Search Results (196)

Ursodeoxycholic acid (UDCA) is widely used to treat cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), yet its molecular mechanisms remain unclear. This study investigated the impact of long-term UDCA therapy on circulating levels of the microRNAs miR-34a and miR-506, which are implicated in PBC pathogenesis, and explored associated changes in inflammatory markers and signaling pathways. Serum samples from patients with PBC and PSC were collected before and after UDCA treatment and analyzed for miRNA expression as well as levels of TREM-2 and sCD163. In vitro studies using human cholangiocytes and lipopolysaccharide (LPS) stimulation assessed changes in the expression of miR-34a, TREM-2, and ADAM17. The results showed that the baseline levels of miR-34a and miR-506 were significantly elevated in PBC patients compared to controls and were significantly reduced after UDCA therapy in PBC but not in PSC. UDCA also decreased serum levels of TREM-2 and sCD163. In vitro, it suppressed the LPS-induced expression of miR-34a and ADAM17 while enhancing TREM-2 expression. Single-cell RNA sequencing of liver tissue and immunofluorescence staining confirmed TREM-2 expression in cholangiocytes. These findings suggest that UDCA modulates key inflammatory pathways and miRNAs in PBC, providing mechanistic insights into its therapeutic effect Full article

Resistance exercise can enhance or preserve muscle mass and/or strength. Modifying factors are secreted following resistance exercise. Biomarkers like cytokines and extracellular vesicles, especially small extracellular vesicles, are released into the circulation and play an important role in cell-to-cell and inter-tissue communications. There is increasing evidence that physical activity itself promotes the release of extracellular vesicles into the bloodstream, suggesting the importance of vesicles in mediating systemic adaptations following exercise. Extracellular vesicles contain proteins, nucleic acids like miRNAs, and other molecules targeting different cell types and tissues of distant organs. Therefore, extracellular vesicles and encapsulated miRNAs are fine tuners of protein synthesis and are important in the adaptation after resistance training. However, there is a lack of strong data supporting the precise mechanisms of these processes. In this literature review, we collected publications related to miRNA and extracellular vesicle profile changes induced by resistance exercise. To the best of our knowledge, the changes in human extracellular vesicle and microRNA profiles following resistance exercise have not been reviewed yet. We aimed to assess the shortcomings and difficulties characterizing this research area, to summarize the existing results to date, and to propose possible solutions that could help standardize the implementation of future investigations. Full article

Background: Endometriosis is a complex, estrogen-dependent condition that can significantly impact women’s quality of life and fertility. Current diagnostic strategies remain invasive and often prolonged, demonstrating the need for reliable, non-invasive biomarkers. In this context, microRNAs (miRNAs), due to their stability in blood and regulatory roles in inflammation and cell proliferation, have emerged as promising candidates. Methods: This review systematically analyzes 17 studies published between 2010 and 2025 that investigated the diagnostic utility of circulating and tissue-based miRNAs in endometriosis. Results: A wide range of dysregulated miRNAs was identified, with miR-125b-5p, miR-451a, and miR-3613-5p showing the most consistent alterations across studies. However, diagnostic performance varied considerably—largely due to methodological heterogeneity. Key differences were observed in sample type (serum, plasma, endometrium), patient selection, and control group definition. The menstrual cycle phase and hormonal status were often not matched or reported, limiting reproducibility. Conclusions: Despite encouraging findings, the current evidence base is weakened by inconsistent protocols and limited validation. Standardized, multicenter research with well-characterized patient cohorts is essential to the establishment of clinically applicable miRNA-based diagnostics. If validated, miRNAs may offer a transformative, non-invasive approach for earlier detection and improved management of endometriosis. Full article

