Search Results (8,181)

Background/Objectives: Moderate consumption of fermented beverages such as traditional beer has been associated with antioxidant and anti-inflammatory effects. MicroRNAs (miRNAs) play key roles in inflammation and oxidative stress, yet the impact of moderate fermented beverage consumption on blood miRNA profiles remains poorly understood. This study investigated the effects of regular, moderate intake of traditional and alcohol-free beer on whole blood miRNA levels in healthy adults. Methods: Whole blood samples were collected at baseline and after a 4-week intervention with alcohol-free beer and traditional beer in healthy overweight/obese adults (n = 36). miRNA profiling was performed using Affymetrix in a discovery subset, followed by targeted validation using real-time PCR in the full cohort. Bioinformatics and system biology analysis were applied to explore potential functional associations. Results: After traditional beer consumption, 202 miRNAs showed differential expression compared to baseline (p < 0.05). Eighteen miRNAs with changes ≥1.5-fold and the two miRNAs with the lowest p-values (p < 0.005) were selected for further analysis. Of them, the six miRNAs with the most consistent expression patterns were validated by real-time PCR. Moderate beer intake was associated with increased levels of miR-144-5p and miR-19a-3p in the overall population. Sex-stratified analyses suggested a tendency toward higher levels in these miRNAs in women following traditional beer intake. In silico analysis showed that predicted target genes of these miRNAs are involved in pathways related to immune regulation and inflammatory signaling. Conclusions: Moderate beer consumption is associated with consistent changes in whole-blood miRNA expression, particularly miR-144-5p and miR-19a-3p, in a healthy overweight/obese population. These findings support a potential role for epigenetic modulation in the biological response to moderate beer intake and provide a basis for future mechanistic studies. Full article

Background: Dengue is a growing mosquito-borne viral infection of global concern. It remains a major public health challenge in Nepal, where reliable biomarkers for disease staging and prognosis are lacking. In this study, we investigated circulating microRNA-1246 (miR-1246) as a potential diagnostic and prognostic marker in dengue infection. Methods: Serum samples from 21 dengue-positive patients and 20 healthy controls were analyzed by quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), with RNU6 as an internal control. Results: Dengue patients showed markedly elevated miR-1246 levels, with a mean 47-fold increase compared to controls (p = 0.001). Expression varied by disease stage, peaking in IgM positive cases, declining in weakly positive IgM patients, and reaching the lowest levels in IgG positive convalescent cases, a pattern consistent with clinical parameters such as platelet recovery. Receiver Operating Characteristic (ROC) analysis further highlighted diagnostic potential, yielding an Area Under the Curve (AUC) of 0.79, sensitivity of 95.24%, and specificity of 60.00%. Conclusions: These findings imply that miR-1246 is drastically dysregulated during dengue infection and could be a useful biomarker for tracking the intensity and course of the illness. Full article

To investigate the regulatory effects of miR-16-5p and miR-142-3p on inflammation and autophagy in human corneal epithelial cells (HCEpiCs) exposed to hyperosmotic stress, a key pathogenic condition in dry eye disease, HCEpiCs were cultured under NaCl-induced hyperosmotic conditions (450 mOsm, 24 h) and transfected with miR-16-5p or miR-142-3p mimics. Expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, IRAK1), autophagy-related genes (ATG5, Beclin-1, ATG16L1, p62), and apoptotic markers (Bax, Bcl-2, caspase-3) was analyzed by qRT-PCR and Western blot. Reactive oxygen species (ROS), autophagic vesicles, and apoptosis were evaluated using DCFH-DA, DAPRed, and Annexin V assays. The expression levels of antioxidant proteins (SOD1, catalase, NRF2) were also measured. Hyperosmotic stress induces marked inflammatory activation and excessive autophagy in HCEpiCs, accompanied by increased ROS generation and apoptosis. Overexpression of miR-16-5p or miR-142-3p significantly attenuated these effects by suppressing NF-κB-mediated cytokine expression and downregulating ATG5 and ATG16L1 expression, while restoring p62 expression. Both miRNAs reduced oxidative stress and COX-2 expression, enhanced antioxidant defenses, and normalized the expression of apoptotic markers. miR-16-5p and miR-142-3p are important regulators of inflammation and autophagy under hyperosmotic stress. Our findings suggest that modulating intracellular miR-16-5p and miR-142-3p levels in corneal epithelial cells may represent a potential approach to protect the ocular surface under hyperosmotic stress, although their systemic roles in autoimmune dry eye require further clarification. Full article

