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Search Results (3,556)

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24 pages, 26164 KB  
Review
Cancer-Derived Exosomes: A Cross-Cancer Comparative Analysis of Exosomal Proteins and MicroRNAs
by Jong Hyun Kim
Int. J. Mol. Sci. 2026, 27(15), 7057; https://doi.org/10.3390/ijms27157057 - 6 Aug 2026
Abstract
Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but [...] Read more.
Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but rarely compared on a common basis; in this review, previously reported molecules from eight cancer categories—blood, breast, colon, kidney, liver, lung, prostate, and stomach—were compiled from curated repositories and re-analyzed within a single functional framework. In total, 3643 exosomal proteins (523 hematologic, 3120 solid-tumor) and 627,225 miRNA–target pairs, derived from 350 unique microRNAs, were organized using Gene Ontology, KEGG, and PANTHER annotation. Across cancers, proteins converged on a reproducible core—signaling, transport, cytoskeletal organization, and extracellular interaction—dominated by binding, catalytic, and transporter functions localized to membrane, vesicle, and extracellular compartments. Comparisons between hematologic and solid malignancies revealed both shared cancer-associated functions and context-dependent patterns linked to tissue origin and disease ecology. Together, these findings indicate that integrated protein-and-microRNA profiling offers a useful framework for understanding tumor communication, refining cancer classification, and advancing biomarker discovery, while underscoring that harmonized workflows, independent validation, and mechanistic follow-up remain necessary before descriptive enrichment outputs can support clinically robust applications. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer and Tumor Microenvironment)
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18 pages, 297 KB  
Review
Urinary Exosomes as Potential Biomarkers for Diagnosis, Disease Activity Assessment, Treatment Monitoring, and Prognosis in Lupus Nephritis
by Krzysztof Benc, Ewa Tabaka, Wiktoria Pabian, Dominika Pisarek, Karolina Marek-Bukowiec, Andrzej Konieczny and Mirosław Banasik
Int. J. Mol. Sci. 2026, 27(15), 7051; https://doi.org/10.3390/ijms27157051 - 6 Aug 2026
Abstract
Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus and remains a major cause of chronic kidney damage and progression to end-stage renal disease. Although kidney biopsy is considered the diagnostic gold standard, its invasive nature, risk of complications, [...] Read more.
Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus and remains a major cause of chronic kidney damage and progression to end-stage renal disease. Although kidney biopsy is considered the diagnostic gold standard, its invasive nature, risk of complications, sampling limitations, and limited suitability for repeated monitoring highlight the need for reliable non-invasive biomarkers. Urinary exosomes have emerged as a promising source of renal molecular information because they are easily accessible and contain stable bioactive molecules, including microRNAs, transfer RNA-derived fragments, messenger RNAs, long non-coding RNAs, and proteins. This review summarizes available evidence on urinary exosomal biomarkers in lupus nephritis, with particular emphasis on their potential utility in diagnosis, assessment of disease activity, monitoring of treatment response, and prognosis. The literature search was conducted in PubMed and Embase using the keywords “lupus nephritis” and “urinary exosomes”. Studies were included if they investigated urinary exosomes in lupus nephritis and evaluated their relevance to disease diagnosis, activity, therapeutic response, histopathological findings, or renal outcomes. Among the analyzed biomarkers, urinary exosomal miR-146a appears to be the most consistently reported diagnostic marker, showing increased expression in active lupus nephritis and the ability to distinguish patients with renal involvement from those without nephritis. Other molecules, including selected miRNAs, tsRNAs, long RNAs, and proteins, have also shown potential clinical relevance, although their validation remains limited. Current evidence suggests that urinary exosomes may provide a non-invasive platform for improving the clinical assessment of lupus nephritis. However, most available studies are limited by small sample sizes, single-center designs, heterogeneous methodologies, and insufficient external validation. Further large-scale prospective studies are required to standardize exosome isolation and biomarker quantification and to determine whether urinary exosomal biomarker panels can complement kidney biopsy in clinical practice. Full article
(This article belongs to the Section Molecular Immunology)
22 pages, 870 KB  
Systematic Review
MicroRNAs as Biomarkers for Adenomyosis: A Systematic Review
by Paula Buehler, Angela Vidal, Cloé Vaineau, Tanya Karrer and Michael Mueller
Biomedicines 2026, 14(8), 1764; https://doi.org/10.3390/biomedicines14081764 - 5 Aug 2026
Abstract
Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence [...] Read more.
Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence implicates disruption of the endometrial–myometrial interface, epithelial–mesenchymal transition, and progesterone resistance in driving tissue invasion and remodeling. Diagnosis relies mainly on imaging modalities, while reliable non-invasive biomarkers are lacking. MicroRNAs, as stable post-transcriptional regulators of gene expression, have emerged as key modulators of proliferation, inflammation, and hormonal signaling, and represent promising candidates for novel diagnostic strategies. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD42025637752). A comprehensive search of the Medline, Embase, Scopus, and Cochrane databases was performed in April 2025. Studies investigating miRNA expression in patients with adenomyosis compared with controls were included. The quality of the studies and the risk of bias were assessed using the Newcastle–Ottawa scale. Two reviewers independently performed study selection, data extraction, and quality assessment. Results: Twenty-seven studies published between 2015 and 2025 met the inclusion criteria. Thirty-nine distinct miRNAs were reported as significantly dysregulated in adenomyosis. Recurrently altered miRNAs included let-7a, miR-145, miR-10b, miR-30c-5p, miR-141-3p, miR-143, and miR-191. Functional analyses have consistently implicated miRNAs in key pathogenic pathways, including Hippo-YAP, PI3K/AKT, MAPK/ERK, JAK/STAT, and Wnt/β-catenin signaling. These alterations were associated with enhanced epithelial–mesenchymal transition, increased cellular proliferation and migration, progesterone resistance, chronic inflammation, and immune modulation. Emerging evidence highlights exosomal and circulating miRNAs as promising non-invasive biomarkers, with a few studies already demonstrating diagnostic potential using serum, plasma, or urine samples. However, substantial heterogeneity in tissue types, sampling timing, and analytical methods precluded meta-analysis. Conclusions: MiRNAs play a central role in the molecular pathogenesis of adenomyosis and show strong potential as non-invasive diagnostic biomarkers. However, large-scale validation studies and standardized methodologies are required before clinical implementation. Full article
(This article belongs to the Special Issue Advanced Research of Non-Coding RNAs in Health and Disease)
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18 pages, 3699 KB  
Article
An Exploratory Study on Transcriptomic Profiling of Circulating miRNA Associated with Hub Genes in the Development of Polycystic Ovary Syndrome
by Yogesh Vetriselvan, Jayakumar Swetha, Manoranjani Murugan, Irisappan Ganesh, Vishnu Bhat Ballambattu, Pushpa Premanath Kotur, Deepa Shanmugam, Marcella Sherin Samuel and Sambandam Ravikumar
Non-Coding RNA 2026, 12(4), 30; https://doi.org/10.3390/ncrna12040030 - 5 Aug 2026
Abstract
Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC > 1, p < 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS’s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications. Full article
(This article belongs to the Section Small Non-Coding RNA)
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25 pages, 454 KB  
Review
Machine Learning Models and Gene Expression Profiles in Epileptic Samples: A Narrative Review
by Claudia Cava, Soudabeh Sabetian, Maria Pagoni and Isabella Castiglioni
Appl. Sci. 2026, 16(15), 7797; https://doi.org/10.3390/app16157797 - 5 Aug 2026
Abstract
Epilepsy is a global public health problem with increasing prevalence. However, the quality and accuracy of diagnostic models in clinical practice remain limited. In recent years, machine learning (ML) models applied to transcriptomic data have been explored as potential tools for improving diagnostic [...] Read more.
