Targeting CDK1 and copper homeostasis in breast cancer via a nanopolymer drug delivery system DOI Creative Commons
Nan Shang,

Lisi Zhu,

Zhiyong Li

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 41(1)

Published: Dec. 26, 2024

The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where management copper levels crucial for treatment success. This research aims to explore influence homeostasis on BRCA therapy, with specific focus role Cyclin-Dependent Kinase 1 (CDK1) and its relationship regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered synergize chemotherapy drug vincristine (VCR) inhibiting tumor growth metastasis. Through comprehensive approach involving bioinformatics analyses, vitro experiments, vivo models, study identified CDK1 as significant factor progression under homeostasis. MBVP-Gel, NPs, developed enhance delivery drugs regulate treatment. formulated chelation VCR effectively suppressed expression, thereby restraining cell metastasis while enhancing therapeutic impact VCR. investigation offers fresh insights experimental validation interaction between BRCA, providing valuable foundation refining future strategies. These findings underscore potential advantages targeting setting stage individualized interventions improved patient consequences.

Language: Английский

Advancements in Colorectal Cancer Treatment: The Role of Metal-Based and Inorganic Nanoparticles in Modern Therapeutic Approaches DOI
Maryam Azarian, Marzieh Ramezani Farani, William C. Cho

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 264, P. 155706 - 155706

Published: Nov. 6, 2024

Language: Английский

Citations

9
Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases DOI Creative Commons

Xiya Ren,

Limei Zhao, Yajie Hao

et al.

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 13, 2025

Copper is a vital cofactor in various enzymes, plays pivotal role maintaining cell homeostasis. When copper metabolism disordered and mitochondrial dysfunction impaired, programmed death such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis, autophagy necroptosis can be induced. In this review, we focus on the metabolic mechanisms of copper. addition, discuss mechanism by which induces deaths. Finally, review examines copper's involvement prevalent kidney diseases acute injury chronic disease. The findings indicate that use chelators or plant extracts mitigate damage reducing accumulation, offering novel insights into pathogenesis treatment strategies for diseases.

Language: Английский

Citations

1
Copper in colorectal cancer patients: a systematic review and meta-analysis DOI Creative Commons
Carlos Muñoz-Bravo,

Inés Marín-Burdallo,

Lucas González-Herrera

et al.

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

Published: Jan. 23, 2025

Abstract Several clinical studies have evaluated the relationship between copper on colorectal cancer (CRC), but results are contradictory. This study aimed to conduct a systematic review and meta-analysis investigate measured in two biological matrices (serum/plasma/blood tissue) dietary intake CRC patients compared healthy controls. We conducted comprehensive search PubMed, Scopus, Embase Web of Science. included that reported levels serum/plasma/blood, tissue or from diet, with observational design (cohort case-control studies). Study quality was assessed Newcastle-Ottawa scale potential causes heterogeneity were evaluated. Standardized mean differences (SMD) 95% confidence interval (CI) pooled using random-effect models. Overall Odds Ratio CI for risk calculated. Twenty-six (23 3 cohort studies) total 227,354 participants included. Most presented low (50%) moderate (42.3%). No serum/plasma/blood (SMD=0.23; 95%CI -0.23, 0.70; I2=97.3%, 19 studies), (SMD=-1.69; -3.41, 0.03; I2=85.6%, 2 copper/zinc ratio (SMD=1.19; 0.54, 1.84; I2=95.3%, 6 found Regarding copper, had lower (SMD=-0.27; -0.51, -0.03; I2=0.0%, However, evidence shows mostly quality, heterogeneous. More prospective an adequate methodological approach needed.

