PDFNat Genet
September 2025
Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR144 and UMR3664, Paris, France.
Maintaining the epigenetic identity of centromeres is essential to prevent genome instability. Centromeres are epigenetically defined by the histone H3 variant CENP-A. Prior work in human centromeres has shown that CENP-A is associated with regions of hypomethylated DNA located within large arrays of hypermethylated repeats, but the functional importance of these DNA methylation (DNAme) patterns remains poorly understood.
View Article and Find Full Text PDFFront Immunol
September 2025
Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
The constitutive androstane receptor (CAR), encoded by the gene, is a nuclear receptor mainly expressed in the liver, where it regulates (xenobiotic) drug and bile acid metabolism, bilirubin clearance and energy homeostasis. CAR has emerged as a promising therapeutic target for diabetes, fatty liver disease and alcoholic liver disease, but it has barely been investigated in the context of sepsis. Since alterations in drug metabolism have been observed in sepsis patients, who may also exhibit increased serum bilirubin and bile acid levels, we hypothesize that CAR function may be impaired during sepsis.
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