Search Results (4,903)

Large genomic rearrangements (LGRs), occurring as copy number alterations (CNAs), represent a clinically relevant class of pathogenic or likely pathogenic variants (P LPVs) in BRCA1/2 (BRCA) genes in ovarian cancer (OC). We evaluated the performance of a high-resolution algorithm integrated into a commercial homologous recombination deficiency (HRD) assay to improve the identification of clinically actionable CNAs in BRCA genes by formalin-fixed paraffin-embedded (FFPE) samples. A total of 760 OC samples were analyzed using a commercial HRD assay incorporating a bioinformatics algorithm for CNA detection. The algorithm was additionally applied to additional homologous recombination repair (HRR) genes, and associations between CNA events and genomic instability (GI) were evaluated. The algorithm demonstrated high sensitivity for both gene and exon-level CNA. The high correlation between CNA positivity cases and GI, in the absence of P/LPVs BRCA single-nucleotide or indels variants, emphasizes the value of integrating CNA detection into routine HRD testing workflows. The extended analysis of additional HRR genes enabled broader characterization of clinically relevant CNAs. This study enables reliable identification of clinically relevant BRCA LGRs from FFPE within HRD testing, supporting a tumor-first diagnostic strategy. This approach may expand the identification of OC patients potentially eligible for PARP inhibitor therapy. Full article

Gla-rich protein (GRP), also known as UCMA, is a vitamin K-dependent protein that has emerged as an important regulator of pathological calcification and inflammation. Vascular calcification is a major complication of chronic kidney disease and cardiovascular disorders and is now recognized as an active and tightly regulated process rather than a passive accumulation of minerals. Increasing evidence indicates that GRP plays a protective role in mineral homeostasis through its strong calcium-binding capacity and its dependence on vitamin K-mediated gamma carboxylation. This work represents a comprehensive narrative review aimed at summarizing and critically discussing the current scientific knowledge on GRP. Available experimental and clinical data are analyzed with respect to gene expression, molecular regulation, vitamin K dependency, and underlying mechanisms of action. Particular emphasis is placed on the dual function of GRP in inhibiting ectopic calcification and modulating inflammatory responses. The evidence linking altered GRP levels or changes in its carboxylation status with chronic kidney disease, vascular calcification, calcific aortic valve disease, osteoarthritis, and tumor-associated microcalcifications is systematically examined. Current findings collectively support the concept that GRP is a multifunctional protein operating at the interface of mineral metabolism, inflammation, and tissue remodeling. Despite promising experimental data, important knowledge gaps remain, including the absence of standardized assays capable of distinguishing different GRP forms and the lack of longitudinal clinical studies evaluating its predictive value. This manuscript highlights the potential of GRP as a biomarker of disturbed mineral homeostasis and cardiovascular risk, while emphasizing the need for further research to clarify its precise biological functions and clinical relevance. Full article

Background: High-grade serous ovarian carcinoma (HG-SOC) remains the most lethal gynecological malignancy, largely due to intrinsic or acquired resistance to platinum-based chemotherapy. Although large-scale sequencing studies have delineated the genomic landscape of HG-SOC, clinically actionable biomarkers predictive of platinum response and outcome are still lacking. This study aimed to identify genomic alterations associated with platinum sensitivity, resistance, or refractoriness, and to assess their prognostic relevance. Methods: Tumor DNA from 24 HG-SOC patients with optimal cytoreductive resection, classified as platinum-sensitive (n = 9), platinum-resistant (n = 8), or platinum-refractory (n = 7) underwent targeted next-generation sequencing of 409 cancer-associated genes. Somatic variants were filtered and classified for oncogenicity using established criteria incorporating predicted functional impact, REVEL scores, and population allele frequencies. Associations between mutational profiles, platinum response, and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. Key findings were validated in the TCGA ovarian serous carcinoma (TCGA-OV) dataset using survival analyses. Results: A total of 1367 protein-altering somatic variants across 301 genes were identified. While TP53 mutations were ubiquitous, platinum-resistant and platinum-refractory tumors showed enrichment of pathogenic alterations affecting DNA repair, transcriptional regulation, epigenetic modification, and oncogenic signaling, including FANCA, ATF1, MAF, NCOA2, PIK3CA, and TET1. Mutations in these genes were associated with reduced overall survival in exploratory analyses (median 2.5–9 months vs. 27.5–45 months). Multivariate analysis identified FANCA and ATF1 as potential independent predictors in exploratory modeling. In the TCGA-OV cohort, patients harboring pathogenic variants in a multi-gene panel derived from this study (excluding BRCA1/2) exhibited significantly worse survival compared with both BRCA1/2-mutated cases and the overall cohort. Conclusions: This exploratory study identifies a set of genomic alterations converging on transcriptional and epigenetic regulation, DNA repair, and oncogenic signaling that are associated with platinum resistance and adverse prognosis in HG-SOC. Independent validation in TCGA supports the potential clinical relevance of this mutational signature. These findings warrant further validation in larger prospective cohorts and functional studies to clarify their role as biomarkers of aggressive disease and therapeutic vulnerability. Full article

