Browsing by Subject "Aptamers"

Now showing 1 - 3 of 3
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    Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease
    (Elsevier, 2023) Sanyal, Arun J.; Williams, Stephen A.; Lavine, Joel E.; Neuschwander-Tetri, Brent A.; Alexander, Leigh; Ostroff, Rachel; Biegel, Hannah; Kowdley, Kris V.; Chalasani, Naga; Dasarathy, Srinivasan; Diehl, Anna Mae; Loomba, Rohit; Hameed, Bilal; Behling, Cynthia; Kleiner, David E.; Karpen, Saul J.; Williams, Jessica; Jia, Yi; Yates, Katherine P.; Tonascia, James; Medicine, School of Medicine
    Background & aims: Despite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD. Methods: Using modified-aptamer proteomics, we assayed 5,220 proteins in each of 2,852 single serum samples from 636 individuals with histologically confirmed NAFLD. We developed and validated dichotomized protein-phenotype models to identify clinically relevant severities of steatosis (grade 0 vs. 1-3), hepatocellular ballooning (0 vs. 1 or 2), lobular inflammation (0-1 vs. 2-3) and fibrosis (stages 0-1 vs. 2-4). Results: The AUCs of the four protein models, based on 37 analytes (18 not previously linked to NAFLD), for the diagnosis of their respective components (at a clinically relevant severity) in training/paired validation sets were: fibrosis (AUC 0.92/0.85); steatosis (AUC 0.95/0.79), inflammation (AUC 0.83/0.72), and ballooning (AUC 0.87/0.83). An additional outcome, at-risk NASH, defined as steatohepatitis with NAFLD activity score ≥4 (with a score of at least 1 for each of its components) and fibrosis stage ≥2, was predicted by multiplying the outputs of each individual component model (AUC 0.93/0.85). We further evaluated their ability to detect change in histology following treatment with placebo, pioglitazone, vitamin E or obeticholic acid. Component model scores significantly improved in the active therapies vs. placebo, and differential effects of vitamin E, pioglitazone, and obeticholic acid were identified. Conclusions: Serum protein scanning identified signatures corresponding to the key components of liver biopsy in NAFLD. The models developed were sufficiently sensitive to characterize the longitudinal change for three different drug interventions. These data support continued validation of these proteomic models to enable a "liquid biopsy"-based assessment of NAFLD.
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    Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants
    (American Physiological Society, 2020-04-01) Arjaans, Sanne; Wagner, Brandie D.; Mourani, Peter M.; Mandell, Erica W.; Poindexter, Brenda B.; Berger, Rolf M.F.; Abman, Steven H.; Pediatrics, School of Medicine
    Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH); however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signaling pathways with the risk for BPD or PH. We prospectively enrolled infants with gestational age <34 wk and collected blood samples during their first week of life. BPD and PH were assessed at 36 wk postmenstrual age. Samples were assayed for each of the 1,121 peptides included in the SOMAscan scan technology, with subsequent pathway analysis. Of 102 infants in the study, 82 had BPD, and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, bone morphogenetic protein 10 [BMP10], hepatocyte growth factor (HGF), ANG-2) were associated with the subsequent diagnosis of BPD; and FGF-19, PF-4, connective tissue activating peptide (CTAP)-III, and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research.
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    Origin of ribonucleotide recognition motifs through ligand mimicry at early earth
    (Taylor & Francis, 2024) Mozumdar, Deepto; Roy, Raktim N.; Pathology and Laboratory Medicine, School of Medicine
    In an RNA world, the emergence of template-specific self-replication and catalysis necessitated the presence of motifs facilitating reliable recognition between RNA molecules. What did these motifs entail, and how did they evolve into the proteinaceous RNA recognition entities observed today? Direct observation of these primordial entities is hindered by rapid degradation over geological time scales. To overcome this challenge, researchers employ diverse approaches, including scrutiny of conserved sequences and structural motifs across extant organisms and employing directed evolution experiments to generate RNA molecules with specific catalytic abilities. In this review, we delve into the theme of ribonucleotide recognition across key periods of early Earth's evolution. We explore scenarios of RNA interacting with small molecules and examine hypotheses regarding the role of minerals and metal ions in enabling structured ribonucleotide recognition and catalysis. Additionally, we highlight instances of RNA-protein mimicry in interactions with other RNA molecules. We propose a hypothesis where RNA initially recognizes small molecules and metal ions/minerals, with subsequent mimicry by proteins leading to the emergence of proteinaceous RNA binding domains.