Background/Objectives: Transposable elements comprise over 50% of the human genome, yet their role in chromatin organization is insufficiently studied. This study was motivated by the hypothesis that transposable elements drive chromatin contacts through homotypic coupling—that is, pairs of identical TEs physically pull genomic regions together. Methods: Analyzing public Micro-C and Hi-C datasets, I compared focal contact areas that stand out from low backgrounds against contact-depleted regions at kilobase resolution. Results: I discovered that transposable elements show enrichment at these focal contact points and even stronger depletion in contact-poor regions. Ancient mammalian transposable element families (MIR, L2) preferentially form homotypic pairs at chromatin contacts, while young primate-specific families (Alu, SVA) actively avoid homotypic pairing. The depletion of homotypic pairs in contact-poor regions exceeded their enrichment at focal contacts, suggesting that homotypically coupled transposable elements may be sequestered in protein-protected compartments. Unexpectedly, sequence-unrelated families like MIR and L2 showed similarly strong pairing behavior, indicating a mechanism independent of DNA sequence similarity. While my data demonstrates clear homotypic specificity patterns reproducible across cell types and individuals, it cannot distinguish whether transposable elements actively drive chromatin contacts or are passive markers of chromatin states. Conclusions: Study findings reveal previously uncharacterized patterns of transposable element organization at chromatin contact and suggest that homotypic pairing may provide anchoring points for coherent chromatin folding. Full article

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease worldwide. Despite advances in metabolic and blood pressure control, the prevalence of DKD continues to rise, creating a significant clinical and socioeconomic burden. Recent studies have revealed that non-coding RNAs, particularly microRNAs (miRNAs), play an important role in the development and progression of DKD. Distinct patterns of miRNA dysregulation have been identified in specific renal cell types, including podocytes, mesangial cells, tubular epithelial cells, endothelial cells, fibroblasts, and macrophages. These alterations drive characteristic cellular injuries such as podocyte loss, mesangial matrix expansion, tubular epithelial–mesenchymal transition, endothelial dysfunction, and interstitial fibrosis. Certain miRNAs, such as miR-21, miR-192, and miR-214, reinforce profibrotic TGF-β/Smad signaling, whereas protective groups, including the miR-29 and miR-30 families, maintain epithelial stability and restrict matrix deposition. Beyond their regulatory roles, circulating and urinary miRNAs have emerged as stable, non-invasive biomarkers that reflect renal injury and disease progression. This review summarizes recent progress in elucidating cell-specific miRNA networks in DKD and highlights their potential as diagnostic indicators and therapeutic targets for precision management of diabetic kidney disease. Full article

In our study, we aimed to investigate the relationship between miRNA-21, miRNA-155, miRNA-34a, IL-6, TGF-β, and TNF-α expression levels and serum trace element levels in the development and progression of bladder cancer. RT-PCR was used to establish miRNA-21, miRNA-155, and miRNA-34a expression levels while serum IL-6, TGF-β, and TNF-α levels were determined using the ELISA and measured with an atomic absorption spectrophotometer. In the patient group, miRNA-21 and miRNA-155 expression levels were significantly higher compared with the healthy control group (p < 0.001). Furthermore, in the patient group, miRNA-34a expression was significantly lower compared with the control group (p < 0.001). IL-6, TNF-α, TGF-β, copper levels, and the copper to zinc ratio were significantly higher in the patient group (p < 0.001). Serum iron and zinc levels in the patient group were significantly lower compared with the control group (p < 0.001). There was a significant positive correlation between miRNA-155 and IL-6 and TNF-α (r = 0.279, p = 0.015*; r = 0.325**, p = 0.004). A significant positive correlation was detected between miRNA-34a and IL-6 and TGF-β (r = 0.294*, p = 0.010; r = 0.447**, p < 0.001). By evaluating these important biomarkers together, it might be possible to implement clinical applications for bladder cancer treatment and develop individual therapeutic strategies. Full article

