Search Results (8,869)

MicroRNAs (miRNAs) are conserved post-transcriptional regulators that play essential roles in cellular development and differentiation. Although miRNAs involved in oligodendrocyte lineage cell (OLLC) differentiation have been extensively studied in rodent models, their functions in human oligodendrocyte (OL) development remain poorly understood. To address this, we used a human embryonic stem cell (hESC) reporter system and an optimized differentiation protocol to generate and isolate well-characterized OLLCs at defined developmental stages. Next-generation sequencing-based miRNA profiling identified stage-specific miRNAs associated with OL lineage specification and maturation. In addition to canonical OL-associated miRNAs, we identified several previously uncharacterized oligodendrocyte progenitor cell (OPC)/oligodendrocyte (OL)-enriched miRNAs, including miR-3943, miR-4286, miR-1296-5p, miR-488-3p, miR-675-5p, and miR-128-3p, as potential novel regulators and molecular markers for human OLLC development. Computational target analysis further identified candidate regulatory genes, including ZNF488, DLX1, CSNK2B, and KCNJ1, and predicted their association with AKT, SMAD2/3, estrogen-receptor, and insulin-signaling pathways. Together, these findings provide a comprehensive stage-specific miRNA resource for human OL lineage development and provide insight into potential miRNA-mediated regulatory networks governing human OL development. Full article

Testicular germ cell tumors (TGCTs) are highly curable malignancies, yet their clinical management still relies heavily on conventional serum tumor markers, including alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase, which have limited sensitivity and specificity in several clinically relevant settings. Circulating microRNAs, particularly miR-371a-3p, have emerged as promising liquid biopsy biomarkers with potential applications across the TGCT disease continuum. This narrative review summarizes the current evidence on the biological basis, diagnostic performance, clinical utility, and limitations of circulating microRNAs in TGCTs. MiR-371a-3p demonstrates high diagnostic accuracy for viable non-teratomatous TGCTs and consistently outperforms classical serum tumor markers in primary diagnosis. Its rapid decline after effective treatment and its association with tumor burden support potential roles in chemotherapy monitoring, early relapse detection during surveillance, and the assessment of selected post-chemotherapy residual masses. However, its inability to detect teratoma remains a major biological limitation, particularly in non-seminomatous residual disease and surveillance settings. Additional barriers to implementation include assay heterogeneity, the lack of universally accepted cutoffs, the variable use of serum versus plasma, and the absence of broad regulatory approval. Emerging translational data suggest that miR-371a-3p may also contribute to tumor–microenvironment communication and cisplatin resistance, although these findings remain preclinical. Overall, miR-371a-3p represents one of the most promising biomarkers in TGCT management, but its routine clinical integration will require standardized analytical protocols and prospective validation in marker-guided decision pathways. Full article

Hypoxia-driven regulatory mechanisms play a critical role in tumor progression and therapeutic resistance in hepatocellular carcinoma (HCC), yet hypoxia-responsive microRNAs (HRMs) remain incompletely characterized. This study aimed to identify HRMs in canine HCC to evaluate their diagnostic potential and translational relevance to human disease. Next-generation sequencing of two canine HCC cell lines under normoxic and hypoxic conditions identified 332 and 321 differentially expressed miRNAs, respectively. Integrating these with tumor tissue data revealed 11 HRMs, featuring consistent upregulation of cfa-miR-210 and cfa-miR-34a, which was validated via RT-qPCR in hypoxic cells and clinical tissues. Both miRNAs were significantly elevated in plasma-derived extracellular vesicles (EVs), highlighting their value as promising circulating biomarkers (AUC 1.00 for miR-210; 0.98 for miR-34a). Target gene and pathway analyses identified shared regulatory nodes, including TGIF2 and SPRED1; and enrichment of MAPK, Ras, PI3K-Akt, and Rap1 signaling, broadly linked to hypoxia adaptation, cellular metabolism, and stress-response signaling. Cross-species comparison with human HCC datasets showed that, while miR-210 associates with poor prognosis in human HCC, miR-34a exhibits tumor-suppressive features. These findings define complementary HRM programs in canine HCC, reflecting conserved adaptive and stress-limiting regulatory mechanisms with potential diagnostic and translational relevance to human HCC. Full article

