Bladder cancer (BCa) is the second most common cancer of the genitourinary tract globally. It has limited treatment options, high recurrence rate, and acquires resistance to platinum-based therapy. Therefore, identifying novel therapeutic targets is urgently needed. Analysis of the TCGA data revealed that the enzyme galactokinase-1 (GALK1) is overexpressed (p < 0.0001) in bladder tumors compared to normal tissue. Our data also confirmed GALK1 protein upregulation in multiple human BCa cell lines and rodent bladder tumors. However, the precise role of GALK1 in BCa progression and effects of its specific inhibitor remain unexamined. In this study, we demonstrate that GALK1 gene silencing using shRNA resulted in a significant reduction in BCa cell proliferation, migration, and invasion. Pharmacological inhibition of GALK1 using small molecule Cpd36 resulted in anticancer efficacy against BCa. Cpd36 inhibited proliferation, migration, and invasion of BCa cells. Further, Cpd36 induced G1 phase cell cycle arrest, apoptosis, mitochondrial membrane depolarization, and ROS production in the BCa cells. Mechanistically, Cpd36-induced reduction in cell proliferation was associated with a decrease in expression of GALK1, PCNA proteins. Inhibition of metastatic potential was accompanied by decreased migration, invasion, and MMP-9 expression. Cell cycle arrest was associated with decrease in Cyclin D1 and increased expression of p21 and p27. Induction of apoptosis was linked with increased expression of cleaved caspase-3 and cleaved PARP, while downregulating p-AKT. Additionally, Cpd36 in combination with cisplatin or gemcitabine showed a strong synergistic effect on BCa cells. Taken together, our findings suggest that GALK1 plays a significant role in BCa cell survival and validates its inhibitors as promising therapeutic options for managing this disease.

Alterations in tight junction (TJ) organization and dysregulation of cancer stem cell (CSC)-associated markers are increasingly recognized as molecular features linked to colorectal cancer (CRC) progression, heterogeneity and clinical outcome. Bioactive dietary compounds such as spermidine (SPD) and eugenol (EUG) have been proposed as modulators of cancer-related molecular pathways; however, their combined effects on CRC spheroid models relevant to molecular characterization remain insufficiently defined. In the present study, the molecular impact of SPD and EUG, administered individually or in combination, was evaluated in primary and metastatic CRC spheroids. First-generation spheroids derived from Caco-2 and SW620 cells were exposed to SPD, EUG, or SPD+EUG at the time of seeding, and spheroid growth and self-renewal capacity were monitored across successive generations. The expression of TJ- and CSC-associated markers was assessed at both the transcript and protein levels using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunohistochemistry. The combined SPD+EUG treatment was associated with a marked reduction in spheroid area and self-renewal capacity in both CRC models. Baseline molecular profiling revealed higher TJ marker expression in Caco-2 spheroids and enrichment of CSC-associated markers in SW620 spheroids. Treatment-induced modulation of CSC- and TJ-related transcripts was observed; however, transcript-level changes were not consistently mirrored at the protein level, indicating the involvement of post-transcriptional regulatory mechanisms. In particular, Occludin (OCLN), Zonula occludens-1 (ZO-1), CD133, ALDH1A1, SOX2 and VE-cadherin exhibited divergent RNA and protein expression patterns depending on cell type and treatment condition. Collectively, these findings underscore the relevance of three-dimensional CRC spheroid models for molecular profiling studies and highlight the importance of integrating transcript- and protein-level analyses when evaluating bioactive compounds with potential diagnostic and translational relevance in colorectal cancer.

