Alleviation of adverse effects associated with α-glucosidase inhibitors by Ocimum basilicum L., Matricaria chamomilla L., and Salvia officinalis L. reveals novel selective inhibition of Bacillus α-glucosidase by acarbose.

Integrative analyses of network pharmacology and bioinformatics reveal the synergistic antitumor effects of cantharidin and ginsenosides Rg3 on hepatocellular carcinoma.

Hydroxy Safflower Yellow A: A Natural Compound from Carthamus tinctorius L. with Potent Activity Against Liver Fibrosis and Cancer.

Single-cell analysis of TIGD genes in hepatocellular carcinoma: Prognostic value and functional characterization.

Time-dependent diffusion MRI combined with enhanced MRI and clinical indicators for preoperative prediction of CK19 expression status in hepatocellular carcinoma: a prospective study.

The Central Qi theory in traditional Chinese medicine: Gut microbiota modulation as a strategic target for hepatocellular carcinoma therapy.

Canine hepatocellular carcinoma (HCC) requires further molecular characterization to identify diagnostic and therapeutic targets, and to establish whether dogs with this condition can model the human disease. Accordingly, we aimed to identify differentially expressed genes (DEGs) in canine HCC and evaluate cross-species transcriptomic dysregulation in canine and human HCC. Liver tissue samples from three dogs with HCC and three healthy dogs were subjected to next-generation sequencing, followed by RT-qPCR validation. Identified DEGs were then targeted in bioinformatics analyses (pathway enrichment, protein-protein interaction network, and hub gene analyses) for molecular characterization and comparison with human HCC datasets. We identified 975 DEGs (upregulated: 604; and downregulated: 371). Extracellular matrix-receptor interaction, focal adhesion, cell adhesion molecule, PI3K/Akt signaling, and cytokine/chemokine-related pathways were enriched. C1R, APOC3, C1QA, APOA1, C1QB, ACTG1, C1QC, CRP, ANXA5, and ANXA2 were identified as hub genes. Canine and human HCCs share 118 DEGs, highlighting conserved alterations in metabolic pathways, PI3K-Akt signaling, focal adhesion, and PPAR signaling pathways. Based on human HCC data, SPP1, NQO1, RRM2, APOA1, APOC3, ALDOB, and IGF1 were identified as prognosticators indicating poor overall survival. This study presents the first cross-species transcriptomic analysis of canine HCC, revealing significant molecular resemblances to human HCC, indicating it may be a promising comparative model for studying tumor biology, drug responses, and novel therapeutic interventions.

Lenvatinib is a first-line treatment option for advanced hepatocellular carcinoma (HCC), but resistance development is a challenge. A comprehensive and in-depth exploration of the molecular mechanisms underlying Lenvatinib resistance may provide novel insights and strategies for enhancing its therapeutic effectiveness. We established Lenvatinib-sensitive (LS) and Lenvatinib-resistant (LR) HCC models both in vitro and in vivo. Dot blot and Western blot analyses confirmed that the m6A methylation levels were elevated in the LR models, while the expression of ALKBH5 was significantly reduced. Lentivirus-mediated transfection of HCC cells was employed to validate the inhibitory role of ALKBH5 in Lenvatinib resistance in HCC. Mechanistically, we integrated sequencing results from mRNA and methylated RNA immunoprecipitation (MeRIP), followed by validation through RNA immunoprecipitation (RIP), MeRIP-qPCR, dual luciferase reporter assays, Liquid chromatography and tandem mass spectrometry (LC-MS/MS), Enzyme-linked immunosorbent assay (ELISA), and animal experiments (including subcutaneous tumor models and HCC orthotopic mouse models). Results confirmed that ALKBH5 deficiency in LR cells elevated m6A methylation of TBX3 mRNA, thereby enhancing its stability. TBX3 bound to the promoter region of CYP27A1, stimulating its transcription and promoting the synthesis of the cholesterol metabolite 27-hydroxycholesterol (27HC). 27HC could inhibit ferroptosis, thereby protecting LR cells from the targeting effects of Lenvatinib. Additionally, T cell-mediated tumor cell killing and flow cytometry assays evaluated that HCC-derived 27HC promoted CD8+ T cell exhaustion. Our findings indicated that the deficiency of ALKBH5 mediated the enhanced synthesis of the cholesterol metabolite 27HC, which in turn inhibited ferroptosis in HCC cells and the cytotoxicity of CD8+ T cells, leading to Lenvatinib resistance in HCC cells. While the specific role of 27HC was strongly supported, the potential contributions of other CYP27A1-derived metabolites to this phenotype remain a possibility.