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article

Cardiac rhythm and pumping function are essential outputs of cardiac homeostasis and depend on precise molecular regulation. The histone acetyltransferases CBP/p300 have been implicated in cardiac remodeling and functional regulation. nej, the Drosophila homolog of CBP/p300, may therefore represent an important regulator of cardiac function. However, the relationship between miR-276a and nej in the heart, as well as the potential involvement of the fat body in this regulatory relationship, remains unclear. Using Drosophila as a model, we first examined the effects of cardiac-specific nej overexpression and knockdown on cardiac function and tested the interaction between miR-276a and the nej 3′ untranslated region using a dual-luciferase reporter assay. We subsequently manipulated miR-276a using Hand-Gal4 and Cg-Gal4 and assessed miR-276a and nej expression in cardiac samples, cardiac function, and climbing ability. Finally, we investigated the effects of an exercise intervention on cardiac miR-276a/nej expression and functional outcomes. Both cardiac-specific overexpression and knockdown of nej impaired cardiac rhythm, reduced pumping function, and decreased climbing ability. The reporter assay supported a functional interaction between miR-276a and the nej 3′ untranslated region, while cardiac-specific miR-276a manipulation was accompanied by inverse changes in nej mRNA expression and by cardiac and climbing abnormalities. Cg-Gal4-mediated miR-276a upregulation or downregulation was associated with altered miR-276a and nej expression in cardiac samples and with cardiac and climbing impairments. Exercise improved cardiac and climbing ability in both cardiac miR-276a knockdown and overexpression groups. It increased cardiac miR-276a expression and decreased nej expression in the cardiac knockdown group but did not significantly alter either transcript in the cardiac overexpression group. Exercise also improved cardiac function in both Cg-Gal4-mediated miR-276a knockdown and overexpression groups. In the Cg-Gal4-mediated knockdown group, this improvement was accompanied by increased miR-276a and decreased nej expression in cardiac samples. These findings indicate that exercise modulates cardiac function and miR-276a/nej expression in a context-dependent manner and suggests a possible contribution of the fat body. Full article

Field cancerization describes molecular alterations occurring in histologically normal tissues surrounding tumors that may contribute to cancer initiation and progression. In prostate cancer (PCa), the molecular characteristics of peritumoral tissue (PTT) remain incompletely understood. Because microRNAs (miRNAs) play key roles in gene regulation, tumor progression, and microenvironmental remodeling, we investigated miRNA expression patterns and regulatory networks across benign tissue (BT), PTT, and tumor tissue (TT). Small RNA sequencing was performed on matched formalin-fixed paraffin-embedded samples from 40 patients with PCa. Differential expression analysis was conducted using DESeq2, adjusting for age and Gleason grade, while functional enrichment analysis and weighted gene co-expression network analysis (WGCNA) were used to identify dysregulated pathways and conserved miRNA modules. PTT exhibited a molecular profile intermediate between BT and TT, consistent with a field cancerization effect. Compared with BT, 102 miRNAs were differentially expressed in TT and 57 in PTT, with 39 miRNAs (68% of the PTT-associated miRNAs) overlapping the tumor signature. Shared dysregulated pathways included PI3K–Akt, p53, and HIF-1 signaling; whereas, PTT showed additional enrichment in pathways related to epigenetic regulation (Polycomb Repressive Complex) and cellular stress responses (mitophagy, protein processing in ER) exclusively through up-regulated miRNAs; no pathways were uniquely enriched from down-regulated miRNAs in PTT. WGCNA identified conserved miRNA modules enriched for members of the let-7, miR-200, miR-103/107, and miR-106a~363 families, which have established roles in epithelial–mesenchymal transition, tumor progression, and microenvironmental remodeling. Collectively, these findings demonstrate that histologically benign peritumoral tissues harbor tumor-associated miRNA programs and regulatory networks that closely resemble those observed in prostate tumors, providing molecular evidence of field cancerization in PCa and identifying potential miRNA-mediated mechanisms relevant to disease progression and biomarker development. Full article