Epilepsy is a global public health problem with increasing prevalence. However, the quality and accuracy of diagnostic models in clinical practice remain limited. In recent years, machine learning (ML) models applied to transcriptomic data have been explored as potential tools for improving diagnostic accuracy. This narrative review aimed to evaluate studies that applied ML algorithms to gene expression data, including both mRNA and miRNA, for the diagnosis of epilepsy. PubMed and Scopus were searched for studies published between 2020 and June 2026. Eligible studies included human epilepsy samples, transcriptomic data was used to train ML classifiers, and only articles reporting AUC were included. A total of 17 studies were included. To provide a clinically meaningful synthesis, studies were grouped according to the biological source of the biomarkers into peripheral blood-based biomarkers and brain tissue-derived biomarkers. Peripheral blood studies investigated whole-blood transcriptomic signatures, peripheral blood mononuclear cells, circulating miRNAs, or extracellular vesicle-derived miRNAs, whereas brain tissue studies mainly analyzed hippocampal or cortical samples. Across studies, commonly used models included random forests, support vector machines, artificial neural networks, logistic regression, and penalized regression methods. Reported diagnostic performance was frequently high, but study designs were heterogeneous, sample sizes were often small, and validation strategies were limited. Studies with external validation generally showed more conservative and likely more realistic performance estimates than those relying on internal validation only. Overall, gene expression-based machine learning models show promising exploratory potential for epilepsy biomarker discovery and diagnostic stratification. However, the current evidence does not yet support clinical implementation because most studies remain limited by small sample sizes, heterogeneous preprocessing strategies, limited independent external validation, and potential risk of overfitting. Future studies should prioritize prospective cohorts, predefined analysis plans, harmonized preprocessing, nested cross-validation, external multicenter testing, and transparent reporting according to TRIPOD-AI/PROBAST-AI principles. Full article
(This article belongs to the Section Computing and Artificial Intelligence)
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24 pages, 2393 KB  
Article
Peripheral Expression Profiles of Glutathione Reductase and miR-144 in Patients with Atrial Fibrillation
by Monika Różycka-Kosmalska, Mikołaj Grabarczyk, Agnieszka Śliwińska, Małgorzata Kozłowska, Marcin Kosmalski, Jerzy Krzysztof Wranicz and Izabela Szymczak-Pajor
Med. Sci. 2026, 14(4), 456; https://doi.org/10.3390/medsci14040456 - 5 Aug 2026
Abstract
Background: Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Glutathione reductase (GR) and microRNA-144 (miR-144) may participate in redox-related pathways. This study aimed to evaluate relative GSR mRNA and miR-144 expression in peripheral blood samples from patients with and without AF [...] Read more.
Background: Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Glutathione reductase (GR) and microRNA-144 (miR-144) may participate in redox-related pathways. This study aimed to evaluate relative GSR mRNA and miR-144 expression in peripheral blood samples from patients with and without AF and to explore their associations with selected clinical characteristics. Methods: This case–control study included 189 hospitalized adults: 95 without AF and 94 with AF. Clinical, anthropometric, biochemical, and echocardiographic data were collected for all participants. GSR mRNA was assessed by quantitative real-time PCR in whole blood samples, whereas circulating miR-144 expression was evaluated in serum. Group differences were assessed using nonparametric tests, correlations were evaluated using Spearman’s rank correlation coefficient, and multivariable logistic regression was used to identify variables independently associated with AF. Model stability was assessed using bootstrap internal validation. Results: Relative GSR mRNA expression was significantly lower in the AF group than in controls (0.1539 vs. 0.2058, p < 0.001), whereas miR-144 expression was significantly higher in patients with AF (0.3636 vs. 0.2550, p = 0.0183). In multivariable logistic regression adjusted for clinical confounders, higher miR-144 (OR = 1.336, p = 0.048) and lower GSR (OR = 0.343, p < 0.001) expression remained associated with AF. Bootstrap internal validation supported the statistical stability of the GSR association (optimism-corrected AUC = 0.709, bootstrapped 95% CI: 0.622–0.785), whereas miR-144 showed only a more modest and less stable association (optimism-corrected AUC = 0.598, bootstrapped 95% CI: 0.519–0.684); both signals remain exploratory and do not yet support routine clinical use as diagnostic or risk-stratification biomarkers in AF. Both markers showed exploratory correlations with selected clinical and biochemical variables. Given the cross-sectional design of the study, all reported relationships should be interpreted as statistical associations rather than as evidence of causality. The observed correlations between molecular markers and clinical parameters are hypothesis-generating and warrant further investigation. Full article
(This article belongs to the Special Issue Dynamics of Cardiovascular Control in Health and Disease)
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51 pages, 5440 KB  
Review
Targeting lncRNAs to Overcome Cancer Therapy Resistance: Advances in RNA Therapeutics and Delivery Strategies
by Christos Drosos, Athina Kapsi, Anthi Nikolaidou and Antonis Giakountis
Cancers 2026, 18(15), 2497; https://doi.org/10.3390/cancers18152497 - 4 Aug 2026
Abstract
Non-coding RNAs (ncRNAs) are increasingly recognized as important regulators of cancer biology. Long non-coding RNAs (lncRNAs), defined as transcripts longer than 200 nucleotides, gain particular attention due to their cancer-specific expression patterns and functional roles in tumor progression, metastasis and therapeutic resistance. Although [...] Read more.