To evaluate the diagnostic potential of microstructural parameters derived from time-dependent diffusion magnetic resonance imaging (Td-dMRI) for distinguishing hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). We established nude mouse models bearing subcutaneous xenografts of HCC (MHCC97H, HepG2 cell lines) and ICC (QBC939 cell line) (n=30). All models underwent Td-dMRI scanning. Microstructural parameters, including cell diameter (d), extracellular diffusion coefficient (Dex), intracellular volume fraction (Vin), and cellularity, were calculated based on the IMPULSED model. Intergroup differences were assessed using independent samples t-test or Mann-Whitney U test (significance threshold: P<0.05). The diagnostic performance of each parameter was evaluated by receiver operating characteristic (ROC) curve analysis. Post-operative liver tissue specimens were subjected to β-catenin immunohistochemical staining to validate the correlation between imaging parameters and pathological findings. The ICC group exhibited significantly higher Dex values compared to the HCC group (P<0.05), whereas d, Vin, and cellularity were significantly lower in the ICC group (P<0.05). The areas under the ROC curve (AUCs) for differentiating HCC from ICC were 0.838 for Dex, 0.779 for d, 0.833 for Vin, and 0.733 for cellularity. The d value measured by Td-dMRI showed a significant positive correlation with pathological results (r=0.634, P<0.05). Notably, combining Vin and cellularity parameters enhanced the AUC to 0.95, outperforming any single parameter. The ICC group exhibited a significantly higher extracellular diffusivity (Dex) compared to the HCC group, whereas the cell diameter (d), intracellular volume fraction (Vin), and cellularity were significantly lower (all P<0.05). The area under the. Td-dMRI enables non-invasive differentiation between HCC and ICC by quantifying distinct tumor microstructural environments. The parameters derived from this technique show promise as potential imaging biomarkers for subtyping liver cancers.

Lenvatinib-resistant liver cancer-derived HSP90α-containing extracellular vesicles enhance drug resistance via macrophage CXCL8 secretion.

Integrative metabolomic and transcriptomic profiling reveals distinct metabolic signatures of hepatocellular carcinoma arising from cirrhosis.

Liver cancer-derived exosomal PTK6 induces the secretion of pulmonary CHI3L1 to facilitate lung metastatic niche formation.

Entinostat suppresses hepatocellular carcinoma metastasis by upregulating AZGP1 through histone acetylation.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, and despite advances in systemic therapies, resistance to targeted therapies such as Sorafenib significantly limits clinical benefit and contributes to poor outcomes. The mechanisms that enable HCC cells to withstand oxidative stress and evade therapy remain incompletely understood. Here, we identify an RNA regulatory role of NAT10 in sustaining redox homeostasis in HCC. We show that NAT10 stabilizes Nrf2 mRNA, a master regulator of antioxidant responses, thereby maintaining Nrf2 protein abundance and reducing intracellular reactive oxygen species (ROS) levels in HCC cells. Genetic silencing or pharmacologic inhibition of NAT10 disrupts this regulatory axis, leading to elevated ROS accumulation, induces DNA damage, and enhances apoptosis. Importantly, NAT10 knockdown markedly sensitizes HCC cells to Sorafenib, and simultaneous inhibition of NAT10 and Nrf2 exhibits a synergistic pro-apoptotic effect, suggesting that oxidative stress overload is a key vulnerability created by targeting this pathway. Together, these finding uncover a NAT10-Nrf2 RNA stability axis that enhances antioxidant capacity and therapeutic tolerance in HCC, and highlight NAT10 as a promising target for overcoming drug resistance and improving treatment response.

