A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(2), P. 98 - 120

Published: June 28, 2023

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific changes underlying mechanism aging in higher vertebrates remain incompletely characterized. Here, we constructed first single-nucleus transcriptomic landscape primate aging, which resolved gene expression fluctuation hepatocytes across three zonations detected aberrant cell-cell interactions between niche cells. Upon in-depth dissection this rich dataset, identified impaired lipid metabolism upregulation chronic inflammation-related genes prominently associated with declined functions during aging. In particular, hyperactivated sterol regulatory element-binding protein (SREBP) signaling was a hallmark aged liver, consequently, forced activation SREBP2 human primary recapitulated vivo phenotypes, manifesting as detoxification accelerated cellular senescence. This study expands our knowledge informs development diagnostics therapeutic interventions for

Language: Английский

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Unveiling the human nitroproteome: Protein tyrosine nitration in cell signaling and cancer

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(8), P. 105038 - 105038

Published: July 12, 2023

Covalent amino acid modification significantly expands protein functional capability in regulating biological processes. Tyrosine residues can undergo phosphorylation, sulfation, adenylation, halogenation, and nitration. These post-translational modifications (PTMs) result from the actions of specific enzymes: tyrosine kinases, tyrosyl-protein sulfotransferase(s), adenylate transferase(s), oxidoreductases, peroxidases, metal-heme containing proteins. Whereas sulfation adenylation modify hydroxyl group tyrosine, halogenation nitration target adjacent carbon residues. Because aberrant has been associated with human disorders animal models disease, we have created an updated curated database 908 nitrated We also analyzed this new resource to provide insight into role cancer biology, area that not previously considered detail. Unexpectedly, found 879 1,971 known sites are phosphorylation suggesting extensive for cell signaling. Overall, review offers several forward-looking opportunities future research perspectives understanding biology.

Language: Английский

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Molecular Genetics of Abnormal Redox Homeostasis in Type 2 Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4738 - 4738

Published: March 1, 2023

Numerous studies have shown that oxidative stress resulting from an imbalance between the production of free radicals and their neutralization by antioxidant enzymes is one major pathological disorders underlying development progression type 2 diabetes (T2D). The present review summarizes current state art advances in understanding role abnormal redox homeostasis molecular mechanisms T2D provides comprehensive information on characteristics biological functions enzymes, as well discusses genetic conducted so far order to investigate contribution polymorphisms genes encoding state-regulating disease pathogenesis.

Language: Английский

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Using the Reactome Database

Current Protocols, Journal Year: 2023, Volume and Issue: 3(4)

Published: April 1, 2023

Abstract Pathway databases provide descriptions of the roles proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway‐centric views these may allow for discovery unexpected functional relationships in data such as gene expression profiles somatic mutation catalogues from tumor cells. For this reason, there is a high demand high‐quality pathway associated tools. The Reactome project (a collaboration between Ontario Institute Cancer Research, New York University Langone Health, European Bioinformatics Institute, Oregon Health & Science University) one database. collects detailed information on pathways processes humans primary literature. content manually curated, expert‐authored, peer‐reviewed spans gamut simple intermediate metabolism to signaling complex events. This supplemented with likely orthologous reactions mouse, rat, zebrafish, worm, model organisms. © 2023 Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1 : Browsing 2 Exploring annotations disease drugs 3 Finding involving or protein Alternate using UniProtKB (SwissProt), Ensembl, Entrez identifier Using advanced search 4 analysis tool identify statistically overrepresented 5 overlay onto diagrams 6 Comparing inferred organism human Species Comparison 7 tissue‐specific Tissue Distribution

Language: Английский

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Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 755, P. 109965 - 109965

Published: March 27, 2024

Language: Английский

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Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 26, 2024

Abstract Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased fragility fracture susceptibility. Our study aims to investigate the potential of kaempferol preventing treating OP through combination network pharmacology molecular experiments. Kaempferol OP-related targets were retrieved from public database. A protein–protein interaction (PPI) common was constructed using STRING database visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO KEGG therapeutic conducted Hiplot platform. Molecular docking performed operating environment (MOE) software, cell experiments validate mechanism OP. Network analysis identified 54 overlapping between OP, 10 core identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, AGE/RAGE pathway, TNF pathway. results indicated stable binding two target proteins, AKT1 MMP9. In vitro demonstrated significant upregulation expression MC3T3-E1 cells ( p < 0.001) treatment, along downregulation MMP9 0.05) compared control group. This predicted treatment pharmacology, validated these findings experiments, suggesting promising avenue future clinical

Language: Английский

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Unraveling the therapeutic potential of quercetin and quercetin-3-O-glucuronide in Alzheimer's disease through network pharmacology, molecular docking, and dynamic simulations

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 27, 2024

Abstract Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. plays significant role in neuroinflammation, which helps reduce Alzheimer's disease (AD) severity. (Q) quercetin 3-O-glucuronide (Q3OG) are some of the most potent antioxidants available from natural sources. However, form converted into Q3OG when reacted intestinal microbes. The study aims to ensure potential Q Q3OG. In this study, molecular targets were first identified using Swiss Target Prediction platform pathogenic AD DisGeNET database. Followed by compound target overlapping, 77 placed that AKT1, EGFR, MMP9, TNF, PTGS2, MMP2, IGF1R, MCL1, MET PARP1 was top-ranked target, estimated CytoHubba plug-in. Molecular docking performed for towards PDB:1UNQ target. binding score − 6.2 kcal/mol 6.58 respectively. dynamics simulation conducted at 200 ns. This study's results help identify multiple sites bioactive compounds. Thus, synthesizing new chemical entity-based on structural modification may aid eradicating complications.

Language: Английский

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Aspartame carcinogenic potential revealed through network toxicology and molecular docking insights

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 20, 2024

Abstract The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects mechanisms of aspartame ( l -α-aspartyl- -phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods beverages globally. In recent years, its safety issues, particularly risk, have garnered widespread attention. study first constructed an interaction map with gastric cancer targets using methods identified key pathways. Preliminary validation was conducted through microarray data analysis survival analysis, were further binding affinity modes action proteins. findings suggest that has impact various cancer-related proteins, potentially raising likelihood cellular carcinogenesis by interfering biomolecular function. Furthermore, found patterns pathways aspartame-related are like known pathways, supporting scientific hypothesis carcinogenicity. However, given complexity vivo environment, we also emphasize necessity validating these molecular-level actual biological systems. introduces fresh method for evaluating food enhancers provides theoretical foundation shaping public health regulations.

Language: Английский

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Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2343 - 2343

Published: July 19, 2024

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role mechanism HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover beneficial effects its detailed UC. Experimental was induced by 2.5% dextran sodium sulfate (DSS) for seven days. ameliorated DSS-induced mice, showing marked improvement weight loss, colon length, colonic pathological severity, levels TNFα IL6 serum. A combination informatics, network pharmacology, molecular docking identified eight key targets multi-pathways influenced As highlight, experimental validation demonstrated that PTGS2, marker ferroptosis, along other indicators ferroptosis (such as ACSL4, Gpx4, lipid peroxidation), were regulated vivo vitro. Additionally, supplement increased diversity gut microbiota, decreased relative abundance Proteobacteria Gammaproteobacteria, restored bacteria (Lachnospiraceae_NK4A136_group Prevotellaceae_UCG-001). In conclusion, an effective nutritional against suppressing modulating microbiota.

Language: Английский

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Novel perspective on particulate matter and Alzheimer's disease: insights from adverse outcome pathway framework

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 125601 - 125601

Published: Jan. 1, 2025

Language: Английский

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