Search Results (38)

The objective of this study is to investigate whether ovarian microvascular endothelial cells (OMECs) from women with polyendocrine metabolic ovarian syndrome (PMOMECs) exhibit altered angiogenic responses compared with cells from healthy oocyte donors (HOMECs). This is a laboratory-based cross-sectional study using HOMECs and PMOMECs obtained from discarded follicular aspirates. Expression of mRNA and protein for VEGF receptors (FLT1, KDR) and PGE2 receptors (PTGER1–4) were assessed using qPCR and immunofluorescence. OMECs were treated in vitro with VEGFA, PGE2, or receptor-selective agonists. Migration was quantified via porous membrane inserts and live cell tracking. Proliferation was measured via BrdU incorporation. FLT1 and KDR mRNA and protein levels were similar between HOMECs and PMOMECs. PTGER2 mRNA was higher and PTGER3 mRNA was lower in PMOMECs. VEGFA and PGE2 significantly stimulated migration and proliferation in HOMECs. In contrast, PMOMECs failed to exhibit increased migration in response to PGE2 or selective PTGER agonists, while VEGFA-induced migration remained comparable to migration of HOMECs. Live cell tracking revealed that PMOMEC migration resulted in decreased overall net distance traveled and reduced directional persistence (less linear movement) compared with HOMECs. These findings demonstrate that ovarian microvascular endothelial cells from women with PMOS display impaired angiogenic responses to PGE2, which may contribute to altered follicle growth and anovulation in PMOS. Full article

Objectives: Adverse drug reactions (ADRs) to antihypertensive medications contribute to poor medication adherence and treatment discontinuation. Pharmacogenomic approaches offer a potential means of identifying genetic variants that predict ADR risks, thereby supporting more tailored antihypertensive therapy and improved tolerability. We systematically identify and synthesize available pharmacogenomic evidence for gene–drug–ADR interaction in hypertension across all major drug classes. Methods: This systematic review follows PRISMA guidelines. Five bibliographic databases were systematically searched for pharmacogenomic studies examining associations between genetic variants and adverse drug reactions in adults receiving antihypertensive therapy. Google Scholar was additionally used as a supplementary source during full-text retrieval and citation screening to identify potentially relevant peer-reviewed publications not captured by the primary database searches. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle–Ottawa Scale. The protocol was registered in PROSPERO (CRD420251247856). Results: Seven studies published between 2002 and 2024 fulfilled the inclusion criteria, encompassing populations from Pakistan, China, Russia, South Africa, Spain, South Korea, and Japan. Notably, no pharmacogenomic evidence was identified for beta-blockers, angiotensin receptor blockers, thiazide diuretics, alpha-blockers, or loop diuretics when used as antihypertensives. The studies focused on two antihypertensive medication classes: angiotensin-converting enzyme inhibitors (ACE-I) and calcium channel blockers (CCBs). Variants in BDKRB2 have significant links to ACE-I-induced cough in different populations, with individual investigations identifying other genes involved in bradykinin metabolism and signalling (MME, PTGER3) and hepatic drug transport (SLCO1B1). Associations between CCB-related peripheral edema and CYP3A5 polymorphisms were found in Chinese Han and Russian Caucasian groups. The quality of the studies varied, but two were rated as good. Conclusions: Preliminary pharmacogenomic evidence linking antihypertensive medications to ADRs is emerging but remains limited in scope and concentrated in two drug classes. These findings represent early-phase, hypothesis-generating contributions to the evidence base required for personalized medicine in hypertension pharmacotherapy. Realizing this potential will require prospective validation in diverse, multi-ethnic cohorts, standardization of ADR reporting and causality assessment, and sustained investment in pharmacogenomic implementation science. Full article

