Search Results (77)

The c-Myc oncoprotein is a central regulator of oncogenic transcriptional programs that remains challenging to inhibit directly, necessitating strategies that target c-Myc–associated protein complexes rather than the protein alone. This study conducted an in silico evaluation of the natural biphenolic lignan pinoresinol as a potential modulator of the c-Myc–TBP–TAF1 (TATA-binding protein (TBP)- Multiple direct interactions of TBP with the MYC oncoprotein) transcriptional complex (PDB ID: 6E16). Prior to molecular docking, the protein structure was subjected to energy minimization using the AMBER ff14SB force field to optimize conformational stability and structural reliability; ligand preparation and docking were performed with standard, widely used tools (e.g., AutoDock Vina v1.1.2; visualization and interface analyses in UCSF Chimera/ChimeraX and SeamDock). Molecular docking and binding-interface analyses identified reproducible interactions within defined pockets P₀, P₁, and P₂, with pocket P₀ exhibiting the highest Drug Score of 0.82. Binding affinities ranged from −5.0 to −7.1 kcal/mol, which are consistent with moderate docking scores typical for small natural ligands. Across multiple ligand poses, LYS327, LYS310, and ASP209 emerged as consistent interaction hotspots, with LYS327 showing the most frequent contacts. Furthermore, in silico ADMET analysis predicted a high probability of cytotoxic inactivity (0.98), suggesting a favorable safety profile compared to traditional agents like vincristine. These results support a protein–protein interface-oriented approach and position pinoresinol as a promising lead scaffold for disrupting c-Myc–associated transcriptional regulation. Full article

Lymphoma remains a major hematological malignancy associated with treatment resistance and systemic toxicity, highlighting the need for novel anticancer agents derived from natural products. In this study, dicentrine (5), an aporphine alkaloid isolated from Stephania venosa, was investigated for its anti-lymphoma activity in Raji and Ramos cells. Among the isolated compounds, dicentrine (5) exhibited the strongest cytotoxic activity, with IC₅₀ values of 9.03 ± 0.53 and 5.16 ± 0.44 µg/mL in Raji and Ramos cells, respectively, while demonstrating favorable selectivity toward lymphoma cells relative to peripheral blood mononuclear cells (PBMCs). Dicentrine (5) significantly suppressed c-Myc and phosphorylated c-Myc expression, reduced lymphoma cell proliferation, and decreased total viable cell numbers in a dose-dependent manner. Cell cycle analysis revealed G0/G1 arrest in Raji cells and G2/M arrest in Ramos cells. Furthermore, dicentrine (5) induced apoptosis, as evidenced by increased Annexin V-positive populations and elevated cleaved caspase-3 expression. Molecular docking analysis demonstrated strong binding affinities of dicentrine (5) toward Akt, PI3K, caspase-3, and caspase-9, while network pharmacology identified AKT1 and the PI3K/Akt signaling pathway as potential targets associated with lymphoma suppression. Western blot analysis further demonstrated that dicentrine (5) significantly reduces total Akt protein expression. Overall, the present findings indicate that dicentrine (5) suppresses lymphoma progression by inhibiting cell proliferation and promoting apoptotic cell death, highlighting its potential as a promising natural therapeutic candidate for lymphoma. Full article

