Search Results (4,122)

Pancreatic cancer poses a major clinical challenge due to its aggressiveness, frequent recurrence, and limited response to current chemotherapeutic approaches. Cancer stem cells (CSCs), particularly pancreatic CSCs (PCSCs), are key drivers of tumor initiation, therapeutic resistance, and disease relapse. MicroRNAs (miRNAs) have emerged as critical regulators of CSC biology and influence self-renewal, pluripotency, and drug resistance through key signaling pathways. To identify PCSC-specific miRNAs, we enriched these cells using the pancreosphere culture method and isolated PCSC+ and PCSC− populations using FACS based on their expression of CD44, CD24, and CD133 surface markers. MicroRNA microarray analysis revealed 31 differentially expressed miRNAs (DEmiRNAs), of which 10 downregulated miRNAs were involved in pathways regulating pluripotency, including the Wnt/β-catenin, TGF-β, MAPK, and PI3K/AKT pathways. Then, 2 of these 10 DEmiRNAs, let-7b-5p and miR-24-3p, were selected for experimental validation. Their overexpression in PCSC+ cells inhibited these pathways, downregulated pluripotency factors, and induced differentiation into endocrine and exocrine phenotypes, as confirmed by RT-qPCR, Western blot, and RNA-seq. Functionally, each miRNA reduced sphere formation, increased gemcitabine sensitivity, and suppressed tumorigenicity in vivo, highlighting their potential as therapeutic candidates. Restoring tumor-suppressive miRNA expression may offer a novel strategy to overcome chemoresistance and improve outcomes in pancreatic cancer. Full article

Canine hepatocellular carcinoma (HCC), the most common primary liver malignancy in dogs, shares many clinicopathological and molecular similarities with human HCC. However, its molecular characteristics remain insufficiently defined, and reliable diagnostic biomarkers are lacking. Elucidating dysregulated microRNAs (miRNAs) may aid in both disease characterization and comparative oncology research. Small RNA sequencing datasets from canine HCC were analyzed to identify significantly dysregulated miRNAs with high expression and biomarker potential. The top candidate was validated in clinical tissues, cell lines, patient’s plasma and plasma exosomes using RT-qPCR. Comparative analyses were conducted using human HCC datasets (TCGA and GEO), followed by target prediction and functional enrichment to identify conserved molecular pathways. Among the 59 differentially expressed miRNAs, cfa-miR-10a showed the highest average expression level and yet was significantly downregulated in canine HCC tissues. RT-qPCR confirmed reduced expression of cfa-miR-10a in canine HCC tissues, whereas plasma exosomes showed significant enrichment, demonstrating excellent diagnostic performance (AUC = 0.94). The mature sequence of cfa-miR-10a is highly conserved with hsa-miR-10a-5p. TCGA datasets confirmed downregulation of hsa-miR-10a-5p in HCC tissues, whereas a GEO dataset showed no significant change in serum exosome levels. Target prediction and functional annotation identified 59 overlapping genes, with the Proteoglycans in cancer pathways being conserved in both species, mediated by ACTG1, SDC1, FRS2, and WNT9B. Collectively, these findings demonstrate distinct intra-tumoral and exosomal expression pattern of miR-10a in canine HCC and support its potential as a non-invasive biomarker with translational relevance. Full article

Alzheimer’s disease (AD) is the leading cause of dementia and is often prefaced by mild cognitive impairment (MCI). Detection of AD-related changes via blood-based biomarkers would enable critical therapeutic interventions early in disease progression. Neuronal enriched extracellular vesicle (NEEV) miRNAs regulate peripheral genes as a response to early AD brain changes and hence may have biomarker potential. Plasma NEEVs were captured from plasma samples of Mexican Americans (MAs) and Non-Hispanic Whites (NHWs) using an antibody against the neuronal surface marker CD171. miRNAs isolated from NEEVs were sequenced and analyzed using miRDeep2/DEseq2 and QIAGEN RNA-seq portal for differential expression between cognitively impaired (CI) and cognitively unimpaired controls. hsa-miR-122-5p was significantly underrepresented in the CI group in both MAs and NHWs compared to the healthy control. Other population-specific miRNAs (MAs: hsa-miR-26a-5p, hsa-let-7f-5p, and hsa-miR-139-5p, NHWs: hsa-miR-133a-3p, hsa-miR-125b-5p, and hsa-miR-100-5p) identified may have biomarker potential in AD precision medicine. Some of these differentially expressed miRNAs were associated with key AD-related comorbidities such as APOE genotype, age, and metabolic burden and were predicted to target genes within NF-κB -regulated inflammatory pathways. Together, these findings suggest that dysregulated miRNA networks may serve as a mechanistic link between comorbidity burden and AD-related neuroinflammation and neurodegeneration. Full article

