Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 24, 2024

Abstract Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of tumor mass. This supports survival growth cancerous plays a critical role in response immune therapy. There is untapped potential targeting cell-ECM interactions improve existing therapy explore novel therapeutic strategies. The most abundant proteins collagen family. 28 different subtypes undergo several post-translational modifications (PTMs), which alter both their structure functionality. Here, we review current knowledge on composition consequences PTMs affecting receptor binding, cell migration stiffness. Furthermore, discuss how these alterations impact responses could be targeted treat cancer.

Language: Английский

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Collagen fibers quantification for liver fibrosis assessment using linear dichroism photoacoustic microscopy

Photoacoustics, Journal Year: 2025, Volume and Issue: 42, P. 100694 - 100694

Published: Feb. 3, 2025

Liver fibrosis represents a progressive pathological condition that can culminate in severe hepatic dysfunction, potentially advancing to cirrhosis and liver cancer. The extent of is intrinsically associated with the quantity collagen fibers. Although biopsy ultrasound imaging are standard diagnostic tools, their application constrained by risks significant complications variability different investigators, respectively. In this study, we utilized linear dichroism photoacoustic microscopy (LDPAM) visualize quantify fibers, which exhibit specific absorption polarized light, subsequently calculating fibers degree (CDOD) score. We obtained high-resolution images structures, an emphasis on within tissue. Using CDOD score, categorized into three distinct stages: normal, early, advanced. For validation purposes, were visualized Sirius-red staining quantitatively assessed through proportional area (CPA) Our results demonstrated correlation between CPA scores, Pearson coefficient 0.95. This approach presents promising non-invasive method for assessing quantifying

Language: Английский

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SIRT3: A potential therapeutic target for liver fibrosis

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 257, P. 108639 - 108639

Published: March 30, 2024

Language: Английский

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Investigating the Antifibrotic Effects of β-Citronellol on a TGF-β1-Stimulated LX-2 Hepatic Stellate Cell Model

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 800 - 800

Published: July 5, 2024

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup extracellular matrix components. This progressive condition significantly raises risk severe diseases like cirrhosis and hepatocellular carcinoma. The lack approved therapeutics underscores urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets drug discovery. study investigated potential Citrus hystrix DC. (KL) its bioactive compound, β-citronellol (β-CIT), human HSC cell line (LX-2). Cells exposed to TGF-β1 induce fibrogenesis were co-treated with crude KL extract β-CIT. Gene expression was analyzed real-time qRT-PCR assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). release metalloproteinase 9 (MMP-9) measured ELISA. Proteomic analysis molecular docking identified signaling proteins modeled protein–ligand interactions. results showed that both β-CIT suppressed activation MMP-9 levels. MAPK pathway emerged as target demonstrates ability inhibit during TGF-β1-induced suggesting role anti-hepatic fibrosis therapies.

Language: Английский

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Advances in intrahepatic and extrahepatic vascular dysregulations in cirrhotic portal hypertension

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 31, 2025

Cirrhotic portal hypertension, the most prevalent and clinically significant complication of liver cirrhosis, manifests as elevated venous pressure is associated with severe complications. Although much research on mechanisms hypertension has focused fibrosis, less attention been given to role intrahepatic extrahepatic vascular dysfunction, particularly respect vasculature. While hepatic fibrosis in cirrhotic undeniable, underlying involving vasculature are highly complex. Sinusoidal capillarization endothelial dysfunction contribute increased resistance. Hemodynamic changes circulation, including splanchnic vasodilation hyperdynamic play a development hypertension. Additionally, therapeutic strategies targeting these diverse, improvement sinusoidal microcirculation, therapies stellate cells activation, pharmacological modulation systemic tone. Therefore, this review, we will discuss vascular-related treatment progress cirrhosis provide new theoretical basis practical guidance for clinical treatment.