Non-coding RNAs (ncRNAs) are increasingly recognized as important regulators of cancer biology. Long non-coding RNAs (lncRNAs), defined as transcripts longer than 200 nucleotides, gain particular attention due to their cancer-specific expression patterns and functional roles in tumor progression, metastasis and therapeutic resistance. Although lncRNAs have been extensively studied as diagnostic, prognostic and predictive biomarkers, growing evidence indicates that they can also act as active mediators of therapeutic resistance, supporting their potential as therapeutic candidates. Here, we summarize how lncRNAs contribute to resistance against radiotherapy, chemotherapy, immunotherapy and targeted therapy, highlighting their molecular mechanisms. Next, we discuss RNA-based therapeutics as a strategy to target disease-relevant transcripts, focusing on antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNA (miRNA) mimics and antimiRs, as well as approved RNA therapeutic agents, oncology-focused candidates in clinical development and emerging preclinical approaches directed against lncRNAs or lncRNA-controlled regulatory axes. Finally, we examine delivery platforms, including lipid-based nanovectors, extracellular vesicles, polymeric systems and other approaches designed to overcome key translational barriers, such as RNA instability, off-target effects, immune activation, renal clearance and inefficient tumor-specific delivery. By connecting lncRNA-mediated resistance mechanisms with RNA therapeutic strategies and delivery technologies, this review highlights lncRNA-directed RNA therapeutics as a promising yet developing approach in oncology. Full article
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24 pages, 26970 KB  
Article
LINC01446/miR-338-3p/APEX1 Axis Promotes Ferroptosis Defense and Progression in Esophageal Squamous Cell Carcinoma
by Yunlong Jia, Jiaxin Si, Zhendong Zhang, Tianxu Liu, Shuman Zhen, Yan Zhao, Yu Wang, Xuexiao Wang, Jiali Wang and Lihua Liu
Cancers 2026, 18(15), 2496; https://doi.org/10.3390/cancers18152496 - 4 Aug 2026
Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis, highlighting the urgent need to elucidate its molecular mechanisms to develop targeted therapies. Long non-coding RNAs (lncRNAs) play a critical role in cancer progression. However, the majority of lncRNAs [...] Read more.
Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis, highlighting the urgent need to elucidate its molecular mechanisms to develop targeted therapies. Long non-coding RNAs (lncRNAs) play a critical role in cancer progression. However, the majority of lncRNAs involved in ESCC progression remain to be elucidated. Methods: We integrated bioinformatic analyses of the TCGA and GEO datasets to identify differentially expressed lncRNAs in ESCC, and the biological functions of the candidate lncRNA LINC01446 were investigated using loss-of-function assays in ESCC cell lines, including colony formation, wound healing, Transwell invasion, C11-BODIPY staining, malondialdehyde (MDA) quantification, and glutathione (GSH) evaluation. A nude mouse xenograft model was established for in vivo validation, and the underlying molecular mechanism was explored through RNA sequencing, fluorescence in situ hybridization (FISH), dual-luciferase reporter assays, AGO2-RIP, and rescue experiments. Results: LINC01446 was significantly upregulated in ESCC tissues and cell lines. Based on univariate analysis, high expression of LINC01446 was associated with poorer overall survival (OS). Functional studies showed that LINC01446 knockdown suppressed ESCC cell proliferation, migration, and invasion, promoted ferroptosis-related changes in vitro and was associated with increased lipid peroxidation and possible ferroptosis-related changes in vivo. Mechanistic analyses supported a regulatory relationship in which LINC01446 may function as a competing endogenous RNA (ceRNA) for miR-338-3p, thereby contributing to the upregulation of its downstream target, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1), in ESCC cells. Moreover, APEX1 was found to be overexpressed in ESCC and associated with poor OS. Conclusions: This study suggests that the LINC01446/miR-338-3p/APEX1 regulatory axis may contribute to ESCC progression and ferroptosis-related regulation. Additionally, LINC01446 and APEX1 represent promising prognostic biomarkers and therapeutic targets for ESCC. Full article
(This article belongs to the Section Molecular Cancer Biology)
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20 pages, 25477 KB  
Article
Multimodal Assessment of Tissue Response After Thyroid Radiofrequency Ablation: Clinical, Imaging, Histopathological and Molecular Insights
by Domenico Parmeggiani, Gerardo Amabile, Alessio Cece, Sergio Surfaro, Giancarlo Moccia, Francesco Miele, Pasquale Luongo, Manuela Miccio, Rossella Sperlongano, Agostino Fernicola, Paola Della Monica, Federica Colapietra, Marina Di Domenico, Eduardo Clery, Massimo Agresti and Renato Franco
J. Clin. Med. 2026, 15(15), 6031; https://doi.org/10.3390/jcm15156031 - 3 Aug 2026
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Abstract
Background: Ultrasound-guided radiofrequency ablation (RFA) has become an established minimally invasive treatment for selected benign and autonomously functioning thyroid nodules. Although clinical outcomes are well documented, the biological mechanisms underlying tissue remodeling after ablation remain incompletely characterized. The integration of imaging, molecular, and [...] Read more.
