The distinct roles of IL-37 and IL-38 in non-small cell lung carcinoma and their clinical implications

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

Published: March 21, 2025

Lung cancer, a significant global health challenge, is primarily classified into non-small cell lung cancer (NSCLC) and small cancer. Despite advancements in targeted therapies immunotherapies, NSCLC outcomes remain poor, with low five-year survival rates. Given the lung’s constant exposure to environment presence of mucosal-associated lymphoid tissues, immunity plays crucial role development. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have shown promise. However, adverse immune events limit their efficacy. This review highlights contrasting roles IL-37 IL-38 pathogenesis. IL-37, an anti-inflammatory cytokine, suppresses tumour growth. It achieves this by modulating macrophage polarization dendritic maturation. Correlations between intra-tumoral expression improved suggest protective NSCLC. may be mediated through VEGF inhibition regulation. Conversely, IL-38, while certain contexts, exhibits pro-tumorigenic enhances progression increasing pro-inflammatory cytokine secretion facilitating evasion, potentially NF-κB signalling. Notably, negatively regulates further promoting tumorigenesis. Emerging data that has therapeutic potential inhibiting metastasis supporting modulation. In contrast, presents target for mitigating microenvironment effects. The distinct these cytokines emphasize complex dynamics Further exploration molecular mechanisms implications warranted. Targeting offer novel strategies enhancing treatment

Language: Английский

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New insights into the classification of the RAC1 P29S hotspot mutation in melanoma as an oncogene

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

The RAC1^P29S hotspot mutation, prevalent in melanoma, drives tumorigenesis by enhancing molecular interactions and hyperactivating key signaling pathways, making it a compelling target for cancer therapy. This study provides comprehensive biochemical characterization of RAC1^P29S compared to wild-type RAC1 mutations T17N F28L. P29S mutation significantly impairs nucleotide binding guanosine triphosphate (GTP) diphosphate, accelerating intrinsic exchange. While minimally affecting regulation dissociation inhibitor 1, exhibits reduced activation via diffuse B-cell lymphoma family guanine exchange factors but retains effective dedicator cytokinesis 2. Critically, the severely GTPase-activating protein-stimulated GTP hydrolysis, most likely contributing hyperactivation prolonging its GTP-bound form. displays stronger affinity IQ motif-containing protein 1 than p21-activated kinase highlighting role former scaffolding RAC1^P29S-driven signaling. In serum-starved cells, predominantly adopts an active state. overexpression activates cancer-associated including extracellular signal-regulated p38 mitogen-activated kinase, reinforcing as oncogenic driver melanoma. These insights suggest potential therapeutic targets melanoma treatment, regulators modulators.

Language: Английский

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Alkaloids from the medicinal plant Incarvillea sinensis: Molecular diversity, synthesis, pharmacological properties and mechanism of action

Fitoterapia, Journal Year: 2025, Volume and Issue: 183, P. 106548 - 106548

Published: April 15, 2025

Language: Английский

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Integrated Analysis of Disulfidptosis-Related Genes Identifies CD2AP as a Potential Therapeutic Target for Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4454 - 4454

Published: May 7, 2025

Hepatocellular carcinoma (HCC) is a deadly cancer with limited treatment options for patients at advanced stages. It urgent to develop reliable prognostic risk models and identify more biomarkers improve the clinical outcomes of HCC. Disulfidptosis newly discovered form regulated cell death (RCD), research on comprehensive roles disulfidptosis-related genes (DRGs) in HCC prognosis development remains limited. In this paper, we systematically analyzed expression levels profiles 26 DRGs samples from The Cancer Genome Atlas (TCGA) cohort developed model using seven hub DRGs. independent value was further validated external cohort. overall survival low-risk group significantly longer than that those high-risk group. Subsequently, protein level CD2-associated (CD2AP) found be highly expressed tissues associated severity vitro experiments demonstrated down-regulation CD2AP attenuated proliferation, migration, invasion, epithelial–mesenchymal transition (EMT) abilities cells. Taken together, our study revealed DRG may serve as potential biomarker offer support prediction

Language: Английский

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Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1357 - 1357

Published: June 8, 2022

Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations treat diseases such as overactive bladder cancers. A promising new target is ubiquitous Rho GTPase Rac1, frequently dysregulated overexpressed pathologies. We analyzed roles Rac1 different including bacterial infections, diabetes-induced dysfunctions The contribution protein tumorigenesis, tumor progression, epithelial-mesenchymal transition cancer cells their metastasis has been analyzed. Small molecules selectively targeting discovered or designed, two them-NSC23766 EHT 1864-have revealed activities against cancer. Their mode interaction with at GTP binding site guanine nucleotide exchange factors (GEF) site, discussed. Our analysis underlines possibility small objective combat reduce lower urinary tract symptoms. Finally, interest inhibitor advanced chemoresistance prostate cancer, while reducing risk associated dysfunction, There hope for better management pathologies via Rac1-targeted approaches.

