Search Results (413)

The persistence of an immunosuppressive microenvironment remains a formidable challenge for cancer immunotherapy, particularly in tumors with immune-excluded or immune-desert phenotypes. Increasing evidence indicates that chronic inflammation and tumor progression are intrinsically linked through shared signaling hubs, including NF-κB and PI3K/Akt. Osthole, a natural coumarin compound, has been reported to exhibit both potent anti-inflammatory and antitumor activities; however, whether these effects reflect a coordinated regulation of the inflammation–cancer axis remains unclear. In this study, we deployed an integrative framework founded on network pharmacology, molecular docking, and rigorous molecular dynamics simulations, complemented by literature-based evidence synthesis, to computationally explore the potential mechanisms underlying Osthole’s dual activities. Our analysis revealed that Osthole’s predicted targets are significantly enriched in signaling pathways bridging inflammatory and oncogenic processes, most notably the PI3K/Akt, NF-κB, and TGF-β/Smad pathways. Crucially, MD simulations provided supportive computational evidence, suggesting that Osthole forms stable, energetically favorable complexes with core protein hubs (AKT1, RELA, and TGFB1) under the simulated conditions. Evidence from representative inflammatory and tumor models supports the biological plausibility of these predictions, including suppression of pro-inflammatory signaling, mitigation of maladaptive tissue remodeling, and induction of apoptosis. Furthermore, in hepatocellular carcinoma models, Osthole-mediated apoptosis appeared linked to HMGB1-related inflammatory signaling, highlighting its potential to modulate the local immune niche. Collectively, this convergence of systems-level predictions and dynamic structural evidence identifies Osthole as a promising multi-target candidate for the coordinated regulation of inflammation-associated tumor progression, providing a robust rationale for further experimental validation. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Background/Objectives: Cervical cancer, primarily driven by persistent high-risk HPV infection, remains a major global health issue. Xiao-ai-fei honey ointment, a traditional Uyghur multi-ingredient preparation, has shown clinical promise in cancer treatment, but its mechanisms against cervical cancer are not fully understood. This study aimed to investigate the potential molecular mechanisms of ethanolic extract of Xiao-ai-fei honey ointment (XAFHO) in cervical cancer using network pharmacology, single-cell RNA sequencing, and experimental validation. Methods: Differentially expressed genes (DEGs) in cervical cancer were identified from TCGA database. Active components and corresponding targets of XAFHO were retrieved from the TCMSP database, and disease targets were obtained from GeneCard, OMIM, and the TTD. Intersection targets were subjected to multivariate Cox and LASSO regression to construct a prognostic model. Immune infiltration, TMB, and MSI were compared between risk groups. Single-cell RNA-seq data were analyzed to determine cellular origins and inter-cellular communication. In vitro assays were performed on HeLa and SiHa cells to assess the anti-cancer activity of XAFHO. Molecular docking evaluated binding affinities between active compounds and core targets. The expression and functional roles of FASN and SPP1 were further validated by RT-qPCR, Western blotting, and siRNA transfection. Results: Sixty-three potential XAFHO targets were identified, and an 11-gene prognostic model was established, effectively stratifying patients into high- and low-risk groups with significantly different overall survival (AUC > 0.7). The high-risk group exhibited an immunosuppressive microenvironment and higher TMB. Single-cell analysis revealed that FASN and ACACA were predominantly expressed in tumor cells, while SPP1 was enriched in macrophages/monocytes. Tumor cells communicated with immune cells via the TGFB1–TGFβR1/R2 axis, promoting immune evasion. In vitro, XAFHO significantly inhibited proliferation, colony formation, migration, and invasion of cervical cancer cells. Molecular docking confirmed the strong binding of quercetin, kaempferol, and isorhamnetin to FASN and SPP1 (binding energy < –6.0 kcal/mol). Functional validation indicated that upregulated FASN and SPP1 contribute to malignant behaviors in cervical cancer cells. Conclusions: This study integrates network pharmacology with single-cell and experimental approaches to demonstrate that XAFHO exerts multi-target and multi-cell anti-cervical cancer effects, potentially by modulating lipid metabolism and immune-related pathways via FASN and SPP1. These findings provide a scientific basis for the therapeutic application of XAFHO in cervical cancer. Full article