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer, but resistance and recurrence remain major clinical challenges. Tumor immune–metabolic reprogramming profoundly affects treatment response and immune evasion; however, the molecular mechanisms of lipid metabolism remodeling and its interaction with T cells after CCRT in cervical cancer are still unclear. This study aimed to investigate how CCRT-induced metabolic changes in cervical cancer cells influence T cell function and immune evasion. Methods: We performed metabolic pathway activity analysis, cell–cell communication prediction, and transcriptomic analysis on paired single-cell transcriptomic data from three cervical cancer patients before and after CCRT (n = 3 paired). Validation was conducted using multiple independent GEO cohorts, in vitro cell culture experiments, and multi-sample immunofluorescence staining. Results: CCRT was associated with upregulation of FABP4/5 in malignant epithelial cells and activation of the PPAR and adipocytokine signaling pathways, leading to lipid metabolic reprogramming. Epithelial cells with high FABP4/5 expression showed enhanced predicted intercellular communication with T cells via the computationally inferred ligand–receptor axes PTGER4 and CXCR4. T cells with high communication intensity exhibited an immunosuppressive phenotype signature, accompanied by metabolic alterations in lipid and carbohydrate pathways and enrichment of regulatory T cell subsets. Validation experiments confirmed the association between FABP4/5 and inhibitory T cells. Conclusions: This study suggests that FABP4/5-mediated lipid metabolism reprogramming may represent a key mechanism contributing to the immunosuppressive crosstalk between cervical cancer epithelial cells and T cells after CCRT. Targeting this axis may reverse T cell dysfunction and provide a potential immunometabolic strategy to reduce post-CCRT recurrence. Full article

The pituitary and gonads serve as central regulatory hubs and functional organs for gametogenesis and maturation. In this study, we performed single-cell RNA sequencing (scRNA-seq) of the pituitary and ovary in pre-spawning Pelteobagrus fulvidraco to elucidate the cellular landscape and regulatory pathways governing gonadal development and oocyte maturation. Pituitaries from four female fish (weight: 43.8 ± 3.2 g; length: 14.1 ± 0.7 cm) and four male fish (weight: 78.2 ± 11.2 g; length: 18.9 ± 1.1 cm) were subjected to single-cell transcriptomic analysis. A total of 17 distinct cell types were identified in the female pituitary, whereas 15 cell types were detected in the male pituitary. Both male and female pituitaries comprised multiple hormone-secreting endocrine populations, indicating a largely conserved cellular composition. However, sex-specific differences were observed in thyrotrope subtypes, suggesting potential sexual dimorphism in pituitary endocrine regulation. Examination of receptor gene expression revealed cell-type-specific regulatory capacities, highlighting gonadotropin, steroid, and neuropeptide responsiveness across pituitary populations. In the ovary, 10 cell types were identified, with granulosa cells (~22.9%) and theca cells (~8.6%) showing distinct transcriptional profiles. Follicle-stimulating hormone receptor (fshr) was highly expressed in granulosa cells, whereas luteinizing hormone receptor (lhcgr) and steroidogenic genes (hsd3b1, pgr) were predominantly localized in theca cells, indicating functional compartmentalization of gonadotropin and steroid signaling. Prostaglandin (PG) and melatonin (MT) pathways were implicated in paracrine regulation: the prostaglandin synthase ptgs2a was expressed in theca, germ, and immune cells, while ptger2a was expressed in granulosa cells; melatonin synthesis genes (aanat1, aanat2, asmtl) were confined to granulosa cells, with receptors (mtnr1ab) in germ cells. These findings suggest that ovarian paracrine signaling complements systemic endocrine control to modulate oocyte maturation and ovulation. This single-cell atlas provides a high-resolution framework of reproductive cell types and signaling networks in P. fulvidraco, offering insights for improving artificial breeding and reproductive management in aquaculture. Full article