Brugada syndrome (BrS) is a rare but potentially life-threatening condition that may lead to sudden cardiac death. Among the causes, dysfunctions of ion channels involved in the cardiac action potential (specifically in SCN5A and SCN10A genes) are particularly significant. Among diagnosed Brugada patients, fever-induced episodes occur in 20–30% of cases. Fever worsens sodium channel dysfunction, as elevated temperature further reduces their conductance. First clinical manifestation of BrS occurs usually during a febrile episode, especially in young people. We performed a multiparametric examination in addition to genetic analysis. We treated a 19-year-old man presenting with subfebrility. During the patient’s subfebrile episodes, 12-lead ECG recordings revealed ST-segment elevations in leads V1–V3. Notably, the patient remained asymptomatic. Targeted genetic testing of SCN5A did not reveal any disease-causing variants as an underlying cause of the syndrome, but the temperature-inducing effect was demonstrated. The occurrence of the Brugada type 1 pattern has also been observed at subfebrile episodes, although significantly rarely. This case demonstrates that in susceptible patients, even a relatively mild elevation in body temperature can trigger ion channel dysfunctions. Timely diagnosis and follow-up are important in preserving quality of life and preventing fatal outcomes. Full article

Introduction: Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value—guiding treatment selection and identifying novel molecular targets—our understanding of their broader clinical implications remains limited. Materials and Methods: We performed next-generation sequencing (NGS; FusionPlex Sarcoma v2, Archer™) and bioinformatic analysis (STAR v.2.7, Arriba) on formalin-fixed paraffin-embedded (FFPE) core needle biopsy specimens. The cohort consisted of patients enrolled in a phase II clinical trial (NCT03651375) who received preoperative chemoradiotherapy according to the UNRESARC protocol. Results: The analysed cohort comprised nine adult patients (median age 66 years; range 44–73) diagnosed with undifferentiated pleomorphic sarcoma (UPS; n = 3), malignant peripheral nerve sheath tumour (MPNST; n = 3), myxofibrosarcoma (MFS; n = 2), and leiomyosarcoma (LMS; n = 1), predominantly high-grade (G3; 5/9) and extremity-localised (6/9). Gene fusions were detected in one-third of patients (3/9), exclusively in G3 tumours. Specifically, we identified an SGSH-PRKCA fusion in MFS (thigh), a LINC01133-OGA fusion in MPNST (thorax), and a concurrent JAZF1-MYH7B (chr7:27995037 intronic-chr20:33563203 exon/splice-site, out-of-frame but preserving myosin domains) with a PRKCA-associated intergenic rearrangement (chr1, retaining C1/kinase domains) in UPS (upper back). Notably, the SGSH-PRKCA and JAZF1-MYH7B pairs have not been previously described in the literature for these STS subtypes. Fusion-positive (F1) cases showed stable radiological disease (RECIST 1.1 SD) and EORTC C/D pathological responses with 5–20% residual viable tumour, whereas fusion-negative (F0) cases showed a wider range of radiological and pathological outcomes, including partial response, progression, and stable disease. Conclusions: Our analysis suggests that broad genomic profiling may provide complementary molecular information in diagnostically challenging cases managed at specialised sarcoma centres, particularly when morphology and immunohistochemistry are insufficient. In the present series, however, the detected rearrangements did not alter systemic treatment, and the data do not support claims of prognostic, predictive, or therapeutic actionability. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Its main contributors are obesity, insulin resistance, diabetes and metabolic syndrome. Liver pathogenesis exacerbates when oxidative stress, inflammation, lipid accumulation, and attenuated autophagy signals coexist together with the main determinants of the liver disease. These findings may indicate that the suppression of the disease requires multi-targeting compounds to alleviate more than one factor, resulting in improved histopathological outcomes. This review studies natural compounds, given as supplements, with antioxidant and anti-inflammatory properties. The compounds included are vitamins, carotenoids, low-molecular-weight thiol-containing compounds, fatty acids and others that have been investigated for their pleiotropic activity alone or in combination. They act at different pathways and signals, and at gene expression control, modulating oxidative stress and inflammation, such as collagen, TNF-α, NF-κB, Nrf2 and PPARs genes. Their mechanism of action and characteristics may be encouraging treatment options as multi-targeting compounds for NAFLD and other diseases whose pathophysiology is closely related to metabolic syndrome. However, extensive study on their safety, toxicity, mechanisms of action and dosage regimen is needed before their final establishment as potential treatment options. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a major pathogen responsible for mastitis in dairy cows. It causes persistent and difficult-to-treat mammary infections, leading to reduced milk production. Baicalein, a flavonoid compound, exhibits anticancer, anti-inflammatory, and antibacterial activities; however, its specific mechanism of action against GBS remains unclear. This study aimed to investigate the mechanism by which baicalein inhibits GBS invasion of bovine mammary epithelial cells (bMECs). The results showed that baicalein at concentrations of 4 μg/mL or higher effectively inhibited 50% of the invasion of bMECs by GBS strain HB31 and exerted a concentration-dependent inhibitory effect on bacterial adhesion. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of baicalein against HB31 were both greater than 1024 μg/mL. Therefore, the antibacterial effect of baicalein alone may not fully account for its mechanism; other pathways likely contribute to the reduced invasiveness of GBS. To elucidate the mechanism by which baicalein inhibits GBS invasiveness, this study investigated both bacterial metabolism and gene expression. Metabolomic analysis revealed that baicalein treatment led to the downregulation of amino acid metabolites, including alanine and aspartic acid, as well as nucleotide metabolites such as adenine and UMP in GBS HB31. Additionally, the NADH/NAD⁺ ratio increased while ATP levels decreased, indicating that the overall metabolic activity of GBS was suppressed. Transcriptomic analysis focused on changes in invasion-associated virulence genes. The results showed that the expression of pbsP, an invasion-associated virulence gene, was significantly reduced, while the expression of hylB and cfb showed downward trends that did not reach statistical significance. In contrast, the expression of cylE and the two-component system vicKR was upregulated. The upregulation of cylE may be related to baicalein-induced oxidative stress in HB31. Furthermore, HB31 suppressed Nrf2-HO-1 mRNA expression, whereas baicalein activated the Nrf2 signaling pathway and reduced HB31-induced IL-6 and NF-κBmRNA expression. These findings provide new insights for the development of anti-virulence therapeutic strategies targeting GBS. Full article

Steatosis, characterized by excessive fat accumulation in the liver, is a significant precursor to chronic liver disease and hepatocarcinoma. This condition is influenced by multiple contributing factors such as obesity, alcohol consumption, and exposure to chemicals or drugs. Systems biology approaches including transcriptomics and metabolomics can aid in grouping chemicals according to their mode of action. In this study, we analyze transcriptomic and metabolomic data from primary human and transformed hepatocytes, respectively, to differentiate between steatotic and non-steatotic chemicals. Rather than assessing each steatotic compound individually, we pooled several steatotic chemicals in order to minimize compound-specific noise and better identify features associated with the underlying process of steatosis. Differential gene expression analysis revealed established mechanisms involved in steatosis, consistent with the recently updated adverse outcome pathway. Likewise, metabolomic data enabled clear discrimination between steatotic and non-steatotic chemicals. These findings highlight the potential of omics technologies to support chemical grouping based on insights into the molecular mechanisms that drive steatosis development. Full article