Language: Английский

Citations

1
Prognostic models of immune-related cell death and stress unveil mechanisms driving macrophage phenotypic evolution in colorectal cancer DOI Creative Commons
Hao Liu, Chuhan Zhang,

Sanfei Peng

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 28, 2025

Tumor microenvironment (TME), particularly immune cell infiltration, programmed death (PCD) and stress, has increasingly become a focal point in colorectal cancer (CRC) treatment. Uncovering the intricate crosstalk between these factors can enhance our understanding of CRC, guide therapeutic strategies, improve patient prognosis. We constructed an immune-related stress (ICDS) prognostic model utilizing machine learning methodologies. Furthermore, we performed enrichment analyses deconvolution algorithms to elucidate complex interactions infiltration processes PCD within substantial array transcriptomic data from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus base (GEO) related CRC. Single-cell sequencing biochemical experiments were used validate interaction genes tumor cells. ICDS exhibited robust predictive performance seven independent cohorts, revealing inverse correlation scores Meanwhile, index was positively correlated with clinical stage. Model analysis indicated that subgroups low heightened activation features elevated activity pathways. further revealed macrophages central drivers characteristics underlying differences model. Pseudotime cellular gene GAL3ST4 promotes transition toward M2 pro-tumor phenotype. communication experimental validation cuproptosis cells suppress expression, thereby inhibiting M2-like macrophage polarization. In summary, uncovered mechanism by which downregulate expression via inhibit polarization, providing new targets biomarkers for CRC treatment prognosis evaluation.

Language: Английский

Citations

1
Focus on cuproptosis: Exploring new mechanisms and therapeutic application prospects of cuproptosis regulation DOI Open Access

Donglin Hao,

Wei Luo,

Yongmin Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117182 - 117182

Published: July 24, 2024

Cuproptosis is a novel form of regulated cell death, which plays an important role in the physiological and pathological processes human body. Despite increasing research on cuproptosis-related genes (CRGs) their correlation with diseases, pathogenesis diseases remains unclear. Furthermore, there lack reviews emerging technologies for regulating cuproptosis disease treatment. This study delves into copper-induced death mechanism, distinguishing from mechanisms like oxidative stress, glutathione synthesis inhibition, ubiquitin-proteasome system inhibition. Several long-standing mysteries such as Wilson's Menkes may be attributed to occurrence cuproptosis. In addition, we also review detection indicators related cuproptosis, providing targets diagnosis summarize application value tumor therapy better elucidate impact copper thus promote prospects possible strategies substances, ion chelators, carriers, nanomaterials, therapy.

Language: Английский

Citations

4
Single-cell and Multi-omics Analysis Confirmed the Signature and Potential Targets of Cuproptosis in Colorectal Cancer DOI Creative Commons
Tao Jiang, Zijing Wang, Zhao Sun

et al.

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1264 - 1280

Published: Jan. 13, 2025

Background: Cuproptosis, a form of copper-mediated programmed cell death, has recently garnered significant attention. However, the mechanisms by which CRGs affect progression CRC remain unclear. Methods: Bioinformatics approaches were employed to analyze transcriptomic datasets and clinical data from 630 patients, focusing on copy number variations, prognostic implications, immune infiltration characteristics associated with CRGs. Key CRG-related genes impacting prognosis identified using LASSO Cox regression methods. A model incorporating various molecular markers parameters was constructed training cohort validated separate validation cohort. This used explore indicators, infiltration, tumor microenvironment in patients. Additionally, single-cell analysis performed investigate biological roles critical genes, expression patterns these assessed via qRT-PCR WB. Results: scoring established based three pivotal prognosis. model, an independent indicator, outperformed traditional clinicopathological features predicting patient outcomes. Kaplan-Meier survival curves demonstrated superior outcomes for individuals low-risk group compared those high-risk group. Model stability reliability confirmed through ROC univariate multivariate analyses. Further revealed correlations between scores presence M0 macrophages memory CD4+ T cells. Differences CDKN2A, PLCB4, NXPE4 across tissues cells characterized WB, IHC qRT-PCR. Conclusion: study not only highlights diverse omics profiles but also introduces novel accurate forecasting.

