Search Results (1,341)

Endometriosis represents a prevalent gynaecological disorder, impacting around 10% of the female population and affecting as many as 50% of women who are facing challenges with infertility. The pathogenesis of the disease encompasses intricate processes such as the formation of adhesions, degradation of the extracellular matrix, angiogenesis, increased cell proliferation, impaired apoptosis, and dysregulation of the immune response. Although endometriosis is common, its precise etiology remains unidentified, despite various hypotheses being suggested. Recent findings underscore the significance of non-coding RNAs, specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which have been identified as important regulators in the development of endometriosis. This literature review integrates findings from various transcriptomic and molecular studies to distinguish between lncRNAs and miRNAs that are associated with direct pathogenic roles and those that simply represent altered gene expression profiles in endometriosis. Particular long non-coding RNAs, such as H19, MALAT1, and LINC01116, are associated with chromatin remodeling, functioning as competitive endogenous RNAs, and influencing critical signaling pathways. Concurrently, specific microRNAs, including the miR-200 family, miR-145, and let-7b, seem to govern processes like epithelial-to-mesenchymal transition, angiogenesis, and cell adhesion. The findings highlight the significant potential of non-coding RNAs to serve as biomarkers for diagnostic purposes and as innovative therapeutic targets. Subsequent research endeavours ought to focus on corroborating these findings and elucidating the specific pathogenic roles of these non-coding RNAs in the context of endometriosis. Full article

Cancer remains a persistent global health challenge, continuously driving the search for novel and effective therapeutic strategies. In the case of breast cancer, treatment decisions are primarily guided by factors such as the disease stage, histological grade, molecular receptor status, and the presence of genetic mutations. Understanding these parameters is crucial for tailoring interventions and improving clinical outcomes. To enhance prognostic and diagnostic accuracy, attention has increasingly turned to identifying molecular targets that play key roles in breast cancer development. Currently, standard treatments include surgery, chemotherapy, and radiotherapy. However, these approaches are often associated with significant side effects and a diminished quality of life. As a result, many breast cancer patients are turning to complementary therapies—including phytotherapy, nutritional interventions, and dietary supplements—to support conventional treatment, alleviate adverse effects, and improve overall well-being. Within the vast realm of medicinal flora, anticancer plants represent a compelling area of study, serving as a rich reservoir of bioactive compounds. These compounds have demonstrated significant promise in the ongoing battle against cancer. Often highlighted in traditional medicinal practices, these plants harbor a wide array of phytochemicals, such as alkaloids, flavonoids, polyphenols, and terpenoids. These phytochemicals manifest diverse biological activities, notably exhibiting pronounced anticancer properties. The exploration of these natural compounds has opened new avenues for developing innovative and targeted therapeutic strategies in cancer treatment. They achieve definitive chemotherapeutic and chemopreventive roles by integrating with specific molecular signals. Their multiple biological functions include antimutagenic, antiproliferative, antimetastatic, anti-angiogenesis, anti-inflammatory, antioxidant, and immunomodulatory properties, which collectively enable them to control cancer progression and intervene at various stages of cancer cell development. Moreover, these compounds are involved in regulating the cell cycle and microRNA, ultimately leading to cancer cell death by promoting apoptosis and autophagy, often mediated through ROS signaling. Thus, based on a large theoretical revision, we conclude that high-quality evidence is necessary in order to advise these products concerning their efficacy and safety. Also, clinical evidence should be supported by a comprehensive individual diagnosis and adequate research protocols in order to evaluate whether the benefits of these plant-produced interventions can outweigh their harms. Full article