Nosema ceranae is a common and highly contagious fungal pathogen that primarily infects the gut of adult honeybees, causing nosemosis. As a chronic disease of the digestive system, it poses a global threat to honeybee health and colony sustainability. This study aimed to investigate the inhibitory effects of different concentrations of Scutellaria baicalensis aqueous extract on N. ceranae in the intestines of infected Apis cerana through feeding experiments. In addition, the therapeutic efficacy of its major active component, baicalin, was evaluated, and its potential molecular mechanisms of action were explored. The results showed that, compared with the control group, administration of S. baicalensis aqueous extract at concentrations of 1 mg/mL, 5 mg/mL, and 10 mg/mL significantly reduced midgut spore loads (p < 0.05). Further experiments showed that a 0.5 mg/mL baicalin sucrose solution, prepared with 0.5% (v/v) DMSO as co-solvent, exhibited optimal solubility and significantly inhibited the proliferation of spores in the honeybee midgut. Transcriptomic analysis of A. cerana revealed varying numbers of significantly differentially expressed genes among the baicalin-treated (HG) group, the co-solvent control (DMSO) group, and the blank control (C) group. Four candidate DEGs associated with the effects of baicalin were further identified, namely LOC108003965, LOC108000905, LOC107996681, and CYP4G11. Gene Ontology enrichment analysis showed that, in the comparison between the HG group and the C group, these DEGs were significantly enriched in six functional categories: iron ion binding, phosphoric ester hydrolase activity, heme binding, tetrapyrrole binding, hydrolase activity (acting on ester bonds), and oxidoreductase activity (acting on paired donors, with incorporation or reduction of molecular oxygen). Collectively, these results demonstrate that S. baicalensis aqueous extract effectively inhibits the proliferation of N. ceranae within the host, and its active component, baicalin, exhibits a similar inhibitory effect. The present study proposes a novel strategy in which baicalin may enhance host endogenous chitinase-related activity to target and disrupt the spore wall, offering a new perspective for the prevention and control of honeybee nosemosis. Full article

Assessing genotoxicity, specifically gene mutations and chromosomal aberrations, is fundamental to chemical risk assessment. Notably, the early identification of an aneugenic mechanism is of crucial importance, allowing, in principle, for a threshold-based risk assessment approach. To investigate this issue while pushing towards innovation in risk assessment by leveraging New Approach Methodologies, in silico approaches stand out as a particularly promising avenue. Building on these premises and given the lack of QSAR models for aneuploidy in the public domain, the present study exploited the genotoxicity-relevant alert lists implemented in the OECD QSAR Toolbox to base the investigation of structure-activity relationships for aneuploidy. To address the lack of relevant structured data resources, a dataset of 65 confirmed aneugenic substances was specifically curated and designed for the study. The results highlighted widely differing performances among the various profilers, confirming a general limited discriminatory power for aneuploidy. On the other hand, a granular analysis of the results from individual structural alerts enabled the successful isolation of some features associated with the aneugenic mode of action. Moreover, a subset of tubulin-binding chemicals was investigated to determine whether targeting a specific protein improves the characterization of toxicological alerts. The findings provide a refined definition of specific toxicity determinants for tubulin binders and serve as a promising tool for early hazard assessment, potentially informing relevant AOPs. While the computational approach appears promising, the overarching challenge that emerges is the limited availability of well-curated experimental data. In fact, reliable data on aneuploidy are scarce and fragmented across the literature. Furthermore, existing compilations of micronucleus study results are often complicated by conflicting interpretations. Full article