Introduction: Proper analysis of high-throughput lipidomic data requires specialized tools for data processing, normalization, visualization, and statistical and bioinformatic analysis. However, limitations in lipid parsing, data processing, and visualization capabilities in existing software packages create challenges for comprehensive lipidomic data analysis. To address these limitations, we developed LipidAnalyst (v 1.0.3), a user-friendly tool designed to facilitate efficient lipid parsing and processing, visualization, and analysis of lipidomic datasets. Methods: LipidAnalyst was developed using the R Shiny framework. It is hosted on MiServer for online work but can also be downloaded from GitHub. Results: LipidAnalyst provides functionalities in three major areas: data processing, visualization, and statistical analysis. Data processing features include quality control filtering, normalization, internal standard-based quantification, and unique capabilities for missing-value imputation, lipid parsing, and aggregation. Visualization tools include box and violin plots for data distribution assessment, principal component analysis (PCA) plots, hierarchical clustering and differential abundance heatmaps, volcano plots, correlation plots, and Debiased Sparse Partial Correlation (DSPC) clustering plots. Statistical analysis modules include t-test, analysis of variance (ANOVA), Partial Least Squares Differential Analysis (PLS-DA), Orthogonal Partial Least Squares Differential Analysis (OPLS-DA), and Random Forest (RF) modeling. Conclusions: LipidAnalyst is a comprehensive platform for optimal processing, visualization, and analysis of lipidomic data. By integrating advanced data processing workflows with extensive visualization and statistical analysis capabilities, LipidAnalyst enables researchers to explore lipidomic datasets more effectively and develop informed analytical strategies. Full article

Grape pomace (GP) is being explored as a sustainable feed ingredient for ruminants due to its fiber and polyphenol content; however, its systemic effects under farming conditions remain unclear. This study tested whether 5% dried grape pomace (GP5) modulates serum circulating miRNAs (cmiRNAs) in dairy sheep. Twelve Sarda ewes were enrolled in a 30-day trial and assigned to a control (CTRL) or GP5 diet. Small RNA sequencing was initially performed in GP5 animals (paired T30 vs. T0 comparison); after quality filtering, five paired animals were included in the sequencing analyses. The differentially expressed (DE) cmiRNAs were validated by RT-qPCR in GP5 and CTRL groups. RT-qPCR confirmed the NGS-derived miRNA signature, identifying miR-143, miR-382-5p, miR-409-3p, and miR-194 as significantly downregulated (p < 0.05) in GP5 animals. Ingenuity Pathway Analysis (IPA) showed that DE miRNAs target shared hubs, with PPAR signaling among the most enriched pathways (BH-adjusted p = 1.35 × 10⁻⁹), predicted to be inhibited (Z = −2.646). Cholecystokinin/gastrin-mediated and S100 signaling were also enriched (BH-adjusted p = 7.08 × 10⁻¹¹ and 3.21 × 10⁻⁸) and predicted to be activated (Z = 2.828 and 3.162). Overall, GP5 supplementation was associated with a selective cmiRNA signature consistent with targeted post-transcriptional regulation. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is characterized by excessive hepatic lipid accumulation and metabolic dysfunction. Although microRNA-34a (miR-34a) has been implicated in hepatic lipid metabolism, the molecular mechanisms underlying its contribution to MASLD remain incompletely understood. Here, we investigated the role of miR-34a in FFA-induced hepatic steatosis using HepG2 cells and explored RXR-associated signaling as a potential therapeutic strategy. RT-qPCR quantified miR-34a expression; direct target interactions were validated using dual-luciferase reporter assays; proteomic alterations were characterized by iTRAQ-based proteomics followed by Ingenuity Pathway Analysis (IPA); and transcriptomic responses to 9-cis-retinoic acid (9-cis-RA) were analyzed by RNA sequencing. FFA treatment significantly increased miR-34a expression, and dual-luciferase assays confirmed that miR-34a directly targets the 3′-UTRs of RXRα, PPARα, and SIRT1. Integrated proteomic and transcriptomic analyses consistently identified LXR/RXR signaling as one of the principal pathways associated with miR-34a dysregulation and 9-cis-RA treatment. Pharmacological activation of RXR-associated signaling with the pan-RXR agonist 9-cis-RA attenuated intracellular lipid accumulation and reduced the expression of key regulators of lipogenesis and fatty acid uptake, including FASN, SCD1, FABP4, and CD36. Collectively, these findings support the miR-34a–RXRα axis as one regulatory component within a broader nuclear receptor network associated with hepatic lipid homeostasis and support further investigation of RXR-associated signaling as a potential therapeutic strategy for MASLD. Nevertheless, confirmation of receptor-specific mechanisms and validation in more physiologically relevant experimental models will be required. Full article

