Search Results (141)

Hybridization effectively enhances breeding efficiency and significantly boosts sheep productivity. However, the epigenetic mechanisms underlying the superior production performance of crossbreds remain largely elusive. In this study, Hu sheep were crossbred with Suffolk rams used as the paternal line. We integrated RNA-seq, ATAC-seq, and CUT&Tag (H3K4me3, H3K4me1, H3K27ac, and H3K27me3) techniques to characterize epigenetic regulatory differences in the longissimus dorsi muscle between Hu sheep (HU) and crossbred progeny (SH). Phenotypic and transcriptomic analyses revealed that SH crossbred sheep exhibited superior growth performance (p < 0.05), and the upregulated genes in the Apelin signaling pathway were significantly correlated with eye muscle area (p < 0.05). Utilizing a Hidden Markov Model, we annotated 15 distinct chromatin states in both HU and SH sheep, systematically characterizing the dynamic epigenomic landscapes across the two breeds. In contrast to SH sheep, the genome of HU sheep exhibited enrichment of repressive chromatin modifications typified by H3K27me3. Strong active enhancers (EnhA) were significantly enriched within upregulated genes in SH. A total of 1862 SH-specific and 691 HU-specific EnhA elements were characterized in this study. Motif analysis revealed that SH-specific EnhA were enriched for myogenic MEF2 family motifs (p < 0.05), which promote muscle and vascular development. By integrating multi-omics data, we constructed a putative regulatory network potentially modulated by SH-specific enhancers, identifying CMKLR1, PPARGC1A, and TLE3 as the core hub genes. Collectively, this study provides a robust data resource, identifying candidate genes and regulatory elements associated with crossbreeding-related muscle phenotypes. Full article

Background/Objectives: Epigenetic factors are increasingly recognized to contribute to the pathogenesis of intestinal diseases, yet the precise mechanisms through which these factors influence ulcerative colitis (UC) remain poorly understood. Methods: Transcriptome profiles pertaining to UC and genes associated with epigenetic factors (EFRGs) were retrieved from publicly accessible datasets. Candidate genes were ascertained through the intersection of differentially expressed genes (DEGs) and EFRGs. Key genes were screened through machine learning algorithms and validated via the Artificial Neural Network (ANN) model. Enrichment analysis and immune infiltration assays were conducted to elucidate the underlying mechanisms of these genes. The hub gene, CBX4 (Chromobox homolog 4), was validated through immunohistochemical analysis of both healthy controls and patients with UC, and the correlation was evaluated using UC-related clinical parameters. Additionally, CBX4 expression was knocked down in dextran sulphate sodium (DSS)-treated mice to examine its regulatory function. Unlike conventional broad-spectrum biomarker screens, this study specifically integrated epigenetic factor-related genes (EFRGs) with machine learning and experimental validation using both clinical samples and animal models. Results: SMARCB1, JAK2, CBX4, and PPARGC1A were identified as key genes, with SMARCB1, JAK2, and CBX4 being upregulated in the UC group, while PPARGC1A was significantly downregulated. The ANN model exhibited excellent diagnostic performance. Enrichment analysis revealed that the key genes were associated with pathways such as the “chemokine signaling pathway”. Immune cell infiltration analysis results revealed marked differences in the abundances of 13 immune cell types between the UC and control groups, and there were notable associations between immune cell infiltration and key genes. Notably, CBX4 expression was elevated in both DSS-treated mice and patients with UC, showing positive correlations with clinical indicators of UC. Further in vivo experiments revealed that silencing CBX4 alleviated DSS-induced colon damage and inflammation. Conclusions: This study identifies four EFRG-related key genes (SMARCB1, JAK2, CBX4, PPARGC1A) in UC, suggesting that CBX4 may play a significant role as an epigenetic regulator. CBX4 is upregulated in UC intestinal tissues, and its knockdown mitigates DSS-induced colitis. These findings provide critical theoretical support for developing targeted therapies for UC. Full article

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of >20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4–6.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan–Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk. Full article