Oral squamous cell carcinoma (OSCC) remains one of the most prevalent and aggressive malignancies worldwide, with late diagnosis contributing to poor survival rates. Recent evidence suggests that periodontitis may act as a co-factor in development of OSCC through persistent inflammation, microbial dysbiosis, and subsequent tissue remodeling. Identifying molecular signatures that link periodontitis with early oral cancerization is therefore of paramount importance for risk assessment, prevention, and timely intervention. This narrative review aims to provide an integrative overview of the current knowledge on molecular, genetic, and epigenetic biomarkers associated with oral cancer risk in patients with periodontitis. Specifically, periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promote oral cancerization by modulating molecular, genetic, and epigenetic pathways, including p53, Cyclin D1, Ki-67, p16^INK4A, DNA methylation, histone modifications, and microRNA regulation. Therefore, this review provides a discussion about the role of inflammatory mediators, oxidative stress-related molecules, microbial-derived products, genetic markers and epigenetic mechanisms as early molecular signals of malignant transformation. The study of these salivary biomarkers (salivaomics) has emerged as a promising non-invasive diagnostic tool, although variability in sampling, biomarker stability, and confounding factors such as coexisting periodontal disease remain significant limitations. By synthesizing the available evidence, this review summarizes recent evidence linking periodontitis to oral cancerization, highlights potential salivary, proteomic, and inflammatory biomarkers, and considers the role of periodontal therapy in improving inflammatory profiles and modulating tumor-related biomarkers. Finally, it explores future perspectives, including the integration of Artificial Intelligence (AI) to enhance biomarker-based diagnosis and risk stratification in OSCC patients. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated disorders characterized by mucosal injury, cycles of inflammation and repair, and tissue damage. Persistent inflammation accelerates epithelial turnover, generates oxidative and replication stress, and remodels the stromal niche, contributing to the risk of colorectal cancer (CRC). Systematic dysplasia surveillance remains essential. Cellular senescence has emerged as a unifying mechanism linking inflammation, impaired epithelial repair, fibrosis, and neoplasia. In UC, p16/p21 upregulation, telomere erosion, and loss of lamin B1 accumulate and adopt a senescence-associated secretory phenotype (SASP) that perpetuates barrier dysfunction. In CD, senescence within stem and stromal compartments limits regeneration, promotes pro-fibrotic remodeling, and sustains cycles of injury and repair via chronic SASP signaling. IBD prevalence continues to rise from environmental factors, dietary changes, antibiotic exposures, and gut microbiota alterations. Pathogenesis integrates genetic factors (e.g., NOD2, IL23R, HLA, and ATG16L1 mutations), environmental modifiers, dysbiosis characterized by loss of short-chain fatty-acid-producing Gram-positive bacteria and expansion of Proteobacteria, and a dysregulated immune system. Therapeutic strategies have shifted toward targeted biologics and small molecules to promote mucosal healing. In this review, we recapitulate the mechanistic axes of inflammation, oxidative stress, and senescence in IBD and then critically evaluate emerging targeted therapies. Topics include anti-TNFα, integrin blockade, IL-12/23 and IL-23 inhibition, JAK inhibitors, S1P receptor modulators, microRNA modulation, senomorphics, mesenchymal cell therapy, and microbiome interventions. We endorse biomarker-guided therapy and propose future directions to break the SASP-driven inflammatory loop and mitigate long-term carcinogenic risk. Full article