Renal cell carcinoma (RCC) is the most common kidney cancer, with increasing global incidence. Despite advances with VEGF-targeted tyrosine kinase inhibitors (TKIs) and immunotherapies, therapeutic resistance remains frequent, limiting long-term benefits. This highlights the need for potential biomarkers of tumor aggressiveness and therapeutic candidates, such as glucose-6-phosphate dehydrogenase (G6PD), whose altered expression has been associated with several cancers. We evaluated G6PD gene and protein expression in 121 RCC samples through immunohistochemistry and assessed functional role in vitro approaches. 786-O and ACHN cells were treated with the inhibitor G6PDi-1 and the anti-VEGF cabozantinib/lenvatinib. G6PD mRNA levels were higher in tumors than in non-neoplastic tissues, indicating shorter overall survival in clear cell (ccRCC) and papillary (pRCC) subtypes. Immunolabeling confirmed a higher expression in pRCC and associations with pathological features. CRISPR and RNAi datasets revealed a stronger G6PD dependency in the ccRCC. A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose-response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models.

Triple-negative breast cancer (TNBC) poses significant therapeutic challenges due to the limited availability of targeted treatment options and the development of resistance to chemotherapy, including doxorubicin (DOX). The objective of this study was to investigate the impact of inhibiting activated pathways in DOX-resistant TNBC and examine the effects on MAPK and PI3K/Akt signaling pathways, cell cycle regulation, and the regulators of the epithelial-mesenchymal transition (EMT) process. Continuous exposure of cells to increasing concentrations of DOX resulted in the selection of resistant cells that exhibited EMT characteristics. We assessed the expression levels of markers related to cell death, survival, mitophagy pathways and EMT using Western blotting and qPCR in both sensitive and resistant cells with activated-pathway inhibitor treatments. Additionally, we demonstrated differences in migration capacity between resistant and sensitive cells with or without inhibitor treatments. It was found that MEK inhibition was less effective than PI3K inhibition in both sensitive and resistant cells. Expression analyses clearly demonstrated that resistant cells exhibited more aggressive behavior, as indicated by EMT- and survival-related gene expressions. The combination of MEK and PI3K inhibitors was more effective in shutting down these signals in both cell types. The ability to induce EMT in DOX-resistant cells revealed that one form of resistance might combine with another, acting as a mediator for cellular switch. Although drug resistance and various inhibitors reduce the proliferative capacity of cells and related parameters, resistance contributes to the acquisition of metastatic characteristics.

Upregulation of glutaminase enzymatic activity promotes tumour cell proliferation. Its overexpression correlates with poor disease outcome in patients, including those with breast cancer. A selective glutaminase inhibitor, CB-839, which targets cancer cells by blocking glutamine conversion to glutamate, has shown promising preclinical results as a therapeutic target in triple-negative breast cancer treatment. The current study aimed to determine the importance of glutaminase in Oestrogen Receptor positive/luminal breast cancer to potentially identify therapeutic targets to treat this subtype. In vitro studies using luminal breast cancer cells were performed to investigate the effects of siRNA knockdown of glutaminase genes (GLS and GLS2) and inhibition using CB-839 on functional assays. Silencing GLS in luminal breast cancer cells significantly reduced cell proliferation whilst inducing apoptosis. A similar impact on cell proliferation was observed when silencing GLS2 in luminal B cells, but there was no observed effect on cell apoptosis and cell cycle. There was little effect of GLS inhibition using CB-839 in luminal breast cancer. This study demonstrates that glutaminase is necessary for luminal breast cancer growth and survival. Co-targeting GLS and GLS2 might be a novel approach for the treatment of this subclass. Further functional studies to evaluate the underlying molecular mechanisms of this process are warranted.

