Dynamic Proteome and Phosphoproteome Profiling Reveals Regulatory Mechanisms in LPS-Stimulated Macrophage Inflammatory Responses

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151341 - 151341

Published: Jan. 1, 2025

Language: Английский

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Inhibition of anti-tumour reactivity of immune cells in the salivary gland cancer: A proteomic approach

Oral Oncology Reports, Journal Year: 2024, Volume and Issue: 9, P. 100160 - 100160

Published: Jan. 10, 2024

Adenoid cystic carcinoma (ACC), mucoepidermoid (MEC), and oral squamous cell (OSCC) respond differently to immunotherapy. Pembrolizumab, an immune checkpoint inhibitor, has been approved by the Food Drug Administration for treatment of carcinomas head neck region. While MEC shown some response pembrolizumab; however, ACC is least responsive. At molecular level, cancers produce immunosuppressive molecules, resulting in evasion. Therefore, we hypothesised that salivary gland cancer cells a higher number proteins cause suppression system's anti-tumour reactivity. To determine differential protein expressions OSCC, MEC, ACC, constructed cancer–immune co-culture models using different cells. We performed SWATH, proteome profilers, gene ontology biological function, functional annotation clustering interaction network analysis all samples models. Analysis acquired data showed overexpressed OSCC participated more metabolic process, while cells, processes, pathway. Upon function found negatively affecting process pathway proteins. Overall, conclude less responsive immunotherapy, possibly because high presence However, further needed verify functions interactive partners each differentially expressed

Language: Английский

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O‐GlcNAcylation: cellular physiology and therapeutic target for human diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(6)

Published: Dec. 1, 2023

Abstract O‐linked‐β‐N‐acetylglucosamine (O‐GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O‐GlcNAc transferase and O‐GlcNAcase, primarily targeting serine or threonine residues in various proteins. This impacts functionality, influencing stability, protein–protein interactions, localization. Its interaction with other modifications such as phosphorylation ubiquitination becoming increasingly evident. Dysregulation O‐GlcNAcylation associated numerous human diseases, including diabetes, nervous system degeneration, cancers. review extensively explores regulatory mechanisms O‐GlcNAcylation, its effects on cellular physiology, role pathogenesis diseases. It examines implications aberrant diabetes tumorigenesis, highlighting novel insights into potential cardiovascular The also discusses interplay impact cell growth metabolism. By synthesizing current research, this elucidates multifaceted roles providing comprehensive reference for future studies. underscores cycle developing therapeutic strategies pathologies.

Language: Английский

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Artemyriantholides A–K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity

Phytochemistry, Journal Year: 2024, Volume and Issue: 222, P. 114100 - 114100

Published: April 16, 2024

Language: Английский

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Identification of Biomarkers of Arrhythmogenic Cardiomyopathy (ACM) by Plasma Proteomics

Medicina, Journal Year: 2025, Volume and Issue: 61(1), P. 105 - 105

Published: Jan. 13, 2025

Background and Objectives: The pathophysiology of arrhythmogenic cardiomyopathy (ACM), previously known as right ventricular (ARVC), its specific biological features remain poorly understood. High-throughput plasma proteomic profiling, a powerful tool for gaining insights into disease at the systems biology level, has not been used to study ACM. This aimed characterizing plasmatic protein changes in patients with ACM, which were compared those healthy controls, exploring potential role identified proteins biomarkers diagnosis monitoring. Materials Methods: Blood samples collected from six ACM patients, four other cardiomyopathies, two controls. Plasma was processed remove high-abundance analyzed by two-dimensional gel electrophoresis. Differential expressions assessed using PDQuest software, Bio-Rad US version 8.0.1. Results: analysis revealed several altered between including plakophilin-2, junctional plakoglobin, desmoplakin, desmin, transmembrane 43, lamin A/C. Conclusions: profiling suggests that is distinct entity characterized unique dysregulation desmosomal proteins. identification associated underscores their improve diagnostic accuracy facilitate early intervention strategies. Further exploration mutations phosphorylation states may provide deeper

Language: Английский

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Sensitive and Deep Coverage Phosphoproteome Detection Method Reveals Spleen as a More Sensitive Organ than Liver in Early Detection of Liver Fibrosis-Related Signaling Protein Dysregulation

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Although cathepsin S is transported from the spleen to liver, where it cleaves collagen XVIII produce endostatin and plays a critical role in onset of early liver fibrosis, relationship between fibrosis function remains underexplored. Given roles phosphorylation disease, understanding its regulatory mechanism crucial. Despite advances mass spectrometry enhancing phosphoproteomics, application limited by small clinical samples subtle protein changes. We optimized phosphoproteomic workflow, adjusting amounts using different enrichment beads varied spectrometers, achieving deep coverage minimal samples. identified over 46,000 phosphosites HepG2 cells 29,000 mouse just 500 μg proteins. Even with as little 50 293T proteins, we detected 11,000 phosphosites, 1.2 times more than recently reported RUPE-phospho. Using Sensitive Deep Coverage Phosphoproteome Detection method, abbreviated SDC-PhosDet, demonstrated that exhibits rapid sensitive changes affecting proteins closely linked signaling metabolism such STAT1, JUN, CBL, ATP7B, PTPN2. These findings highlight spleen's offer new avenues for investigating molecular mechanisms diagnosis, intervention beyond itself. Moreover, this method holds promise applying phosphoproteomics early-stage microsamples.