Bighead carp (Hypophthalmichthys nobilis) is a key aquaculture species, with the head and its orbital fat being a commercially valuable product. To elucidate the molecular basis of growth variation, we performed comparative transcriptome analysis of orbital fat from extreme growth phenotypes at juvenile (6 months) and market-size (18 months) stages. In juveniles, slow growth was linked to upregulation of stress-responsive genes (sgk1, fkbp5, lipg), while fast growth correlated with higher expression of stress-buffering (crhbp) and nutrient-signaling (rbp2, mgea5) genes. At 18 months, divergent growth aligned with opposing lipid metabolic states: a pro-anabolic profile (dgat2, fads2) supported fast growth, whereas a catabolic profile (cpt1b, ppargc1a) was associated with slow growth. These results demonstrate stage-specific transcriptional reprogramming in orbital fat underlying growth variation. This study provides a molecular framework for orbital fat-mediated growth regulation and highlights potential candidate genes for molecular breeding in bighead carp. Full article

Background: Obesity is associated with hypothalamic dysfunction characterized by neuroinflammation and altered transcriptional programs. While resveratrol (RSV) has shown beneficial metabolic effects in peripheral tissues, its central effects on hypothalamic gene expression in obesity remain poorly understood. This study provides the first predictive transcriptomic analysis of the hypothalamic response to RSV in a mouse model of diet-induced obesity. C57BL/6 male mice were fed a high-fat diet (HFD) to induce obesity and then subsequently treated with RSV. Methods: Hypothalamic RNA was extracted and analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified and functionally analyzed through KEGG pathway analysis. Results: Although RSV did not significantly alter body weight, it reversed the expression of several HFD-induced DEGs. Key genes modulated by RSV included Aqp7, Ccl27a, Lta, Rilp, M6pr-ps, C1ra, Snail1, Gbgt1, and Ppargc1b, which are involved in inflammation, lipid metabolism, mitochondrial function, and immune signaling. Pathway enrichment analysis revealed significant modulation of TNF and NF-κB signaling, cytokine–cytokine receptor interactions, glycosphingolipid biosynthesis, and phagosome-related activity. Remarkably, 45% of RSV-responsive transcripts were non-coding RNAs, suggesting epigenetic regulation. Conclusions: RSV reprograms the hypothalamic transcriptome in obesity, targeting both coding and non-coding RNAs associated with inflammation and metabolic regulation, independently of weight loss. These findings identify RSV as a potential central modulator of metabolic dysfunction and highlight the hypothalamus as a promising therapeutic target in obesity-related disease. Full article

Background/Objectives: COVID-19 has made a tremendous impact, causing a massive number of deaths worldwide. The inadequacy of health facilities resulted in shortage of resources and exhaustion of frontline workers who had to manage in a short time many patients with no tools to prioritize those at high risk. This study intended to disclose the architecture of such complex disease and enhance the management of hospitalized patients, preventing severe outcomes. Methods: We performed a retrospective multicenter study aimed at refining the best predictive model for COVID-19 mortality, integrating 19 genetic and 13 clinical features. We trained three machine learning (ML) models (GBM, XGB and RF) on a dataset of 532 COVID-19 hospitalized Italian patients, among the 605 recruited during the first wave of the pandemic, when vaccines were not available. Results: All the models achieved great values for accuracy, AUROC, f1, f2 and PR-AUC metrics. XGB f1 optimization resulted in better performance providing fewer false positives (N_f1 = 26 versus N_f2 = 27, N_PR-AUC = 29), and mostly false negatives (N_f1 = 63 versus N_f2 = 69, N_PR-AUC = 69), being the main goal to answer. We next delved into the feature importance to understand which features contribute to the model decision: age was the main driver of mortality prediction, followed by ventilation. The remainder was equally distributed between genetic (HLA-DRA rs3135363, PPARGC1A rs192678, CRP rs2808635, ABO rs657152) and other clinical features, demonstrating that genetic data did not confound, but rather implemented, the power of the model. Conclusions: Our results suggest that integrating genetic and clinical data into ML models is crucial for identifying high-risk cases within the vast disease heterogeneity, enabling the P4-medicine approach to improve patient outcomes and support the healthcare system. Full article

