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58,286 results on '"DIFFERENTIAL EXPRESSION"'

12. Differential expression of miRNAs associated with pectoral myopathies in young broilers: insights from a comparative transcriptome analysis

Author

Pizzol, Mariane Spudeit Dal, Ibelli, Adriana Mércia Guaratini, Cantão, Maurício Egídio, Campos, Francelly Geralda, de Oliveira, Haniel Cedraz, de Oliveira Peixoto, Jane, Fernandes, Lana Teixeira, de Castro Tavernari, Fernando, Morés, Marcos Antônio Zanella, Bastos, Ana Paula Almeida, and Ledur, Mônica Corrêa

Published
2024
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21. Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis.

Author

Spagnolo P, Cela E, Patel MA, Tweddell D, Daley M, Clarson C, Stranges S, Cepinskas G, and Fraser DD

Subjects
Humans, Male, Child, Female, Adolescent, Case-Control Studies, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 metabolism, Proteome metabolism, Biomarkers blood, Computational Biology methods, Child, Preschool, Diabetic Ketoacidosis blood, Diabetic Ketoacidosis metabolism, Blood Proteins metabolism, Signal Transduction, Proteomics methods
Abstract

Background: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case-control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables., Methods: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes. Proximity extension assays were used to quantify 3072 plasma proteins. Data analysis was performed using multivariate statistics, machine learning, and bioinformatics., Results: This study identified 214 differentially expressed proteins (162 upregulated, 52 downregulated; adj P < 0.05 and a fold change > 2), reflecting cellular dysfunction and metabolic stress in severe DKA. We characterized protein expression across various organ systems and cell types, with notable alterations observed in white blood cells. Elevated inflammatory pathways suggest an enhanced inflammatory response, which may contribute to the complications of severe DKA. Additionally, upregulated pathways related to hormone signaling and nitrogen metabolism were identified, consistent with increased hormone release and associated metabolic processes, such as glycogenolysis and lipolysis. Changes in lipid and fatty acid metabolism were also observed, aligning with the lipolysis and ketosis characteristic of severe DKA. Finally, several signaling pathways were associated with clinical biochemical variables., Conclusions: Our findings highlight differentially expressed plasma proteins and enriched signaling pathways that were associated with clinical features, offering insights into the pathophysiology of severe DKA., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Western University, Human Research Ethics Board (HREB; #17908E; #15996E). Consent was obtained from the legal guardians of all pediatric patients admitted with DKA, and both guardian consent and patient assent were secured for insulin-controlled patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Published
2025
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38. Differential expression of components of the CGRP-receptor family in human coronary and human middle meningeal arteries: functional implications.

Author

de Vries T, Schutter D, van den Bogaerdt A, Vincent A, Dammers R, Danser AHJ, and MaassenVanDenBrink A

Subjects
Humans, Middle Aged, Male, Female, Receptor Activity-Modifying Protein 1 metabolism, Receptor Activity-Modifying Protein 1 genetics, Calcitonin Gene-Related Peptide metabolism, Receptor Activity-Modifying Protein 3 metabolism, Receptor Activity-Modifying Protein 3 genetics, Receptor Activity-Modifying Protein 2 metabolism, Receptor Activity-Modifying Protein 2 genetics, Vasodilation drug effects, Vasodilation physiology, Calcitonin Gene-Related Peptide Receptor Antagonists pharmacology, Peptide Hormones, Meningeal Arteries drug effects, Meningeal Arteries metabolism, Adrenomedullin metabolism, Adrenomedullin pharmacology, Adrenomedullin genetics, Receptors, Calcitonin Gene-Related Peptide metabolism, Coronary Vessels drug effects, Coronary Vessels metabolism, Calcitonin Receptor-Like Protein metabolism, Calcitonin Receptor-Like Protein genetics
Abstract

Background: Different responses in human coronary arteries (HCA) and human middle meningeal arteries (HMMA) were observed for some of the novel CGRP receptor antagonists, the gepants, for inhibiting CGRP-induced relaxation. These differences could be explained by the presence of different receptor populations in the two vascular beds. Here, we aim to elucidate which receptors are involved in the relaxation to calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2) in HCA and HMMA., Methods: RNA was isolated from homogenized human arteries (23 HCAs; 12 F, 11 M, age 50 ± 3 years and 26 HMMAs; 14 F, 12 M, age 51 ± 3 years) and qPCR was performed for different receptor subunits. Additionally, relaxation responses to CGRP, AM or AM2 of the human arteries were quantified using a Mulvany myograph system, in the presence or absence of the adrenomedullin 1 receptor antagonist AM 22-52 and/or olcegepant., Results: Calcitonin-like receptor (CLR) mRNA was expressed equally in both vascular beds, while calcitonin receptor (CTR) and receptor activity-modifying protein 3 (RAMP3) expression was low and could not be detected in all samples. RAMP1 expression was similar in HCA and HMMA, while RAMP2 expression was higher in HMMA. Moreover, receptor component protein (RCP) expression was higher in HMMA than in HCA. Functional experiments showed that olcegepant inhibits relaxation to all three agonists in both vascular beds. In HCA, antagonist AM 22-52 did not inhibit relaxation to any of the agonists, while a trend for blocking relaxation to AM and AM2 could be observed in HMMA., Conclusion: Based on the combined results from receptor subunit mRNA expression and the functional responses in both vascular tissues, relaxation of HCA is mainly mediated via the canonical CGRP receptor (CLR-RAMP1), while relaxation of HMMA can be mediated via both the canonical CGRP receptor and the adrenomedullin 1 receptor (CLR-RAMP2). Future research should investigate whether RAMP2 predominance over RAMP1 in the meningeal vasculature results in altered migraine susceptibility or in a different response to anti-migraine medication in these patients. Moreover, the exact role of RCP in CGRP receptor signalling should be elucidated in future research., (© 2024. The Author(s).)

Published
2024
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