Pricing coupon longevity bonds (CLBs) is challenging in illiquid markets due to the incompleteness of insurance markets and the unavailability of longevity payout data. In addition, pension funds may experience significant surges in annual mortality-improvement reserves (MIRs), consistent with systematic longevity drift and cohort-survival effects. We propose a Bayesian pricing model based on the Integrated Nested Laplace Approximation (INLA) for CLBs in pension-fund applications. The term structure of interest rates is modeled using a two-factor Cox–Ingersoll–Ross (CIR) specification, while mortality dynamics are captured using a CIR affine jump–diffusion model to capture abrupt longevity shocks. Posterior inference is performed via INLA and benchmarked against Markov chain Monte Carlo (MCMC). Using South African government bond yield data, pension-fund MIR series, and population survival-rate reports, we show that INLA provides a computationally efficient approximation to the MCMC posterior with substantially reduced computation time. Longevity Greeks derived from the model support hedge construction and evaluation of strategies aimed at mitigating rising longevity-linked cash flows. Empirically, model-implied longevity payouts are positively skewed with high dispersion and exhibit frequent jump episodes over a broad range, underscoring the importance of jump risk in CLB valuation and hedging. Full article

The prognostic relevance of IDH1 mutations remains unclear in acute myeloid leukemia (AML). This study, representing the first Turkish AML cohort characterized for IDH1 mutations, aimed to determine the frequency of IDH1, FLT3 and NPM1 mutations and to describe the associated clinical characteristics. We retrospectively analyzed clinical, cytogenetic, and molecular data for 57 AML patients. Bone marrow aspirates were evaluated cytogenetically using G-banding, and molecular mutations were assessed by PCR or NGS (MiSeq-Illumina). IDH1 mutations were detected in 7% of patients; FLT3 and NPM1 mutations were detected in 38.6% and 19.3% of patients, respectively. A significant positive correlation existed between IDH1 and NPM1 mutations (r = 0.388, p = 0.003). Overall mortality was 56.1% and remission was achieved in 43.9%. Older age (p = 0.029) and comorbidities (p = 0.009) were significantly linked to mortality. Mortality was 100% in the four IDH1-mutant patients and significantly higher in NPM1-mutant patients. Overall survival was shorter in IDH1-mutants, although the difference did not reach statistical significance (log-rank p = 0.057). Relapse occurred in 26.3%, rising to 50% in the IDH1-mutated subgroup. In this limited cohort, IDH1-mutant cases were associated with shorter overall survival and higher mortality; however, the small number of IDH1-mutant patients (n = 4) precludes definitive prognostic conclusions. Outcomes in NPM1-mutated patients were also less favorable than typically expected, possibly related to co-occurring IDH1 mutations. These descriptive findings characterize the molecular landscape of AML in an underrepresented Turkish population and may provide a foundation for larger, multicenter studies rather than confirming a prognostic role for these mutations. Full article

The development of more accessible perfumes (non-counterfeit replicas) that offer a similar scent to luxury perfume brands is an emerging trend in the perfume market. In this context, it is important to develop simple, rapid, cost-effective, and environmentally friendly alternative analytical tools capable of differentiating original perfumes from their non-counterfeit replicas. In this work, three vibrational spectroscopic techniques, namely near-infrared (NIR), mid-infrared (MIR), and Raman spectroscopy, were evaluated for the discrimination between original perfume samples and their non-counterfeit replicas. Several original perfume samples and their non-counterfeit replicas were scanned through these vibrational spectroscopic techniques and analyzed with two chemometric tools: principal component analysis (PCA) and hierarchical cluster analysis (HCA). Different pre-processing techniques were also tested in PCA and HCA to attest to the robustness of the findings. The results revealed that all vibrational spectroscopic techniques tested demonstrated high efficiency in differentiating original perfumes from their non-counterfeit replicas. NIR spectroscopy revealed the least similarity among the samples across all pre-processing techniques. In this context, these vibrational spectroscopic techniques are a rapid, cost-effective, non-destructive, and interesting alternative for discriminating between original perfume samples and non-counterfeit replicas. Although further studies, including the application of supervised classification methods to a larger sample set, are needed to attest to the robustness of these results, these preliminary results are very interesting and promising. To the best of our knowledge, this was the first time that vibrational spectroscopic techniques were applied and compared in the analysis of perfume and non-counterfeit replicas. Full article