Hepatocellular carcinoma (HCC) is the most common type of liver cancer that is mostly preceded by cirrhosis, with a high mortality rate. Therefore, diagnosis is critical in the early stages. In this study, we explored the liver expression of metabotropic glutamate receptor 3 (mGluR3), a group II mGluR, during the progression from fibrosis to cirrhosis and, ultimately, to HCC induced by diethylnitrosamine (DEN) in rats. We found that mRNA expression of mGluR3 (Grm3) was upregulated in HCC, while the protein level was significantly increased from the cirrhosis stage, and even more in HCC. Grm3 correlated with interleukin-6 (Il6) and transforming growth factor-β (Tgfb) mRNA expression. Furthermore, serum and intrahepatic glutamate concentrations were augmented in HCC. Immunohistochemical analysis revealed that mGluR3 is expressed in hepatocytes and non-parenchymal cells (endothelial cells and macrophages), and we observed a positive signal in the cytoplasmic membrane, cytoplasm, and nuclei of tumor and non-tumor cells. We confirmed that normal hepatocytes (C9 cell line) express low levels of mGluR3 protein and HCC-derived cells (HepG2) express high levels of this receptor. Using HepG2 cells, we observed that mGluR3 activation by glutamate and the group II-selective agonist LY354740 treatments were functional, as both inhibited cAMP generation induced by forskolin and increased cellular viability with no effect on dead cells. These results showed that mGluR3 is differentially expressed throughout the progression of liver pathologies, is associated with the inflammatory environment, and plays a role in HCC cell survival, with potential utility as an early biomarker and therapeutic target. Full article

Background/Objectives: Nuclear receptor corepressors NCOR1 and NCOR2 are key regulators of transcriptional repression, chromatin remodelling, and immunometabolic signalling. While NCOR1 has already been linked to vascular biology, its relevance in abdominal aortic aneurysm (AAA) remains unclear, particularly for NCOR2. This study aimed to investigate the expression, cellular localisation, and molecular interactions of NCOR1/2 in human AAA tissue. Methods: Human AAA samples (elective and ruptured) (n = 45) and non-aneurysmal control aortas (n = 18) were obtained from our Swiss Vascular Biobank. Transcriptomic profiling was performed using ribosomal RNA-depleted RNA sequencing. Differential expression and correlation analyses were performed using DESeq2/EdgeR and Spearman rank correlation with Benjamini–Hochberg correction. Cellular localisation was assessed through immunohistochemistry (IHC). Results: Bulk transcriptomic analyses showed no significant differences in NCOR1 or NCOR2 expression between AAA and controls. IHC revealed that NCOR1 was found in endothelial cells (ECs), smooth muscle cells (SMCs), and inflammatory infiltrates, while NCOR2 was primarily associated with macrophages. Correlation analyses suggest that NCOR1 interacts with various cellular markers, proteolytic enzymes, inflammatory mediators, and epigenetic regulators, including the lncRNA MALAT1. NCOR2 showed distinct associations with remodelling enzymes, TGFB1 signalling, selective epigenetic modifiers, and lncRNA H19. Conclusions: The lack of transcriptional differences in NCOR1 and NCOR2 between AAA and controls does not exclude cell-type-specific regulation or functional relevance. The specific cellular distributions and molecular associations in human AAA imply that NCOR1 and NCOR2 play non-redundant roles in vascular remodelling, inflammation, and epigenetic regulation. Our findings highlight NCOR pathways as potential modulators of AAA pathophysiology and promising targets for future therapies. Full article

Background/Objectives: Improving rabbit welfare through alternative housing systems requires a better understanding of how environmental conditions modulate physiological and immune responses at the molecular level. This study aimed to evaluate the influence of different rearing systems on the expression of genes associated with inflammation, immune regulation, and stress response in Termond White rabbits. Methods: After weaning (35 days of age), Termond White females (n = 16 per group) were allocated to five housing systems differing in space allowance and activity opportunities: hutches with outdoor runs, rabbit tractor cages with outdoor runs, single-floor indoor cages without bedding, indoor pens on deep litter, and modified indoor cages (two cages connected with a plastic pipe). At slaughter weight (2600–2900 g; 90–120 days), blood and spleen samples were collected. The relative expression of IL6, CXCR1, IL10, TGFB1, IL8, PTGS2, IL1B, and TNF was quantified by RT-qPCR using the 2^−ΔΔCt method, with ACTB and B2M as reference genes. Results: The housing system significantly affected the expression of most analysed genes in peripheral blood (IL6, CXCR1, IL1B, PTGS2, IL8, TNF, and IL10; p ≤ 0.05), whereas in the spleen significant differences were observed only for selected genes (IL1B, TNF, CXCR1, IL10, and TGFB1), with no effect detected for IL6, IL8, and PTGS2 (p > 0.05). In blood, system-dependent differences were observed for both pro-inflammatory and regulatory genes, with some housing conditions associated with higher expression of inflammatory markers. In the spleen, the response was more selective and gene-specific, suggesting tissue-dependent modulation of immune-related pathways. Conclusions: Rearing environment influences the expression of immune-related genes in Termond White rabbits; however, these effects appear to be tissue-dependent and vary among specific genes. The observed transcriptional changes suggest potential associations between housing conditions and immune responses, but further studies integrating behavioural, physiological, and protein-level data are required to confirm their relevance for animal welfare assessment. Full article