Microvascular complications of diabetes include retinopathy (DR), diabetic kidney disease (DKD), and neuropathy (DN), which play a crucial role in diabetes management, as they significantly impair the functionality of the patient and remain major causes of morbidity despite advances in glycaemic control. The aim of this review was to summarize multi-omics findings in DR, DKD, and DN. Multi-omics studies consist of genomic, epigenomic, transcriptomic, proteomic, and metabolomic research. These studies provided comprehensive insights into the complex mechanisms underlying microvascular complications of diabetes, such as inflammation, angiogenesis, and apoptosis in the retina, kidneys, and nervous system. They also enabled the search for emerging diagnostic, prognostic, and therapeutic biomarkers. Moreover, changes in microRNA levels were found to differentiate patients with non-proliferative and proliferative DR. In addition, different proteins and metabolites concentrations were noticed in diabetes macular oedema and tractional retinal detachment—serious complications of DR. Specific molecular signatures, such as miR-146a and miR-27 dysregulation, changes in levels of HLA-DRA, AGER, and HSPA1A proteins, and alterations in tyrosine, alanine, 2,4-dihydroxybutanoic acid, ribonic acid, myoinositol, ribitol, 3,4-dihydroxybutanoic acid, valine, glycine, and 2-hydroxyisovaleric acid, were found to be characteristic for all microvascular complications of diabetes. In the future, more studies in multi-omics are expected to help improve precision medicine approaches to treating diabetes, allowing for personalized prediction, prevention, and treatment of microvascular complications. Full article

Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches—including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence—that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25–45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing. Full article

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks. Full article

Multimodal question answering (QA) involves integrating information from both visual and textual inputs and requires models that can reason compositionally and accurately across modalities. Existing approaches, including fine-tuned vision–language and prompting, often struggle with generalization, interpretability, and reliance on task-specific data. In this work, we propose a Mixture-of-Reasoning Agents (MiRA) framework for zero-shot multimodal reasoning. MiRA decomposes the reasoning process across three specialized agents—Visual Analyzing, Text Comprehending, and Judge—which consolidate multimodal evidence. Each agent operates independently using pretrained language models, enabling structured, interpretable reasoning without supervised training or task-specific adaptation. Evaluated on the ScienceQA benchmark, MiRA achieves 96.0% accuracy, surpassing all zero-shot methods, outperforming few-shot GPT-4o models by more than 18% on image-based questions, and achieving similar performance to the best fine-tuned systems. The analysis further shows that the Judge agent consistently improves the reliability of individual agent outputs, and that strong linear correlations (r > 0.95) exist between image-specific accuracy and overall performance across models. We identify a previously unreported and robust pattern in which performance on image-specific tasks strongly predicts overall task success. We also conduct detailed error analyses for each agent, highlighting complementary strengths and failure modes. These results demonstrate that modular agent collaboration with zero-shot reasoning provides highly accurate multimodal QA, establishing a new paradigm for zero-shot multimodal AI and offering a principled framework for future research in generalizable AI. Full article