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer deaths, with resistance to targeted therapies posing a major clinical challenge. Drug-tolerant persister (DTP) cells are key contributors to resistance, and targeting them offers new strategies to enhance existing treatments. MicroRNAs (miRNAs), particularly the tumour-suppressive miR-15/107 family, offer promise due to their ability to target multiple oncogenic pathways. This study evaluated a synthetic consensus miRNA mimic, conmiR-15/107, in NSCLC cell line models. Dose-response assays showed robust, dose-dependent growth inhibition in both EGFR-mutant (PC9) and KRAS-mutant (H358 and A549) lung adenocarcinoma cells, but not in the human bronchial epithelial cell line BEAS-2B. When combined with EGFR inhibitors (osimertinib and gefitinib) in PC9 cells, the mimics showed a higher rate of growth inhibition compared with the controls and reduced IC50 values. Similarly, conmiR-15/107 enhanced growth inhibition by the KRAS inhibitors sotorasib and adagrasib in H358 cells. RT-qPCR confirmed downregulation of conmiR-15/107 targets, including MEK1, BCL2 and BRCA1, suggesting a multi-target mechanism of action. Long-term assays showed that the mimics reduced the survival and delayed the proliferation of DTPs in osimertinib-treated PC9 cells as well as sotorasib-treated H358 cells. These findings support conmiR-15/107 as a potential adjunct to targeted therapy, capable of enhancing treatment efficacy and delaying resistance in lung adenocarcinoma.

Listeria monocytogenes (LM) is a major foodborne pathogen causing illnesses ranging from gastroenteritis to severe systemic infections. The key virulence factors include bacterial motility, hemolysin and lecithinase production, and invasion of host tissues. This study investigated the anti-virulence effects of cannabidiol (CBD), the main non-psychoactive compound in Cannabis sativa, against LM. The minimum inhibitory concentration (MIC, 2289 μM; 719.8 µg/mL) and sub-inhibitory concentration (SIC, 11.92 μM; 3.75 µg/mL) of CBD were determined for LM strains Scott A and ATCC 19115. Cultures were treated with SIC, 6× SIC, 1/4× MIC, and MIC to assess effects on motility, hemolysin and lecithinase production, and adhesion and invasion of human intestinal (Caco-2) and brain endothelial (HBMEC) cells, alongside virulence gene expression by RT-qPCR. Cannabidiol's efficacy was also determined using a Galleria mellonella larval infection model at SIC and 6× SIC. Cannabidiol at 6× SIC significantly reduced motility, toxin production, and host cell adhesion and invasion (p < 0.05). RT-qPCR revealed downregulation of key virulence genes, including prfA, hly, plcA, plcB, iap, motA, motB, actA, inlA, and inlB. In vivo, CBD enhanced larval survival in a dose-dependent manner and cytotoxicity was observed at concentrations above 33.75 µg/mL. These results indicate that CBD, at non-bactericidal levels, effectively suppresses multiple virulence mechanisms in LM, highlighting its potential as a novel anti-virulence agent for food safety and therapeutic applications.

BASIC PENTACYSTEINE (BPC) transcription factors are plant-specific and play crucial roles in regulating plant development and responses to abiotic stresses. However, the genomic characteristics of the BPC gene family in Brassica juncea and its regulatory mechanisms in response to light and salicylic acid remain poorly understood. In this study, we identified 25 BjuBPC genes in the B. juncea genome using bioinformatic approaches. All BjuBPC proteins were predicted to localize exclusively to the nucleus, with their distribution scattered across 14 chromosomes of B. juncea. Phylogenetic analysis classified these BjuBPC genes into three subfamilies (A, B, and C). The 25 BjuBPC genes showed strong collinearity with BPC orthologs from Arabidopsis thaliana, Brassica rapa, and Brassica nigra, and members of the same subfamily shared highly conserved exon-intron architectures and motif compositions, and a highly conserved canonical GAGA DNA-binding domain. Expression profiling across tissues revealed both tissue-specific and constitutive expression patterns among BjuBPC members. Subsequent expression analyses under four light qualities and exogenous salicylic acid treatment demonstrated that BjuBPC1, BjuBPC9, and BjuBPC24 were specifically responsive to both light and salicylic acid signals, with markedly strong induction by blue light. These findings provide valuable insights for future functional characterization of BjuBPC genes and enhance our understanding of their biological roles in B. juncea.