Objectives: The objective of the study was to investigate the mRNA expression of critical gene patterns, including IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1, and their associations with adverse postoperative outcomes in reconstructive and plastic surgery patients, depending on age. Methods: A total of 95 women participated in this prospective longitudinal cohort study and underwent reconstructive/plastic surgery. The mean age was 35.48 ± 6.61 years (range: 19–57). mRNA expression of IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1 genes was evaluated in peripheral blood leukocytes using a PCR-based method with reverse transcription of cDNA. Results: The risk of postoperative complications significantly increased with elevated expression levels of IL-6 and COL3A1 (7.5-fold, p = 0.007), CCL2 (6.2-fold, p = 0.012), and MAPK1 (25.5-fold, p < 0.001). Increased expression of MAPK8, IL-10, and MMP9 was associated with a 13.2-fold higher risk (p < 0.001). The strongest association was observed for COL1A1 overexpression, which increased complication risk by 58.33-fold (p < 0.001). Risk stratification using the Molecular Complication Risk Index (MCRI), incorporating weighted gene contributions, identified an unfavorable molecular profile predominantly among women aged ≥ 40 years. Receiver operating characteristic analysis confirmed the model’s discriminative ability (AUC = 0.78; 95% CI 0.68–0.87), with an optimal cut-off value of MCRI ≥ 8.5 (sensitivity 76%, specificity 71%, p < 0.05). Conclusions: The transcriptional activity of IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1 is associated with postoperative wound healing risk. Women aged over 40 years are at the highest risk of complications. Implementation of the MCRI model may enable early identification of high-risk patients, support targeted preventive strategies, and improve personalized surgical planning. Full article

Background: Cisplatin resistance remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been implicated in chemotherapy resistance, their specific roles and underlying mechanisms remain incompletely understood. This study aimed to identify lncRNAs associated with cisplatin resistance in NSCLC and to elucidate the role and mechanism of NR2F1-AS1 (NAS1) in this process. Methods: Cisplatin-resistant NSCLC cell lines were established and subjected to transcriptome-wide RNA sequencing. NAS1 expression was validated by quantitative real-time PCR, and its clinical relevance was assessed using The Cancer Genome Atlas (TCGA) dataset. NAS1 and NR2F1 knockdown, together with NR2F1 overexpression and rescue experiments, were performed to evaluate their effects on cisplatin sensitivity. Downstream mechanisms were investigated by public dataset analysis, qPCR, and Western blotting, and NF-κB signaling was functionally assessed using the inhibitor DHMEQ. Results:NAS1 was consistently downregulated in multiple cisplatin-resistant NSCLC cell lines and was also decreased in NSCLC tissues. NAS1 knockdown enhanced cisplatin resistance. Mechanistically, loss of NAS1 reduced NR2F1 protein expression without significantly affecting its mRNA level, indicating translational regulation. NR2F1 downregulation also conferred cisplatin resistance, phenocopying the effect of NAS1 loss, whereas NR2F1 re-expression restored cisplatin sensitivity. Further analyses identified TGFB1 as a downstream effector derepressed by loss of the NAS1-NR2F1 axis, leading to activation of NF-κB signaling. Inhibition of NF-κB partially reversed cisplatin resistance in resistant cells. Conclusions: Collectively, our findings delineate a NAS1/NR2F1/TGFB1/NF-κB signaling axis critical for cisplatin resistance in NSCLC, revealing a potential therapeutic target for overcoming platinum resistance. Full article