Language: Английский

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Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Biochemical and histological analysis of collagen content in lungs, liver and kidneys of rats treated with Beta vulgaris L. var. cicla

Acta Medica Nicomedia, Journal Year: 2025, Volume and Issue: 8(1), P. 76 - 83

Published: Feb. 28, 2025

Objective: Collagen is a fundamental component of the extracellular matrix (ECM) and plays critical role in organ structure, cellular functions, wound healing. Beta vulgaris L. var. cicla (chard) known for its diverse bioactive compounds, including vitamins, flavonoids, nitrates. Chard has been associated with numerous health benefits, such as antioxidant, anti-inflammatory, antidiabetic effects. This study investigates impact chard on collagen content vital organs, specifically lungs, liver, kidneys. Methods: The rats divided into two groups: control given group. extract was administered to at dose 100 mg/kg per day 7 days. On 8th day, were sacrificed, tissues from kidneys, liver collected. measured using both biochemical histological analyses. Results: administration exhibited tissue-specific effects content: it increased decreased significantly, had no effect kidney collagen. These changes supported by results lungs kidneys; however, significant observed liver. varied might be related differences metabolism regulatory mechanisms across tissues. Conclusion: findings suggest that chard, due distinct synthesis ECM remodeling, holds promise potential therapeutic agent applications healing, tissue strengthening, antifibrotic therapy. Further studies underlying these are necessary fully understand clinical applications.

Language: Английский

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Skullcapflavone II induces G2/M phase arrest in hepatic stellate cells and suppresses hepatic fibrosis

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177522 - 177522

Published: March 1, 2025

Language: Английский

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Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation

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

Published: April 10, 2025

Glutathione peroxidase 3 (GPX3) is a strong antioxidant. While elevated GPX3 levels are linked to diverse pathologies, its role in liver failure (LF) remains underexplored. This study investigates GPX3's diagnostic potential and mechanistic contributions LF pathogenesis. We integrated two high-quality tissue datasets (GSE38941 GSE14668) from the Gene Expression Omnibus (GEO) database. Ontology Kyoto Encyclopedia of Genes Genomes analyses were conducted identify biomarkers associated with failure. The Comparative Toxicogenomics Database was used predict function GPX3. In addition, our study, we verified target gene mRNA expression level 40 patients acute or chronic (ACHBLF) by RT-QCPR experiment detect methylation status promoter ACHBLF specific PCR (MSP). results demonstrate that drives pathogenic mechanisms through oxidative stress-related pathways (e.g., collagen cross-linking, extracellular matrix remodeling) immune dysregulation macrophage activation, PD-1/CTLA-4 signaling). CPX8, PRDX6, GPX4, GSS, GSR, TXN, GPX7, PPARGC1A, ALOX15, ALOX5 have been identified as key immune-related genes. Furthermore, there significant differences cell infiltration between high low groups groups. Immune analysis demonstrated correlations markers (p < 0.05), suggesting modulating inflammatory responses. Additionally, increased susceptibility aerosols, cyclosporin dexamethasone observed much higher than other patients, group methylated had mortality those without. conclusion, promising biomarker for Its may serve prognostic indicator, highlighting therapeutic potential.

Language: Английский

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Traditional Chinese Medicine targeting the TGF-β/Smad signaling pathway as a potential therapeutic strategy for renal fibrosis

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

Published: May 20, 2025

Renal fibrosis (RF) is an inevitable outcome of nearly all progressive chronic kidney diseases (CKD). However, effective therapies that can halt or reverse the development RF and CKD progression remain limited. Traditional Chinese Medicine (TCM) offers a unique therapeutic approach, demonstrating significant anti-fibrotic potential through its antioxidant anti-inflammatory pharmacological properties. comprehensive reviews focusing on role TCM in targeting signaling pathways associated with are still scarce. In this review, literature was screened according to clarity relevance TCM, including types mechanisms TCM. We summarize pivotal TGF-β/Smad pathway provide overview single botanical drug, their active ingredients, compounds ameliorate by modulating pathway, aiming establish solid foundation for future basic clinical research field RF. While holds advantages treating RF, limitations need be addressed scientific technological innovation. Future studies will focus elucidating mechanisms, improving quality control, validating efficacy, fostering international collaboration promote global application modern medicine.

Language: Английский

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