Leishmaniasis and Chagas disease, caused by Leishmania spp. and Trypanosoma cruzi, are neglected tropical diseases with significant global health burden, particularly in resource-limited regions. Despite their impact, diagnosis and treatment remain challenging due to limited diagnostic tools and the toxicity of available therapies. Our objective is to propose the incorporation of markers for the diagnosis of leishmaniasis and Chagas disease using ncRNA. This narrative review evaluates studies published between 2010 and 2024 (PubMed, Scopus, Google Scholar) using the SANRA scale to assess the potential of non-coding RNAs (ncRNAs) as biomarkers for these infections. Both parasites release small RNAs via extracellular vesicles that modulate host–pathogen interactions and gene expression. Although RNA interference machinery is absent in T. cruzi and most Leishmania species, it persists in early-diverging lineages. In leishmaniasis, distinct miRNA expression profiles—including miR-155-5p, miR-5011-5p, miR-6785-5p, and miR-361-3p—demonstrate high diagnostic accuracy for detecting infection (AUC up to 1.0). Serum long ncRNAs such as MALAT1 and NUTM2A-AS1 show potential diagnostic value, though clinical validation remains pending. For Chagas disease, the available evidence on ncRNAs primarily addresses the diagnosis of clinical manifestations rather than initial infection. Host miRNAs, including miR-21, miR-145, miR-146a/b, and miR-19a-3p, correlate with cardiac involvement, immune dysregulation, and inflammation during chronic T. cruzi infection. Circulating miRNAs exhibit modest sensitivity (57–67%) and specificity (57–80%) for diagnosing chronic Chagas cardiomyopathy, indicating their utility in assessing disease progression and organ damage rather than detecting early infection. This review distinguishes between ncRNAs that diagnose infection and those that evaluate disease severity or organ involvement. Altered ncRNA expression profiles represent promising biomarkers for species differentiation, treatment monitoring, and assessing cardiac complications in Chagas disease, with broader diagnostic applications emerging for leishmaniasis. Full article

Climate-change-induced thermal stress poses a significant threat to cold-adapted aquatic species, particularly fish endemic to high-altitude ecosystems such as Gymnocypris eckloni, which is native to the Qinghai-Tibetan Plateau. To elucidate the molecular and metabolic mechanisms underlying their response to elevated temperatures, we integrated RNA-seq, miRNA-seq, and LC-MS-based metabolomic analyses of liver tissue from fish exposed to chronic thermal stress (HT) versus control (CT) conditions. Although no significant differences were observed in growth parameters, histopathological examination revealed structural damage under heat stress. Transcriptomic analysis identified widespread dysregulation of genes involved in energy metabolism, with significant downregulation of pathways related to amino acid, fatty acid, glucose, and oxidative phosphorylation. In contrast, upregulated DEGs were enriched in N-glycan biosynthesis, protein processing in the endoplasmic reticulum, and phagosome. Concomitant miRNA profiling revealed differentially expressed miRNAs, including miR-196a-5p, miR-132-3p, and miR-181b-5p, which were predicted to regulate key metabolic genes such as ugt1a1, pepck, and calr. Metabolomic analysis further demonstrated significant alterations in metabolic profiles, with glutathione metabolism, tryptophan metabolism, steroid hormone biosynthesis, and pyruvate metabolism emerging as central pathways in the heat stress response. Integrated multi-omics analysis confirmed coordinated regulation of these pathways, highlighting the critical role of glutathione and tryptophan, as well as disruptions in purine and energy metabolism. The DEMiR-DEG-DEM networks involving miR-196a-5p-pepck-PEP, miR-133a-3p-gne-UDP-GlcNAc, and miR-132-3p-ugt1a1-Bilirubin may play an important role in thermal stress. This study provided a new perspective on the molecular, regulatory, and metabolic adaptations of Gymnocypris eckloni to thermal stress, identifying potential biomarkers and regulatory networks that may inform conservation strategies for cold-water fish under global warming. Full article

Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional level, yet data on circulating miRNAs in human SCI remain scarce. This study aimed to characterize acute plasma miRNA expression patterns in isolated traumatic SCI that may indicate SCI-specific signatures. Plasma was collected from five SCI patients at admission and 48 h post-injury and five healthy controls (HCs), and next-generation sequencing (NGS) was performed on plasma RNAs. Differentially expressed miRNAs were identified, and selected candidate miRNAs were validated by droplet digital PCR (ddPCR) in an expanded cohort of SCI patients, polytrauma patients without neurotrauma (PT), and HC (each n = 8). Pathway enrichment and validated target analysis were performed to assess biological relevance of candidate miRNAs. At emergency room admission, 46 miRNAs were differentially expressed in SCI plasma (18 upregulated, 28 downregulated). By 48 h, a global downregulation was observed, with 47 miRNAs significantly decreased compared with HC. ddPCR validation revealed markedly stronger suppression of miR-182-5p, miR-190a-5p, miR-144-5p, and miR-30c-5p expression levels in SCI compared with PT. Pathway analysis indicated enrichment of mitochondrial oxidative phosphorylation pathways, and target prediction suggested that the identified miRNAs may be linked to neuroprotective and regenerative functions. Our findings demonstrate early and profound alterations in circulating miRNAs after acute SCI. The downregulation of the identified miRNAs may reflect maladaptive changes that promote neuroinflammation and hinder axonal regeneration, although the exact functional consequences remain to be clarified. These data suggest that circulating miRNAs could hold promise as diagnostic and prognostic biomarkers and, potentially, as therapeutic targets to influence secondary injury processes. However, given the exploratory nature and limited sample size of this study, the findings should be validated in larger, sufficiently powered cohorts to robustly delineate differences between patient groups. Full article

Chronic heart failure (CHF) carries high morbidity and mortality. Circulating biomarkers of myocardial stretch, injury, and remodelling aids diagnosis and prognosis, but utility varies, especially in HFpEF, where natriuretic peptide (NP) values may be lower or normal in obesity. We systematically searched PubMed, Scopus, and Web of Science (2010–2025) for primary adult chronic-HF studies evaluating blood-based biomarkers: NPs, high-sensitivity troponins (hs-cTn), galectin-3, soluble ST2 (sST2), and microRNAs. Secondary sources (reviews/meta-analyses/guidelines) informed context only. Acute-HF studies were not pooled with chronic-HF analyses. Where appropriate, log hazard ratios were meta-analysed with random effects models. Twenty-nine studies met criteria. NT-proBNP remained the diagnostic/prognostic reference; across five prognostic cohorts, the pooled HR was 1.68 (95% CI 1.54–1.82; I² ≈ 55%). hs-cTn consistently improved risk stratification. Galectin-3 and sST2 were associated with adverse outcomes but typically provided modest incremental value beyond NPs/hs-cTn; galectin-3 is influenced by renal function, and sST2 is commonly interpreted around ~28–35 ng/mL. MicroRNAs (e.g., miR-21, miR-210-3p, miR-22-3p) showed promising yet heterogeneous signals across platforms and preanalytical workflows; therefore, findings were synthesised narratively without pooling. NT-proBNP and hs-cTn form the evidence-based backbone for biomarker-guided assessment in chronic HF. Galectin-3 and sST2 add adjunct prognostic information, while microRNAs remain investigational, pending standardised methods and external validation. Overall, evidence supports a multimarker, phenotype-tailored approach, with core NPs + hs-cTn and selective adjunct use of sST2/galectin-3 in context (HFrEF vs. HFpEF, obesity, renal function) to refine risk stratification and guide clinical decision-making. Full article