Fruit anthocyanins are primary determinants of color, sensory quality, and nutritional value in grapes; however, their endogenous biosynthesis is governed by complex interactions among genetic, environmental, agronomic, and postharvest factors. This review elaborates recent advances in physiology and molecular biology to clarify the biosynthetic mechanisms in grapes, including the coordinated action of structural enzymes, MYB–bHLH–WD40 regulatory complexes, hormone-mediated signaling pathways, and vacuolar transport processes. Key environmental factors, such as temperature fluctuations, light exposure, water availability, and soil properties, regulate these networks, contributing to significant variation in pigmentation profiles across cultivars and growing regions. Strategic agronomic practices, including canopy management, regulated deficit irrigation, balanced nutrient management, and temperature-mitigation techniques, further influence pigmentation by modifying the microclimate of the fruit zone during development. Based on these mechanistic insights, this review evaluates targeted strategies for enhancing anthocyanin accumulation, highlighting recent progress in genetic improvement through CRISPR/Cas genome editing, transgenic approaches, and marker-assisted selection (MAS), which enable precise modulation of biosynthetic and regulatory genes. Complementary postharvest interventions, such as optimized cold storage, modified-atmosphere packaging, hormonal elicitors, and controlled oxidative technologies, provide additional opportunities to maintain or enhance pigment stability after harvest. Collectively, these advances establish a comprehensive framework linking molecular regulation with practical vineyard, breeding, and postharvest strategies, offering an integrated pathway to improve anthocyanin consistency, berry quality, and the phenolic characteristics of grape-derived products. Full article

Neuroblastoma is characterized by noticeable resistance to chemotherapy, largely driven by the ability of tumour cells to reorganize stress-adaptive signalling networks rather than relying on single oncogenic drivers. We conducted a study to investigate the pharmacological mode of action of doxorubicin in modifying adaptive signalling pathways in SH-SY5Y neuroblastoma cells, and whether the capacity of plant metabolites can exploit emergent biochemical vulnerabilities. Transcriptomic profiling through RNA sequencing conducted 48 h post-doxorubicin exposure unveiled the organized disruption of pathways linked with amyloidogenic processes, oncogenic signalling pathways, oxidative stress, and DNA repair. The protein–protein interactions, coupled with Kyoto Encyclopedia of Genes and Genomes pathway evaluations, revealed five network-central-hubs: BRAF, GSK3β, PARP1, BACE1, and MAOB. Structural docking integrated with 200 ns molecular dynamics simulations illustrated binding stability across multiple targets driven by three metabolites, Lactol binding to BRAF (−54.13 kcal/mol) and MAOB (−39.08 kcal/mol), Amino(1H-indol-2-yl)acetic acid to BACE1 (−41.07 kcal/mol) and GSK3β (−47.38 kcal/mol), and Quercetin-3-(6″-malonyl-glucoside) binding to PARP1 (−46.03 kcal/mol). In vitro Cell Counting Kit-8 proliferation assays validated the significant anti-neuroblastoma efficacy, with the lowest IC₅₀ (0.2397 µM) being exhibited by Amino(1H-indol-2-yl)acetic acid, followed by Lactol (1.226 µM) and Quercetin-3-(6″-malonyl-glucoside) (1.301 µM), which mirrored the cytotoxic action of doxorubicin (1.306 µM). These results suggest that plant-derived metabolites may interact with stress-adaptive signalling pathways connected with neuroblastoma. However, direct experimental validation of target engagement and pathway modulation will be required to confirm these predicted interactions. Full article