Background: Identifying liquid biopsy biomarkers with high efficacy is crucial for cancer diagnosis. Exosomal cargo, including miRNAs and proteins, offers enhanced stability in biofluids compared with their free circulating forms, but direct comparisons of their diagnostic performance remain limited. This study evaluates and compares the diagnostic value of selected miRNAs and protein markers in exosomal versus non-exosomal fractions across stages of lung carcinogenesis in a rat model. Methods: Lung cancer was induced in rats, and blood and lung tissue samples were collected at consecutive stages of tumor induction. We investigated the expression patterns of key miRNAs (miR-19b, miR-21, and miR-145) in exosomes, serum, and tissue and quantified levels of tumor biomarkers CEA and CYFRA 21-1 in exosomal and serum fractions. Results: Our results revealed distinct expression patterns of the evaluated miRNAs across exosomes, serum, and tissue, throughout different stages of tumor induction. The expression of exosomal miRNAs dynamically changed in parallel with the tumor induction process, demonstrating high diagnostic efficacy. Specifically, exosomal miR-19b and miR-21 were significantly upregulated from an early induction stage, whereas their serum and tissue forms increased only during the late stages of induction. On the other hand, miR-145 was consistently downregulated across all fractions at every stage. Both exosomal and serum CEA levels increased significantly during tumor induction, while serum CYFRA 21-1 outperformed its exosomal counterpart. Strong positive correlations linked exosomal miR-19b and miR-145 with their non-exosomal counterparts, while moderate correlations were seen for miR-21 and the protein markers. Conclusions: Our findings underscore the value of integrating exosomal biomarkers in liquid biopsies, highlighting their potential to improve early detection and monitoring of lung cancer development. Full article

Preeclampsia (PE) remains a significant obstetric challenge, having complex pathophysiology and limited early diagnostic and therapeutic options. MicroRNAs (miRNAs) have emerged as critical regulators in PE, offering insight into the molecular mechanisms underlying placental dysfunction and impaired maternal adaptation. Differentially expressed miRNAs in both placental tissue and maternal circulation, such as miR-155, play key roles in regulating angiogenesis, trophoblast invasion, and inflammatory pathways, all of which are central to the development of PE. Ongoing investigations increasingly highlight miRNAs as promising non-invasive molecular indicators for the early diagnosis and risk stratification of PE. Furthermore, therapeutic strategies targeting miRNA pathways using mimics or inhibitors show promise in correcting molecular dysfunctions and improving maternal and fetal outcomes. However, clinical translation faces several challenges, including targeted delivery, off-target effects, and the assessment of long-term efficacy. Overall, miRNAs hold significant potential as both diagnostic tools and therapeutic agents, marking a promising direction for improving care in PE pregnancies. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance. Full article

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disorder characterized by three main pathological features: microangiopathy, immunological alterations, and excessive synthesis of extracellular matrix (ECM) proteins, leading to fibrosis of the skin and internal organs. Although the etiology of SSc is still unknown, recent studies have revealed the potential role of genetic and epigenetic factors in disease pathogenesis. They are involved in the regulation of cell metabolism, cell hyperactivity, and the accumulation of extracellular matrix proteins. Short endogenous noncoding RNA molecules (microRNAs; miRNAs) negatively regulate gene expression at the posttranscriptional level and play a significant role in disease pathogenesis. Altered miRNA expression in circulation and disease-specific tissues could serve as biomarkers and potential therapeutic targets in SSc. Full article

Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications. Full article

MicroRNAs (miRNAs) are crucial in physiological and pathological processes and serve as biomarkers for various diseases. We previously validated seven miRNA biomarkers and nine in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In this study, we observed distinct clustering patterns of LUAD or LUSC tissues compared to paired normal tissues based on miRNA expression levels, suggesting the potential involvement of circulating miRNAs in non-small-cell lung cancer (NSCLC) progression. To elucidate their biological function, we identified the most significant differentially expressed miRNAs (DE-miRNAs)—hsa-miR-451a, hsa-miR-139-5p and hsa-miR-126-5p—using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. We then performed protein–protein interaction (PPI) analysis and constructed a miRNA-hub gene regulatory network based on targets predicted by several miRNA-target prediction tools. Additionally, we evaluated the biological functions of these miRNA biomarkers through EdU and wound healing assays in A549 cells. Our study identifies three miRNAs that may contribute to lung cancer progression by modulating cancer-related targets and highlights their potential as biomarkers. Future mechanistic investigations may provide novel insights into NSCLC pathogenesis and open new therapeutic avenues. Full article

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets. Full article

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, expensive, and limited in assessing tumor heterogeneity and monitoring disease processes, including therapy response. Therefore, early and accurate detection, coupled with minimal invasion and cost-effective strategies, are critical for improving patient outcomes. Liquid biopsy has emerged as a promising, minimally invasive alternative, enabling the detection of tumor-derived components. This approach is increasingly utilized in clinical settings. The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs(miRNAs), and circular RNAs (circRNAs), and tumor-educated platelets (TEPs). These methods provide valuable insights into genetic and epigenetic tumor alterations, and serve as indicators for early detection, treatment monitoring, and recurrence prediction. However, challenges such as assay standardization and variability in sensitivity persist. This review delves into the clinical applications of liquid biopsy in CRC management, highlighting the transformative roles of ctDNA, CTCs, and non-coding RNAs, TEPs in early detection, prognostic assessment, and personalized therapy. In addition, it addresses current limitations and explores potential advancements to facilitate their integration into routine clinical practice. Full article

