Identification of MEOX1 as a potential target in metabolic dysfunction-associated steatohepatitis-related liver fibrosis DOI Creative Commons

Xinyue Jiao,

Linying Lai, Yiting Qian

и другие.

The International Journal of Biological Markers, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Background The mechanisms underlying the occurrence and progression of metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis remains poorly understood. This study aims to identify key transcription factors involved in development MASH patients, thereby providing potential targets for drug discovery. Methods Microarray data were retrieved from biopsy specimens patients exhibiting varying stages via Gene Expression Omnibus database. Differentially expressed (DETFs) identified through application Weighted Co-expression Network Analysis. A set vitro vivo experiments conducted investigate role MEOX1 MASH-related fibrosis. To delineate mechanisms, transcriptomic RNA sequencing (RNA-seq), Alphafold, PyMOL used. Results total six DETFs (MEOX1, SOX4, LEF1, SOX9, MYC, CBX2) as being positively correlated with was increased mouse model diet-induced hepatic stellate cells (HSCs) stimulated by transforming growth factor-β1. Knockdown markedly suppressed activation, proliferation, migration HSCs. RNA-Seq analysis serine protease inhibitor family E member 1 (SERPINE1) critical target within protein interaction sites SERPINE1 predicted using Alphafold PyMOL. Conclusion In summary, a pivotal factor, activates HSCs SERPINE1, promoting associated MASH. Inhibition MEOX1-SERPINE1 pathway could offer novel therapeutic avenue treating

Язык: Английский

Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy DOI Creative Commons
Yibo He,

Qianran Hong,

Shiliang Chen

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 3, 2025

Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), tumor-associated macrophages (TAMs), plays key role tumor progression, immune evasion, therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 immunosuppressive M2 phenotypes, with the latter predominating GC contributing outcomes. Recent advancements focus on targeting TAMs, including inhibiting polarization, reprogramming combining TAM-targeted approaches checkpoint inhibitors. Innovations nanotechnology, metabolic reprogramming, pathways such as interleukin-6 C-C motif ligand 2/C-C chemokine receptor 2 further enhance these strategies. However, challenges remain, spatial functional heterogeneity of within TME need for selective avoid disrupting homeostasis. Ongoing research TAM origins, functions, interactions is crucial developing precise effective therapies. These advances hold promise not only improving outcomes but also addressing other cancers similarly complex microenvironments.

Язык: Английский

Процитировано

1
Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells DOI Creative Commons
Wenlu Zhang, Chunyan Xu

Molecular Medicine Reports, Год журнала: 2025, Номер 31(3)

Опубликована: Янв. 23, 2025

Exosomes are small extracellular vesicles that naturally released into body fluids by cells. They rich in bioactive molecules such as proteins. Sphingosine kinase 1 (SphK1) is an important potential drug target for the treatment of cancer due to its functions regulate cell migration, growth, apoptosis and angiogenesis. Tumor exosomes abundantly surround primary tumors, exchanging transferring information between cells modulating progression. Given importance exosomes, involvement exosomal SphK1 from colorectal (CRC) migration these activation hepatic stellate was investigated. Firstly, plasma protein expression, tested ELISA, compared patients with CRC without metastasis those liver metastasis. The results revealed levels were significantly upregulated CRC. Secondly, different expression SphK1, which regulated transfection, isolated evaluate their effect on E‑cadherin vimentin cells, assessed western blotting. demonstrated depletion partially reversed exosome‑induced caused decreased increased levels. Thirdly, effects investigated, α‑SMA, TNF‑α TGF‑β blotting LX‑2 Moreover, AKT phosphorylated (p‑)AKT also activated upregulating p‑AKT, this effect. Furthermore, application agonist inhibition activation, induced SphK1. Finally, investigation viability, analyzed CCK‑8 assay, assessment PCNA a proliferation marker, blot, culture supernatant promoted viability Overall, regulating p‑AKT. This suggests may serve key role potentially

Язык: Английский

Процитировано

0
Prospect of extracellular vesicles in tumor immunotherapy DOI Creative Commons

Wenbo Xia,

Yunhan Tan,

Y.-P. Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 26, 2025

Extracellular vesicles (EVs), as cell-derived small vesicles, facilitate intercellular communication within the tumor microenvironment (TME) by transporting biomolecules. EVs from different sources have varied contents, demonstrating differentiated functions that can either promote or inhibit cancer progression. Thus, regulating formation, secretion, and intake of becomes a new strategy for intervention. Advancements in EV isolation techniques spurred interest EV-based therapies, particularly immunotherapy. This review explores multifaceted various immunotherapy, highlighting their potential vaccines adoptive cell therapy. Furthermore, we explore nanoparticle delivery systems Finally, discuss current state clinical settings future directions, aiming to provide crucial information advance development application treatment.

Язык: Английский

Процитировано

0
Significance of PAI-1 on the development of skin cancer: optimal targets for cancer therapies DOI Creative Commons
Taku Fujimura

Biomedical Journal, Год журнала: 2025, Номер unknown, С. 100850 - 100850

Опубликована: Март 1, 2025

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that plays critical role in cancer progression, particularly skin cancers. PAI-1 widely recognized for its inhibiting fibrinolysis; however, emerging evidence suggests it also contributes to tumor progression through multiple mechanisms, including angiogenesis, immunomodulation, and stromal cell regulation. In the microenvironment (TME), influences tumor-associated macrophages (TAMs) cancer-associated fibroblasts (CAFs), promoting an immunosuppressive environment supports growth therapy resistance. Furthermore, has been implicated regulation of programmed death-ligand 1 (PD-L1) expression via JAK/STAT signaling pathway, thereby influencing immune evasion various The significance as therapeutic target demonstrated melanoma other cutaneous malignancies, where inhibition shown promise overcoming resistance checkpoint inhibitors. Additionally, clinical trials evaluating inhibitors, such TM5614, highlight potential adjunctive angiosarcoma. This review comprehensively explores PAI-1's influence on tumor-stromal interactions, target.

Язык: Английский

Процитировано

0
Identification of MEOX1 as a potential target in metabolic dysfunction-associated steatohepatitis-related liver fibrosis DOI Creative Commons

Xinyue Jiao,

Linying Lai, Yiting Qian

и другие.

The International Journal of Biological Markers, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Background The mechanisms underlying the occurrence and progression of metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis remains poorly understood. This study aims to identify key transcription factors involved in development MASH patients, thereby providing potential targets for drug discovery. Methods Microarray data were retrieved from biopsy specimens patients exhibiting varying stages via Gene Expression Omnibus database. Differentially expressed (DETFs) identified through application Weighted Co-expression Network Analysis. A set vitro vivo experiments conducted investigate role MEOX1 MASH-related fibrosis. To delineate mechanisms, transcriptomic RNA sequencing (RNA-seq), Alphafold, PyMOL used. Results total six DETFs (MEOX1, SOX4, LEF1, SOX9, MYC, CBX2) as being positively correlated with was increased mouse model diet-induced hepatic stellate cells (HSCs) stimulated by transforming growth factor-β1. Knockdown markedly suppressed activation, proliferation, migration HSCs. RNA-Seq analysis serine protease inhibitor family E member 1 (SERPINE1) critical target within protein interaction sites SERPINE1 predicted using Alphafold PyMOL. Conclusion In summary, a pivotal factor, activates HSCs SERPINE1, promoting associated MASH. Inhibition MEOX1-SERPINE1 pathway could offer novel therapeutic avenue treating

Язык: Английский

Процитировано

0