Climate change increasingly challenges viticulture, demanding innovative and sustainable strategies to preserve grapevine productivity and grape quality. MicroRNA-encoded peptides (miPEPs) have emerged as natural regulators of gene expression, providing a novel mechanism for fine-tuning plant metabolism. Here, we evaluated whether exogenous application of miPEP164c, previously shown to repress VviMYBPA1 in vitro, can modulate flavonoid pathways in field-grown grapevines (Vitis vinifera L. cv. Vinhão). Grape clusters were sprayed with 1 µM miPEP164c before and during véraison, and molecular, biochemical, and metabolomic analyses were performed at harvest. miPEP164c treatment significantly upregulated pre-miR164c transcripts, leading to post-transcriptional silencing of VviMYBPA1 and strong downregulation of the proanthocyanidin-related genes VviLAR1, VviLAR2, and VviANR. Correspondingly, LAR and ANR activities were reduced by up to 75%, and total proanthocyanidin content decreased by nearly 30%. Metabolomic profiling showed reduced flavan-3-ols and moderate shifts in phenolic acids and stilbenoids, while anthocyanins increased slightly. Overall, miPEP164c reprogrammed flavonoid metabolism under vineyard conditions, selectively lowering tannin biosynthesis without affecting other key phenolics. These findings establish miPEPs as promising biostimulants for precise modulation of grape berry composition, offering new tools for urgently needed sustainable and precision viticulture and improved wine quality under climate change and the increasing environmental challenges it poses. Full article

Background: Hypertrophic cardiomyopathy (HCM) is increasingly recognized as a disorder shaped not only by sarcomeric mutations but also by complex immunogenetic and metabolic interactions. Emerging transcriptomic and single-cell analyses implicate immune dysregulation, RNA methylation, and necroptosis as critical modulators of myocardial remodeling. Objectives: This scoping review synthesizes bioinformatic, transcriptomic, and experimental data to delineate the immunogenetic architecture of HCM and identify candidate molecular targets for immune–metabolic modulation. Methods: Following Joanna Briggs Institute and PRISMA-ScR guidelines, we systematically searched PubMed, Embase, Web of Science, and GEO through September 2025 for studies evaluating immune infiltration, RNA regulation, and necroptosis in human HCM. Data were narratively synthesized across histologic, clinical, and multi-omics domains. Results: Among 8191 screened records, 25 studies met the inclusion criteria. Key immune–epigenetic regulators included the lncRNA–mRNA pair MIR210HG–BPIFC, m6A readers IGFBP3 and YTHDC1, and necroptosis gene JAK2. The HCM myocardium exhibited the depletion of reparative M2 macrophages and Tregs; enrichment of cytotoxic CD8⁺ T cells; and activation of the TNFα–NFκB, IL-6–JAK–STAT3, and PI3K–Akt pathways. Machine learning biomarkers (RASD1, FCN3, and PIK3R1) exhibited diagnostic accuracy (AUC > 0.85). Drug target predictions identified ruxolitinib and celecoxib as potential immunometabolic modulators (agents predicted to modulate both immune and metabolic pathways based on gene expression signatures). Conclusions: These findings support a hypothesis that HCM may involve immunogenetic mechanisms, rather than being exclusively sarcomeric in nature, although this remains to be validated. The integration of molecular and imaging biomarkers may enable precision immunotherapy, redefining HCM from a structural cardiomyopathy to a biologically stratified condition. Full article

Triple-negative breast cancer (TNBC) exhibits diverse histological and molecular characteristics. TNBC patients also have the poorest prognoses among those with various breast cancer subtypes, and no effective treatment strategy has been established for TNBC beyond non-specific chemotherapy. Recent studies have reported that the dysregulation of miRNAs is associated with tumor behavior, prognosis, and treatment responses in TNBC patients. Therefore, this study was conducted to identify miRNAs and key target proteins potentially associated with TNBC prognosis. Fresh-frozen tissue from relapsing and non-relapsing TNBC cases was examined for differentially expressed miRNAs using the Affymetrix GeneChip miRNA 4.0 array, while target genes and proteins were predicted using the miRwalk 2.0 database. The clinical significance of each differentially expressed miRNA was evaluated using the BreastMark database. Additional bioinformatics analyses were conducted to reveal associations with tumor-related signaling pathways; these analyses included protein–protein interaction network construction and Kyoto Encyclopedia of Genes and Genomes pathway annotation. Gene chip analysis identified three upregulated miRNAs (miR-500a, miR-501-3p, and miR-502-3p) and two downregulated miRNAs (miR-6798-5p and miR-7150) in patients with recurrence, and further bioinformatics analyses revealed that target proteins were significantly associated with cell cycle pathways. In addition, low expression of the miR-500a target protein UBE2Z was significantly associated with a poor prognosis. The expression levels of miR-500a and UBE2Z might be useful prognostic biomarkers in TNBC. Full article