Calcific aortic valve disease (CAVD) is characterized by progressive valve remodeling and calcification. Moreover, microRNAs (miRNAs) are emerging as key regulators of cardiovascular pathology and potential circulating biomarkers. We performed high-throughput miRNA profiling in calcified aortic valve tissue and matched patient serum samples using an array that included 98 human miRNAs. Expression data were log10-transformed and filtered to identify biologically relevant miRNAs. Shared miRNAs between tissue and serum were further validated by quantitative real-time polymerase chain reaction (qRT-PCR) in patients and healthy controls. Of the 49 actively expressed miRNAs, 18 were shared between valve tissue and serum. Thus, qRT-PCR validation revealed significant downregulation of miR-17-5p and miR-29a-3p in CAVD patient serum compared to controls. These results indicate that disease-associated miRNA alterations in calcified valves are mirrored in circulation. miR-17-5p and miR-29a-3p represent promising circulating biomarkers for CAVD, reflecting underlying pathological remodeling and extracellular matrix dysregulation. Our findings provide a framework for non-invasive monitoring of valve calcification and highlight miRNA-mediated pathways as potential therapeutic targets. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia. Recent studies have identified microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, as modulators of pathways involved in T2DM pathophysiology. Dysregulated miRNA expression has been detected in various samples collected from patients with T2DM, implicating these molecules in disease onset and progression. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: “miRNA AND gliclazide”, “miRNA AND glibenclamide”, “miRNA AND gliquidone”, “miRNA AND glimepiride”, “mirRNA AND metformin”, “miRNA AND pioglitazone”, “miRNA AND rosiglitazone”, “miRNA AND sitagliptin”, “miRNA AND vildagliptin”, “miRNA AND alogliptin”, “miRNA and saxagliptin”, “miRNA AND linagliptin”, “miRNA AND liraglutide”, “miRNA and dulaglutide”, “miRNA AND semaglutide”, “miRNA AND tirzepatide”, “miRNA AND lixisenatide”, “miRNA AND empagliflozin”, “miRNA AND dapagliflozin”, miRNA AND insulin glargine”, “miRNA AND insulin detemir”, “miRNA AND insulin degludec”, “miRNA AND insulin aspart”, “miRNA AND insulin glulisine”, and “miRNA AND insulin lispro”. Additionally, gray literature was searched in ClinicalTrials.gov, the EU Clinical Trials Register (EudraCT), and the ISRCTN Registry to identify unpublished studies. Studies were eligible for inclusion if they were clinical interventional studies assessing the impact of currently available antidiabetic treatments on miRNA expression. Only articles published in English were considered. The risk of bias was evaluated using the RoB2 (Risk of Bias 2) and ROBINS-I (Risk Of Bias In Non-randomized Studies—of Interventions) tools. Study characteristics and major findings were tabulated. Results: A total of 1263 manuscripts was identified initially. After removing duplicates, 726 articles remained for further screening. Ultimately, 17 manuscripts reporting interventional clinical trials on the effects of antidiabetic treatment on miRNA were included, encompassing a total of 1093 patients. Key findings included treatment-associated changes in miRNA expression and their potential utility for the prediction of clinical outcomes. Conclusions: Current evidence supports the hypothesis that antidiabetic treatments modulate miRNA expression, with some findings showing predictive value for metabolic outcomes. However, the available data remain limited and of low grade of certainty, and further large-scale clinical studies are needed to provide deeper insights into these associations. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Mature erythrocytes are traditionally regarded as anucleate cells lacking nuclear DNA. However, evidence shows they retain residual genetic material, including mitochondrial DNA (mtDNA) and RNA fragments. This review explores the role of such genetic material in cellular function, diagnostics, and erythropoiesis. A comprehensive literature review was conducted, focusing on (i) erythropoiesis, (ii) enucleation of erythroid precursors, (iii) the presence of DNA in red blood cells (RBCs), and (iv) RNA fragments such as messenger RNA (mRNA), microRNA (miRNA), and other non-coding RNAs. Mature RBCs harbor small amounts of DNA and diverse RNA species. Residual DNA can act as damage-associated molecular patterns (DAMPs), triggering immune responses when released under stress or injury. RNA fragments reflect the transcriptional activity of precursor cells and have been linked to potential diagnostic applications. Studies suggest that RBC-derived RNA signatures may serve as non-invasive biomarkers for diseases such as diabetes, cardiovascular conditions, and hematological disorders. These profiles mirror changes in erythropoiesis and provide insights into systemic pathophysiology. Residual genetic material in RBCs extends their role beyond oxygen transport. It contributes to immune modulation and may provide novel diagnostic and therapeutic opportunities, enhancing disease detection and understanding of erythropoiesis. Full article

Background: Ulcerative colitis (UC), a chronic and relapsing form of inflammatory bowel disease (IBD), arises from a multifactorial interplay of genetic predisposition, immune dysregulation, and environmental triggers. Despite advances in understanding UC pathogenesis, the identification of reliable biomarkers and key regulatory genes remains essential for unraveling disease mechanisms. Such insights are crucial for improving diagnostic precision and developing personalized therapeutic strategies. Methods: In this study, gene expression profiles from publicly available microarray and RNA-sequencing datasets were systematically analyzed using advanced bioinformatics tools. Differentially expressed genes (DEGs) were identified through statistical comparisons, and functional enrichment analyses were performed to explore their biological relevance. A total of 141 overlapping DEGs were extracted from three GEO datasets, and 20 key DEGs were further prioritized via protein–protein interaction (PPI) network construction. Hub genes, relevant signaling pathways, associated transcription factors (TFs), and microRNAs (miRNAs) linked to disease progression were identified. Potential therapeutic compounds were also predicted through computational drug–gene interaction analysis. Results: The analysis revealed a panel of novel biomarkers-TLR2, IFNG, CD163, CXCL9, CCL4, PRF1, TLR8, ARG1, LILRB2, FPR2, and PPARG-that function as key hub genes implicated in ulcerative colitis (UC) pathogenesis. These genes were associated with critical biological processes including signal transduction, inflammatory and immune responses, proteolysis, lipid transport, and cholesterol/triglyceride homeostasis. Furthermore, transcription factors (FOXC1, GABPA, GATA2, SUPT5H) and microRNAs (hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-24-3p, hsa-miR-23a-5p, hsa-miR-26a-5p) revealed key regulatory networks influencing post-transcriptional gene regulation. Molecular docking analysis predicted Apremilast and Golotimod as promising therapeutic candidates for UC intervention. Conclusions: In conclusion, this study enhances our understanding of ulcerative colitis pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies. Full article