Background: Ultrasound-guided radiofrequency ablation (RFA) has become an established minimally invasive treatment for selected benign and autonomously functioning thyroid nodules. Although clinical outcomes are well documented, the biological mechanisms underlying tissue remodeling after ablation remain incompletely characterized. The integration of imaging, molecular, and histopathological data may provide a more comprehensive understanding of treatment response. Methods: We conducted a prospective monocentric observational translational cohort study including 60 patients undergoing ultrasound-guided RFA for benign or autonomously functioning thyroid nodules between November 2024 and December 2025. Patients underwent standardized pre-procedural assessment including high-resolution ultrasound with volumetric evaluation, three-dimensional reconstruction, and collection of peripheral blood samples for exploratory extracellular vesicle (EV)-derived microRNA (miRNA) profiling. Clinical outcomes, volumetric changes, vascular remodeling, and procedural complications were assessed during scheduled follow-up visits (mean follow-up duration: 11 months; range: 5–17 months). A subgroup of patients who subsequently required surgery because of insufficient volumetric response underwent thyroidectomy, allowing histopathological evaluation of post-ablation tissue changes. Clinical, imaging, molecular, and pathological data were integrated within a multimodal translational framework. Results: RFA resulted in a mean nodule volume reduction of 56% at early follow-up, with progressive volumetric reduction observed during longitudinal ultrasound evaluation. A clinically relevant improvement in compressive symptoms was observed, with a 44% reduction in symptom burden. Doppler ultrasound demonstrated progressive changes in vascular patterns consistent with post-ablation devascularization and tissue remodeling. Ten patients underwent thyroidectomy after RFA because of insufficient volumetric response, providing histological validation of treatment-induced tissue alterations, including coagulative necrosis, fibrosis, inflammatory changes, and architectural remodeling. Exploratory EV-derived miRNA profiling was incorporated into the translational workflow to investigate potential molecular correlates of treatment response; however, molecular findings require further validation in larger cohorts. Conclusions: This study provides a multimodal translational characterization of tissue response after thyroid RFA by integrating clinical outcomes, ultrasound imaging, histopathology, and exploratory EV-derived miRNA analysis. The proposed framework may contribute to a deeper understanding of biological changes following thermal ablation and support future investigations aimed at identifying reliable biomarkers of treatment response. Full article
(This article belongs to the Special Issue Surgical Oncology: Clinical Application of Translational Medicine)
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34 pages, 7884 KB  
Article
Integrated Epidemiological and Extracellular Vesicle Profiling Identifies miR-126-3p, miR-21-5p, miR-92a-3p and SNAIL as Candidate Biomarkers of Endothelial Dysfunction and Cardio-Metabolic Risk
by Luis Alberto Gómez-Grosso, Gladis Estella Montoya Ortiz, Jhon Jairo Osorio-Méndez, María Paula Aulestia-Vacca, Shirley Natali Iza Rodríguez and Ana Yiby Forero Torres
Int. J. Mol. Sci. 2026, 27(15), 6966; https://doi.org/10.3390/ijms27156966 - 3 Aug 2026
Viewed by 234
Abstract
Non-communicable diseases (NCDs), including type 2 diabetes mellitus (DM), hypertension (HTA), obesity (OB), and cardiovascular disease (CVD), represent a major global health burden and disproportionately affect socially vulnerable populations. Small extracellular vesicles (EVs) are stable carriers of proteins and regulatory RNAs that may [...] Read more.
