A novel STING variant triggers endothelial toxicity and SAVI disease DOI Creative Commons
Erika Valeri, Sara Breggion, Federica Barzaghi

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(9)

Published: July 2, 2024

Gain-of-function mutations in STING cause STING-associated vasculopathy with onset infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report characterize a novel variant (F269S) identified SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation interferon (IFN) inflammatory pathways across cell types striking prevalence circulating naïve T cells was observed. Inducible F269S expression conferred enhanced signaling through ligand-independent translocation the protein to Golgi, protecting from viral infections but preventing their efficient immune priming. Additionally, endothelial promoted further exacerbated cytokine secretion cells, resulting inflammation damage. Our findings identify mutation as pathogenic causing SAVI, highlight importance crosstalk between context disease, contribute better understanding how aberrant can pathology.

Language: Английский

Network pharmacology and experimental verification based research into the effect and mechanism of Aucklandiae Radix–Amomi Fructus against gastric cancer DOI Creative Commons
Siyuan Song,

Jiayu Zhou,

Ye Li

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 7, 2022

To investigate the mechanism of Aucklandiae Radix-Amomi Fructus (AR-AF) herb pair in treating gastric cancer (GC) by using network pharmacology and experimental verification. Using traditional Chinese medicine system database analysis platform (TCMSP), major active components their corresponding targets were estimated screened out. Cytoscape 3.7.2 software, a visual was established AR-AF GC. Based on STRING online database, protein interaction vital built analyzed. With Database for Annotation, Visualization, Integrated Discovery (DAVID) server, gene ontology (GO) biological processes Kyoto Encyclopedia Genes Genomes (KEGG) signaling pathways target enrichment performed. AutoDock Vina used to perform molecular docking calculate binding affinity. The mRNA expression levels hub analyzed Oncomine, GEPIA, HPA databases TIMER tool, predicted verified qRT-PCR vitro. Eremanthin, cynaropicrin, aceteugenol identified as compounds, AKT1, MAPK3, IL6, MAPK1, well EGFR considered targets. These exerted therapeutic effects GC regulating cAMP pathway, PI3K-Akt pathway. Molecular revealed that these compounds showed good interactions. validation different most results consistent with this paper. confirmed eremanthin could inhibit proliferation AGS reducing As validated results, exerts antitumor through multiple components, targets, pathways, thereby providing novel ideas clues development preparations treatment

Language: Английский

Citations

20
Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data DOI Creative Commons
Lenin González-Paz, Carla Lossada, María Laura Hurtado-León

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(8), P. 8923 - 8939

Published: Feb. 14, 2024

Recent reports have suggested that the susceptibility of cells to SARS-CoV-2 infection can be influenced by various proteins potentially act as receptors for virus. To investigate this further, we conducted simulations viral dynamics using different cellular systems (Vero E6, HeLa, HEK293, and CaLu3) in presence absence drugs (anthelmintic, ARBs, anticoagulant, serine protease inhibitor, antimalarials, NSAID) been shown impact recognition spike protein based on experimental data. Our revealed simulated cell was similar across all tested systems. Notably, CaLu3 exhibited highest infection, due other than ACE2, which may account a significant portion observed susceptibility. Throughout study, compounds showed thermodynamically favorable stable binding protein. Among compounds, anticoagulant nafamostat demonstrated most characteristics terms thermodynamics, kinetics, theoretical antiviral activity, potential safety (toxicity) relation protein-mediated infections lines. This study provides mathematical bioinformatic models aid identification optimal lines compound evaluation detection, particularly studies focused repurposed their mechanisms action. It is important note these observations should experimentally validated, research expected inspire future quantitative experiments.

Language: Английский

Citations

4
A Review for Artificial-Intelligence-Based Protein Subcellular Localization DOI Creative Commons

Hanyu Xiao,

Yijin Zou,

Jieqiong Wang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 409 - 409

Published: March 27, 2024

Proteins need to be located in appropriate spatiotemporal contexts carry out their diverse biological functions. Mislocalized proteins may lead a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where target protein resides within cell will give insights into tailored drug design for As the gold validation standard, conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, biomarker tags subcellular location identification. However, booming era proteomics high-throughput sequencing generates tons newly discovered proteins, making localization by wet-lab experiments mission impossible. To tackle this concern, past decades, artificial intelligence (AI) machine learning (ML), especially deep methods, have made significant progress research area. In article, we review latest advances AI-based method development three typical types approaches, including sequence-based, knowledge-based, image-based methods. We also elaborately discuss existing challenges future directions field.

Language: Английский

Citations

4
Proteomics appending a complementary dimension to precision oncotherapy DOI Creative Commons
Zhaokai Zhou, Ruiqi Zhang,

Aoyang Zhou

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 1725 - 1739

Published: April 21, 2024

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers opportunity to comprehensively analyze molecular signatures plentiful medical or disease pattern cell lines. Along with data analysis and integration, proteomics could be efficiently consolidated employed recognize elementary mechanisms decode individual biomarkers, guiding precision treatment tumors. Herein, we review a broad array progress methods for integration further discuss how better merge medicine clinical settings.

Language: Английский

Citations

4
A novel STING variant triggers endothelial toxicity and SAVI disease DOI Creative Commons
Erika Valeri, Sara Breggion, Federica Barzaghi

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(9)

Published: July 2, 2024

Gain-of-function mutations in STING cause STING-associated vasculopathy with onset infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report characterize a novel variant (F269S) identified SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation interferon (IFN) inflammatory pathways across cell types striking prevalence circulating naïve T cells was observed. Inducible F269S expression conferred enhanced signaling through ligand-independent translocation the protein to Golgi, protecting from viral infections but preventing their efficient immune priming. Additionally, endothelial promoted further exacerbated cytokine secretion cells, resulting inflammation damage. Our findings identify mutation as pathogenic causing SAVI, highlight importance crosstalk between context disease, contribute better understanding how aberrant can pathology.

Language: Английский

Citations

4