Leucine-rich repeat-containing 8A (LRRC8A; also known as SWELL1), the essential subunit of volume-regulated anion channels (VRACs), is amplified in multiple malignancies and has been implicated in tumor progression and therapeutic resistance. Three-dimensional (3D) cancer spheroids have been well-established as in vitro models that recapitulate characteristics of tumor stemness and intrinsic drug resistance. In the present study, spheroid formation in human breast cancer cell lines, YMB-1 and MDA-MB-468, conferred resistance to multiple anticancer drugs, including doxorubicin (DOX), gemcitabine (GEM), and 5-fluorouracil (5-FU), thereby mimicking the characteristic properties of breast cancer stem-like cells. LRRC8A expression was upregulated in 3D spheroids compared with adherent 2D monolayers, and its pharmacological inhibition induced membrane hyperpolarization accompanied by intracellular Cl- accumulation. Inhibition of LRRC8A significantly sensitized spheroids to DOX, GEM, and 5-FU. Spheroid formation increased the expression of multidrug resistance-related protein 3 (MRP3) and the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4), whereas LRRC8A inhibition suppressed their expression. The transcriptional upregulation of MRP3 and CYP3A4 was mediated through the NRF2-CEBPB/D transcriptional axis. Collectively, these findings suggest that LRRC8A inhibition may represent a therapeutic strategy to overcome chemoresistance by repressing MRP3 and/or CYP3A4 expression in breast cancer stem cells.

Deuterium abundance has been proposed as a modulator of cellular metabolism; however, its influence on cancer-associated gene expression networks remains incompletely characterized. We analyzed A549 lung adenocarcinoma cells cultured across four deuterium concentrations (40, 80, 150, and 300 ppm) using NanoString nCounter profiling. Expression data were processed through multistep filtering, symbolic trajectory encoding, and density-based spatial clustering (DBSCAN) to identify extreme expression responders, and Gaussian mixture modeling (GMM-6) to resolve coordinated gene-expression modules. DBSCAN identified 11 outlier genes under deuterium depletion, including reduced expression of multidrug-resistance-associated ABCB1 (-42% at 80 ppm), proliferative signaling component FGFR4 (-19%), and transcriptional amplifier MYCN (-24%). In contrast, enrichment at 300 ppm produced a broad increase in oncogenic expression (mean +44%), with marked elevation of inflammation-related (IL6, TGFBR2) and invasion-associated (MMP9) genes. GMM-6 clustering of the remaining core network resolved six functional modules, indicating that depletion preferentially reduces expression of genes associated with plasticity-related programs (Cluster 5: TGFB1, S100A4), while basal survival-associated genes (Cluster 6: BIRC5, RET) remain comparatively stable. Together, these results indicate that deuterium concentration acts as a bidirectional modulator of gene expression programs in the A549 model, with enrichment broadly elevating oncogenic expression and moderate depletion associated with selective downregulation of genes linked to resistance, signaling, and invasive behavior. Significance: Deuterium depletion is associated with reduced expression of genes involved in multidrug resistance, growth-factor signaling, and transcriptional amplification, revealing deuterium-responsive transcriptional vulnerabilities within the A549 lung adenocarcinoma model.

Hydrogen peroxide (H2O2) regulates plant metabolism. This study examined its effect on the biosynthesis of specialized metabolites in Baccharis conferta, a medicinal plant rich in phenolics and terpenes. Plants were elicited with 25 µM and 250 µM H2O2. Phenolic changes were evaluated by total phenolic content (TPC), total flavonoid content (TFC), phenylalanine ammonia-lyase (PAL) activity, and LC-MS analysis of flavonoids and hydroxycinnamic acids. Meanwhile, terpene changes were evaluated by HPTLC, total terpene content (TTC), and expression of the 1-deoxy-D-xylulose-5-phosphate synthase (Bco-DXS1) gene. H2O2 markedly modulated both pathways. Phenolic metabolism was activated, particularly under 25 µM H2O2, with PAL activity increasing by 52%, TPC by 42%, and TFC by 50% relative to the control. Chemical analysis revealed that five compounds, including chlorogenic acid, differed significantly across treatments. Gene expression analysis showed that 25 µM H2O2 upregulated Bco-DXS1 and increased TTC, whereas 250 µM H2O2 repressed gene expression but still enhanced terpene accumulation. Overall, these results suggest that moderate H2O2 levels function as a signaling molecule in B. conferta, simultaneously boosting phenolic and terpene pathways. This highlights controlled H2O2 elicitation as an effective biotechnological approach to increase the production of valuable metabolites in medicinal plant cultures.

Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tree with increasing global incidence and mortality and limited therapeutic options. Intrahepatic cholangiocarcinoma (iCCA) metabolism exhibits enhanced glycolysis, oxidative phosphorylation, and glutamine utilization. In this study, we investigated the therapeutic potential of targeting glutaminolysis in iCCA, identifying glutamate dehydrogenase (GDH)-which converts glutamate to α-ketoglutarate-as a key metabolic hub. We evaluated the effects of pomegranate waste extract (PWE), a by-product of industrial pomegranate juice production, on cell viability, proliferation, migration, ATP production, and extracellular acidification in CCLP1 cells, an established iCCA model. Our results are consistent with an altered cellular energy metabolism. We further assessed GDH enzymatic activity, expression, and transcriptional regulation in the presence or absence of PWE and its major components, punicalagin and ellagic acid. GDH expression was downregulated by PWE in a dose-dependent manner through inhibition of NF-κB signaling, revealing a new mechanistic link between NF-κB and GDH. In addition, GDH enzymatic activity was dose-dependently inhibited by PWE, as well as punicalagin and ellagic acid. Notably, punicalagin was identified as a novel competitive inhibitor of GDH. Overall, these findings provide the first evidence that modulation of glutaminolysis through GDH targeting impairs iCCA cell growth and metabolism, supporting GDH as a promising metabolic target. This study highlights pomegranate-derived compounds as potential leads for the development of adjunctive or preventive strategies in intrahepatic cholangiocarcinoma.

The small molecule SR8278 was initially identified as an antagonist of the REV-ERB (reverse c-ERBAa) nuclear receptor proteins, which play important roles in metabolism and circadian rhythms. Though SR8278 has been shown to have beneficial physiological effects in a variety of different preclinical disease contexts, its impact on gene expression and cell proliferation in keratinocytes has not previously been examined. We therefore carried out an RNA-seq analysis and found that genes involved in the G1/S transition of the cell cycle were significantly impacted by SR8278 treatment, and these effects were confirmed at both the RNA and protein level by RT-qPCR and Western blotting, respectively. Cell proliferation assays showed that SR8278 slowed cell growth but did not induce genotoxic stress or apoptosis. Finally, the use of CRISPR/Cas9 genome editing and siRNA-mediated disruption of REV-ERB gene expression showed that the loss of the REV-ERB proteins did not impact the effect of SR8278 on gene expression and cell proliferation. We conclude that the anti-proliferative effects of SR8278 are not mediated by the REV-ERB proteins, and, thus, care should be taken when interpreting studies involving this compound unless complementary genetic approaches are also shown, particularly in studies involving cell proliferation.