Maize (Zea mays L.) productivity is severely constrained by drought stress. Although the maize SET domain-containing gene family has previously been investigated, the earlier analysis was based on the incomplete B73 RefGen_v2 genome assembly, and the drought-responsive functions of individual ZmSET members remain largely uncharacterized. In this study, 47 ZmSET genes were identified using the updated B73 RefGen_v5 genome and systematically analyzed for their physicochemical properties, chromosomal distribution, gene structures, conserved motifs, and promoter cis-acting elements. The ZmSET family exhibited substantial evolutionary conservation, while its promoters contained numerous stress- and hormone-responsive elements. Transcriptome analysis identified ZmSET9 as a drought-responsive gene, and RT-qPCR showed that it maintained relatively high expression throughout drought treatment. Heterologous overexpression of ZmSET9 in Arabidopsis thaliana enhanced drought tolerance and supported plant growth under drought stress. Compared with wild type plants, the transgenic lines exhibited higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities and lower malondialdehyde (MDA) contents, indicating enhanced antioxidant capacity and reduced membrane lipid peroxidation. Under PEG induced osmotic stress, AtCAT1 and AtMYC2 were more strongly induced in the transgenic lines. Protein–protein interaction prediction and yeast two-hybrid assays further demonstrated that ZmSET9 physically interacts with FERTILIZATION-INDEPENDENT ENDOSPERM 1 (FIE1), a core component of Polycomb repressive complex 2. These findings update the genomic characterization of the maize SET family and suggest that ZmSET9 contributes to drought tolerance by enhancing antioxidant defense and regulating stress-responsive gene expression. Full article

Reactive oxygen species (ROS)-regulated antioxidant defense is closely linked to non-small cell lung cancer (NSCLC) progression and therapy resistance. Wogonin (WGN), a flavonoid from Scutellaria baicalensis, has antitumor activity, but whether it is associated with ROS-dependent ferroptotic and mitochondrial stress in NSCLC remains incompletely defined. A549 and BEAS-2B cells, male BALB/c nude mouse A549 xenografts, patient-derived NSCLC organoids, and public transcriptomic cohorts were analyzed using viability, colony formation, migration/invasion, DCFH-DA ROS, JC-1, Annexin V/PI, Fe²⁺ and lipid ROS probes, RT-qPCR, Western blotting, immunofluorescence, inhibitor rescue, and c-Myc gain- and loss-of-function assays. WGN suppressed A549 growth and motility with weaker effects on BEAS-2B cells. WGN markedly increased intracellular ROS, Fe²⁺ accumulation and lipid peroxidation, decreased mitochondrial membrane potential, promoted Caspase-related apoptosis, reduced c-Myc/GPX4 and SLC7A11, and increased ACSL4. N-acetylcysteine, Z-VAD-FMK and Ferrostatin-1 partially rescued WGN-induced injury. c-Myc overexpression partially restored GPX4 and reduced lipid ROS/Fe²⁺ accumulation, whereas c-Myc knockdown decreased GPX4. Xenografts and organoids reproduced tumor inhibition and selected redox-associated molecular changes. Collectively, WGN suppresses A549-associated NSCLC phenotypes in association with ROS accumulation, ferroptosis-related lipid injury, mitochondrial dysfunction-associated apoptosis, and c-Myc/GPX4 downregulation. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Gastric cancer (GC) is the fifth leading cause of cancer-related mortality worldwide. Treatment options for advanced GC remain limited, owing to the frequent emergence of drug resistance. This highlights an urgent clinical need for novel therapeutic targets. Abnormal energy metabolism is a hallmark feature of cancer. MYC_V1-driven metabolic reprogramming plays a pivotal role in tumor progression. However, the specific mechanisms by which MYC_V1-related genes regulate energy metabolism in GC remains poorly understood. We employed single-sample gene set enrichment analysis (ssGSEA) to evaluate multiple tumor hallmarks in GC. A prognostic risk model was constructed based on MYC_V1-related genes, with the risk score (RS) used to stratify patients into distinct risk groups. A nomogram was developed and validated using calibration curves. Through the systematic molecular docking screening of 8327 compounds, potential therapeutic agents were identified. Functional experiments, including the CCK-8 assay, wound-healing assay and ATP production assay, were conducted to validate the role of NDUFV2 in GC progression. This study identified MYC_V1 as the primary risk factor affecting the overall survival (OS) in GC patients (p = 0.038). A prognostic risk model was successfully constructed based on eight MYC_V1-related genes (KPNA2, MCM2, MCM4, NDUFV2, PDK4, MPO, IGFBP1, and STC2). The RS was confirmed as an independent prognostic factor. The prognostic risk model accurately predicted patient 1-, 3-, and 5-year OS in GC patients. Tumor microenvironment analysis revealed significant differences in immune cell infiltration patterns between high-risk and low-risk groups. High-throughput drug screening and molecular docking identified camptothecin (CPT) and vinblastine as showing strong therapeutic potential for high-risk patients. Experimental validation demonstrated that NDUFV2 was significantly overexpressed in GC tissues, and its knockdown markedly suppressed the proliferation, migration capacity, and intracellular ATP production in GC cells, confirming the critical role of NDUFV2 in GC progression. These findings establish NDUFV2 as a potential therapeutic target in GC. Full article

