Therapeutic implications of endoplasmic reticulum stress gene CCL3 in cervical squamous cell carcinoma

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 20, 2025

This study investigated ERS-related gene expressions in CESC, identifying two molecular subtypes, P1 and P2, constructing a precise prognostic model based on these subtypes. TCGA's whole-genome expression profiles were used to recognize subtypes through the ConsensusClusterPlus method, further refining models with univariate Lasso Cox regression analyses validated by GSE39001 dataset. The analyzed distribution of ERS marker genes within T cell subgroups using scRNA-seq data (GSE168652), highlighting diversity. critical role CCL3 was examined explicitly CD8 + cells from healthy individuals CESC patients. Elevated levels observed patients' compared controls. Functional experiments involving knockdown overexpression HeLa SiHa lines conducted investigate its impact proliferation, migration, invasion. These findings subsequently nude mouse model. results demonstrated that suppressing inhibited invasion significantly, while promoted processes. In model, silencing reduced tumor growth decreased Ki-67 labeling tissues, indicating therapeutic potential targeting treatment, possibly regulation. contributes new assessment tools personalized treatment options for patients, paving way more targeted therapies discovering gene, presenting significant clinical implications.

Language: Английский

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Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 3, 2025

Pluripotent stem cells (PSCs) possess the extraordinary capability to differentiate into a variety of cell types. This is tightly regulated by epigenetic mechanisms, particularly histone modifications. Moreover, reprogramming somatic or fate-committed induced pluripotent (iPSCs) largely relies on these modifications, such as methylation and acetylation histones. While extensive research has been conducted utilizing mouse models, significance modifications in human iPSCs gaining increasing recognition. Recent studies underscore importance regulators both process regulation cancer (CSCs), which are pivotal tumor initiation development treatment resistance. review elucidates dynamic alterations that impact emphasizes necessity for balance between activating repressive marks. These marks influenced enzymes DNA methyltransferases (DNMTs) deacetylases (HDACs). Furthermore, this explores therapeutic strategies aimed at targeting enhance efficacy while advancing understanding pluripotency reprogramming. Despite promising developments creation inhibitors histone-modifying enzymes, challenges selectivity therapy resistance continue pose significant hurdles. Therefore, future endeavors must prioritize biomarker-driven approaches gene-editing technologies optimize therapies.

Language: Английский

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Integration of single-nuclei and spatial transcriptomics to decipher tumor phenotype predictive of relapse-free survival in Wilms tumor

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

Published: March 3, 2025

Background Wilms tumor (WT) is the most common childhood renal malignancy, with recurrence linked to poor prognosis. Identifying molecular features of phenotypes that drive and discovering novel targets are crucial for improving treatment strategies enhancing patient outcomes. Methods Single-nuclei RNA sequencing (snRNA-seq), spatial transcriptomics (ST), bulk RNA-seq, mutation/copy number data were curated from public databases. The Seurat package was used process snRNA-seq ST data. Scissor analysis applied identify subpopulations associated relapse-free survival (RFS). Univariate Cox LASSO analyses utilized reduce features. A prognostic ensemble machine learning model developed. Immunohistochemistry validate expression key in tissues. CellChat Commot infer cellular interactions. PERCEPTION computational pipeline predict response cells chemotherapy targeted therapies. Results By integrating RNA-seq data, we identified a subtype Scissor+ RFS, predominantly derived cap mesenchyme-like blastemal fibroblast-like subgroups. These displayed nephron progenitor signatures cancer stem cell markers. constructed based on signature accurately RFS. TGFA as significant feature this validated by immunohistochemistry. Cellular communication revealed strong associations between cancer-associated fibroblasts (CAFs) through IGF, SLIT, FGF, PDGF pathways. primarily located immune-desert niche surrounded CAFs. Despite reduced responsiveness conventional chemotherapy, sensitive EGFR inhibitors, providing insights into clinical intervention WT patients at high risk recurrence. Conclusion This study relapse-associated resembling cells, residing niches interactions proposed could relapse, offering promising method stratification. Targeting these combination may provide potential therapeutic strategy patients.