Cervical cancer (CCa) is the fourth leading cause of cancer-related deaths among women worldwide, with nearly 90% of cases in low- and middle-income countries, especially in Sub-Saharan Africa. This study explores the roles of circular ribonucleic acids (circRNAs), hsa_circ_0001038 and circRNA_400029, and the impact of the serine/arginine-rich splicing factor 3 (SRSF3) inhibitor, theophylline, in CCa cell lines. We utilized cell cycle fluorescence-activated cell sorting (FACS) and Annexin V/propidium iodide (PI) assays to evaluate theophylline’s effects on SiHa and C33A cell lines. Results showed S-phase arrest in SiHa and G2/M arrest in C33A, with significant cytotoxic effects indicated by apoptosis analysis. Using CircAtlas, we identified micro ribonucleic acids (miRNAs) binding to hsa_circ_0001038, particularly miR-205-5p, which has a tumour-suppressive role. miRTarBase identified miR-16-5p as a key interacting miRNA for circRNA_400029. We constructed a competing endogenous ribonucleic acid (ceRNA) network, revealing multiple miRNA targets. Pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted critical signalling pathways involved in CCa oncogenesis. In conclusion, theophylline demonstrates cytotoxicity in CCa cells, suggesting its potential for repurposing in CCa theranostics, though further optimization is necessary. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent known for its efficacy; however, it induces several adverse effects, most notably cachexia, which is characterized by progressive loss of skeletal muscle mass, weakness, and reduced body weight. N-acetylcysteine (NAC) a compound with antioxidants properties, has been shown to mitigate CIS-induced neurotoxicity in experimental models. This study aimed to investigate the myoprotective effects of NAC during CIS treatment and explore the redox and molecular mechanisms involved in this response. For this, female Wistar rats were divided into four experimental groups: Control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p for 5 days), and NAC + CIS (NAC for 8 days, with CIS administered from day 4 onward). After treatment, muscle strength, redox status, mitochondrial biogenesis, expression of myogenic microRNAs and morphological changes were evaluated. CIS treatment caused muscle atrophy, decreased GSH/GSSG ratio, impaired cellular function, increased lipid peroxidation and altered antioxidant enzymes activity. These effects were mitigated by NAC coadministration. CIS also reduced the mtDNA/nDNA ratio; however, NAC treatment tended to increase TFAM and PGC-1α expression levels. Furthermore, CIS suppressed the expression of muscular miR-1-3p, miR-133a-3p and miR-206-3p, while NAC restored their levels when co-administered with CIS. These findings suggest that NAC may serve as a promising adjuvant therapeutic strategy to counteract CIS-induced myotoxicity through redox regulation and modulation of molecular pathways related to muscle integrity and regeneration. Full article

Shrimp aquaculture ponds are dynamic ecosystems in which water quality and microbial interactions play a central role in animal health. This study aimed to investigate the relationship between the intestinal microbiota of Penaeus monodon and the microbial community of polyculture pond water. Shrimp and water samples were collected from polyculture ponds at four time points during the rearing period. Water-quality parameters were measured, and microbial community structures were analyzed by high-throughput 16S rRNA sequencing. Statistical analyses, including one-way ANOVA, revealed significant variations in water-quality parameters and microbial diversity among sampling stages (p < 0.05). Water quality indicators showed progressive changes from July to September, with pH decreasing from 8.1 to 7.5 but remaining within a suitable range. Nitrogen compounds, including ammonia, nitrite, and nitrate, increased steadily, with total nitrogen rising from 0.71 to 1.86 mg·L⁻¹, while phosphate and total phosphorus reached 0.31 and 0.36 mg·L⁻¹, respectively, exceeding thresholds commonly associated with algal bloom risk. Microbial community profiling using Illumina MiSeq sequencing revealed 166 OTUs shared between shrimp intestine and pond water, while both habitats contained more than 350 OTUs overall. Alpha diversity analysis showed higher microbial richness in water than in shrimp intestines, dominated by unclassified taxa, whereas shrimp guts were enriched in specific genera such as Vibrio. Cluster analysis indicated partial overlap but distinct grouping of gut and water microbiota, with the PMB intestinal community diverging most strongly. These findings highlight a close link between water quality and microbial composition, emphasizing the importance of pond management for maintaining ecological stability and shrimp health. Full article

Through binding to complementary mRNAs, microRNAs (miRNAs) mediate gene silencing. The stability and half-life of microRNAs are controlled by two isoforms of the RNA-binding protein Roquin. This study aimed at identifying the role of Roquin to miRNA-dependent regulation of the transcriptome in the post-ischemic heart. Both Roquin isoforms are highly conserved between rats and humans and constitutively expressed in cardiomyocytes. In both cell species, hypoxia induces a down-regulation of Roquin-1 and Roquin-2. An integrative miRNA-and-mRNA analysis (MMIA) identified miR-23b-5p as a potential interaction partner of Roquins. The open data bank TargetScan8.0 suggests that the transcription factor ZBTB20 is a potential target of miR-23b-5p. The level of expression of ZBTB20 correlated with the functional recovery of rat hearts after myocardial infarction. Moreover, the down-regulation of Roquin-2 in AC16 cells by siRNA under normoxic conditions was associated with an up-regulation of miR-23b-5p and a down-regulation of ZBTB20. Furthermore, in the case of hypoxia-dependent down-regulation of Roquin, the subsequent down-regulation of ZBTB20 was reversed with the help of an antagomir against miR-23b-5p. In conclusion, hypoxia-induced down-regulation of the two Roquin isoforms was associated with an increased stability of miR-23b-5p, a Roquin-2-dependent miRNA, which subsequently led to silencing of the transcription factor ZBTB20. 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