Geopropolis, a complex natural product composed of propolis, wax, plant resins, and soil produced by Meliponine (stingless) bees, has traditionally been used for its therapeutic properties. Its chemically diverse composition and broad biological activities have recently attracted growing scientific interest. In this study, we characterized the physicochemical and immunomodulatory properties of a hydroalcoholic extract of geopropolis (HEG) from Melipona quadrifasciata (Mandaçaia). Physicochemical characteristics were determined by measuring moisture, ash, and wax content, and its bioactive constituents were identified by GC–MS. THP-1-derived macrophages were exposed to increasing HEG concentrations to assess cytotoxicity, and two sublethal doses were selected for immunomodulatory assays with or without LPS stimulation. Cytokine and chemokine secretion were quantified by CBA, and the expression of key immunoregulatory and angiogenic genes was evaluated by RT-qPCR. Chemical profiling revealed a high wax content and a predominance of di- and triterpenoids, largely derived from coniferous sources. In mccrophages stimulated with LPS, HEG at 31.25 and 62.50 µg/mL significantly reduced the secretion of pro-inflammatory mediators (IL-6, CCL2, CCL5, CXCL9, and CXCL10) while preserving cell viability. In unstimulated macrophages, HEG upregulated the expression of genes VEGFA and TGFB1 as well as the protein CXCL8, all of them associated with angiogenesis and tissue repair. These findings demonstrate that M. quadrifasciata geopropolis extract modulates macrophage activity, promoting a shift toward a reparative phenotype that integrates inflammatory resolution with pro-healing effects. These results underscore its pharmacological potential as a terpenoid-rich natural product with complementary anti-inflammatory and regenerative activities. Full article

With the rising prevalence of feline kidney diseases, effective preventive and therapeutic strategies are urgently needed. This study evaluated the effects of Cybister chinensis extracts (CCME) and Periplaneta americana residue extracts (PAE) on inflammation-associated, oxidative stress-related, and fibrosis-related responses in Crandell-Rees Feline Kidney (CRFK) cells. Using MTT assays, flow cytometry, and qPCR, we assessed cytoprotection in models of lipopolysaccharide (LPS)-, hydrogen peroxide (H₂O₂)-, and palmitic acid (PA)-induced injury. Preliminary HPLC fingerprint analysis of three batches of a combined extract from Periplaneta americana residues and Cybister chinensis Motschulsky (CPCE) revealed similar chromatographic profiles, indicating good batch-to-batch consistency. Within non-cytotoxic ranges, CPCE increased cell viability and reduced apoptosis in injured CRFK cells. Anti-inflammatory effects were evidenced by significant downregulation of TNF-α and IL-6 mRNA. Potential antioxidant-related effects were suggested by decreased expression of oxidative stress–responsive genes SOD1, CAT, and GSTP1. In the PA model, anti-fibrotic potential was supported by reduced TGFB1 expression, accompanied by improvements in inflammatory and oxidative stress markers, and by decreased levels of fibrosis-associated markers α-SMA, COL I, and HCB III. These findings suggest that CPCE exerts cytoprotective effects in vitro, potentially through modulation of inflammation, oxidative stress, and fibrosis. Full article

To characterize the transcriptional and physiological alterations induced by manganese stress in Coilia nasus, juveniles (mean weight 5.0 ± 0.2 g) were subjected to either manganese exposure (5.50 ± 0.03 mg/L) or control (0 mg/L) for a 12 h period. Subsequently, gill tissues were excised for evaluation of antioxidant parameters and RNA-Seq analysis. A total of 753 DEGs were identified in the manganese exposure group compared to controls, comprising 287 up-regulated and 466 down-regulated genes. GO and KEGG enrichment analysis of DEGs showed that most of the DEGs were involved in immune and metabolic pathways, which disturbed the biological processes related to immunity and metabolism at the molecular level. The acute manganese stress initiated a multi-level antioxidant response to cope with oxidative stress in Coilia nasus. This finding was further supported by the significant increase in MDA content and significant decrease in GSH content and GSH-Px activity under manganese exposure, while SOD and CAT activities were significantly increased. Simultaneously, the acute manganese stress triggered profound metabolic reprogramming to cope with energy pressure in Coilia nasus, which showed that manganese exposure significantly down-regulated energy metabolism-related genes (pfkm, pgam2, eno3, pkm, aqp9, apoa1, tkt, sds); furthermore, the overall energy metabolism network was widely inhibited, while lipid metabolism-related genes (fabp3, cpt1a) were significantly up-regulated to compensatorily activate fatty acid transport and β-oxidation pathways. In addition, the acute manganese stress initiated a complex immune response pattern to cope with cell damage in Coilia nasus, which showed that manganese exposure significantly enhanced the expression of inflammatory signaling genes (mapk1, stat1, tgfb3); furthermore, certain inflammatory pathways were activated, while the expressions of immune regulatory genes (traf6, il-10) were significantly decreased. In summary, these results indicated that manganese exposure could impair immune function, disrupt metabolism, and induce oxidative stress in Coilia nasus. Full article