Non-communicable diseases (NCDs), including type 2 diabetes mellitus (DM), hypertension (HTA), obesity (OB), and cardiovascular disease (CVD), represent a major global health burden and disproportionately affect socially vulnerable populations. Small extracellular vesicles (EVs) are stable carriers of proteins and regulatory RNAs that may reflect endothelial dysfunction and cardiometabolic stress. This study explored plasma-derived EV-associated biomarkers in adults from La Guajira, Colombia, with emphasis on miR-126-3p, miR-21-5p, miR-92a-3p, and SNAIL. Anthropometric, clinical, and biochemical data were obtained from a cross-sectional cohort. Representative plasma samples were selected for EVs isolation by size-exclusion chromatography. Vesicles were characterized by nanoparticle tracking analysis, scanning transmission electron microscopy, protein quantification, Western blotting, and bead-based flow cytometry. Candidate miRNAs were identified by small RNA sequencing and validated by stem-loop RT-qPCR. Bioinformatic enrichment analyses were performed using miRNet 2.0 and KEGG pathway analysis. The epidemiological cohort showed a high cardiometabolic burden, with waist-to-height ratio (WHtR) and triglyceride-glucose (TyG) index emerging as key markers of central adiposity and metabolic dysfunction. Plasma-derived EVs displayed the expected nanoscale morphology and expressed canonical vesicle markers. Protein cargo analyses revealed EMT- and remodeling-associated proteins, including SNAIL and GAL-3. EV-associated miR-126-3p, miR-21-5p, and miR-92a-3p were enriched predominantly in hypertensive and hypertensive-diabetic groups. In an exploratory sub-cohort, CD31-positive EVs showed a trend toward increased expression in individuals with previous myocardial infarction or stroke (p = 0.057). KEGG enrichment analysis linked the identified miRNA signature to pathways involved in endothelial dysfunction, inflammation, vascular remodeling, apoptosis, and extracellular matrix organization. Plasma-derived EVs from individuals with cardiometabolic disorders carry molecular signatures consistent with endothelial stress and vascular remodeling. These findings identify miR-126-3p, miR-21-5p, miR-92a-3p, SNAIL, and CD31-positive EVs as exploratory candidate biomarkers that require validation in larger prospective cohorts. Full article
(This article belongs to the Special Issue Advances in Cardiovascular and Vascular Biology)
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16 pages, 1539 KB  
Article
Salivary microRNA Expression and Co-Expression Patterns in Periodontal Disease: A Cross-Sectional Analysis of miR-34a, miR-155 and miR-146a
by Elena-Teodora Tâlvan, Liviuța Budișan, Călin Ilie Mohor, Valentin Grecu, Ioana Berindan-Neagoe, Cornelia Braicu, George Călin Oprinca, Cosmin-Ioan Mohor and Adrian Nicolae Cristian
Cells 2026, 15(15), 1392; https://doi.org/10.3390/cells15151392 - 31 Jul 2026
Viewed by 112
Abstract
MicroRNAs (miRNAs) have been proposed as promising biomarkers for periodontal disease because of their role in regulating inflammation and tissue remodeling. This study evaluated the salivary expressions of miR-34a, miR-155, and miR-146a and their relationships with periodontal disease and its clinical severity. Saliva [...] Read more.
MicroRNAs (miRNAs) have been proposed as promising biomarkers for periodontal disease because of their role in regulating inflammation and tissue remodeling. This study evaluated the salivary expressions of miR-34a, miR-155, and miR-146a and their relationships with periodontal disease and its clinical severity. Saliva samples were collected from 35 patients with periodontal disease and 35 healthy controls, and miRNA expression was quantified by quantitative real-time PCR (qRT-PCR). Fold-change values were log2-transformed, and analyses included differential expression (Mann–Whitney U with Benjamini–Hochberg correction), Spearman correlation with clinical attachment loss (CAL), logistic regression/ROC modeling with internal cross-validation, and an exploratory differential co-expression analysis. None of the three miRNAs was significantly differentially expressed between groups (all FDR-adjusted p > 0.40; the result was unchanged after adjustment for age), and none correlated with CAL after accounting for the healthy-versus-diseased separation. miR-34a showed poor stand-alone diagnostic performance (AUC = 0.58; five-fold cross-validation 0.56). Patients were significantly older than controls (41.1 vs. 37.1 years; p < 0.001), and age was the strongest single discriminator (AUC = 0.82), indicating that age acts as an important confounder. In an exploratory analysis, the positive co-expression observed among the three miRNAs in healthy controls was attenuated in disease (e.g., miR-155/miR-146a Spearman rho = 0.68 vs. 0.27; permutation p approximately 0.06). These findings indicate that salivary miR-34a, miR-155 and miR-146a abundance do not discriminate periodontitis in this cohort, but underline age as a critical confounder and suggest that altered miRNA co-expression, rather than differential abundance, may warrant further investigation in larger, age-matched studies. In addition, miR-34a and miR-146a showed reduced expression dispersion in disease; because the reduced dispersion and the reduced co-expression cannot be fully separated in a sample of this size, these network-level observations are regarded as jointly hypothesis-generating. Full article
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24 pages, 43209 KB  
Article
PSPH Promotes Hepatocellular Carcinoma Progression by Upregulating HIF-1α and Is Regulated by LncRNA GSEC/miR-101-3p
by Yi Yang, Hang Min, Yuanting Huang, Lingjing Tao, Hao Zhou, Wenbo Zhang, Xiaoshuai Ren, Changyun Huang, Yang Deng and Jun Zhou
Curr. Issues Mol. Biol. 2026, 48(8), 784; https://doi.org/10.3390/cimb48080784 - 31 Jul 2026
Viewed by 131
Abstract
Hepatocellular carcinoma (HCC) lacks effective early diagnostic markers and is heavily driven by angiogenesis and hypoxia. Emerging evidence indicates that metabolic enzymes and noncoding RNAs coordinate these processes. Here, we reveal that phosphoserine phosphatase (PSPH), a serine biosynthesis enzyme, is significantly upregulated in [...] Read more.