Language: Английский

Citations

0
Cuproptosis-related gene ACAD8 inhibits the metastatic ability of colorectal cancer by inducing cuproptosis DOI Creative Commons

HuiE Zhuang,

Yizhen Chen,

Sifu Huang

et al.

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

Published: April 3, 2025

Background Distant metastasis of colorectal cancer (CRC) significantly impacts patient prognosis. Cuproptosis is a new form copper ion-dependent cell death. However, whether cuproptosis-related genes (CRGs) play role in the metastatic potential CRC remains unclear. This study focuses on CRGs-ACAD8 to explore its and mechanism (mCRC). Methods Clinical sample data from TCGA, GEO, Fujian Provincial Hospital patients were integrated analyze ACAD8 expression association with diagnosis prognosis CRC. Small interfering RNA, immunohistochemistry, colony formation, wound-healing assays so used evaluate biological functions ACAD8. Bioinformatics was applied investigate relationships immune infiltration, chemotherapy sensitivity, signaling pathways. Results reduced mCRC demonstrated excellent diagnostic performance. Patients high had better survival. closely associated enhanced sensitivity. Pathway enrichment analysis suggested that might inhibit by regulating pathways such as response metal ions tight junction organization. Finally, experiments confirmed positive correlation between levels mRNA expression, CuCl 2 upregulating expression. Knockdown induced cuproptosis. inhibited proliferation, stemness, migratory abilities cells, while si attenuated these effects. Moreover, sensitivity cells oxaliplatin 5-fluorouracil, whereas diminished this chemosensitizing effect. Conclusion As novel tumor suppressor, low holds prognostic value may contribute precise treatment infiltration

Language: Английский

Citations

0
Synthesis, Characterization, and Biomolecular Interactions of a novel Copper(II) Complex: DNA and BSA Binding Studies DOI

Amineh Mashkoori,

Maryam Mohamadi, S. Yousef Ebrahimipour

et al.

Journal of Fluorescence, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Cuproptosis and its potential role in musculoskeletal disease DOI Creative Commons
Zijian Xiang, Heng Mei, Honglin Wang

et al.

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

Published: April 11, 2025

Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, plays critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, mitochondrial dysfunction. Distinct other death mechanisms, cuproptosis is characterized by ion binding to acetylated respiratory chain proteins, leading pathogenic protein aggregation, iron-sulfur cluster depletion, cellular collapse. Emerging evidence underscores aberrant accumulation resultant proteotoxic stress as pivotal contributors the pathogenesis musculoskeletal pathologies, osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, biofilm-associated orthopedic infections. Understanding spatiotemporal regulation may provide novel opportunities for advancing diagnostic therapeutic approaches medicine. This review synthesizes current insights into molecular mechanisms cuproptosis, its diseases, potential biomarker-driven interventions.

Language: Английский

Citations

0
Targeting PTBP3‐Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis DOI Creative Commons
Yajing Zhou,

Dong Chao,

Xiaochun Shen

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Numerous aberrant splicing events are implicated in tumor progression, yet comprehensive reports on factors and associated with peritoneal metastasis gastric cancer (GCPM) lacking. In this study, PTBP3 is found to be significantly overexpressed metastatic tissues of compared primary tissues, higher expression correlates poorer prognosis. Using cells patient‐derived organoids (PDO), the role promoting invasion proliferation investigated. Mechanistically, through full‐length transcriptome sequencing, mediates exon 4 skipping its target gene COX11, leading shorter transcripts that impair COX11 protein function, reducing mitochondrial copper content enabling evade cuproptosis. Antisense oligonucleotide (ASO) drugs targeting short effectively degrade mRNA, disrupting homeostasis. PDO‐based xenograft models, exogenous ionophores combined ASO induce excessive accumulation mitochondria, triggering proteotoxic stress Overall, PTBP3‐mediated pre‐mRNA critical for cell survival progression GCPM, offering potential therapeutic strategies metabolism.

Language: Английский

Citations

0