Background/Objectives: MYC-driven tumors exhibit significant glutamine addiction, but the metabolic adaptation mechanisms enabling their survival under glutamine deprivation remain incompletely understood. Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate while generating NADPH, linking central carbon metabolism to redox homeostasis. This study investigates whether and how ME1 and ME2 mediate cell adaptation to glutamine starvation and explores their functional division in relation to p53 status. Methods: Using MYC-amplified, p53-mutant (G266E) SF188 glioblastoma cells, we performed siRNA-mediated knockdown, overexpression, and rescue experiments. Cell survival was assessed by trypan blue exclusion and Annexin V/PI staining. ROS levels and NADP⁺/NADPH ratios were measured by DCFH-DA fluorescence and enzymatic assays. Metabolite tracing was conducted using [U-¹³C₅] glutamine followed by LC-MS. Key findings were validated in additional cell lines including HCT116, U2OS and MDA-MB-231. Results: ME1 and ME2 promote SF188 cell survival under glutamine deprivation, an effect that depends on their catalytic activity but is independent of TCA cycle anaplerosis. ME1 maintains redox balance by generating NADPH, and antioxidant treatment rescues the survival defect caused by ME1 knockdown. In contrast, ME2 does not contribute to redox regulation but stabilizes mutant p53 (G266E) via proteasome inhibition. Both of these pro-survival functions are attenuated upon MYC knockdown, suggesting a dependency on MYC expression. Across all cell lines tested, ME1 and ME2 also promote survival through redox maintenance, although the isoform responsible for antioxidant function differs. Conclusions: ME1 and ME2 support metabolic adaptation to glutamine starvation through distinct, isoform-specific mechanisms that depend on MYC expression and p53 mutation status. These findings suggest malic enzymes as potential therapeutic targets in MYC-driven, p53-mutant tumors. Full article

The widespread occurrence of emerging mycotoxins (EMs) produced by Fusarium, Aspergillus, and Penicillium species has raised increasing concerns regarding food and feed safety. Mitigation strategies currently applied to control regulated mycotoxins in feed may also be effective in reducing contamination by EMs. This study comparatively evaluated the in vitro adsorption efficacy of two leonardites, eight natural smectites, and two modified clays (organoclays) against EMs produced by Fusarium, Aspergillus, and Penicillium spp. All materials were tested at two inclusion levels (0.1 and 0.5% w/v) under two pH conditions (pH 3 and 7), simulating the gastrointestinal environment of monogastric animals. Adsorption performance was strongly influenced by mycotoxin chemistry, adsorbent type, inclusion rate, and medium pH. Organoclays exhibited the highest and most consistent efficacy, achieving near-complete adsorption of beauvericin (BEA) and enniatins (ENNs) (>98–100%) at 0.1% (w/v), as well as high removal of mycophenolic acid (MYC. A.) and citrinin (CIT) (>90%) across both pH conditions. Natural smectites showed high but more selective adsorption, removing >90% of BEA and ENNs at low inclusion rates, while displaying limited efficacy toward fusaric acid (FA) and patulin (PAT). Leonardites demonstrated intermediate and material-dependent performance; leonardite L1 adsorbed approximately 90% of BEA at 0.1% (w/v), whereas ENN adsorption ranged from ~36% to 80% at the same inclusion rate and exceeded 90% only at higher dosages. None of the tested materials effectively adsorbed patulin (PAT) at pH 7; however, at pH 3, four smectites exhibited partial adsorption, and one trioctahedral smectite achieved more than 90% PAT adsorption under acidic conditions. Overall, organoclays displayed the broadest adsorption spectrum across structurally diverse mycotoxins, while smectites exhibited high selectivity driven by surface charge density and interlayer interactions. Leonardite-based materials showed moderate but highly variable adsorption performance, likely influenced by heterogeneity in humic functional groups and physicochemical properties. These findings highlight the need for tailored adsorbent selection or combined mitigation strategies to achieve effective mycotoxin control in the animal feed industry. Full article

