AI Article Synopsis

  • Lipodystrophy is a rare disease that lacks effective diagnosis due to its low prevalence and diverse symptoms, highlighting the need for new biomarkers to improve diagnosis and treatment, especially for congenital generalized lipodystrophy (CGL).* -
  • Researchers analyzed dataset GSE159337 to identify differentially expressed genes (DEGs) related to CGL, which led to the identification of potential biomarkers and their functionality through various analytical techniques, including receiver operating characteristic (ROC) and machine learning methods.* -
  • A total of 71 DEGs were identified, with several genes (like CXCR2 and TNFSF10) showing promise as biomarkers for CGL diagnosis, while ibuprofen was highlighted as a potential treatment targeting these

Article Abstract

Background: Lipodystrophy is a rare disease that is poorly diagnosed due to its low prevalence and frequent phenotypic heterogeneity. The main therapeutic measures for patients with clinical lipodystrophy are aimed at improving general metabolic complications such as diabetes mellitus, insulin resistance, and hypertriglyceridemia. Therefore, there is an urgent need to find new biomarkers to aid in the diagnosis and targeted treatment of patients with congenital generalized lipodystrophy (CGL).

Methods: Dataset GSE159337 was obtained via the Gene Expression Omnibus database. First, differentially expressed genes (DEGs) between CGL and control samples were yielded via differential expression analysis and were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment to explore the functional pathways. Next, protein-protein interaction analysis and the MCC algorithm were implemented to yield candidate genes, which were then subjected to receiver operating characteristic (ROC) analysis to identify biomarkers with an area under the curve value exceeding 0.8. Moreover, random forest (RF), logistic regression, and support vector machine (SVM) analyses were carried out to assess the diagnostic ability of biomarkers for CGL. Finally, the small-molecule drugs targeting biomarkers were predicted, and ibuprofen was further validated in lipodystrophy mice.

Results: A total of 71 DEGs in GSE159337 were sifted out and were involved in immune receptor activity, immune response-regulating signaling pathway, and secretory granule membrane. Moreover, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN were considered as biomarkers by performing ROC analysis on 10 candidate genes. Meanwhile, RF, logistic regression, and SVM analyses further described that those biomarkers had an excellent diagnosis capability for CGL. Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice.

Conclusion: Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236084PMC
http://dx.doi.org/10.3389/fendo.2024.1414908DOI Listing

Publication Analysis

Top Keywords

ibuprofen targeting
8
metabolic disturbance
8
lipodystrophy
8
disturbance lipodystrophy
8
candidate genes
8
roc analysis
8
logistic regression
8
svm analyses
8
cxcr2 tnfsf10
8
tnfsf10 nlrc4
8

Similar Publications

Basal Cell Carcinoma (BCC) and Actinic Keratosis (AK) are prevalent skin conditions with significant health complications. The molecular mechanisms underlying these conditions and their potential shared pathways remain ambiguous despite their prevalence. Therefore, this study aims to elucidate the common molecular pathways and potential therapeutic targets for BCC and AK through comprehensive computational network analysis.

View Article and Find Full Text PDF

Evaluating remyelination compounds for new applications in opioid use disorder management.

J Addict Dis

January 2025

Departments of Anesthesiology and Perioperative Medicine and Pharmacology, Penn State College of Medicine, Hershey, PA, USA.

Opioid use disorder (OUD) is associated with a reduction in brain white matter, affecting critical areas involved in decision-making, impulse control, and reward processing. The FDA has approved several drugs and natural compounds that enhance myelination, targeting oligodendrocyte progenitor cells (OPCs), directly enhancing oligodendrocyte (OL) function, or acting as cofactors for myelin production. This retrospective case study aimed to assess whether current clinical evidence supports the use of myelin-enhancing agents to promote remission in OUD.

View Article and Find Full Text PDF

Occurrence of emerging and persistent organic pollutants in the rivers Cam, Ouse and Thames, UK.

Sci Total Environ

January 2025

Centre for Agroecology Water and Resilience (CAWR), Coventry University, Wolston Lane, Ryton on Dunsmore, CV8 3LG, UK. Electronic address:

The widespread occurrence of new and emerging and persistent organic pollutants (NEPs and POPs) in surface water poses a risk to drinking water supply and consequently human health. The aim of this work was to investigate the occurrence and potential transport of 42 target NEPs and POPs (including per-and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides and bisphenols) along the rural and urban environments of three rivers in England. The type and concentrations of pollutants varied between the sampling days and points.

View Article and Find Full Text PDF

This work reports the synthesis of a copper metal complex with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, and 2,2'-dipyridylamine employing microwave-assisted synthesis (MWAS). To the best of authors knowledge, this is the first study reporting a NSAID-based complex achieved through MWAS. The coordination compound was characterised by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetry, and ultraviolet-visible spectrophotometry.

View Article and Find Full Text PDF

Molecular insights into kinetic stabilization of amorphous solid dispersion of pharmaceuticals.

Phys Chem Chem Phys

January 2025

Department of Physical Chemistry, University of Chemistry and Technology Prague, Technická 5, CZ-166 28 Prague 6, Praha, Czech Republic.

Poor aqueous solubility of crystalline active pharmaceutical ingredients (APIs) restricts their bioavailability. Amorphous solid dispersions with biocompatible polymer excipients offer a solution to overcome this problem, potentially enabling a broader use of many drug candidate molecules. This work addresses various aspects of the design of a suitable combination of an API and a polymer to form such a binary solid dispersion.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!