Search Results (2,167)

Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention. Full article

Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article

Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article

Background and Objectives: Nicotine is the most well-studied toxic substance in cigarette smoke and e-cigarette vape. However, smoke and vape are composed of other components that have a negative impact on health. The objective of this study is to investigate whether nicotine has a distinctive impact on molecular mechanisms in stem cells. Methods: The cellular impact of nicotine on the regenerative capacity of human dental pulp stem cells (DPSCs) and the microRNA (miRNA) profile was examined. Bioinformatic analysis was performed to identify miRNA-regulated cellular pathways associated with nicotine exposure. These pathways were then compared to those induced by cigarette smoke condensate (CSC). Results: Prolonged exposure to nicotine significantly impaired the regeneration of DPSCs and changed the expression of miRNAs. Nicotine upregulated the expression of hsa-miR-7977, hsa-miR-3178, and hsa-miR-10400-5p compared to vehicle control. Interestingly, nicotine did not change the expression of hsa-miR-29b-3p, hsa-miR-199b-5p, hsa-miR-26b-5p, or hsa-miR-26a-5p compared to the control. However, the expressions of these miRNAs were significantly altered when compared to CSC treatment. Further analysis revealed that nicotine was distinctively associated with certain miRNA-targeted pathways including apoptosis, ErbB, MAPK signaling, PI3K-Akt, TGF-b signaling, and Wnt signaling. Conclusions: Our work provides evidence on the distinctive miRNA signature induced by nicotine. The information will be important for identifying the unique molecular pathways downstream of nicotine from smoking and vaping in different individuals, providing a new direction for personalized disease prevention, prognosis, and treatment. Full article

Metformin is one of the most commonly used medications to treat type 2 diabetes. In addition to lowering blood sugar, it can also promote the regeneration of certain organs or tissues. Planarian Dugesia japonica, with its remarkable regenerative capacity, has become an important model organism for studying pharmacology and regenerative medicine. Planarian eyespot regeneration involves precise tissue regeneration via mechanisms like cell proliferation, differentiation, and gene regulation following body damage. Experiments on planarian eyespot regeneration have confirmed that 1 mM metformin significantly promotes regeneration. Through analysis of the regenerating planarian miRNA database and the metformin-treated transcriptome database, combined with target gene prediction by TargetScan, the DjmiR-27b/DjPax6 axis was finally determined as the research focus. qPCR showed that metformin significantly affects the expression levels of DjmiR-27b and DjPax6. DjPax6 was identified as the target gene of DjmiR-27b through dual luciferase reporter gene analysis. Functional experiments revealed that metformin regulates the expression of DjPax6 via DjmiR-27b, thereby influencing the regeneration of planarian eyespots. In situ hybridization showed that both DjmiR-27b and DjPax6 are expressed throughout the entire body. This study reveals the molecular mechanism of metformin regulating planarian regeneration through miRNA, providing further insights into its role in the field of regeneration. Full article

The pupal stage in necrophagous flies represents the longest and least morphologically distinct phase of development, posing a persistent challenge for accurately estimating postmortem intervals (PMI) in forensic investigations. Here, we present a novel molecular approach to pupal age estimation in Sarcophaga peregrina, a forensically important species, by profiling microRNA (miRNA) expression dynamics. High-throughput sequencing across early, mid, and late pupal stages identified 191 known miRNAs, of which nine exhibited distinct monotonic temporal trends. Six miRNAs (miR-210-3p, miR-285, miR-927-5p, miR-956-3p, miR-92b, and miR-275-5p) were validated by qRT-PCR and demonstrated consistent time-dependent expression patterns. Polynomial regression models revealed a strong correlation between miRNA abundance and developmental age (R² = 0.88–0.99). Functional enrichment analyses of predicted miRNA targets highlighted their roles in key regulatory pathways, including ecdysteroid signaling, hypoxia response, autophagy, and energy metabolism. This study establishes, for the first time, a robust miRNA-based framework for estimating pupal age in forensic entomology, underscoring the potential of miRNAs as temporally precise biomarkers for PMI estimation. Full article

Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with CTC-537E7.3 expression lost in 95% of cases (*** p < 0.0001). It demonstrated excellent diagnostic performance in discriminating tumor from non-tumor tissue (AUC = 0.95), which was maintained in early-stage (I/II) disease. Low CTC-537E7.3 expression correlated with shorter overall and disease-free survival and was inversely associated with serum α-fetoprotein (AFP) levels, highlighting its complementary clinical value. Mechanistic investigation revealed a potential competing endogenous RNA (ceRNA) axis. The microRNA miR-190b-5p was highly expressed in tumors and predicted to bind CTC-537E7.3, while its target, PLGLB1, was significantly suppressed. Survival analysis confirmed that concurrent high expression of CTC-537E7.3 and PLGLB1 conferred superior outcomes. These findings establish CTC-537E7.3 as a liver-specific, ceRNA-mediated tumor suppressor with robust diagnostic and prognostic potential. It represents a promising adjunct to existing HCC surveillance strategies, such as ultrasound and AFP measurement, for high-risk populations. Full article