Language: Английский

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A novel pathway for stemness propagation and chemoresistance in non-small cell lung cancer via phosphorylated PKM2-loaded small extracellular vesicles

Theranostics, Journal Year: 2025, Volume and Issue: 15(8), P. 3439 - 3461

Published: Feb. 24, 2025

Rationale: Non-small cell lung cancer (NSCLC) is a predominant cause of cancer-related mortality, with its progression and treatment resistance significantly influenced by stem cells (CSCs) their complex intercellular communication mechanisms. Small extracellular vesicles (sEVs) have emerged as pivotal mediators signaling, affecting tumor microenvironment modulation therapeutic resistance. This study investigates the role CSC-derived sEVs in transmitting stemness traits through selective sorting pyruvate kinase M2 phosphorylated at Y105 site (pY105-PKM2), mediated adaptor protein IQGAP1, which supports CSC maintenance drug NSCLC. Methods: In vitro vivo experiments, including proteomic transcriptomic analyses, were conducted to identify key regulators sEV-mediated signaling. Immunoprecipitation, proximity ligation assays, immunofluorescence used examine IQGAP1 pY105-PKM2 into sEVs. Functional sphere formation, chemoresistance tests, metabolic assessments, cycle analysis, evaluate effects delivery on recipient cells. Additionally, immunohistochemistry survival analysis performed samples from NSCLC patients establish clinical correlations. Results: We unveiled novel mechanism transmit replenish pool enriched pY105-PKM2, correlating enhanced stemness, chemoresistance, poor outcomes. Mechanistically, was identified an facilitating interactions ESCRT component TSG101. Recipient treated exhibited reprogramming, slower progression, chemoresistance. The synergistic confirmed, highlighting critical contributions malignant progression. Conclusion: highlights therapy IQGAP1-mediated pY105-PKM2. By uncovering this pathway, our findings provide valuable insights replenishment mechanisms NSCLC, identifying promising targets for mitigating CSC-driven malignancy enhancing efficacy.

Language: Английский

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Advances in Neurological Pain Management: Bridging Scientific Innovations and Clinical Practice

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Neuronal pain, including neuropathic migraines, and chronic pain syndromes, presents a significant global health challenge. This literature review covers studies conducted until 2024 using major databases, PubMed Google Scholar, with the search terms "Neuropathic Pain/therapy" OR "Chronic "Pain Management/methods" "Neuromodulation/methods" "Spinal Cord Stimulation" "Deep Brain "Transcranial Magnetic Direct Current "Nav1.7 Voltage-Gated Sodium Channel" "Biologics/pharmacology" "Drug Delivery Systems/methods" "Regenerative Medicine/methods" "Stem Cell Transplantation/methods" "Platelet-Rich Plasma/therapeutic use" "Tissue Engineering/methods" "Biomarkers/metabolism" "Machine Learning" "Precision Medicine." explores contemporary advancements in neurological therapy, emphasizing analytical that translate into clinical applications. The research foundation is built on modern examining mechanisms, pharmaceutical innovations, neuromodulation strategies, personalized management, regenerative medicine. Notable include neuroinflammation research, molecular genetic factor discoveries, development of selective Nav1.7 inhibitors, biologics, advanced drug delivery systems. Neuromodulation techniques, both invasive (e.g., deep brain stimulation (DBS), spinal cord (SCS)) noninvasive transcranial direct current (tDCS), magnetic (TMS)), play crucial role modulation. Regenerative approaches, stem cell platelet-rich plasma (PRP), tissue engineering, offer promising solutions for repair symptom relief. Additionally, genomic data, biomarkers, machine learning enhance precision management. Ethical considerations regarding treatment accessibility opioid alternatives remain critical, particularly Hispanic Americans facing language barriers programs like Optum. Selective serotonin reuptake inhibitors (SSRIs) continue to be widely used mental treatment. In conclusion, convergence translational innovative therapies, medicine marks transformative era improving patient outcomes quality life.

Language: Английский

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