Hepatocellular carcinoma (HCC) lacks effective early diagnostic markers and is heavily driven by angiogenesis and hypoxia. Emerging evidence indicates that metabolic enzymes and noncoding RNAs coordinate these processes. Here, we reveal that phosphoserine phosphatase (PSPH), a serine biosynthesis enzyme, is significantly upregulated in HCC, correlating with angiogenic markers and poor prognosis. Clinical data and functional assays demonstrated that miR-101-3p directly targets the PSPH 3′ UTR to suppress its expression, while lncRNA GSEC acts as a competing endogenous RNA to sponge miR-101-3p. In vitro, GSEC knockdown or miR-101-3p overexpression decreased PSPH and HIF1α levels, strongly inhibiting HCC angiogenesis, migration, invasion, and proliferation. Crucially, these anti-tumor effects were reversed by restoring PSPH. In vivo, modulating the GSEC/PSPH axis significantly altered xenograft tumor growth and vascularization. Conclusively, the GSEC/miR-101-3p/PSPH regulatory axis drives HIF1α-dependent angiogenesis and HCC progression, highlighting PSPH as a promising diagnostic biomarker and therapeutic target. Full article
(This article belongs to the Section Molecular Medicine)
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40 pages, 26578 KB  
Article
Identification of a CSC-Associated miRNA Signature in NSCLC and Functional Characterization of hsa-let-7a-3p
by Ángela Y. García Fonseca, Carlos Javier Alméciga-Díaz and Andrés F. Aristizábal-Pachón
Biomedicines 2026, 14(8), 1737; https://doi.org/10.3390/biomedicines14081737 - 31 Jul 2026
Viewed by 258
Abstract
Background: Metastasis is the leading cause of mortality in lung cancer and is regulated by multiple molecular mechanisms, including microRNAs (miRNAs). Although cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) contribute to metastatic progression, the miRNA networks underlying these phenotypes remain poorly [...] Read more.
Background: Metastasis is the leading cause of mortality in lung cancer and is regulated by multiple molecular mechanisms, including microRNAs (miRNAs). Although cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) contribute to metastatic progression, the miRNA networks underlying these phenotypes remain poorly characterized in non-small cell lung cancer (NSCLC). Aim: To identify miRNA signatures associated with CSCs and EMT in NSCLC and functionally characterize hsa-let-7a-3p. Methods: EMT was induced in A549 and NCI-H1975 cells by dCas9-mediated activation of TWIST, whereas CSC-enriched populations were generated by CD133-based sorting and stem cell culture conditions. Small RNA sequencing, bioinformatic analyses, qPCR validation, and functional assays were performed to identify and characterize phenotype-associated miRNAs. Results: Small RNA sequencing identified distinct miRNA expression profiles associated with EMT and CSC enrichment. Comparative analysis identified 13 commonly downregulated and 13 commonly upregulated miRNAs shared by CSCs from A549 and H1975 cells, suggesting conserved post-transcriptional regulatory mechanisms. Functional enrichment and miRNA–target interaction network analyses linked the miRNA signatures to pathways involved in epithelial plasticity, stemness, and tumor progression, including Wnt, TGF-β, mTOR, focal adhesion, adherens junction, and regulation of the actin cytoskeleton. Among the dysregulated miRNAs, hsa-let-7a-3p was consistently upregulated in CD133+ CSC-enriched cells from both NSCLC cell lines. Functional assays showed that hsa-let-7a-3p overexpression significantly reduced clonogenic capacity and showed a trend toward decreased invasion without affecting proliferation. Conclusion: This study identifies miRNA signatures associated with CSC-enriched and EMT-associated phenotypes in NSCLC and demonstrates that these signatures represent coordinated post-transcriptional regulatory programs involved in epithelial plasticity, stemness, and metastatic progression. Functional validation of hsa-let-7a-3p further supports its role as a context-dependent regulator of CSC biology and highlights the potential of miRNA signatures as diagnostic biomarkers in NSCLC. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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50 pages, 2727 KB  
Review
Extracellular-Vesicle-Associated Nucleic Acids in the Diagnosis and Treatment of Respiratory Diseases: A Narrative Review
by Shuairong Lin, Ruixu Lan, Xiaoyan Zhu, Rui Shen, Ruiying Liu, Jinzhou Cheng and Xiaoliu Liu
Pharmaceutics 2026, 18(8), 945; https://doi.org/10.3390/pharmaceutics18080945 - 30 Jul 2026
Viewed by 288
Abstract
Respiratory diseases impose a substantial global burden; however, early diagnosis, disease-activity monitoring, and the clinical translation of nucleic acid therapeutics are constrained by the lack of robust biomarkers and efficient delivery systems. This narrative review focuses on four classes of RNA—messenger RNA (mRNA), [...] Read more.