Apigenin, a naturally occurring flavonoid with low toxicity, exhibits anticancer activity, yet its effects on microRNAs (miRNAs) and downstream gene networks in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we evaluated apigenin's antitumor effects in TE-1 and Eca-109 cells, assessing proliferation, apoptosis, colony formation, and invasion. Differentially expressed miRNAs were identified via small RNA sequencing, and candidate target genes were predicted, annotated using GO and KEGG analyses, and validated by qRT-PCR, revealing miRNA-mediated regulatory mechanisms underlying apigenin's inhibitory effects in ESCC. Apigenin markedly suppressed cell proliferation, clonogenic growth, wound closure, and invasive capacity, while promoting apoptosis in a dose-dependent manner. In TE-1 cells, apigenin upregulated hsa-let-7c-3p, hsa-miR-374c-3p, hsa-miR-3177-3p hsa-miR-4454, and hsa-miR-4728-3p, while downregulating hsa-miR-573, hsa-miR-548az-5p, hsa-miR-33b-5p, hsa-miR-4479, and hsa-miR-3198. Correspondingly, tumor-associated target genes including ALDH3A2, SEMA3F, MAP4K5, and TRIP13 were upregulated, whereas PIK3IP1, AGO2, MMP2, and RALBP1 were suppressed. In Eca-109 cells, apigenin altered the expression of distinct miRNAs, including the upregulation of hsa-miR-891-5p, hsa-miR-3170, hsa-miR-4421, and hsa-miR-675-5p and the downregulation of hsa-miR-153, hsa-miR-3188, and hsa-miR-4435, thereby modulating key oncogenic targets such as MAPK1, SALL4, and COX15. Functional enrichment analyses indicated that apigenin-regulated genes are involved in multiple cancer-related pathways across cytoplasmic and nuclear compartments. Overall, these results suggest that apigenin suppresses ESCC progression via coordinated miRNA-mRNA regulation, highlighting its potential as a therapeutic agent.

Loss of ovarian hormones following menopause or ovariectomy is associated with increased anxiety, cognitive impairment, and dysregulation of hypothalamic neuroendocrine pathways. MicroRNAs (miRNAs) and tRNA-derived fragments (tRFs) are emerging classes of small non-coding RNAs that act as post-transcriptional regulators of stress, inflammation, and synaptic function; however, their coordinated involvement in estradiol-mediated hypothalamic regulation remains poorly understood. In this study, adult female mice were assigned to control, estradiol-treated, ovariectomized (OVX), or OVX plus estradiol groups. Anxiety- and cognition-related behaviors were assessed using the open field, Y-maze, and elevated plus maze tests. Circulating estradiol levels and hypothalamic gonadotropin-releasing hormone (GnRH) expression were quantified by ELISA. Hypothalamic mRNA, miRNA, and tRF expression profiles were analyzed by RNA sequencing, followed by differential expression analysis, functional enrichment, integrative network construction, and quantitative real-time PCR validation. Ovariectomy induced anxiety-like behaviors, impaired working memory, reduced estradiol levels, and increased hypothalamic GnRH expression, all of which were reversed by estradiol treatment. Transcriptomic analysis identified 376 differentially expressed miRNAs, 182 differentially expressed tRFs, and 439 differentially expressed mRNAs, enriched in pathways related to stress responses, neuroendocrine regulation, synaptic signaling, metabolic homeostasis, and neuroinflammation. Integrated miRNA-mRNA and tRF-mRNA network analyses revealed several estradiol-responsive miRNAs (including miR-200a-5p, miR-182/183-5p, miR-381-3p, miR-148a-3p, and miR-10 family members) predicting key hub genes such as Gcg, Wnt4, Prkacb, Sgk1, Fpr2, and Aldoa, and key tRFs like tRFdb-1003, tRFdb-1013, tRFdb-1026, tRFdb-3001a and tRFdb-5020a, targeting hub genes such as Wnt4, Prkacb, Sh3rf2, Hpse, Cxcr2 and Zbtb16 respectively. Collectively, these findings demonstrate that estradiol ameliorates OVX-induced behavioral and endocrine dysfunction by reorganizing hypothalamic miRNA- and tRF-mediated regulatory networks involved in stress adaptation, synaptic homeostasis, and neuroimmune signaling.

Obesity is a multifactorial chronic disease resulting from sustained energy imbalance and modulated by environmental and demographic factors, and it is associated with numerous comorbidities. DNA methylation is an epigenetic modification associated with obesity. Modulation of DNA methylation is a viable target for obesity control strategies. The flavanol (-)-epicatechin (EC) exerts beneficial effects in overweight individuals, suggesting that EC may influence gene regulation through signaling pathways and epigenetic mechanisms. We evaluated whether EC modulates obesity-associated DNA methylation changes using complementary in silico, in vitro, and in vivo approaches.