Background/Objectives: Consumption of a Mediterranean diet (MD) has been associated with reduced incidence of non-communicable diseases and reduced overall mortality, with epigenomic effects representing plausible mediators. The aim of this pilot study was to explore potential epigenetic associations between DNA methylation markers in blood and adherence to an MD in pregnancy. Methods: Fifty-two pregnant women with high or low adherence to an MD throughout pregnancy, who participated in the BioMood ORIGINS study, were selected using an extremes-of-exposure design. DNA methylation (DNAm) profiles from whole blood were generated using the TWIST human methylome panel. We conducted both genome-wide and candidate gene-based differential methylation analyses to identify epigenetic variations between the study groups. Furthermore, we explored potential associations between blood methylation patterns and circulating inflammatory markers (GlycA, GlycB and SPC) previously observed to exhibit differential abundance in the same cohort of women. Results: There were no genome-wide significant differences in methylated dinucleotides between MD groups (p-value < 5 × 10⁻⁸); however, a region-based analysis identified 2210 differentially methylated regions (DMRs) (FDR < 0.05, absolute maximum logFC > 1) annotated to 1537 genes, significantly enriched in metabolic, inflammatory and neuronal signaling pathways. Leveraging publicly available data, we replicated nine novel DMR associations. Changes in circulating phospholipid inflammatory markers were significantly associated with a small methylation difference in Lipin-1 (LPIN1), albeit with a small effect size (p-value < 5 × 10⁻⁸). A look-up analysis of previously reported MD-associated genes in this cohort detected small but statistically significantly different methylation of CpGs located within collagen type XVIII alpha 1 (COL18A1) and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B) gene regions. Conclusions: We provide preliminary evidence for modest methylation changes in specific genes associated with adherence to an MD. Full article

Thermoregulatory dysfunction is a major pathophysiological consequence of aging, affecting many elderly individuals. Growth hormone secretagogue receptor (GHSR) regulates energy homeostasis and immune function. We previously showed that global GHSR deletion improves thermogenic adaptation of brown adipose tissue (BAT) in aging, but the responsible cell type remained unclear. GHSR is expressed in macrophages, and its expression in macrophages increases with aging. Here, we studied myeloid-specific Ghsr-deleted male mice (LysM-Cre; Ghsr^f/f denoted as “KO”) to assess their metabolic and immune responses to cold stress at young and old ages. Old mice showed impaired thermogenesis, marked by reduced core body temperature under 4 °C cold exposure, a blunted cold-induced increase in glucose levels, reduced BAT mass, and increased infiltration of pro-inflammatory CD38⁺ macrophages in BAT. In contrast, KO mice exhibited enhanced cold tolerance in both young and old mice. Notably, aged KO mice showed preserved BAT mass and a pronounced shift in resident macrophages toward an anti-inflammatory state. Consistently, aged KO mice showed reduced pro-inflammatory markers (Ccl2, Nos2) and increased expression of the thermogenic gene Ppargc1a and UCP1 protein under cold exposure. Together, these findings demonstrate that macrophage GHSR drives age-associated pro-inflammatory remodeling of BAT, and that its deletion promotes an immune environment favorable for thermogenic activation. Thus, targeting macrophage GHSR may offer a new therapeutic strategy to restore thermogenesis and enhance thermal resilience in aging. Full article

