Functional & Integrative Genomics, Journal Year: 2023, Volume and Issue: 23(2)
Published: June 1, 2023
Language: Английский
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 113006 - 113006
Published: Aug. 29, 2024
Pyroptosis, a newly identified form of programmed cell death intertwined with inflammatory responses, is facilitated by the Gasdermin family's pore-forming activity, leading to lysis and release pro-inflammatory cytokines. This process double-edged sword in innate immunity, offering protection against pathogens while risking excessive inflammation tissue damage when dysregulated. Specifically, pyroptosis operates through two distinct signaling pathways, namely Caspase-1 pathway Caspase-4/5/11 pathway. In context chronic liver diseases like fibrosis cirrhosis, emerges as central contributing factor their pathogenesis. The identification characterized activation immune cells secretion cytokines such IL-1α, IL-1β, TNF-α. review explores interrelationship between inflammasome, protein complex located that recognizes danger signals initiates activation, resulting IL-1β IL-18. article delves into influence inflammasome on various disorders, specific focus molecular pathophysiological mechanisms. Additionally, potential therapeutic implications targeting for are highlighted future consideration.
Language: Английский
Citations
3
Cancers, Journal Year: 2022, Volume and Issue: 14(22), P. 5713 - 5713
Published: Nov. 21, 2022
Background: Studies on prognostic potential and tumor immune microenvironment (TIME) characteristics of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are limited. Methods: A multigene signature model was constructed using the least absolute shrinkage selection operator (LASSO) Cox regression analysis. The multivariate cox analysis bulk RNA-seq-based infiltration were performed. results verified two cohorts. enrichment CRGs T cells based single-cell RNA sequencing (scRNA-seq) Real-time polymerase chain reaction (RT-PCR) multiplex immunofluorescence staining performed to verify reliability conclusions. Results: four-gene risk scoring constructed. Kaplan−Meier curve showed that high-risk group had a worse prognosis (p < 0.001). time-dependent receiver operating characteristic (ROC) OS score prediction performance good. These further confirmed validation queue. Meanwhile, Tregs macrophages enriched TIME HCC. Conclusions: CRGs-based could predict Treg significantly HCC, which associated with depletion proliferating cells.
Language: Английский
Citations
15
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 3, 2023
Treatment of cancer with pyroptosis is an emerging strategy. Molecular subtypes based on pyroptosis-related genes(PRGs) seem to be considered more conducive individualized therapy. It meaningful construct a molecular subtypes-related prognostic signature (PMSRPS) predict the overall survival (OS) patients pancreatic adenocarcinoma(PAAD) and guide treatment.Based transcriptome data 23 PRGs, consensus clustering was applied divide TCGA GSE102238 combined cohort into three PRGclusters. Prognosis-related differentially expressed genes(DEGs) among PRGclusters were subjected LASSO Cox regression analysis determine PMSRPS. External in vitro experiments conducted verify this The CIBERSORT algorithm, ESTIMATE algorithm Immunophenoscore (IPS) used analyze infiltrating abundance immune cells, tumor microenvironment (TME), response immunotherapy, respectively. Wilcoxon compare mutational burden (TMB) RNA stemness scores (RNAss) between groups. RT-qPCR functional for evaluating expression function SFTA2.Based PRGclusters, 828 DEGs obtained PMSRPS subsequently constructed. In internal external validation, high-risk group had significantly lower OS than those low-risk confirmed independent risk factor PAAD good predictive performance. Immune cell infiltration TME indicate have typical immunosuppressive characteristics. Analysis IPS suggests responded better novel checkpoint inhibitors (ICIs) PD1/CTLA4. higher TMB RNAss. addition, 10 potential small-molecule compounds screened out. Finally, we found that mRNA SFTA2 gene highest coefficient paracancerous tissues, knockdown it delayed progression PAAD.PMSRPS can well prognosis, immunotherapy PAAD, identify drugs, provide treatment guidance individual needs.