Background: Enterococcus faecalis is an opportunistic pathogen that is capable of causing bacterial encephalitis under specific pathological conditions. MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs, typically approximately 21 nucleotides in length. As master regulators of gene expression, they orchestrate critical pathways across diverse organisms and a broad spectrum of diseases; however, their role during E. faecalis neuro-invasion remains unexplored. Methods: A lamb model of E. faecalis-induced encephalitis was established. Integrated analysis of high-throughput sequencing data identified oar-miR-29b as a key differentially expressed miRNA during infection. To first verify its association with inflammation, primary SBMECs were stimulated with lipoteichoic acid (LTA), confirming that oar-miR-29b expression was significantly upregulated under inflammatory conditions. Subsequently, independent gain- and loss-of-function experiments in SBMECs were performed, with inflammatory cytokine expression assessed by qPCR and tight-junction protein levels evaluated by Western blotting. Results: Functional studies demonstrated that oar-miR-29b acts as a pro-inflammatory mediator, significantly upregulating IL-1β, IL-6, and TNF-α while degrading tight-junction proteins (ZO-1, occludin, and claudin-5), thereby compromising endothelial barrier integrity. Mechanistically, bioinformatic prediction and dual-luciferase reporter assays confirmed C1QTNF6 as a direct target of oar-miR-29b. The oar-miR-29b/C1QTNF6 axis is thus defined as a novel regulatory pathway contributing to neuro-inflammation and blood-brain barrier disruption. Conclusions: Collectively, our findings identify the oar-miR-29b/C1QTNF6 axis as a novel pathogenic mechanism that exacerbates E. faecalis-induced neuroinflammation and blood-brain barrier disruption. Full article

Background/Objectives: Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide. While existing screening tools are effective, their high cost and limited availability restrict widespread adoption, particularly in low- and middle-income settings. The identification of affordable, non-invasive biomarkers is therefore critical to improve early CRC detection and survival outcomes. Methods: A systematic literature search was performed through PubMed, ScienceDirect, Medline, ISI Web of Knowledge, and Google Scholar to identify studies reporting stool- and blood-based biomarkers for CRC detection. Data were extracted using a standardized template, including study details, specimen type, detection method, and diagnostic performance parameters such as sensitivity and specificity. Results: DNA methylation biomarkers demonstrated high diagnostic potential. Syndecan 2 (SDC2) and Short Stature Homeobox 2 (SHOX2) achieved a combined stool sensitivity of 91.35%. Other methylation markers, including NDRG4, SEPT9, and BCAT1, showed a composite sensitivity of 82.7%. Plasma-based methylation markers such as GATA5, FOXE1, and SYNE1 reported sensitivities ranging from 18–47% and specificities of 93–99%. Hypermethylation of SFRP2 and WIF-1 achieved 81.3% sensitivity in CRC and precursor lesions. Matrix metalloproteinases (MMP-2 and MMP-9) were elevated in CRC patients, with stool MMP-9 yielding 72.2% sensitivity and 95% specificity. A stool gene panel (UBE2N, IMPDH1, DYNC1LI1, HRASLS2) reached 96.6% sensitivity and 89.7% specificity, while a methylation-based panel (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM) achieved 90.7% sensitivity. MicroRNAs (miR-21, miR-92a, miR-223, miR-182) showed excellent diagnostic performance, with sensitivities exceeding 96% and specificities above 75%. Conclusions: DNA methylation and microRNA biomarkers hold strong promises for non-invasive CRC screening. Multi-marker panels demonstrate superior diagnostic accuracy and may provide a cost-effective, scalable approach for early CRC detection in resource-limited settings. Full article