Integrative Analysis of Metabolite Changes and Potential Health Effects in Pomegranate Juice Fermentation

Food Bioscience, Год журнала: 2025, Номер unknown, С. 105934 - 105934

Опубликована: Янв. 1, 2025

Язык: Английский

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EHMT2‐mediated R‐loop formation promotes the malignant progression of prostate cancer via activating Aurora B

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract Background Chromosomal instability (CIN), a hallmark of cancer, is commonly linked to poor prognosis in high‐grade prostate cancer (PCa). Paradoxically, excessively high levels CIN may impair cell viability. Consequently, understanding how tumours adapt critical for identifying novel therapeutic targets. Methods Bioinformatic analyses were conducted identify genes overexpressed PCa tissues using The Cancer Genome Atlas (TCGA) and GEO datasets. Western blotting immunohistochemistry assays applied determine the expression euchromatic histone lysine methyltransferase 2 (EHMT2), pT232‐Aurora B Cullin 3 (CUL3). proliferation cells was measured through CCK‐8 tests, clonogenesis subcutaneous xenografts human BALB/c nude mice. Live imaging, immunofluorescence (IF) flow cytometry used confirm role EHMT2 mitosis. Co‐immunoprecipitation, IF further elucidated underlying molecular mechanisms. Results highly expressed metastatic exhibiting elevated strongly associated with adverse clinical outcomes patients PCa. Silencing impaired division, inducing G2/M‐phase arrest mitotic catastrophe cells. Mechanistically, indispensable ensure full activation Aurora centromeric R‐loop‐driven ATR–CHK1 pathway, protein peaking during G2/M‐phase. Moreover, CUL3 identified as binding partner EHMT2, mediating its polyubiquitination destabilising levels. Conclusions This study reveals CUL3–EHMT2–Aurora regulatory axis that safeguards accurate chromosome segregation cells, supporting potential application inhibitors. Key points Euchromatic (EHMT2) advanced restraining catastrophic chromosomal (CIN) enhancing fitness. functions via ATR–CHK1–Aurora pathway promote stability. confers enzalutamide resistance activating B. (CUL3) promotes destabilisation deubiquitination.

Язык: Английский

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Identification of prostate cancer bone metastasis related genes and potential therapy targets by bioinformatics and in vitro experiments

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(15)

Опубликована: Авг. 1, 2024

The aetiology of bone metastasis in prostate cancer (PCa) remains unclear. This study aims to identify hub genes involved this process. We utilized machine learning, GO, KEGG, GSEA, Single-cell analysis, ROC methods for PCa using the TCGA and GEO databases. Potential drugs targeting these were identified. validated results 16 specimens from patients with analysed relationship between clinical features. impact APOC1 on was assessed through vitro experiments. Seven AUC values 0.727-0.926 APOC1, CFH, NUSAP1 LGALS1 highly expressed tissues, while NR4A2, ADRB2 ZNF331 exhibited an opposite trend. Immunohistochemistry further confirmed results. oxidative phosphorylation pathway significantly enriched by identified genes. Aflatoxin B1, benzo(a)pyrene, cyclosporine as potential drugs. expression correlated features metastasis. Silencing inhibited cell proliferation, clonality, migration vitro. 7 that potentially facilitate mitochondrial metabolic reprogramming. emerged a promising therapeutic target prognostic marker

Язык: Английский

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The RNA binding protein CARHSP1 facilitates tumor growth, metastasis and immune escape by enhancing IL-17RA mRNA stabilization in prostate cancer

Cell & Bioscience, Год журнала: 2025, Номер 15(1)

Опубликована: Март 7, 2025

Abstract Background Calcium-regulated heat-stable protein 1 (CARHSP1) has been identified as a cold shock domain (CSD) family member, participating in the regulation of ribosomal translation, mRNA degradation, and rate transcription termination. However, there is an extremely limited understanding function CARHSP1 RNA binding (RBP) prostate cancer (PCa). Methods The expression pattern correlation between clinical prognosis PCa patients were analyzed by using multiple public databases. In vitro vivo functional assays conducted to assess role CARHSP1. mechanisms on IL-17RA pull-down stability assays. A co-culture model Jurkat cells was established investigate potential tumor immunity PCa. Results highly expressed PCa, correlated with advanced characteristics unfavorable patients. Moreover, knockdown significantly dampened capacity proliferation, migration, invasion, immune evasion vivo. Mechanistically, RNA-binding selectively bound IL-17RA, resulting increased both protein. Downregulating shortened half-life reduced its expression. Subsequently, downstream pathways JAK-STAT3 signaling pathway NF-κB pathway, activated contributed malignant phenotype cells. Conclusions conclusion, our results demonstrated that prognosis, may promote progression through enhancing activating pathways. These suggest important regulator microenvironment CARHSP1-IL-17RA axis could be novel therapeutic targets for