Language: Английский
Citations
8
Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 10, 2023
Background: Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive. Method: We obtained patients’ RNA expression data and follow-up information from University California Santa Cruz (UCSC) The Cancer Genome Atlas (TCGA). analyzed the mRNA level Cuproptosis-related genes (CRGs) performed univariate Cox analysis. Liver (LIHC) was chosen for further investigation. Real-Time quantitative PCR (RT-qPCR), Western blotting (WB), Immunohistochemical (IHC), Transwell assays were used to determine patterns functions CRGs LIHC. Next, we identified CRGs-related lncRNAs (CRLs) differentially expressed CRLs between HCC normal cases. Univariate analysis, least absolute shrinkage selection operator (LASSO) analysis regression construct prognostic model. multivariate assess risk model can act as an independent factor overall survival duration. Different groups immune correlation tumor mutation burden (TMB), Gene Set Enrichment Analysis (GSEA) different groups. Finally, assessed performance predictive drug sensitivity. Results: levels have significant differences tissues. High Dihydrolipoamide S-Acetyltransferase ( DLAT ) correlated metastasis cells indicated poor prognosis patients. Our consisted four cuproptosis-related lncRNA (AC011476.3, AC026412.3, NRAV, MKLN1-AS). well predicting rates. results suggested that score serve element durations. Survival revealed low patients extended periods compared with those high risk. has positive B CD4 + T Th2, while negative relationship endothelial hematopoietic cells. Besides, checkpoint higher folds high-risk set than low-risk set. group had rates genetic having shorter time. GSEA signaling pathways enriched mostly immune-related, metabolic-related group. Drugs sensitivity our ability predict efficacy clinical treatment. Conclusion: formula novel predictor
Language: Английский
Citations
8
Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11
Published: May 5, 2023
Liver cancer is now one of the main causes leading to death worldwide. To achieve reliable therapeutic effects, it crucial develop efficient approaches test novel anticancer drugs. Considering significant contribution tumor microenvironment cell’s response medications, in vitro 3D bioinspiration cell niches can be regarded as an advanced strategy improve accuracy and reliability drug-based treatment. In this regard, decellularized plant tissues perform suitable scaffolds for mammalian culture create a near-to-real condition drug efficacy. Here, we developed natural scaffold made from tomato hairy leaves (hereafter called DTL) mimic human hepatocellular carcinoma (HCC) pharmaceutical purposes. The surface hydrophilicity, mechanical properties, topography measurement molecular analyses revealed that DTL ideal candidate liver modeling. cells exhibited higher growth proliferation rate within scaffold, verified by quantifying expression related genes, DAPI staining, SEM imaging cells. Moreover, prilocaine, drug, showed effectiveness against cultured on compared 2D platform. Taken together, new cellulosic confidently proposed chemotherapeutic testing drugs carcinoma.
Language: Английский
Citations
8
Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 1286 - 1286
Published: Feb. 6, 2023
Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets necessary. Methods: Data were downloaded from the GEO database. "glmnet" package was used to identify differentially expressed genes (DEGs). model constructed by univariate Cox LASSO regression analyses. Validation expression prognosis immunohistochemistry (IHC) in vitro. Drug sensitivity immune cell infiltration analyzed CTR-DB ImmuCellAI. Results: We that identified gene set (DLAT, IDH3B, MAP3K4), which validated real-world cohort. Next, seven transcription factors (TFs) identified. ceRNA network included three mRNAs, four miRNAs, lncRNAs. Finally, we found associated with drug response six clinical trial cohorts. Moreover, level inversely correlated CD8 T HCC. Conclusions: established model. Upstream transcriptome analysis provided clues for mechanism exploration. mutant profile, sensitivity, further guided precise diagnosis treatment strategies.
Language: Английский
Citations
7
European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)
Published: Dec. 6, 2023
Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers in world and a nonnegligible health concern on worldwide scale. Disulfidptosis novel mode cell death, which mainly caused by collapse actin skeleton. Although many studies have demonstrated that various types death are associated with cancer treatment, relationship between disulfidptosis HCC has not been elucidated. Methods Here, we applied bioinformatics methods to construct related risk model patients. Specifically, transcriptome data clinical information were downloaded from Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC) The Atlas (TCGA) database. A total 45 co-expressed genes extracted disulfidptosis-related (DRGs) differential expression (DEGs) liver hepatocellular (LIHC) TCGA LIHC cohort was divided into two subgroups different prognosis k-mean consensus clustering functional enrichment analysis performed. Subsequently, three hub (CDCA8, SPP2 RDH16) screened Cox regression LASSO analysis. In addition, signature constructed high score low compare prognosis, features immune landscape subgroups. Finally, prognostic independent factors verified. Conclusions High DRGs-related individuals predict poor immunotherapy response, indicates assessment can be utilized guide treatment strategy.
Language: Английский
Citations
7
Genes & Genomics, Journal Year: 2024, Volume and Issue: 46(7), P. 785 - 801
Published: May 20, 2024
Abstract Background Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, prognosis. There still no research on relationship between PCD-related genes UVM. A novel PCD-associated prognostic model urgently needed to improve treatment strategies. Objective We aim screen signature investigate its proliferation ability apoptosis UVM cells. Methods clinical information RNA-seq data patients were collected from TCGA cohort. All classified using consensus clustering by selected genes. After univariate Cox regression PPI network analysis, then submitted LASSO analysis build model. level immune infiltration 8-PCD high- low-risk was analyzed xCell. prediction chemotherapy immunotherapy response assessed GDSC TIDE algorithm. CCK-8, western blot Annexin V-FITC/PI staining used explore roles HMOX1 Results total constructed risk score PCD negatively correlated overall survival, indicating strong predictive independent value. positively CD8 Tcm, Tem Th2 Immune cells high-risk group had poorer survival. drug sensitivity demonstrated that cisplatin might impact progression better responsiveness group. Finally, Overespression (OE-HMOX1) decreased viability induced Recuse experiment results showed ferrostatin-1 (fer-1) protected MP65 necrosis caused OE-HMOX1. Conclusion may have significant microenvironment, clinicopathological characteristics, prognosis sensitivity. More importantly, depletion greatly growth inhibited fer-1 This work provides foundation for effective therapeutic strategy tumour treatment.
Language: Английский
Citations
2
Materials Today Communications, Journal Year: 2024, Volume and Issue: 39, P. 109318 - 109318
Published: May 22, 2024
Language: Английский
Citations
2
Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(3), P. 2767 - 2785
Published: July 20, 2024
Language: Английский
Citations
2