Cytotechnology. 2026 Jun;78(3):119. doi: 10.1007/s10616-026-00993-x. Epub 2026 May 14.

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer worldwide, with increasing incidence and mortality rates. Although several targeted therapies are currently available, the therapeutic outcomes remain unsatisfactory due to the high heterogeneity and drug resistance of HCC. Therefore, novel molecular mechanisms and therapeutic strategies urgently need to be explored. In this study, we obtained the GSE39791 dataset from the GEO database and identified 1,186 differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was conducted to obtain 776 key module genes, which were intersected with 11,671 HCC-related genes from the GeneCards database, resulting in 226 candidate genes. A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 20 hub genes were identified using the MNC algorithm in Cytoscape. Among these, the five most significant hub genes-RFC4, TOP2A, AURKA, HSP90AA1, and MCM4-were selected for further analysis. KEGG enrichment analysis was performed to explore their functional pathways. Potential therapeutic agents were predicted using the CMap database, and molecular docking was conducted via AutoDock Vina. To validate the computational predictions, a quercetin intervention model was established. The optimal dose was determined through CCK-8 assays in HepG2 cells, and the expression of the five hub genes was examined in normal liver cells (LO2), HepG2 cells, and HepG2 cells treated with quercetin using RT-qPCR. The five hub genes-RFC4, TOP2A, AURKA, HSP90AA1, and MCM4-were significantly overexpressed in both HCC tissues and cell lines. Enrichment analysis revealed that these genes were mainly involved in cancer-related pathways, including the cell cycle, p53 signaling pathway, and FoxO signaling pathway. Drug prediction analysis showed that quercetin exhibited a negative regulatory pattern with respect to HCC and displayed binding energies below - 5 kcal/mol with all five hub proteins. CCK-8 assays confirmed the dose-dependent inhibitory effect of quercetin on HepG2 cell viability. RT-qPCR results demonstrated that quercetin significantly downregulated the expression of the five hub genes, consistent with the bioinformatics predictions. This study integrated multi-omics analysis and experimental validation to identify five core genes closely associated with HCC and suggested that quercetin may exert anti-HCC effects partly associated with the regulation of these genes. Our findings offer new insights into the molecular mechanisms of HCC and provide a promising strategy for the development of targeted therapeutics.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-00993-x.

PMID:42145839 | PMC:PMC13176377 | DOI:10.1007/s10616-026-00993-x

J Ethnopharmacol. 2026 Mar 30;365:121612. doi: 10.1016/j.jep.2026.121612. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Airway inflammation is one of the primary pathological characteristics of asthma. Soufeng Yuchuan (SFYC) decoction, a compound formula derived from multiple traditional Chinese medicine prescriptions, is widely applied clinically and exhibits significant therapeutic efficacy against asthma. However, its anti-asthmatic mechanisms remain incompletely understood.

MATERIALS AND METHODS: Asthmatic rat models induced by ovalbumin (OVA) and ferroptosis models induced by erastin in BEAS-2B cells were established. Proteomics and metabolomics analyses were conducted on lung tissues and serum. Key ferroptosis-related targets (GPX4, SLC7A11/SLC3A2, GCLC, GSS, and VDAC2) were validated using Western blotting, RT-qPCR, and biochemical assays. The direct anti-ferroptosis effects of SFYC-containing serum were compared with ferrostatin-1 and blank serum in vitro.

RESULTS: Integrated omics analysis revealed that ferroptosis, glutathione metabolism, and ROS signaling pathways were the core targets modulated by SFYC. In vivo, SFYC significantly reduced airway inflammation and ROS accumulation, restored pulmonary GSH levels, upregulated the expression of GPX4, GCLC, GSS, SLC7A11, and SLC3A2, and downregulated VDAC2 expression (P < 0.05). In vitro, SFYC-containing serum effectively reversed erastin-induced lipid peroxidation, iron overload, GSH depletion, ROS elevation, and apoptosis in BEAS-2B cells, demonstrating comparable or superior efficacy to ferrostatin-1.

CONCLUSION: SFYC alleviates airway inflammation in asthma primarily by inhibiting ferroptosis. This study provides evidence that SFYC exerts anti-asthmatic effects, at least in part, via the regulation of ferroptosis pathways.

PMID:41921764 | DOI:10.1016/j.jep.2026.121612

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w