Circular RNAs (circRNAs) are non-coding RNAs that can significantly influence the regulation of gene expression in health and disease, including ischemic stroke. We identified 597 differentially expressed circRNAs (DECs) (fold change > 1.5; Padj < 0.05) in the striatum region encompassing the ischemic lesion and penumbra 24 h after ischemia–reperfusion injury (tMCAO) in rats, according to high-throughput RNA sequencing data (RNA-Seq). The DECs predominantly increased expression levels relative to those in sham-operated animals. In this study, we also compared these data with DECs we previously identified in the frontal cortex region containing the penumbra and healthy tissue. Furthermore, we bioinformatically constructed a network of competitive circRNA-microRNA-mRNA interactions characterizing the possible functions of DECs in brain areas with varying degrees of ischemic injury. We found that in both tissues, the identified DECs were involved in regulating the expression of genes associated with inflammation and neurotransmission. Moreover, in the striatum, most DECs decreased their expression, while in the frontal cortex, most DECs increased their expression. Thus, we demonstrated different circRNA activities in brain areas with varying degrees of injury. This result may indicate a role for these molecules in regulating brain cell responses, including those important for functional recovery after cerebral ischemia. Full article

Cancer exhibits diverse and complex phenotypes driven by multifaceted molecular interactions. Recent biomedical research has emphasized the comprehensive study of such diseases by integrating multi-omics datasets (genome, proteome, transcriptome, epigenome). This approach provides an efficient method for identifying genetic variants associated with cancer and offers a deeper understanding of how the disease develops and spreads. However, it is challenging to comprehend complex interactions among the features of multi-omics datasets compared to single omics. This study investigates multi-omics lung cancer data obtained from The Cancer Genome Atlas (TCGA) repository. Differentially expressed genes were identified using four statistical approaches: LIMMA, T-test, Canonical Correlation Analysis (CCA), and the Wilcoxon test applied across gene expression (GE), DNA methylation, and microRNA (miRNA) datasets. Kernel Machine Regression (KMR) was subsequently employed to perform data fusion across the multi-modal datasets. The empirical results highlight notable interactions among GE, miRNA expression, and DNA methylation in lung cancer. Our analysis identified 38 genes that show significant associations with lung cancer. Among these, 8 genes of highest ranking (PDGFRB, PDGFRA, SNAI1, ID1, FGF11, TNXB, ITGB1, and ZIC1) were highlighted by rigorous statistical analysis. Furthermore, in silico studies identified three top-ranked potential candidate drugs (Selinexor, Orapred, and Capmatinib) that may offer promising therapeutic potential against lung cancer. The effectiveness of these candidate drugs is further reinforced by evidence from independent research studies, which emphasize their potential in lung cancer treatment. Full article

MicroRNAs (miRNAs), small non-coding RNAs, have emerged as promising diagnostic and prognostic biomarkers for various diseases. However, their role in the pathogenesis of type 2 diabetes mellitus (T2DM) remains insufficiently defined. This case–control study investigated associations between genetic variants in miRNA genes and susceptibility to T2DM in a Greek population. A total of 716 individuals with T2DM and 569 controls (HbA1c < 6.5% and fasting plasma glucose < 126 mg/dL) were included. Genomic DNA was extracted from whole blood and genotyped using the Illumina Infinium PsychArray platform. Polymorphisms in MIR124a, MIR27a, MIR146a, MIR34a, MIRLET7A2, MIR128a, MIR196a2, MIR499a, MIR4513, and MIR149 were analyzed, with all SNPs within 20 kb upstream and downstream of each gene assessed. Allele frequencies were compared between cases and controls using PLINK. Significant associations with increased T2DM risk were observed for rs1531212 (OR = 1.375, p = 0.018) in MIR23aHG (containing MIR27a) and rs6120777 (OR = 1.27, p = 0.018) in MYH7B, upstream of MIR499a. Conversely, rs2425012 (OR = 0.794, p = 0.018) upstream of MIR27a, as well as rs883517 (OR = 0.728, p = 0.024) and rs2961920 (OR = 0.80, p = 0.041) upstream of MIR146a, appeared protective. Under the dominant model, two additional associations emerged: rs3746435 (OR = 1.239, p = 0.025) in MYH7B (upstream of MIR499a) and rs3746444 (OR = 1.235, p = 0.046) in MIR499a. In conclusion, this study identifies three novel genetic variants near MIR27a and MIR499a that may influence susceptibility to T2DM. These findings warrant validation in larger cohorts and functional studies to clarify their role in T2DM pathogenesis. Full article