Fungal pathogens pose a major threat to global agriculture and human health, necessitating alternative antifungal strategies with high efficacy and low resistance potential. Antifungal proteins (AFPs) from filamentous fungi are promising candidates due to their stability, selectivity, and diverse mechanisms of action. Here, we characterize Beauveria brongniartii antifungal protein (BbroAFP), a novel cysteine-rich protein from the entomopathogenic fungus B. brongniartii, and investigate its antifungal activity against Botrytis cinerea. Recombinant BbroAFP was expressed in Pichia pastoris, purified, and verified by liquid chromatography–tandem mass spectroscopy (LC–MS/MS) and in silico modeling. BbroAFP showed potent antifungal activity with minimum inhibitory concentrations (MICs) as low as 1 µM against several phytopathogenic fungi, while exhibiting no significant antibacterial activity. Activity was maintained across a wide range of pH and temperature conditions. Confocal microscopy revealed rapid surface binding followed by cytosolic internalization without major cell wall disruption. BbroAFP induced a rapid, transient burst of reactive oxygen species (ROS), accompanied by nuclear DNA fragmentation. Gene expression analysis revealed a transient increase in aif1, whereas mca1 expression decreased at later time points and mca2 remained largely unchanged, suggesting a metacaspase-independent response. Detached tomato leaf assays showed effective protection against B. cinerea without detectable phytotoxicity. Cytotoxicity assays confirmed a favorable safety profile, supporting further evaluation of BbroAFP for plant protection. Full article

Background: Prostate cancer (PCa) is the leading male urinary malignancy globally. Our previous article demonstrated the anti-PCa activity of Euphorbia humifusa Willd water extract (EHW) and some of its compounds via downregulating AR expression, but the anti-PCa active compounds from Euphorbia humifusa Willd (EH) and their mechanisms of action are yet to be clarified. Thus, the current article studied the in vitro anti-PCa effects of 3,3′-di-O-methylellagic acid (3,3′-di-O-Me-EA) derived from EHW and the related mechanism involved. Methods: 3,3’-di-O-Me-EA was isolated from EHW applying bioassay-guided fractionation. The spectroscopic methods were used to determining the structure of 3,3′-di-O-Me-EA. The drug-likeness and ADMET properties (absorption, distribution, metabolism, excretion, and toxicity) of 3,3′-di-O-Me-EA were analyzed in silico. Molecular docking and real-time surface plasmon resonance (SPR) analysis were performed to measure the interaction of 3,3′-di-O-Me-EA and VDAC1 protein. The viability and apoptosis of 22RV-1 and DU145 PCa cells were determined using MTT and Annexin V-FITC staining assay, respectively. q-PCR and Western blot experiments were used to analyzing the gene and protein expressions of VDAC1. Results: 3,3′-di-O-Me-EA was isolated and purified from EHW with a purity of ≥90.06%, and its structure was identified by HRTOF mass, NMR, and an authentic standard. In silico ADMET analysis indicated its favorable drug-like and pharmacokinetic properties. Molecular docking and SPR results confirmed that 3,3′-di-O-Me-EA could bind with the VDAC1 protein. Moreover, 3,3′-di-O-Me-EA dose- and time-dependently inhibited 22RV-1 and DU145 PCa cell viability, and induced apoptosis in a dose-dependent manner (p < 0.05). RT-qPCR and Western blot results showed that 3,3′-di-O-Me-EA dose-dependently up-regulated VDAC1 gene and protein expression levels in 22RV-1 and DU145 cells (p < 0.05). Meanwhile, in VDAC1-depleted 22RV-1 and DU145 cells, 3,3′-di-O-Me-EA down-regulated VDAC1 gene and protein expression levels, increased cell viability, and inhibited apoptosis compared to 22RV-1 and DU145 cells (p < 0.05). Furthermore, 3,3′-di-O-Me-EA enhanced VDAC1 gene and protein expression levels, inhibited cell viability, and induced apoptosis in VDAC1-overexpressed 22RV-1 and DU145 cells compared with 22RV-1 and DU145 cells (p < 0.05). Overall, EH active compound 3,3′-di-O-Me-EA may inhibit viability and induce apoptosis of 22RV-1 and DU145 PCa cells via up-regulating VDAC1 gene and protein expression levels. Conclusion: The results indicated that the 22RV1 and DU145 PCa cell viability inhibitory effects of 3,3′-di-O-Me-EA isolated from EH may be mediated by induction of apoptosis through up-regulation of VDAC1 gene and protein expression levels. Full article