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. Full article

Whole-genome sequencing (WGS) is a powerful tool for uncovering genome-wide variation, identifying selection signatures, and guiding genetic improvement in livestock. Royal White (RW) and White Dorper (WD) sheep are economically important meat-type hair breeds in the U.S., yet their genomic architecture remains poorly characterized. In this study, WGS was performed on 20 ewes (n = 11 RW, n = 9 WD) to identify and annotate SNPs and small insertions and deletions (indels). Functional annotation, gene enrichment, population structure, and selective sweep analysis were also performed. Selective sweep analysis was conducted by integrating the fixation index (F_ST), nucleotide diversity ($\pi$), and Tajima’s D to identify candidate regions under putative recent positive selection. A total of 21,957,139 SNPs and 2,866,600 indels were identified in RW sheep, whereas 18,641,789 SNPs and 2,397,368 indels were identified in WD sheep. In RW sheep, candidate genes under selection were associated with health and parasite resistance (NRXN1, HERC6, TGFB2) and growth traits (JADE2). In WD sheep, selective sweep regions included genes linked to immune response and parasite resistance (TRIM14), body weight (PLXDC2), and reproduction (STPG3). These findings were supported by sheep-specific quantitative trait loci (QTL) annotations and previously reported SNP–trait associations. This study provides the first WGS-based genomic comparison between RW and WD sheep, establishing a foundation for future genetic improvement, including targeted selection for enhanced immune function, disease resistance, and other economically important traits in these breeds. Full article

Elevated plasma lactate is a significant risk factor in pulmonary hypertension (PH), and endothelial-mesenchymal transition (EndoMT) is a major contributor to this pathological process, yet its specific role in driving endothelial-mesenchymal transition (EndoMT) remains unclear. Using in vivo and in vitro models, we demonstrate that modulating lactate levels critically influences PH progression. In a hypoxic PH mouse model, inhibition of lactate production ameliorated hemodynamic and vascular remodeling, whereas exogenous lactate exacerbated these pathologies. In human pulmonary arterial endothelial cells under hypoxia, lactate promoted a pro-remodeling phenotype, enhancing migration, proliferation, and EndoMT. Mechanistically, lactate induced Twist1 lactylation via enhanced association with p300/CBP, promoting its nuclear translocation. This upregulated TGFB1 transcription and activated the Smad2 pathway, thereby driving EndoMT—an effect abolished by Twist1 knockdown. Our findings reveal a previously unrecognized lactate-Twist1 lactylation-TGFB1 axis that promotes vascular remodeling in PH, identifying novel therapeutic targets. Full article

The greater amberjack (Seriola dumerili) is a globally important aquaculture fish species belonging to the family Carangidae. However, current research on the ovarian development and regulation of the greater amberjack is limited, particularly with regard to early ovarian development in artificially bred individuals. Therefore, this study aims to analyze the ovarian transcriptomes at the primary growth stage in one-year-old fish at the chromatin nucleolar stage and two-year-old fish at the perinucleolar stage to suggest how early ovarian development takes place in artificially bred greater amberjacks. To do this, the study constructed ovarian mRNA expression profiles of different stages of artificially bred fish and identified differentially expressed genes (DEGs), Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways important for various physiological processes. A functional analysis revealed that the DEGs closely related to ovarian development were involved in cell growth and death (e.g., ccnd1, cdk1, cdc6, cdc25b, fbxo43, cdkn1a and cdkn1d), the TGF-beta signaling pathway (e.g., gdf6, bmpr1b, gsdf, amh, tgfb3, and smad6), steroid hormone biosynthesis (e.g., hsd3b1, hsd11b2, hsd17b12 and hsd20b2), and the endocrine system (e.g., mapk8a, mapk11, mapk12a, mapk13 and adcy9). These findings suggest that ovarian development is the result of the coordinated regulation of various genes responsible for various functions. This study provides a theoretical basis for exploring the underlying molecular mechanisms of early ovarian development in artificially bred greater amberjacks. Full article