Background/Objectives: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men. While localized PCa carries a favorable prognosis, progression to locally advanced disease substantially worsens outcomes. There is an unmet need for molecular markers that reliably distinguish indolent from aggressive tumors. MicroRNAs (miRNAs), small non-coding RNAs that post-transcriptionally regulate gene expression, are implicated in cancer development and progression, and their expression profiles may serve as putative biomarkers of disease stage. Methods: We performed small RNA sequencing on formalin-fixed paraffin-embedded (FFPE) prostate tumor tissues from nine patients (five localized, four locally advanced-stage). Differentially expressed miRNAs were identified using a bioinformatics pipeline (fold-change ≥ 2, p < 0.05). Target gene prediction, KEGG pathway enrichment, and miRNA–mRNA interaction network analyses were conducted, followed by in silico validation using two independent public mRNA datasets (GSE46602 and GSE21034, a subseries of GSE21032). Results: Seven unique mature miRNAs were differentially expressed between localized and locally advanced PCa. Five miRNAs (miR-145-5p, miR-205-5p, miR-206, miR-24-1-5p, and hsa-miR-3648) were downregulated in locally advanced tumors, while hsa-miR-625-3p and miR-324-5p were upregulated. Network analysis identified CLTC and CDK6 as putative downstream targets co-targeted by multiple downregulated miRNAs. Independent validation using GSE46602 and GSE21034 consistently demonstrated significantly higher expression of CLTC and CDK6 in locally advanced prostate cancer following Benjamini–Hochberg correction. Conclusions: This exploratory pilot analysis identified several miRNAs that differ between localized (pT2) and locally advanced (pT3–T4/N+) prostate cancer. Independent validation across two publicly available mRNA cohorts supports CLTC and CDK6 as candidate stage-associated genes. However, these findings remain hypothesis-generating and require validation in larger prospective cohorts together with functional confirmation before biomarker or therapeutic claims can be made. Full article

The increasing demand for plant-based beverages as alternatives to dairy milk requires rapid and reliable methods to assess their composition and authenticity. This study investigated the feasibility of mid-infrared (MIR) and near-infrared (NIR) spectroscopy for classifying plant-based beverages and predicting their nutritional profile. A total of 57 commercial beverages from five categories (oat, almond, soybean, rice, and coconut) were analyzed. Canonical discriminant analysis was used to discriminate among beverage categories, and modified partial least-squares regression models were developed using reference chemical analyses and spectral data to predict protein, fat, sugars, ash, acidity traits, minerals, and amino acid composition. Both MIR and NIR successfully discriminated among the five beverage categories. Quantitative prediction models were generally more accurate with MIR than with NIR. The most robust MIR models were obtained for protein, fat, glucose, ash, and selected minerals (P and K), reaching accuracy levels suitable for quality-control applications. Protein was predicted with excellent accuracy by both technologies. The most robust prediction models were achieved for amino acid composition, with all amino acids except phenylalanine showing satisfactory predictive performance, particularly with MIR spectroscopy. In conclusion, these results demonstrate the feasibility of infrared spectroscopy for the authentication and compositional assessment of plant-based beverages. In particular, MIR spectroscopy showed considerable potential for integration into routine quality-control workflows, similar to those currently implemented for dairy milk analysis. Full article

Background: MicroRNAs are key post-transcriptional regulators of gene expression and contribute to cancer progression, tumor heterogeneity, and context-dependent regulatory rewiring. However, most computational approaches rely on sequence-based target prediction or bulk expression association and are not designed to jointly model regulatory priors, expression context, and heterogeneous cancer states, particularly when matched single-cell microRNA/mRNA co-profiling data are scarce. Methods: We developed a context-aware graph transformer framework for microRNA–gene regulatory analysis across biological resolutions. The framework represents microRNAs, genes, and biological contexts as a heterogeneous graph, where contexts correspond to individual cells in single-cell data and tumor samples or subtype-defined profiles in bulk cohorts. Heterogeneous graph transformer learning generated regulatory embeddings, Bayesian topology optimization refined candidate microRNA–gene interactions, and a dominance-based competition layer with Dominance Share scoring identified master regulators and cooperative target modules. Results: We applied miR-CellMap to matched single-cell miRNA/mRNA co-sequencing data from K562 leukemia cells and paired bulk cancer datasets spanning pan-cancer and subtype-specific cohorts, including breast, colon, glioblastoma, lower-grade glioma, and ovarian cancer. The framework identified recurrent and dataset-specific miRNA regulatory programs, including regulators such as miR-186-5p, miR-214-3p, miR-27a-3p, and let-7 family members. Embedding-derived context analysis showed that predicted miRNA target programs were consistently closer to observed context-specific gene programs than random matched gene programs across all seven datasets. Dominance Share analysis further identified cooperative target modules and co-repressed target programs, supporting the use of miR-CellMap for interpretable cancer-focused miRNA regulatory discovery. Conclusions: This framework provides an interpretable strategy for mapping conserved, cancer-specific, and context-dependent microRNA–gene regulatory programs across single-cell and bulk cancer datasets. Full article