Background/Objectives: To mine single-cell sequencing data for colorectal cancer (CRC), identify CRC epithelial cell subtypes, and explore the heterogeneity of epithelial cells and their impact on the tumor microenvironment (TME). Methods: The GSE201348 dataset, including normal, colorectal adenoma, high-grade colorectal intraepithelial neoplasia, and CRC tumor tissue samples, was downloaded from the Gene Expression Omnibus. The Seurat package of R software was used for data quality control, data integration, normalization, and clustering. The Feature Plot and the Recode function were executed to annotate and group the epithelial cells. Finally, genetic differences, copy number variant heterogeneity, pseudotime, cell–cell communication, and Gene Set Variation Analysis (GSVA) were further conducted. Results: In total, 26,335 gene matrices from 263,872 cells were obtained for subsequent analyses. Four cell clusters, including immune cells, fibroblasts, endothelial cells, and epithelial cells, were identified. Epithelial cells were further divided into 11 subgroups characterized by MKI67, SLC27A6, PLCE1, NKD1, KCNMA1, GDA, CLCA4, BEST4, LRMP, ACTG2, and ASPM. GSVA enrichment analysis suggested a role of the “P53 pathway,” “Wnt–β-catenin signaling,” and “MYC targets V1” pathways in epithelial cells during the malignant progression of tumors. Survival analysis indicated that downregulation of KCNMA1 and upregulation of MKI67 were associated with poor prognosis. Cell–cell communication analysis suggested a bidirectional regulatory role between epithelial and fibroblast subsets. Conclusions: This study analyzed the gene expression characteristics of 11 types of epithelial cells during the malignant progression of CRC. KCNMA1⁺ and MKI67⁺ epithelial subpopulations are important indicators for the malignant progression of CRC. Full article

Poorly differentiated gastric carcinoma (PGC) is aggressive, yet subtype-specific genomics are under-characterized. We queried AACR Project GENIE^® (cBioPortal v18.0-public; 12 August 2025) for PGC and analyzed somatic alterations from targeted panels (depth ≥ 100×; variant allele frequency ≥ 5%). Mutation and copy number frequencies were summarized, co-occurrence and exclusivity were tested, and primary versus metastatic tumors were compared using chi-square with Benjamini–Hochberg correction. The cohort included 189 tumors from 188 patients (71% primary; 25% metastatic), with primary and metastatic tumor samples being collected from different patients. Recurrently mutated genes were TP53 (48.7%), CDH1 (31.2%), ARID1A (21.2%), KMT2C (8.5%), and POLD1 (7.4%); additional alterations involved ERBB3, KMT2D, KEL, CDKN2A, and FAT1 (≈1–7%). Amplifications in CCNE1 (8.2%) and FGFR2 (7.6%) were common, alongside gains in MET, MYC, KRAS, and ERBB2 and losses in CDKN2A/CDKN2B, CDH1, and PTEN. Significant co-occurrence was observed for POLD1–KMT2D (p < 0.001), POLD1–ARID1A (p < 0.001), and ARID1A–KMT2D (p < 0.001), while TP53 was mutually exclusive with ARID1A (p = 0.029) and CDH1 (p = 0.041). CDH1 (48.9% vs. 29.6%; p = 0.021) and MLH1 (8.5% vs. 1.5%; p = 0.040) were enriched in metastases, and CCNE1 alterations showed female predominance (p = 2.83 × 10⁻⁴). Several “primary-only” findings likely reflect small denominators and require replication. PGC demonstrates a mutational framework dominated by TP53, CDH1, ARID1A, and recurrent CCNE1/FGFR2 amplifications, underscoring dysregulation of cell cycle and chromatin-remodeling pathways as key drivers. Co-occurrence of POLD1, ARID1A, and KMT2D suggests coordinated disruption of DNA repair and epigenetic regulation, whereas mutual exclusivity of TP53, ARID1A, and CDH1 indicates distinct tumorigenic routes. Metastatic enrichment of CDH1 and MLH1 supports their roles in invasion and therapeutic resistance. Together, these findings highlight candidate biomarkers and actionable pathways warranting validation in larger, multi-omic cohorts to refine precision treatment strategies for this aggressive gastric cancer subtype. Full article