Language: Английский

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Identification of signaling networks associated with lactate modulation of macrophages and dendritic cells

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e42098 - e42098

Published: Jan. 1, 2025

The advancement in the understanding of cancer immune evasion has manifested development immunotherapeutic approaches such as checkpoint inhibitors and interleukin agonists. Although immunotherapy breakthroughs have demonstrated improved potency for treatment, only a fraction patients effectively respond to these treatments. Moreover, there is compelling evidence indicating that cells develop unique microenvironment through adaptive metabolic reprogramming, which aberrantly modulates host immunity evade immunosurveillance. As part tumor cell switch, lactate produced released into environment. Recent studies shown significantly functions, especially innate cells. Dendritic (DCs) macrophages (MΦs) are specialized antigen-presenting serving key players anticancer-associated responses. most affects phenotypes (e.g., surface protein expression cytokine production), signaling network mediated by not fully understood. In present study, we identified pathways bone marrow-derived DCs MΦs were changed cancer-relevant concentrations lactate. First, transcriptome analysis was used guide notable Subsequently, biomolecular techniques, including immunoblotting, flow cytometry, immunofluorescence imaging performed corroborate changes at level. results indicated differentially impacted biochemical networks MΦs. While mainly altered STAT3, ERK, p38 MAPK cascades DCs, STAT1 GSK-3β major This study identifies lactate, advances our interplay between immunity.

Language: Английский

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Conservation of OFD1 Protein Motifs: Implications for Discovery of Novel Interactors and the OFD1 Function

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1167 - 1167

Published: Jan. 29, 2025

OFD1 is a protein involved in many cellular processes, including cilia biogenesis, mitotic spindle assembly, translation, autophagy and the repair of double-strand DNA breaks. Despite potential interactors identified high-throughput studies, only few have been directly confirmed with their binding sites identified. We performed an analysis evolutionary conservation sequence three clades: 80 Tetrapoda, 144 Vertebrata or 26 Animalia species, 59 protein-binding motifs localized regions conserved various clades. Our results indicate that contains 14 post-translational modification (PTM) targeted by at least eight kinases, seven bound proteins recognizing phosphorylated aa residues site for phosphatase 2A. Moreover, harbors both motif enables its phosphorylation mitogen-activated kinases (MAPKs) specific docking these proteins. Generally, our suggest forms scaffold interaction tightly regulated PTMs ligands. Future research on should focus regulation function localization.

Language: Английский

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Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Conditional control of protein activity is important in order to elucidate the particular functions and interactions proteins, their regulators, substrates, as well impact on behavior a cell or organism. Optical provides perhaps optimal means introducing spatiotemporal over function it allows for tunable, rapid, noninvasive activation its native environment. One method optical through introduction photocaged photoswitchable noncanonical amino acids (ncAAs) genetic code expansion cells animals. Genetic incorporation photoactive ncAAs at key residues tool activation, sometimes deactivation, activity. Importantly, site can typically be rationally selected based structural, mechanistic, computational information. In this review, we comprehensively summarize applications lysine, tyrosine, cysteine, serine, histidine, glutamate, aspartate derivatives, phenylalanine analogues. The extensive diverse list proteins that have been placed under demonstrates broad applicability methodology.

Language: Английский

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Berries as Nature’s Therapeutics: Exploring the Potential of Vaccinium Metabolites in Gastric Cancer Treatment Through Computational Insights

Life, Journal Year: 2025, Volume and Issue: 15(3), P. 406 - 406

Published: March 5, 2025

Berries from the Vaccinium genus, known for their rich array of bioactive metabolites, are recognized antioxidant, anti-inflammatory, and anticancer properties. These compounds, including anthocyanins, flavonoids, phenolic acids, have attracted significant attention potential health benefits, particularly in cancer prevention treatment. Gastric (GC), a leading cause cancer-related deaths worldwide, remains challenging to treat, especially its advanced stages. This study investigates therapeutic species GC treatment using computational methods. RNA sequencing revealed upregulated genes associated with GC, while network pharmacology molecular docking approaches identified strong interactions between cyanidin 3-O-glucoside (C3G), key metabolite. Furthermore, dynamics simulations HSP90AA1-C3G complex demonstrated stable binding structural integrity, suggesting that C3G may inhibit HSP90AA1, protein involved progression. findings highlight offering novel approach by targeting pathways. research provides valuable insights into role berries as natural therapeutics, supporting integration future gastric strategies.

Language: Английский

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