Heterosis or hybrid vigor is a well-recognized biological phenomenon, where crossbred progeny exhibit superior growth performance, stress tolerance, and productivity compared to their purebred parents. However, the molecular mechanisms underlying heterosis for meat quality traits in pigs remain poorly understood. In this study, we compared the longissimus dorsi muscle transcriptomes of Songliao Black Pig (SBP), Large White × Landrace pig (LWLDP), and their crossbred progeny (BXW) to uncover genetic mechanisms contributing to hybrid vigor in meat quality. Results identified 4290 differentially expressed genes (DEGs) in SBP vs. BXW and 3820 in LWLDP vs. BXW. Among these, 1358 genes displayed overdominant expression in BXW, indicating potential heterotic activation. Functional enrichment analysis identified key pathways involved in lipid metabolism, energy homeostasis, and muscle growth, including mTOR, AMPK, insulin, PI3K-Akt, MAPK, and calcium signaling. Over dominantly expressed genes such as FASN, CPT1A, PPARG, ACACA, PPARA, SREBF1, FABP4, DGAT1, PPARGC1A, LIPC, ACSL5, PLCG2, and members of the COX family were closely associated with intramuscular fat deposition, oxidative metabolism, and tenderness. Phenotypically, BXW exhibited improved meat color, moderate fat deposition, and lower shear force compared with parental breeds, clearly aligning with transcriptomic findings. These transcriptomic findings offer valuable insights into precision breeding strategies targeting superior meat quality through genomic selection and crossbreeding programs. Full article

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus–oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER–mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose–response relationships using expanded embryo-quality endpoints. Full article

Whole-genome bisulfite sequencing (WGBS) was employed in this article to map blood DNA methylation profiles at single-base resolution in Yili horses before a 5000 m speed race, with comparative analysis of epigenetic differences between the ‘elite group’ and ‘ordinary group’ across six four-year-old stallions. The overall methylation level in the elite group was generally higher than that in the ordinary groups, with a minority of regions showing hypomethylation. For instance, the promoter regions of key metabolic and neuro-related genes exhibited significant hypomethylation. The article identified over 10,000 CG differential methylation regions (DMRs), predominantly enriched in promoter and CpG island regions, anchoring 7221 differentially methylated genes (DMGs). These DMGs were significantly enriched in key biological processes including oxidative phosphorylation, protein binding, axon guidance, glutamatergic synapses, and the Hedgehog signalling pathway. Among these, six genes—ACTN3, MSTN, FOXO1, PPARGC1A, ND1, and ND2—were selected as core candidate genes closely associated with muscle strength, energy metabolism, and stress adaptation. The study confirms that the differences in athletic ability among Yili horses have a significant epigenetic basis, with DNA methylation participating in the epigenetic regulation of athletic traits by modulating the expression of genes related to energy metabolism and neuroplasticity. The constructed “promoter hypomethylated DMR panel” holds promise for translation into non-invasive blood-based epigenetic markers for early performance evaluation and targeted breeding in racehorses. This provides a theoretical basis and molecular targets for improving equine athletic phenotypes and optimising training strategies. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a highly prevalent hepatic condition closely linked to metabolic syndrome (MetS). Epigenetic regulators such as microRNAs (miRNAs) have emerged as critical modulators of the molecular pathways underlying MASLD pathogenesis, offering new perspectives for non-invasive diagnosis and targeted therapy. This study aimed to identify and characterize target genes and pathways regulated by two key hepatic miRNAs, namely miR-122 and miR-29a, through a comprehensive in silico bioinformatics approach, to better understand their functional roles in MASLD and MetS. Methods: Target genes of miR-122 and miR-29a were predicted using three databases (TargetScan, DIANA-microT-CDS, and miRWalk), and those identified by at least two databases were selected for downstream analyses. Functional enrichment was performed using Gene Ontology and KEGG pathway analysis. Gene networks and biological process maps were constructed using Metascape, clusterProfiler and Cytoscape. Results: miR-122 was found to negatively regulate genes involved in lipid metabolism, insulin signaling, and inflammatory pathways, including PPARGC1A, PPARA, LPL, TLR4, and HMGCR, contributing to insulin resistance and liver dysfunction. By contrast, miR-29a demonstrated potential hepatoprotective effects by targeting LEP, INSR, IL13, and IL18, enhancing insulin sensitivity and reducing fibrogenic activity. Enrichment analysis revealed strong associations with biological processes, such as STAT phosphorylation, lipid homeostasis, and inflammatory signaling, as well as associations with cellular components, including lipoproteins and plasma membranes. miR-122 and miR-29a exhibit opposing regulatory functions in MASLD pathogenesis. Whereas miR-122 is associated with disease progression, miR-29a acts protectively. These miRNAs may serve as promising biomarkers and therapeutic targets in MASLD and related metabolic conditions. Further validation through experimental and clinical studies is warranted. Full article