Язык: Английский

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Integrative multi-omics analysis and machine learning refine global histone modification features in prostate cancer

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 12

Опубликована: Март 12, 2025

Background Prostate cancer (PCa) is a major cause of cancer-related mortality in men, characterized by significant heterogeneity clinical behavior and treatment response. Histone modifications play key roles tumor progression resistance, but their regulatory effects PCa remain poorly understood. Methods We utilized integrative multi-omics analysis machine learning to explore histone modification-driven PCa. The Comprehensive Machine Learning Modification Score (CMLHMS) was developed classify into two distinct subtypes based on modification patterns. Single-cell RNA sequencing performed, drug sensitivity identified potential therapeutic vulnerabilities. Results High-CMLHMS tumors exhibited elevated activity, enriched proliferative metabolic pathways, were strongly associated with castration-resistant prostate (CRPC). Low-CMLHMS showed stress-adaptive immune-regulatory phenotypes. revealed differentiation trajectories related aggressiveness Drug that high-CMLHMS more responsive growth factor kinase inhibitors (e.g., PI3K, EGFR inhibitors), while low-CMLHMS demonstrated greater cytoskeletal DNA damage repair-targeting agents Paclitaxel, Gemcitabine). Conclusion CMLHMS model effectively stratifies unique biological characteristics. This study provides new insights suggests targets, contributing precision oncology strategies for advanced

Язык: Английский

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MRI-based habitat analysis of vascular and nerve invasion in the tumor microenvironment: an advanced approach for prostate cancer diagnosis

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 17, 2025

This study aims to detect vascular and neural invasion in prostate cancer through MRI, utilize habitat analysis of the tumor microenvironment, construct a radiomic feature model, thereby enhancing diagnostic accuracy prognostic assessment for cancer, ultimately improving patients' quality life. We retrospectively collected records 400 patients with pathologically verified from January December 2023. developed features model within using MRI data identified independent risk factors multivariate clinical model. Finally, we assessed performance these DeLong test (through area under receiver operating characteristic curve, AUC), evaluated calibration curve Hosmer-Lemeshow test, performed decision analysis. In training set, optimal algorithm based on intratumoral heterogeneity score had an AUC value 0.882 (CI: 0.843-0.921); was 0.860 0.792-0.928). The traditional radiomics (considering entire tumor) 0.761 0.695-0.827) set 0.732 0.630-0.834) set. combined that integrates scores Gleason 0.889 0.8509-0.9276) 0.886 0.8183-0.9533) outperforming single models. By deeply analyzing microenvironment combining models, precision predictive nerve can be significantly improved. approach provides valuable tool optimizing treatment plans, patient prognosis, reducing unnecessary medical interventions.

Язык: Английский

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Investigating the Genetic Links Between Immune Cell Profiles and Bladder Cancer: A Multidisciplinary Bioinformatics Approach

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1203 - 1203

Опубликована: Май 15, 2025

Background: Bladder cancer (BC) is a common malignancy in the urinary system, with an increasing incidence rate. Immune cell infiltration within tumor microenvironment (TME) plays crucial role BC progression and treatment response. However, immune composition of TME presents significant challenge to effectiveness current therapeutic strategies. Methods: We performed bidirectional Mendelian randomization (MR) analysis investigate impact cells on risk. Single nucleotide polymorphisms (SNPs) related were annotated, candidate genes associated risk identified. Differential expression identified immune-related differentially expressed (iDEGs), protein-protein interaction (PPI) network along functional enrichment conducted explore their roles development. Machine learning-based feature selection was applied identify potential biomarkers targets. Results: MR revealed eight subtypes significantly BC. Using SNPs linked these cells, 129 through SNPense tool cross-referenced BC, resulting identification 28 iDEGs. learning five diagnostic (COLEC12, TMCC1, CEP55, KLK3, COL4A1) AUC 0.903, which are implicated modulation progression. Conclusions: This study provides new insights into mechanisms identifies promising for early diagnosis intervention.