Differential fecundity in goats is a complex trait governed by coordinated molecular regulation across reproductive and endocrine tissues. In this study, we performed integrated metabolomic profiling of follicular fluid, serum, thyroid tissue, and uterine luminal fluid together with transcriptomic sequencing of follicular, thyroid, and uterine horn tissues from high-fecundity (HF) and low-fecundity (LF) Yangtze River Delta White goats. In addition, weighted gene co-expression network analysis (WGCNA) was conducted to elucidate the molecular mechanisms underlying differential litter size. High-fecundity goats exhibited enhanced follicular steroidogenesis, superior corpus luteum function, and more stable hypothalamic–pituitary–thyroid (HPT) axis activity, accompanied by increased uterine gland density and greater myometrial thickness. Metabolomic profiling identified 6640 metabolites displaying tissue-specific differential abundance patterns. Pathway enrichment analysis highlighted steroid hormone biosynthesis and energy metabolism in follicular fluid, PPAR signaling and tyrosine metabolism in thyroid tissue, and glycerophospholipid and one-carbon metabolism in uterine luminal fluid as major pathways associated with fecundity. Transcriptomic analysis identified 1596 differentially expressed genes (DEGs), including 20 genes shared across all examined tissues, constituting a systemic molecular signature associated with fecundity. WGCNA further revealed three functional tissue axes associated with follicular development (ELOVL4, INHA, NR5A2), thyroid endocrine regulation (GRHL2, NAPRT), and uterine receptivity (RSPO1, AGTR2, PTGER3). Low-fecundity-associated modules were predominantly concentrated in follicular and thyroid tissues, whereas the high-fecundity-specific module was mainly enriched in uterine horn. These findings provide a multi-tissue molecular framework underlying differential fecundity in goats and identify candidate hub genes and metabolites that may serve as candidate biomarkers for fecundity assessment and selective breeding programs. Full article

Prostaglandin E₂ (PGE₂) plays a critical role in regulating uterine endometrial function and supporting embryonic development during early pregnancy in ruminants. However, its precise roles in shaping the uterine microenvironment remain unclear. Herein, 1 mg PGE₂ was infused daily into the uterus of dairy heifers from days 12 to 14 of the estrus cycle. ULF was subsequently collected for integrated proteomic, metabolomic, and targeted lipidomic analyses. In addition, bovine endometrial epithelial cells were used to evaluate the effects of PGE₂ on epithelial adhesion and responsiveness to interferon tau (IFNT). PGE₂ infusion resulted in 909 differentially abundant proteins (DAPs), which are primarily associated with early embryonic development, immune regulation, and cell adhesion. Untargeted metabolomics analysis identified 587 altered metabolites, which were enriched in sphingolipid, arachidonic acid, phenylalanine, and tryptophan metabolism. Proteomic–metabolomic analyses showed that these alterations were primarily associated with early embryonic development, immune regulation, and cell adhesion. Targeted lipidomic analysis showed a global reduction in lipid accumulation, with glycerophospholipid metabolism and choline metabolism most significantly affected. In vitro, PGE₂ reduced epithelial microvilli density, increased osteopontin (OPN) expression, and decreased the expression of junctional proteins (zona occludens-1 (ZO-1), E-cadherin (CDH1), and fibronectin 1 (FN1)). Moreover, PGE₂ enhanced the responsiveness of bEECs to IFNT by interferon alpha/beta receptor 1 (IFNAR1) and IFNAR2, and prostaglandin E receptor 4 (PTGER4) was identified as the primary receptor mediating this response. Collectively, these findings suggest that PGE₂ may modulate lipid metabolism and adhesion-related processes in the endometrium and influence endometrial responsiveness to IFNT, providing insights into molecular mechanisms associated with pregnancy establishment in dairy cows. Full article