Metabolic reprogramming allows cancer cells to proliferate rapidly, survive nutrient limitation, and resist stress, making tumor metabolism an important therapeutic target. However, pharmacological inhibition of metabolic enzymes often causes systemic toxicity and compensatory pathway activation. To overcome these limitations, recent studies have highlighted an alternative host-centered strategy based on increasing systemic energy expenditure. Recent studies highlight an alternative strategy in which the host increases energy expenditure through uncoupling protein 1 (UCP1) dependent thermogenesis, thereby lowering systemic glucose, fatty acid, and nucleotide availability for tumors. Engineered beige adipocytes overexpressing UCP1, PR domain-containing protein 16 (PRDM16), or peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A/PGC1A) suppress tumor growth through nutrient competition, suggesting that activating endogenous UCP1 may provide a non-genetic and physiologically aligned anticancer approach. Building on this concept, natural products such as polyphenols, terpenoids, alkaloids, and carotenoids have emerged as promising UCP1 activators that stimulate beige and brown adipocyte thermogenesis through pathways involving AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), PGC1A, PRDM16, and mitochondrial biogenesis. In parallel, computational studies further indicate that several plant-derived compounds bind directly to the central cavity of UCP1 with high affinity, offering structural support for their thermogenic action. Importantly, many of these compounds also inhibit cancer cell intrinsic metabolism by reducing glycolysis, oxidative phosphorylation, lipid synthesis, and amino acid dependent anaplerosis. This review integrates UCP1 biology, natural product mediated thermogenesis, molecular docking evidence, and tumor metabolic suppression, proposing a unified framework in which natural compounds impose coordinated metabolic pressure on cancer through both adipocyte-driven nutrient competition and direct inhibition of tumor metabolism. Full article

The rising incidence of cancer has demanded the development of new anti-cancer chemical sources. The presence of phenolics in hazelnut cell cultures has led to the development of new and potential pharmacotherapeutic uses. Hazelnut extract has emerged as a promising candidate due to its high phytochemical content. HCT-116 colorectal cancer IC₅₀ cell viability of Palaz and Tombul hazelnut extracts was determined as 400 μg/mL and 200 μg/mL, respectively. Flow cytometry annexin V-fluorescein isothiocyante (FITC) apoptosis detection indicated apoptosis of Tombul hazelnut extract and Palaz hazelnut extract as 23.53% and 17.47%, respectively. The apoptosis result of flow cytometry was also supported at the protein level. Hazelnut extracts resulted in an increased loss of MMP as well. The loss of MMP has significantly increased from an average of 0.61% to 16.17% in Tombul hazelnut extract and to 20.38% in Palaz hazelnut extract. This is further supported by screening MICU1, MICU2, PPAR-γ, PPARGC1A, UCP1, UCP2, and UCP3 gene expressions. Targeting apoptosis pathways, particularly MMP, is an effective strategy for cancer prevention and treatment. Hazelnut extract contains phenolic compounds, which activate these pathways, resulting in enhanced apoptosis in colorectal cancer cells. The phenolic contents of Palaz and Tombul hazelnut extracts were determined as 271.72 ± 5.3 mg gallic acid equivalent (GAE)/100 g sample dry weight (DW) and 85.23 ± 2.2 mg GAE/100 g sample DW, respectively. Further, hazelnut extract may reduce oxidative stress, contributing to its anti-cancer properties. The extracts could be utilized as functional ingredients in foods and nutraceuticals to assist with cancer prevention and treatment. Full article