Vicadrostat, a selective aldosterone synthase inhibitor, reduced albuminuria with concurrent renin–angiotensin system inhibition and empagliflozin, suggesting additive efficacy for chronic kidney disease (CKD) treatment. Specific urinary extracellular vesicle microRNAs (uEV miRNAs) may reflect key mechanisms of kidney injury. We investigated how vicadrostat alone or with empagliflozin affected uEV miRNA expression in study participants. Small RNA sequencing was conducted on uEV miRNAs from 435 participants with CKD who completed 14 weeks treatment in the phase II trial of vicadrostat given with or without empagliflozin. Differentially expressed uEV miRNAs in participants with ≥30% UACR (urine albumin–creatinine ratio) reduction treated with 10 or 20 mg vicadrostat were pooled and evaluated with or without empagliflozin. Changes in miRNA-142-5p correlated significantly with changes in UACR in participants treated with vicadrostat alone, whereas changes in expression of eight additional uEV miRNAs (miR-192-5p, miR-194-5p, miR-6882-5p, miR-27a-5p, miR-381-3p, miR-192-3p, miR-513a-5p, and miR-199b-3p) correlated with ≥30% UACR improvements in patients treated with vicadrostat plus empagliflozin. Cellular deconvolution revealed that these miRNAs were expressed in various kidney cell types. Vicadrostat plus empagliflozin altered uEV miRNAs involved in immunomodulatory and fibrotic pathways irrespective of participant diabetes status. Regulation of miRNAs may provide insights into synergistic mechanisms of vicadrostat and empagliflozin in CKD treatment. Full article

Olive leaf tea (OLT), rich in phenolics, exhibits antioxidant, anti-inflammatory, and potential anticancer effects; however, the in vivo efficacy remains unclear. This study evaluated the chemopreventive and systemic effects of OLT in a murine Ehrlich Ascites Tumor (EAT) model, with a focus on the treatment timing. OLT was prepared by aqueous infusion and characterized for total phenolic content (TPC: 25.74 mg GAE/g), DPPH scavenging (197.88 µmol TE/g), FRAP activity (81.23 µmol Fe²⁺/g), and LC-MS/MS profile (oleuropein 77.6%). Mice received OLT orally before or after tumor inoculation. Prophylactic OLT reduced EAT cell counts (from 31.48 × 10⁷ to 21.15 × 10⁷), ascites volume (from 4.58 to 2.98 mL), elevated miR-155-5p (14.34-fold), normalized ALT/AST, and restored hepatic antioxidants without histopathological damage. Co-treatment with 5-FU preserved efficacy while reducing hepatotoxicity. In conclusion, OLT provides timing-dependent anticancer and systemic protective effects in the EAT model, supporting its potential as a cost-effective nutraceutical for cancer prevention and adjunctive therapy. Full article

Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| > 0.1, p < 0.05) and miRNAs (|log2FC| > 1, p < 0.05). Experimentally validated targets from miRTarBase/TarBase were intersected with dysregulated genes, followed by WikiPathways/GO enrichment. ceRNA networks were constructed via co-expression analysis. RT-qPCR validated miR-145-3p expression in A549/MRC-5 cells and NSCLC tissues. GEPIA assessed FN1/CCND1 clinical relevance. Results: We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = −1.24, p = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR < 0.05) and TGF-β-mediated EMT within the dysregulated geneset. Six immune-linked hub genes emerged. LncRNAs LOC729919 and LOC100134412 showed strong co-expression with hub genes and competitively bind miR-145-3p, derepressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-dependent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p < 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (p = 0.0017). Conclusions: We characterize a novel LOC729919/LOC100134412–miR-145–FN1/CCND1 ceRNA axis in NSCLC pathogenesis. FN1’s prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption. Full article