Renal fibrosis (RF) represents a major pathological outcome of chronic kidney disease, currently accompanied by extremely limited therapeutic strategies. To decipher key cellular and molecular drivers, we integrated single-cell and bulk transcriptomic profiles for comprehensive analysis. Based on the RF-related single-cell and bulk transcriptomic data, key cell subtypes were identified through Scissor analysis, custom signature matrix construction via CIBERSORTx, and Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, key subtype-related biomarkers were identified through the expression analysis, and functional enrichment analysis for biomarkers was conducted to elucidate the potential mechanisms by which biomarkers regulate RF. Through comprehensive profiling, thick ascending limb (TAL) cells were predominant and displayed marked heterogeneity in renal fibrosis (RF), with cortical TAL (CTAL) and adaptive TAL (aTAL) identified as principal subtypes. A set of candidate biomarkers was identified. Quantitative polymerase chain reaction (qPCR) validation in mouse models confirmed aberrant expression of these biomarkers, with STAT1 and PARP8 upregulated and HS6ST2, PTGER3, and TMEM207 downregulated in RF. Furthermore, functional enrichment analyses indicated that these biomarkers were associated with pathways underlying metabolic reprogramming and immune perturbation. Our study implicates CTAL and aTAL as central cellular players in RF and identifies their associated biomarkers. These experimentally validated biomarkers provide novel targets and repurposing opportunities for RF therapeutic intervention. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Glioblastoma (GBM) remains one of the most lethal brain tumors, characterized by extensive immune evasion and a macrophage-dominated tumor microenvironment (TME). However, the molecular determinants governing tumor-associated macrophage (TAM) states and their immunoregulatory functions remain poorly understood. We integrated bulk- and single-cell transcriptomic datasets (TCGA, CGGA, Ivy GAP, and Brain Immune Atlas) to systematically characterize the expression, prognostic relevance, and immune contexture of the myeloid biomarker membrane-spanning 4-domain A6A, MS4A6A, in GBM. Differential expression, survival, and pathway enrichment analyses were performed. Single-cell mapping and CellChat modeling delineated MS4A6A-associated TAM subpopulations, intercellular communication networks, and ligand–receptor signaling dynamics. Spatial transcriptomic validation and pharmacogenomic modeling were conducted to assess anatomic enrichment and therapeutic vulnerabilities. High MS4A6A expression predicted unfavorable survival and correlated with increased stromal and immune infiltration. Single-cell analyses localized MS4A6A predominantly to TAMs, especially Regulatory- and Ribo-TAM states enriched for antigen presentation, T-cell regulation, and ribosomal biogenesis pathways. CellChat analysis revealed that MS4A6A-high TAMs exhibited markedly enhanced communication with CD4⁺ T cells and Tregs through upregulated PGE₂–PTGER2/PTGER4, PECAM1–CD38, and THBS1–CD36 signaling axes, implicating MS4A6A in prostaglandin-driven immune suppression. Spatial profiling confirmed preferential localization of MS4A6A within perivascular and angiogenic niches. Pharmacogenomic prediction indicated that MS4A6A-high tumors were more sensitive to ERK, mTOR, and CDK4/6 inhibition. MS4A6A defines a macrophage-centered, immunosuppressive ecosystem in GBM, mediated by the activation of the PGE₂ signaling axis. These findings position MS4A6A both as a prognostic biomarker and as a potential therapeutic node linking myeloid reprogramming to actionable pathway vulnerabilities in glioblastoma. Full article

Prostaglandin E₂ (PGE₂) has been implicated in multiple biological processes during pregnancy in ruminants. However, the regulatory effects of PGE₂ on endometrial function during the diestrus period and its underlying molecular mechanisms remain poorly understood. Herein, PGE₂ treatment promoted the accumulation of lipid droplets and induced cytoskeletal reorganization in bEECs. As a well-established inducer of lipid droplet formation, oleic acid (OA) treatment significantly increased the number of lipid droplets in bEECs, altered the distribution of F-actin and disrupted the expression patterns of key adhesion-related proteins. Transcriptomic analysis revealed that the PPAR signaling pathway was the key pathway that responded to PGE₂ treatment in bEECs, and its downstream target gene FABP3 was markedly up-regulated. Knockdown of FABP3 led to a reduced number of BTC spheroids and down-regulation of adhesion-related proteins in bEECs while increasing the density of microvilli and up-regulating the expression of epithelial markers. Prostaglandin E receptor 4 (PTGER4) was the primary receptor that responded to PGE₂ treatment, and PTGER4 knockdown or pharmacological inhibition with GW-627368 suppressed FABP3 expression in bEECs. Moreover, uterine samples from dairy cows at different stages of the estrous cycle showed that FABP3 expression was significantly elevated in the endometrium tissue during mid-diestrus compared to metestrus, with predominant localization in the luminal and superficial glandular epithelium. Collectively, these findings indicate that FABP3 regulates lipid droplet accumulation and adhesion ability in bEECs via the PGE₂/PTGER4/PPAR signaling axis, providing new insights into the metabolic regulation of endometrial receptivity in ruminants. Full article