Hemibagrus guttatus is a commercially valuable freshwater fish in the Pearl River Basin, renowned as the “King of Freshwater Fish.” Due to habitat degradation and overfishing, its wild population has declined sharply, leading to its listing as a National Key Protected Wild Animal of Class II in China. Artificial breeding is therefore crucial for conservation, yet progress is hindered by the lack of clear sexual dimorphism and poor understanding of its sex differentiation mechanism. In this study, we performed high-throughput RNA sequencing (RNA-seq) to compare gonadal transcriptomes of male and female H. guttatus. A total of 3245 differentially expressed genes (DEGs) were identified, including 3122 male-biased and 123 female-biased DEGs, which clustered into three distinct expression patterns. Enrichment analysis revealed that genes associated with the TGF-β (Transforming Growth Factor-beta) and GnRH (Gonadotropin-Releasing Hormone) signaling pathways were significantly enriched in the female gonads, suggesting their potential roles in gonadal differentiation. From the DEG set, we further highlighted five genes with pronounced sex-biased expression: rbm46 (RNA Binding Motif Protein 46) exhibited gonad-specific expression, whereas myc (v-myc avian myelocytomatosis viral oncogene homolog), angptl4 (Angiopoietin-Like 4), sox9 (SRY-Related HMG-Box Gene 9), and fzd2 (Frizzled Class Receptor 2) showed marked expression differences between male and female gonads. These findings provide insights into the molecular mechanisms underlying sex differentiation in H. guttatus, offer potential molecular markers for sex identification, and establish a scientific basis for germplasm conservation and the optimization of breeding techniques. Full article

Cancer involves uncontrolled cell growth, leading to tumor formation, and remains a major cause of mortality worldwide. Colorectal cancer (CRC) arises from abnormal proliferation of colon glandular epithelial cells. We assessed the cytotoxic and molecular effects of lithium carbonate (Li₂CO₃) and lithium chloride (LiCl) in two CRC cell lines (HCT-116 and SW-620) and a non-tumorigenic line (CRL-1790). Viability assays revealed dose-dependent cytotoxicity, with HCT-116 being the most sensitive cell line (IC₅₀: 8.14 mM for Li₂CO₃). Notably, long-term lithium exposure reduced proliferation, lowering colony-forming efficiency (CFE) and a phenotypic shift from holoclones to meroclones and paraclones, indicating diminished self-renewal capacity. Minimal membrane damage was observed (LDH assay), suggesting non-lytic mechanisms consistent with apoptosis. TUNEL and Annexin-V/IP assays confirmed apoptosis in >40% of cells, without caspase-3 cleavage, suggesting a caspase-independent pathway. PARP-1 cleavage occurred only in SW-620 cells. Western blotting exposed cell-specific modulation of GSK-3β: increased inactive form (p-Ser9) in CRC cells and decreased in CRL-1790 cells, implying differential disruption of Wnt/β-catenin signaling. c-Myc levels remained unchanged, suggesting possible post-translational regulatory effects. Overall, these findings indicate that lithium salts selectively reduce CRC cell viability, impair stem-like characteristics, and induced caspase-independent apoptosis. Therefore, we expand the proof of concept of the potential of lithium-based compounds as low-toxicity adjuvant agents in colorectal cancer therapy. Full article