Background: Preeclampsia is a complex hypertensive disorder of pregnancy associated with significant maternal and foetal morbidity and mortality. Its pathogenesis involves placental hypoxia, oxidative stress, and impaired trophoblast invasion. Recent evidence highlights the role of microRNAs, particularly microRNA-210 (miR-210), in the molecular disruptions underlying preeclampsia. Aim: This study aims to explore the pathogenic, diagnostic, and therapeutic significance of miR-210 in preeclampsia, with emphasis on its molecular mechanisms, biomarker potential, and prospects as a therapeutic target. Methods: A systematic narrative review was conducted following PRISMA guidelines. A total of 498,184 articles were identified through eight scientific databases, and, after duplicate removal and eligibility screening, 111 peer-reviewed studies published between 2015 and 2025 were included in the final analysis. The selected literature focused on miR-210’s expression in placental tissue and maternal circulation, its molecular targets, and its clinical relevance. Results: miR-210 is consistently upregulated in preeclamptic placentas and maternal plasma. It contributes to shallow trophoblast invasion, impaired angiogenesis, mitochondrial dysfunction, and the activation of a hypoxia-induced HIF-1α feedback loop. These mechanisms are central to the disease’s pathophysiology. Clinically, miR-210 demonstrates high stability in circulation and early detectability, making it a promising diagnostic and prognostic biomarker. Experimental models have also demonstrated the therapeutic potential of miR-210 inhibition using antisense oligonucleotides or HIF-1α modulators. Conclusions: miR-210 is both a marker and mediator of preeclampsia. Its integration into diagnostic protocols and therapeutic strategies, alongside clinical validation and standardisation, may enhance early detection and personalised care in high-risk pregnancies. Full article

Bats are natural reservoirs for diverse viruses, yet they rarely develop disease, suggesting unique antiviral adaptations. In this study, we performed a comprehensive genome-wide analysis in the common vampire bat (Desmodus rotundus), integrating comparative genomics, functional annotation, microRNA (miRNA) discovery, target prediction, and network-based analyses. Comparative genomic analysis revealed that Phyllostomus discolor exhibits the highest protein homology (97.4%) with D. rotundus. Alignment of interferon regulatory factors (IRFs) indicated strong conservation of IRF1, IRF5, and IRF8, while IRF4 and IRF7 showed divergence, reflecting bat-specific modulation of interferon signaling. Functional annotation of previously uncharacterized proteins identified immune-related elements, including toll-like receptor 4, syncytin-1, and endogenous retroviral sequences, highlighting the integration of viral components into host immunity. We further identified 19 novel miRNAs in D. rotundus, with high-confidence target genes such as SOD2, TRIM28, and FGFR1 involved in antiviral defense, apoptosis regulation, and oxidative stress response. Functional enrichment analyses revealed processes associated with wound healing, apoptosis suppression, infection response, and longevity. Network entropy analysis highlighted central regulatory hubs, including MYC, BCL2, and KIF1B, influencing cell cycle, survival, and immune balance. Collectively, these results demonstrate that D. rotundus employs an integrated regulatory network combining conserved immune factors, lineage-specific gene divergence, and miRNA-mediated fine-tuning to achieve viral tolerance without pathology. This study expands our understanding of bat antiviral biology and provides candidate molecular targets for future functional and translational research. Full article

Emerging evidence highlights extracellular vesicles (EVs), especially exosomes, as critical molecular messengers linking pediatric obesity to multi-organ complications. This scoping review synthesizes current knowledge on EVs-mediated intercellular communication that exacerbates inflammation, insulin resistance, endothelial dysfunction and organ-specific damage. Data demonstrate that adipose- and endothelial-derived EVs carry bioactive cargo, microRNAs, proteins, and lipids, that modulate key pathways driving metabolic derangements and vascular injury, often preceding detectable clinical biomarkers. Notably, maternal obesity influences EVs composition in breast milk, shaping early-life metabolic programming and offspring risk of obesity. Recent studies underscore the diagnostic and therapeutic potential of EVs in obesity-related conditions such as metabolic-associated fatty liver disease (MAFLD), early renal injury, and cardiovascular dysfunction in children. Furthermore, EVs released in response to exercise or bariatric surgery may mediate systemic metabolic improvements, offering a novel window into personalized interventions. Despite promising findings, standardization of EV isolation and profiling in pediatric research is lacking, and large-scale longitudinal studies are urgently needed. By deepening our understanding of EVs biology, clinicians may advance early detection, risk stratification, and targeted therapies to interrupt the progression from childhood obesity to lifelong metabolic and cardiovascular disease. Full article