Background: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignancies, accounting for approximately 5% of head and neck cancers. Despite their rarity, advances in molecular profiling have revealed a variety of genetic and molecular pathways, many of which are potentially actionable with targeted therapies. Methods: We reviewed the current literature involving the molecular landscape of SGCs, encompassing the diagnostic and prognostic value of tissue and liquid biomarkers and the potential therapeutic targets across various histological subtypes. Results: Our review highlights key molecular diagnostic findings such as the CRTC1-MAML2 fusion in mucoepidermoid carcinoma and MYB-NFIB rearrangements in adenoid cystic carcinoma, but also targetable alterations such as HER2 and AR positivity in salivary duct carcinoma and ETV6-NTRK3 fusion in secretory carcinoma. Liquid biopsy (both blood- or salivary-based), including circulating tumor DNA, circulating tumor cells, and miRNAs, offers novel, noninvasive approaches for disease monitoring and personalized treatment. Emerging therapies such as HER2 inhibitors, androgen deprivation therapy, and TRK inhibitors underscore the shift towards precision oncology in managing these malignancies. Conclusions: Despite promising advances, challenges remain due to the rarity and phenotypic heterogeneity of SGCs, emphasizing the need for molecularly stratified clinical trials. This review presents an overview of tissue and liquid biomarkers, focusing on molecular targets and therapeutic innovations that lay the foundation for improved diagnostic and treatment strategies for SGCs. Full article

Both continuous aerobic training (CAT) and high-intensity interval training (HIIT) are recommended to promote health and prevent diseases. Exercise-induced circulating extracellular vesicles (EX-EVs) have been suggested to play essential roles in mediating organ crosstalk, but corresponding molecular mechanisms remain unclear. To assess and compare the systemic effects of CAT and HIIT, five healthy male volunteers were assigned to HIIT and CAT, with a 7-day interval between sessions. Plasma EVs were collected at rest or immediately after each training section, prior to proteomics and miRNA profile analysis. We found that the differentially expressed (DE) miRNAs in EX-EVs were largely involved in the regulation of transcriptional factors, while most of the DE proteins in EX-EVs were identified as non-secreted proteins. Both CAT and HIIT play common roles in neuronal signal transduction, autophagy, and cell fate regulation. Specifically, CAT showed distinct roles in cognitive function and substrate metabolism, while HIIT was more associated with organ growth, cardiac muscle function, and insulin signaling pathways. Interestingly, the miR-379 cluster within EX-EVs was specifically regulated by HIIT, involving several biological functions, including neuroactive ligand–receptor interaction. Furthermore, EX-EVs likely originate from various tissues, including metabolic tissues, the immune system, and the nervous system. Our study provides molecular insights into the effects of CAT and HIIT, shedding light on the roles of EX-EVs in mediating organ crosstalk and health promotion. Full article

Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood–brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke. In our longitudinal prospective cohort study, we collected data from acLVO stroke patients at four critical time intervals post-symptom onset: 0–6 h, 6–12 h, 12–24 h, and 5–7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke. Within the first 6 h of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke. This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes. Full article

Circulating microRNAs (miRNAs), especially transported by extracellular vesicles (EVs), have recently emerged as major new participants in interorgan communication, playing an important role in the metabolic coordination of our tissues. Among these, adipose tissue displays an extraordinary ability to secrete a vast list of EV-carried miRNAs into the circulation, representing new hormone-like factors. Despite the limitations of current methodologies for the unequivocal identification of the origin and destination of EV-carried miRNAs in vivo, recent investigations clearly support the important regulatory role of adipose-derived circulating miRNAs in shaping the metabolism and function of other tissues including the liver, muscle, endocrine pancreas, cardiovascular system, gastrointestinal tract, and brain. Here, we review the most recent findings regarding miRNAs transported by adipose-derived EVs (AdEVs) targeting other major metabolic organs and the implications of this dialog for physiology and pathology. We also review here the current and potential future diagnostic and therapeutic applications of AdEV-carried miRNAs. Full article