Respiratory diseases impose a substantial global burden; however, early diagnosis, disease-activity monitoring, and the clinical translation of nucleic acid therapeutics are constrained by the lack of robust biomarkers and efficient delivery systems. This narrative review focuses on four classes of RNA—messenger RNA (mRNA), circular RNA (circRNA), small interfering RNA (siRNA), and microRNA (miRNA)—using exosomes as a representative subtype of extracellular vesicles (EVs) to discuss EV biogenesis, transport, uptake, and engineered cargo loading. We summarize the diagnostic and therapeutic applications of EV-associated nucleic acids in chronic or non-severe respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis, as well as in severe acute conditions such as acute respiratory distress syndrome and severe pneumonia. Biofluid-derived EV-associated RNAs can reflect inflammation, immune dysregulation, epithelial injury, infection, and fibrosis, supporting their potential use in disease classification, monitoring, and prognostic assessment. Natural EVs may modulate inflammation and tissue repair through their endogenous cargo, while engineered EVs can deliver therapeutic nucleic acids to exert anti-inflammatory, anti-infective, antifibrotic, and barrier-restorative effects. However, clinical translation is limited by non-standardized isolation and characterization methods, product heterogeneity, variable cargo loading, and insufficient stability and quality-control frameworks. Continued advances in EV isolation, characterization, nucleic acid loading, potency assessment, and manufacturing control are required to realize the diagnostic and therapeutic potential of EV-associated nucleic acids in respiratory diseases. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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17 pages, 3614 KB  
Article
Identification of Candidate miRNAs Associated with Shear Force and Intramuscular Fat in Pig Breeds
by Qi Zhang, Jing-Bo Zhang, Yun-Peng Zhang, Jing Xu, Suthar Teerath Kumar, Yuan Zhao and Shu-Min Zhang
Foods 2026, 15(15), 2693; https://doi.org/10.3390/foods15152693 - 30 Jul 2026
Viewed by 207
Abstract
In this comparative study of 12 pigs (six Songlei black [SL] and six Duroc × Landrace × Yorkshire [DLY]), small RNA sequencing was performed on longissimus dorsi muscle samples to identify miRNAs associated with meat quality traits. A total of 343 known and [...] Read more.
In this comparative study of 12 pigs (six Songlei black [SL] and six Duroc × Landrace × Yorkshire [DLY]), small RNA sequencing was performed on longissimus dorsi muscle samples to identify miRNAs associated with meat quality traits. A total of 343 known and 191 novel miRNAs were identified, including 21 differentially expressed miRNAs (DE-miRNAs) between breeds. Enrichment analysis showed that their target genes were enriched in the PI3K-Akt, MAPK, and calcium signaling pathways. Integration of miRNA and transcriptome datasets identified a regulatory network comprising five key miRNAs (ssc-miR-10383, ssc-miR-127, ssc-miR-370, ssc-miR-874, and a novel miRNA, novel_494) and 32 target genes annotated to autophagy, AMPK, mTOR, and FoxO signaling pathways. All five miRNAs were negatively correlated with IMF content (r = −0.77 to −0.95) and positively correlated with shear force (r = 0.62 to 0.76). This study provides the first miRNA expression profile of the longissimus dorsi muscle in SL and DLY pigs. These findings suggest that coordinated miRNA regulation may contribute to breed-specific differences in fat deposition and meat tenderness, providing candidate biomarkers for improving pork quality. Full article
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