Background/Objectives: Seasonal reproduction in mammals is primarily regulated by the hypothalamic–pituitary–ovarian (HPO) axis, yet its molecular mechanisms in subterranean rodents living in light-restricted environments remain poorly understood. This study aimed to characterize the transcriptional regulation of the HPO axis during seasonal estrus in the Manchurian zokor (Myospalax psilurus, M. psilurus), a fossorial rodent exhibiting distinct breeding cycles despite perpetual darkness. Methods: Hypothalamic, pituitary, and ovarian tissues were collected from female zokors during estrus and anestrus (n = 5 per group). RNA sequencing was performed, followed by de novo transcriptome assembly and bioinformatic analyses. Differentially expressed genes (DEGs) were identified using edgeR, and functional enrichment was assessed via GO and KEGG analyses. Key DEGs were validated by RT-qPCR. Results: A total of 513, 292, and 138 DEGs were identified in the hypothalamus, pituitary, and ovary, respectively. GO analysis highlighted enrichment in G-protein-coupled receptor signaling, oxidation–reduction processes, and calcium ion binding. KEGG pathway analysis revealed significant enrichment of the neuroactive ligand–receptor interaction pathway across all three tissues. Key candidate genes included Trh and Mc3r in the hypothalamus, Pitx2 and NR4A2 in the pituitary, and PTGER2 and Sphk1 in the ovary. Conclusions: This study provides the first comprehensive transcriptomic profile of the HPO axis in Manchurian zokors during seasonal estrus. The neuroactive ligand–receptor interaction pathway appears central to reproductive regulation, and several tissue-specific genes were identified as potential regulators of seasonal breeding. These findings enhance our understanding of reproductive adaptation in subterranean mammals and offer a foundation for further functional studies. Full article

The Pelargonium genus, encompassing over 280 species, remains markedly underexplored despite extensive traditional use for respiratory, gastrointestinal, and dermatological disorders. This review of aqueous, alcoholic, and hydroalcoholic extracts reveals critical research gaps: only 10 species have undergone chemical characterization, while 17 have been evaluated for biological activities. Phytochemical analysis identified 252 unique molecules across all studies, with flavonoids emerging as the predominant class (n = 108). Glycosylated derivatives demonstrated superior bioactivity profiles compared to non-glycosylated analogs. Phenolic acids (n = 43) and coumarins (n = 31) represented additional major classes. Experimental studies primarily documented antioxidant, antibacterial, and anti-inflammatory effects, with emerging evidence for antidiabetic, anticancer, and hepatoprotective activities. However, methodological heterogeneity across studies limits comparative analysis and comprehensive understanding. In silico target prediction analysis was performed on 197 high-confidence molecular structures. Glycosylated flavonols, anthocyanidins, flavones, and coumarins showed strong predicted interactions with key inflammatory targets (ALOX15, ALOX5, PTGER4, and NOS2) and metabolic regulators (GSK3A and PI4KB), providing mechanistic support for observed therapeutic effects and suggesting potential applications in chronic inflammatory and metabolic diseases. These findings underscore the substantial therapeutic potential of underexplored Pelargonium species and advocate for systematic research employing untargeted metabolomics, standardized bioassays, and compound-specific mechanistic validation to fully unlock the pharmacological potential of this diverse genus. Full article

Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and disruption of chondrocyte homeostasis. Although retinoic acid (RA) has been used in OA models, its precise targets are not clear. A translational framework was employed, integrating RNA-sequencing results, network pharmacology prediction, computational ligand-receptor molecular docking, and biological experimental validation, to systematically elucidate RA’s disease-modifying targets in OA pathogenesis. RNA-sequencing of RA-treated chondrocytes revealed 656 differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment [Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)] highlighted key pathways, including extracellular matrix (ECM) reorganization and PI3K-Akt-mediated mechanotransduction and others. Network pharmacology analysis identified 42 shared targets between RA and OA. PPI analysis and functional enrichment (GO/KEGG) highlighted pathways including the renin–angiotensin system and the neuroactive ligand–receptor interaction, among others. Molecular docking ranked candidate targets by binding affinity of RA in descending order as MAPK14 (p38α), PTGER3 (PGE2 receptor), CA2 (CA2), and others. Five intersecting targets CA2, ACE, PTGS1 (COX-1), PGR, and EDNRA (ETAR) were identified by integrating RNA-sequencing (RNA-seq) results and network pharmacology predictions. These interactions were experimentally validated via western blot, RT-qPCR and immunofluorescence. RA increased the expression of MMP13, CA2 and ACE, and decreased the expression of COL2A1 in chondrocytes. siRNA-mediated knockdown of both CA2 (human CA2 homolog) and ACE (human ACE homolog) inhibit cartilage degradation through downregulating MMP13 and upregulating COL2A1. This study not only elucidates potential molecular mechanisms by which RA modulates chondrocyte catabolism but also offers a valuable reference for the development of novel OA therapeutics. Full article

Background/Objectives: The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: In this study, the structural and transcriptomic characteristics of endometrial tissue from the fixed and nonfixed sides of 20-day gestation embryos in Mongolian horses were investigated to search for important genes and potential molecular markers associated with the fixation phase of equine embryos. Results: A comparison of the structures of the endometrial tissues of the two sides revealed that the endometrium on the fixed side presented distinctive features, which were characterized mainly by the development of glands on the fixed side compared with those on the nonfixed side. A total of 3987 differentially expressed genes were identified in the transcriptome, among which 1931 genes were highly expressed on the fixed side of the embryo, including CDH1, DRA, DQB, CLND2, BOLA-DQB, CLDN10, PTGER2, and PTGFR. The differentially expressed genes were enriched in biological processes such as cell adhesion, morphogenesis, NOD signaling, and vitamin uptake, as well as prostatic hormones. Conclusions: These results suggest that equine embryo fixation may depend at least on the regulation of prostaglandins and the establishment of cellular connections. This provides a foundation for exploring the molecular mechanisms of key genes and pathways related to equine embryo fixation and offers new insights into feeding management and the monitoring of mares in the early stages of pregnancy. Full article

Clausena lansium (Lour.) Skeels, commonly known as Wampee, are valued for their edible and medicinal qualities, yet their pericarp and seeds are often discarded, resulting in wasted resources. This study investigates the anti-tumor potential of these by-products, focusing on their chemical composition and underlying mechanisms of action. A combination of metabolomics, network pharmacology, molecular docking, and experimental validation was employed in our study. Cytotoxicity screening demonstrated that the pericarp extract exhibited notable anti-tumor effects against MDA-MB-231 breast cancer cells, while the seed extract showed no similar activity. Chemical profiling identified 122 compounds in the pericarp and seeds, with only 26.23% overlap, suggesting that distinct compounds may drive the pericarp’s anti-tumor activity. Network pharmacology and molecular docking analyses identified PTGER3, DRD2, and ADORA2A as key targets, with several alkaloids, flavonoids, coumarins, and sesquiterpenes exhibiting strong binding affinities to these proteins. Western blot analysis further validated that the pericarp extract upregulated DRD2 and downregulated ADORA2A, indicating a possible mechanism for its anticancer effects. These findings suggest that Wampee pericarp holds promise as a source of active compounds with therapeutic potential for breast cancer, with implications for its use in the food and pharmaceutical industries. Full article