Saquinavir induces pyroptosis through the OTUD5-JAK1-GSDME axis in hepatocellular carcinoma.

DNMT1 and DNMT3A drive hepatocellular carcinoma progression via epigenetic regulation and are inhibited by 5-azacytidine.

Hepatocarcinogenesis arising from liver cirrhosis is a major contributor to hepatocellular carcinoma (HCC), but effective interventions remain limited Objective: This study aimed to elucidate the molecular mechanism by which icariin suppresses cirrhosis-to-cancer progression through the ROS/NLRP3/miR-145 axis. Fifty Sprague-Dawley rats were randomly assigned to five groups: control, model, low-dose icariin (ICA-L), high-dose icariin (ICA-H), and positive control. In vitro, SMMC-7721 and HepG2 cells were treated with TGF-β1 and various concentrations of icariin to assess their effects on hepatocellular carcinoma cell activity. Compared with the model group, icariin significantly reduced the liver index, serum AFP levels, Ki-67 positivity, and hepatic ROS levels in rats, suppressed NLRP3 expression, upregulated miR-145, and effectively ameliorated liver fibrosis and dysplasia (P<0.05). In SMMC-7721 cells, icariin inhibited TGF-β1-induced proliferation, migration and invasion, promoted apoptosis and G0/G1 phase arrest, while concurrently increasing exosomal miR-145 levels (P<0.05). Further mechanism verification confirmed that miR-145 directly targets and inhibits NLRP3 expression. Icariin effectively inhibits cirrhosis-associated carcinogenesis by suppressing the ROS-NLRP3 pathway and upregulating miR-145, providing a theoretical basis for the prevention and treatment of cirrhosis and hepatocellular carcinoma.

Dietary L-Se-methylselenocysteine suppresses liver tumor progression via integrated antioxidant, immune, and apoptotic modulation in mice.

The main objective of this study is to investigate the prognostic value of serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) in predicting postoperative outcomes for hepatocellular carcinoma (HCC) patients after surgical resection. Serum PIVKA‑II levels were compared between early‑stage (stage I+II) and advanced‑stage (stage III+IV) HCC patients. Correlations between PIVKA‑II and clinicopathological features were examined. Kaplan‑Meier curves were plotted to assess overall survival (OS) and recurrence‑free survival (RFS) by PIVKA‑II levels. Receiver operating characteristic (ROC) analysis compared the predictive performance of PIVKA‑II and α ‑fetoprotein (AFP), with DeLong 's test evaluating differences in area under the curve. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors for postoperative survival and recurrence. Serum PIVKA‑II levels were significantly elevated in HCC patients compared with controls ( P < 0.01), and were higher in advanced‑stage than early‑stage HCC ( P < 0.01). PIVKA‑II correlated significantly with tumor diameter, tumor node metastasis classification, lymph node infiltration, distant metastasis, differentiation, and complication incidence (all P < 0.05). Patients with high PIVKA‑II (≥100 mAU/ml) had shorter median OS and RFS than those with low levels (<100 mAU/ml) ( P < 0.01). PIVKA‑II outperformed AFP in predicting 5‑year survival and recurrence ( P < 0.05), and combined use improved predictive accuracy ( P < 0.05). Multivariate Cox regression identified PIVKA‑II ≥100 mAU/ml as an independent prognostic factor for both OS and RFS ( P < 0.05). Our study confirms that serum PIVKA-II can serve as a prognostic predictor for HCC patients after surgical treatment.

Tumor stiffness as an imaging biomarker of tyrosine kinase inhibitor response: A preclinical study.