Background: Despite the high mortality associated with angiosarcoma, its low prevalence has limited sample sizes in prior studies. To address these gaps, we analyzed the AACR Project GENIE registry, a large, multi-institutional database. Methods: 359 tumor samples from 346 patients with angiosarcoma were identified from the AACR Project GENIE v18.0-public database using cBioPortal. Somatic mutations and copy number alterations were assessed. Statistical significance was assessed by t-test for continuous variables and a chi-squared test for categorical data, with significance set at p < 0.05. Results: Recurrent mutations included TP53 (20.6%), KDR (13.6%), and PIK3CA (10.6%). Copy number alterations occurred in MYC (27.3%), CRKL (10.4%), FLT4 (5.5%), and KDR (4.8%). Homozygous deletions occurred in CDKN2A (6.6%), CDKN2B (6.56%), and MTAP (3.81%). Significant co-occurrence included FAT1-NOTCH2, TP53-ATRX, and NOTCH1-ARID1A. Mutual exclusivity was seen with KDR-FLT4 and KDR-ATRX. Females exhibited enrichment in MYC and HRAS, while males exhibited enrichment in POT1, NTRK2, and FAT1. Compared with primary tumors, metastatic tumors more often displayed ZFHX4, FGFR1, MSI2, HIST1H1C, and TOP1 mutations, while MAPK7 mutations occurred only in primary tumors. Conclusions: In one of the largest genomic analyses of angiosarcoma to date, we identified recurrent alterations, suggesting potential future therapeutic targets. Full article

MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from forty (40) EC patients and twenty (20) healthy controls using qPCR panels. POLE exonuclease domain mutations (P286R, V411L) were genotyped, and subgroup analyses were conducted between POLE-mutated (n = 7) and POLE-wild-type (n = 33) tumors. Bioinformatic analyses included validated miRNA–mRNA interactions, target enrichment, and Gene Ontology (GO) pathway mapping. Comparison of EC versus healthy endometrium revealed 50 significantly dysregulated (∣log₂ (FoldReg)∣ > 1 and BH FDR < 0.05) miRNAs, including up-regulation of the oncogenic hsa-miR-181a-5p, hsa-miR-23a-3p, hsa-miR-200c-3p, and down-regulation of tumor-suppressive let-7 family members. Target enrichment implicated canonical oncogenic regulators such as MYC, TP53, and VEGFA. POLE-mutated tumor analysis demonstrated a miRNA signature, with 19 miRNAs significantly down-regulated, including let-7f-5p and hsa-miR-200b-3p. Findings for the EC versus healthy endometrium comparison were validated against TCGA-UCEC sequencing data which confirmed concordant dysregulation of key miRNAs across platforms. Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC. Full article

Ascorbate oxidases (AAOs) are key regulators of extracellular redox homeostasis and plant stress responses, but their roles in grapevine defense remain unclear. Here, we performed a genome-wide analysis and characterization of the AAO gene family in grapevine Vitis amurensis, identifying 10 VaAAO genes that are unevenly distributed across six chromosomes, with notable clustering on chromosome 7. Promoter analysis revealed multiple phytohormone- and stress-responsive cis-elements (e.g., ARE, STRE, and TCA-element) and transcription factor binding sites (e.g., MYC/MYB, and WRKY), suggesting involvement in redox- and stress-related signaling pathways. Analysis of previously published transcriptomic data under Botrytis cinerea infection identified VaAAO7 as a key pathogen-responsive gene. VaAAO7 was rapidly induced by H₂O₂, and its transient ectopic overexpression in susceptible V. vinifera ‘Red Globe’ leaves significantly reduced lesion development. Together, these results demonstrate that VaAAO7 functions as a positive regulator of B. cinerea resistance and highlight its potential for genetic engineering to enhance systemic defense and develop disease-resistant grapevine cultivars. Full article