Osteosarcoma, the most common primary malignant bone tumour, presents significant treatment challenges due to its complex tumour microenvironment and the development of chemoresistance. This study employs single-cell transcriptomics to investigate chemotherapy-induced changes in osteosarcoma at both the cellular and molecular levels. Single-cell RNA sequencing data were analysed to identify cell subpopulations and their responses to chemotherapy. Differential gene expression and pathway enrichment analyses were performed to elucidate chemotherapy-induced changes. Additionally, we developed and validated a predictive model based on pyroptosis-related genes, named Pyroscore, using 101 different machine-learning algorithms. Chemotherapy led to an increased proportion of osteoclasts, endothelial cells, mesenchymal stem cells and pericytes, while decreasing T and NK cells, B cells, chondroblasts, monocytes and macrophages. Chemotherapy markedly upregulates the pyroptosis pathway in tumour cells, suggesting that chemotherapy induces programmed cell death in cancer cells through the activation of pyroptosis. Metabolic pathway analysis revealed significant inhibition of sulphur metabolism, starch and sucrose metabolism, pentose phosphate pathway, inositol phosphate metabolism, nitrogen metabolism and fatty acid metabolism. The Pyroscore model, which incorporates BAK1, CASP1, CASP5 and CASP6, demonstrated robust prognostic value across multiple data sets, with high scores correlating with improved survival outcomes. This study highlights the impact of chemotherapy on osteosarcoma cell subpopulations and the tumour microenvironment. The activation of the pyroptosis pathway and the development of the pyroscore prognostic model provide new insights into the mechanisms of chemotherapy response and potential therapeutic targets. These findings underscore the importance of personalized treatment strategies in improving outcomes for osteosarcoma patients.

Hongwu mixture (HWM) consists of Taxus chinensis, Marsdenia tenacissima, Rhizoma Curcumae, and Semen coicis. The objective of this study was to ascertain the potential role of the Hongwu mixture (HWM) in the treatment of triple-negative breast cancer (TNBC). TNBC cells were treated with low, medium, and high doses of HWM, and CCK-8 assays were conducted to evaluate the impact of different doses of HWM on TNBC cell viability. The target molecules of HWM were predicted using RNA-sequencing, and molecular docking models between HWM components and target proteins were developed. As the dose of HWM increased, TNBC cell viability gradually decreased. HWM inhibited the proliferation and mobility of TNBC cells, slowed the tumor growth, and upregulated the apoptosis of TNBC cells. HWM promoted Zinc finger protein 143 (ZNF143)-mediated transcriptional activation of salvador family WW domain-containing protein 1 (SAV1) by stabilizing ZNF143 protein expression, leading to phosphorylation of large tumor suppressor homolog 1 (LATS1) and Yes-associated protein 1 (YAP1). Knockdown of ZNF143/SAV1 signaling impaired the therapeutic effect of HWM, and treatment with verteporfin, pharmacological inhibition of YAP/TAZ, reversed the effects of knockdown of SAV1. Therefore, HWM might offer a potent strategy for managing TNBC effectively.

Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) remains a substantial clinical obstacle in treating lung adenocarcinoma (LUAD). Identifying pro-survival pathways that allow tumor cells to evade TKI-induced apoptosis is critical for overcoming this resistance. The transcriptional repressor transducin-like enhancer of split 1 (TLE1) was previously identified as a crucial oncogenic factor that promotes survival in resistant cells. This study investigates the mitochondrial protein Bcl-2 inhibitor of transcription 1 (Bit1) as a key pro-apoptotic signal that overrides the TLE1-mediated survival program.

Gastric cancer (GC) remains a major public health concern both in Taiwan and worldwide. While advances in public health have reduced its incidence rate, clinical outcomes of advanced GC remain suboptimal with current standard therapy. The Wnt/β-catenin signaling pathway is frequently up-regulated in GC, promoting tumor progression. This study investigated the anti-tumor effects of PKF118-310, a small molecule inhibitor of the β-catenin-TCF/LEF interaction, in GC cell lines and patient-derived models.