Language: Английский

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MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(12), P. 1817 - 1828

Published: Nov. 6, 2023

Although the oncogenic roles of regulator G protein signaling 20 (RGS20) and its upstream microRNAs (miRNAs) have been reported, their involvement in hepatocellular carcinoma (HCC) remains unexplored. We utilized starBase, miRDB, TargetScan, mirDIP databases, along with a dual-luciferase reporter assay cDNA chip analysis to identify miRNAs targeting RGS20. miR-204-5p was selected for further experiments confirm direct downregulation RGS20 expression. To study miR-204-5p/RGS20 axis HCC, were increased PLC/PRF/5/Hep3B cells, viability, hyperplasia, apoptosis, cell cycle, invasion/migration cells assessed. exhibited optimism, while pessimism tumors. directly targeted downregulated expression, whereas high expression indicated poor prognosis. Transfection inhibited migration, invasion HCC but promoted apoptosis influenced levels cyclin-dependent kinase 2 (CDK2), cyclin E1, B-cell lymphoma-2 (Bcl-2), Bax, cleaved caspase-3/8. These effects reversed by overexpression recognized as an RGS20, thereby inhibiting progression downregulating may prove be potential target treatment, might seem like miRNA gene therapy.

Language: Английский

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Insights about circadian clock in glioma: From molecular pathways to therapeutic drugs

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 28(12), P. 1930 - 1941

Published: Sept. 6, 2022

Abstract Glioma is characterized as the most aggressive brain tumor that occurred in central nervous system. The circadian rhythm an essential cyclic change system generated by endogenous clock. Current studies found clock affects glioma pathophysiology. It still controversial whether disruption a cause or effect of tumorigenesis. This review discussed association between cell cycle and provided prominent molecular theoretical basis for therapy. We illustrated external factors affecting including thermodynamics, hypoxia, post‐translation, microRNA, while internal characteristics concerning involve stemness, metabolism, radiotherapy sensitivity, chemotherapy sensitivity. also summarized pathways therapeutic drugs involved rhythm. There are many questions this field waiting further investigation. results chronotherapy sensitizing radiation therapy have shown great potential improving clinical outcomes. These findings will help us understand

Language: Английский

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A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15950 - e15950

Published: Aug. 24, 2023

The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope surgical resection. It also affects long-term efficacy systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), γ-glutamyl transferase (GPR), are less accurate predicting HCC patients. We aimed build a novel decision tree model improve diagnostic accuracy cirrhosis. Mann-Whitney U test, χ2 multivariate logistic regression analysis were used identify independent predictors. A was developed using machine learning algorithms training cohort 141 Internal validation conducted 99 calibration established evaluated receiver operating characteristic (ROC) curves, respectively. Sex count identified as integrating imaging-reported cirrhosis, APRI, FIB-4, GPR established. had an excellent performance cohorts, with area under curve (AUC) values 0.853 0.817, Calibration curves Hosmer-Lemeshow test showed good model. (DCA) indicated that could provide larger net benefit predict Our successfully patients, which may be helpful clinical decision-making.

Language: Английский

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Characterization of neutrophil extracellular traps related gene pair for predicting prognosis in hepatocellular carcinoma

The Journal of Gene Medicine, Journal Year: 2023, Volume and Issue: 25(11)

Published: July 3, 2023

Hepatocellular carcinoma (HCC) is a malignant disease with high incidence rate, mortality and poor prognosis. Neutrophil extracellular traps (NETs), as an reticular structure, promote the development progression of cancer in tumor microenvironment, have promising prospect prognostic indicator. In present study, we elucidated value NET-related genes.The NETs gene pair The Cancer Genome Atlas cohort was constructed by least absolute shrinkage selection operator analysis. Samples from International Consortium were performed to verify its feasibility. Kaplan-Meier analysis used compare overall survival (OS) rate two subgroups. independent predictors OS determined univariate multivariate Cox Furthermore, Gene Ontology term Kyoto Encyclopedia Genes Genomes pathway analyzed set enrichment single sample method deplore relationship risk score immune microenvironment. GSE149614 dataset applied cell RNA level validation. PCR detect mRNA expression profiles NETs-related genes.Our model provides high-risk group patients significantly reduced. important predictor HCC Nomogram suggested favorable classification performance. drug resistance sensitivity cells chemotherapeutics correlated expression. status groups showed marked difference.The novel landscape could predict prognosis provide new understanding immunotherapy HCC.

Language: Английский

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New insights into fibrotic signaling in hepatocellular carcinoma

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 22, 2023

Hepatocellular carcinoma (HCC) mostly occurs in the background of liver fibrosis, and activated hepatic stellate cells (HSCs) exist HCC tissues adjacent tissues. HSC activation is involved throughout development precancerous lesions, which has gradually attracted attention related researchers. In addition, can promote HSCs, turn accelerates occurrence by promoting tumor angiogenesis. this review, we reviewed 264 studies from PubMed ScienceDirect to summarize analyze current significant fibrotic signaling HCC. As a result, found 10 pathways that are closely activation, proliferation, invasion, migration, promotion apoptosis cells. crosstalk between various HCC, hypoxia-induced energy metabolic reprogramming cells, matrix stiffness stemness ferroptosis HSCs latest research hotspots. Furthermore, drugs have been target these listed. Our study provides new reference for developing anti-HCC drugs.

Language: Английский

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