Gene expression profiles of precursor cells identify compounds that reduce NRP1 surface expression in macrophages: Implication for drug repositioning for COVID-19 DOI Creative Commons
Akira Iwata, Sarvesh Chelvanambi, Takaharu Asano

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 24, 2024

Coronavirus disease 2019 (COVID-19) is transitioning from a pandemic to an endemic phase through recurring mutations. Initial efforts focused on developing strategies mitigate infection of lung epithelial cells which are the primary targets SARS-CoV-2 virus using affinity spike protein human ACE2 receptor. SARS-CoV-2, however, infects additional cell types present in such as macrophages alternate entry receptor Neuropilin 1 (NRP1). Developing novel therapeutic prevent crucial for immunosurveillance could thus be integral treat post-acute sequelae COVID-19 (PASC). Since traditional drug development process takes long time, it imperative establish new that can rapidly deployed combat dynamic nature evolution and contribute prevention future pandemics. We obtained gene expression profiles THP-1 monocytes L1000-based Connectivity Map CLUE, cloud- based software platform analysis perturbational datasets identify compounds reduce level NRP1. Out 33,590 compounds, we analyzed 45 their ability NRP1 expression. selected top five small molecule inhibitors predicted decrease validation studies. All showed low cytotoxicity at tested doses surface was evaluated monocytes, THP-1-derived macrophage like peripheral blood mononuclear (PBMC)-derived macrophages. Five with largest reduction decreased measured flow cytometry fluorescent microscopy assays both line Using our computational approach, identified potentially effect monocytes. Validation studies approach help repositioning target absent L1000 database. Our proposed applicable rapid compound exploration provide molecular bases drugs.

Language: Английский

Parps in immune response: Potential targets for cancer immunotherapy DOI
S Wang,

Jingling Huang,

T. X. Zeng

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 234, P. 116803 - 116803

Published: Feb. 16, 2025

Language: Английский

Citations

2
Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery DOI Creative Commons
Xin Li, Yongcheng Song

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 29(1), P. 103832 - 103832

Published: Nov. 16, 2023

Language: Английский

Citations

12
PAR level mediates the link between ROS and inflammatory response in patients with type 2 diabetes mellitus DOI Creative Commons
Michele Zampieri,

Katsiaryna Karpach,

Gerardo Salerno

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103243 - 103243

Published: June 18, 2024

Type 2 diabetes mellitus (T2DM) is characterized by disrupted glucose homeostasis and metabolic abnormalities, with oxidative stress inflammation playing pivotal roles in its pathophysiology. Poly(ADP-ribosyl)ation (PARylation) a post-translational process involving the addition of ADP-ribose polymers (PAR) to target proteins. While preclinical studies have implicated PARylation interplay between T2DM, direct clinical evidence humans remains limited. This study investigates relationship stress, PARylation, inflammatory response T2DM patients.

Language: Английский

Citations

4
Interactions between NAD+ metabolism and immune cell infiltration in ulcerative colitis: subtype identification and development of novel diagnostic models DOI Creative Commons

Linglin Tian,

Huiyang Gao,

Yao Tian

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa with increasing incidence worldwide. Growing evidence highlights pivotal role nicotinamide adenine dinucleotide (NAD+) metabolism in UC pathogenesis, prompting our investigation into subtype-specific molecular underpinnings and diagnostic potential NAD+ metabolism-related genes (NMRGs). Transcriptome data from patients healthy controls were downloaded GEO database, specifically GSE75214 GSE87466. We performed unsupervised clustering based on differentially expressed (DE-NMRGs) to classify cases distinct subtypes. GSEA GSVA identified biological pathways active within these subtypes, while CIBERSORT algorithm assessed differential immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) combined expression was used pinpoint specific NMRGs UC. Robust features for subtyping diagnosis selected using two machine learning algorithms. Nomograms constructed their effectiveness evaluated receiver operating characteristic (ROC) curves. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) conducted verify lines. In study, classified subtypes DE-NMRGs levels, Cluster A exhibiting enhanced self-repair capabilities during responses B showing greater inflammation tissue damage. Through comprehensive bioinformatics analyses, we four key biomarkers (AOX1, NAMPT, NNMT, PTGS2) subtyping, (NNMT, PARP9) its diagnosis. These are closely linked various cells microenvironment, particularly NAMPT PTGS2, which strongly associated neutrophil developed demonstrated high predictive accuracy, achieving area under curve (AUC) values up 0.989 0.997 training set 0.998 0.988 validation sets. RT-qPCR showed significant upregulation NNMT PARP9 inflamed versus normal epithelia, underscoring relevance. Our study reveals UC, identifying findings could suggest therapeutic targets contribute advancing personalized treatment strategies potentially improving patient outcomes.