Язык: Английский

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A tumour‐associated macrophage‐based signature for deciphering prognosis and immunotherapy response in prostate cancer

IET Systems Biology, Год журнала: 2024, Номер 18(5), С. 155 - 171

Опубликована: Авг. 13, 2024

Abstract For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour‐associated macrophage is an essential contributor. Although immunotherapy important promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition exploring new therapeutic targets, it imperative identify highly immunotherapy‐sensitive individuals. This research aimed establish a signature risk model, which derived from macrophage, assess immunotherapeutic responses predict prognosis. Data UCSC‐XENA, GEO TISCH databases were extracted analysis. Based on both single‐cell datasets bulk transcriptome profiles, macrophage‐related score (MRS) consisting 10‐gene panel was constructed using gene set variation MRS correlated hypoxia, angiogenesis, epithelial‐mesenchymal transition, suggesting its potential as indicator. Moreover, poor worse prognostic performance observed in high‐MRS group various cohorts. Additionally, APOE, one constituent genes MRS, affected polarisation macrophages. particular, reduced level M2 tumour suppression xenografts implanted Apolipoprotein E‐knockout mice. The has robust prediction tool, can aid selection PCa, especially options.

Язык: Английский

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Causal relationship between inflammatory proteins and glioblastoma: a two-sample bi‑directional mendelian randomization study

Frontiers in Genetics, Год журнала: 2024, Номер 15

Опубликована: Май 9, 2024

Background: Observational studies have indicated a potential correlation between glioblastoma and circulating inflammatory proteins. Further investigation is required to establish causal relationship these two factors. Methods: We performed Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary of 91 inflammation-related proteins (N = 14,824) assess their impact on glioblastoma. The GWAS data for included 243 cases 287,137 controls. inverse variance weighted (IVW) method was used as the primary analytical causality. Four additional MR methods [simple mode, MR-Egger, median, mode] were supplement IVW results. Furthermore, several sensitivity analyses heterogeneity, horizontal pleiotropy, stability. Reverse also performed. transcriptomic from Cancer Genome Atlas (TCGA) analyzed validate findings obtained through MR, while pathway functional enrichment conducted predict underlying mechanisms. Results: Our employing in our forward provide robust evidence supporting elevated levels Cystatin D, well decreased fibroblast growth factor 21 (FGF21) circulation. Moreover, reverse revealed that may contribute increased concentrations C-X-C motif chemokine 9 (CXCL9) Interleukin-33 (IL-33) bloodstream. Transcriptomic showed FGF21 expression inversely associated with risk developing glioblastoma, whereas an linked CXCL9 IL-33. Pathway suggested D might exert its effects intracellular protein transport, affect via glucose response Conclusion: These results indicate significant susceptibility. Glioblastoma affects such Interleukin-33, providing new insights into mechanisms genesis clinical research.

Язык: Английский

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Tripartite Motif-Containing Protein 65 Promotes Proliferation and Inhibits Ferroptosis in Prostate Cancer via Enhancing NKD Inhibitor of WNT Signaling Pathway 2 Ubiquitination

Rejuvenation Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 23, 2024

As a typical E3 ligase, tripartite motif-containing 65 (TRIM65), is implicated in the modulation of biological processes, such as metastasis, proliferation, and apoptosis. However, function TRIM65 prostate cancer (PCa) its potential mechanism have not yet been excavated. In this work, we affirmed Tripartite protein (TRIM65) new oncogene PCa, which accelerated PCa cell proliferation impeded ferroptosis. vivo, depletion inhibited tumorigenesis metastasis. Mechanically, our findings uncovered that enhances NKD inhibitor WNT signaling pathway 2 (NKD2) degradation via ubiquitin-proteasome signaling. facilitated restricted ferroptosis downregulating NKD2 levels. Moreover, activated wingless-integrated/β-catenin cells inhibiting NKD2. Taken together, these data controls regulates Wnt/β-catenin directly targeting for ubiquitination degradation. Our study provides insights into multifaceted regulatory role development laying foundation exploring therapeutic approaches.

Язык: Английский

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