Language: Английский

Citations

0
Structure and function of vimentin in the generation and secretion of extracellular vimentin in response to inflammation DOI Creative Commons
Zhiyao Yuan, Paul A. Janmey, Christopher A. McCulloch

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 18, 2025

The canonical functions of vimentin in cell mechanics and migration have been recently expanded by the discovery new roles for extracellular (ECV) immune responses to infection, injury cancer. In contrast with predominantly filamentous form intracellular vimentin, ECV exists largely as soluble oligomers. release from intact cells is dependent on mechanisms that regulate assembly disassembly which are influenced discrete post-translational modifications. this review we highlight processes promote conversion insoluble filaments secretion mechanisms. Insights into regulation stromal could provide diagnostic therapeutic approaches assessing controlling inflammatory diseases.

Language: Английский

Citations

0
PARP9 affects myocardial function through TGF-β/Smad axis and pirfenidone DOI Creative Commons
Nannan Chen, Lianzhi Zhang, Zhong Zhang

et al.

Biomolecules and Biomedicine, Journal Year: 2024, Volume and Issue: 24(5), P. 1199 - 1215

Published: March 9, 2024

Cardiac arrhythmias are often linked to the overactivity of cardiac fibroblasts (CFs). Investigating impact poly (ADP-ribose) polymerase 9 (PARP9) on Angiotensin II (Ang II)-induced fibroblast activation and therapeutic effects pirfenidone (PFD) offers valuable insights into arrhythmias. This study utilized weighted gene co-expression network analysis (WGCNA), differential expression (DEG) analysis, protein–protein interaction (PPI), receiver operating characteristic (ROC) GSE42955 dataset identify hub with a significant diagnostic value. The ImmuCellAI tool revealed an association between PARP9 immune cell infiltration. Our in vitro assessments focused influence PFD myofibroblast differentiation, transforming growth factor-beta (TGF-β) expression, Ang II-induced proliferation migration CFs. Additionally, we explored fibrosis markers TGF-β/Smad signaling pathway context overexpression. Analysis as central high clinical value, seven types cells. studies demonstrated that significantly mitigates CF proliferation, migration, fibrosis. It also reduces decreases markers, including TGF-β, collagen I, III, α-SMA. Notably, overexpression can partially counteract PFD’s inhibitory CFs modify fibronectin, CTGF, α-SMA, MMP2, MMP9, p-Smad2/3 pathway. In summary, our findings suggest effectively counteracts adverse fibrosis, modulates expression. identifies potential approach for managing myocardial

Language: Английский

Citations

1
Pathological and physiological roles of ADP-ribosylation: established functions and new insights DOI
Karla L. H. Feijs, Nonso Josephat Ikenga, Roko Žaja

et al.

Biological Chemistry, Journal Year: 2024, Volume and Issue: 405(9-10), P. 567 - 581

Published: July 26, 2024

Abstract The posttranslational modification of proteins with poly(ADP-ribose) was discovered in the sixties. Since then, we have learned that enzymes involved, so-called poly(ADP-ribosyl)polymerases (PARPs), are transferases which use cofactor NAD + to transfer ADP-ribose their targets. Few PARPs able create poly(ADP-ribose), whereas majority transfers a single ADP-ribose. In last decade, hydrolases were reverse mono(ADP-ribosyl)ation, detection methods developed and new substrates defined, including nucleic acids. Despite continued effort, relatively little is still known about biological function most PARPs. this review, summarise key functions ADP-ribosylation introduce emerging insights.

Language: Английский

Citations

1
Gene expression profiles of precursor cells identify compounds that reduce NRP1 surface expression in macrophages: Implication for drug repositioning for COVID-19 DOI Creative Commons
Akira Iwata, Sarvesh Chelvanambi, Takaharu Asano

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 24, 2024

Coronavirus disease 2019 (COVID-19) is transitioning from a pandemic to an endemic phase through recurring mutations. Initial efforts focused on developing strategies mitigate infection of lung epithelial cells which are the primary targets SARS-CoV-2 virus using affinity spike protein human ACE2 receptor. SARS-CoV-2, however, infects additional cell types present in such as macrophages alternate entry receptor Neuropilin 1 (NRP1). Developing novel therapeutic prevent crucial for immunosurveillance could thus be integral treat post-acute sequelae COVID-19 (PASC). Since traditional drug development process takes long time, it imperative establish new that can rapidly deployed combat dynamic nature evolution and contribute prevention future pandemics. We obtained gene expression profiles THP-1 monocytes L1000-based Connectivity Map CLUE, cloud- based software platform analysis perturbational datasets identify compounds reduce level NRP1. Out 33,590 compounds, we analyzed 45 their ability NRP1 expression. selected top five small molecule inhibitors predicted decrease validation studies. All showed low cytotoxicity at tested doses surface was evaluated monocytes, THP-1-derived macrophage like peripheral blood mononuclear (PBMC)-derived macrophages. Five with largest reduction decreased measured flow cytometry fluorescent microscopy assays both line Using our computational approach, identified potentially effect monocytes. Validation studies approach help repositioning target absent L1000 database. Our proposed applicable rapid compound exploration provide molecular bases drugs.

Language: Английский

Citations

1