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, triggering persistent inflammation and ulceration, resulting in a severe impact on patients’ quality of life. Currently, the standard diagnostic methods for UC include invasive procedures such as colonoscopy and the use of non-specific inflammatory markers like C-reactive protein, which can be inconvenient or painful and lack specificity. This underscores the need for non-invasive and highly specific biomarkers for UC. MicroRNAs (miRNAs) are small non-coding RNAs, typically 22 nucleotides in length, which are well described as gene expression regulators. Several studies have reported their differential expression in various pathological conditions, including UC. Due to their role in gene regulation and stability in biological fluids, miRNAs present a promising opportunity as biomarkers. This systematic review explores the potential use of miRNAs as diagnostic biomarkers to distinguish between active and inactive ulcerative colitis. Following PRISMA guidelines and based on inclusion and exclusion criteria, seven studies, encompassing a total of 514 participants (181 with active UC and 116 with inactive UC), were included. Multiple miRNAs exhibiting differential expression between active and inactive UC were identified. Most notably, miR-21, miR-126, miR-146b-5p, and miR-223 exhibited consistent upregulation in active UC, suggesting their potential as diagnostic biomarkers. Supporting these findings is the fact that these miRNAs are involved in inflammatory pathways, further highlighting their relevance to the pathogenesis of UC. This review emphasizes the need for further validation studies with larger cohorts to confirm the utility of miRNAs as diagnostic tools for UC disease activity differentiation, which could enhance non-invasive disease monitoring and inform therapeutic decision-making. Future research should also evaluate the prognostic potential of these miRNAs for predicting treatment responses and long-term disease outcomes. Full article

Arteriovenous malformations (AVMs) are congenital vascular anomalies defined by abnormal direct connections between arteries and veins due to their complex structure or endovascular approaches. Pharmacological strategies targeting the underlying molecular mechanisms are thus gaining increasing attention in an effort to determine the mechanism involved in AVM regulation. In this study, we examined 30 human tissue samples, comprising 10 vascular samples, 10 human fibroblasts derived from AVM tissue, and 10 vascular samples derived from healthy individuals. The pharmacological agents thalidomide, U0126, and rapamycin were applied to the isolated endothelial cells (ECs). The pharmacological treatments reduced the proliferation of AVM ECs and downregulated miR-135b-5p, a biomarker associated with AVMs. The expression levels of angiogenesis-related genes, including VEGF, ANG2, FSTL1, and MARCKS, decreased; in comparison, CSPG4, a gene related to capillary networks, was upregulated. Following analysis of these findings, skin samples from 10 AVM patients were reprogrammed into induced pluripotent stem cells (iPSCs) to generate AVM blood vessel organoids. Treatment of these AVM blood vessel organoids with thalidomide, U0126, and rapamycin resulted in a reduction in the expression of the EC markers CD31 and α-SMA. The establishment of AVM blood vessel organoids offers a physiologically relevant in vitro model for disease characterization and drug screening. The authors of future studies should aim to refine this model using advanced techniques, such as microfluidic systems, to more efficiently replicate AVMs’ pathology and support the development of personalized therapies. Full article

Cardiac remodeling in feline hypertrophic cardiomyopathy (HCM) is poorly understood. To investigate underlying molecular mechanisms, we determined microRNA–mRNA interactions, regulatory networks, and upstream regulators using left ventricle (LV) and left atrium (LA) mRNA and microRNA sequencing datasets from cats with HCM and controls. Upstream regulators, molecules, and pathways associated with ischemia, inflammation, fibrosis, and cellular changes were observed in the HCM heart. In both the HCM LV and LA, TNFα, IL1β, and TGFβ were identified as upstream regulators, along with FGF23, THBS4, and FAMB177 as the top increased molecules. Relevant microRNAs included upstream regulator miR-132, enriched miR-124-3p, miR-122b-3p, miR-146-5p (HCM LV and LA), miR-370, miR-1185-5p, miR-12194-3p (HCM LV), miR-153-3p, miR-185-5p, and miR-185-3p (HCM LA). Macrophage pathways were activated, and granulocyte and agranulocyte adhesion and diapedesis were the most connected pathways. The HIF1α signaling pathway in the HCM LV, upstream regulators miR-1-3p and miR-204, and reduced miR-29 and miR-122-5p suggest cardioprotective mechanisms. Observed in the healthy heart and suspected to be involved in cardiac homeostasis were upstream regulators miR-96, inhibited WNT3A and miR-145, as well as miR-140-5p, miR-141-3p, miR-208b-3p, and miR-885-3p. This study provides further insights into the pathogenesis of HCM, and identifies the factors involved in the maintenance of a healthy LV and LA. Full article

Any failure in frontonasal development can lead to malformations at the middle facial region, such as frontonasal dysplasia, midfacial clefts, and hyper/hypotelorism. Various environmental factors influence morphogenesis through epigenetic regulations, including the action of noncoding microRNAs (miRNAs). However, it remains unclear how miRNAs are involved in the frontonasal development. In our analysis of publicly available miRNA-seq and RNA-seq datasets, we found that miR-28a-5p, miR-302a-3p, miR-302b-3p, and miR-302d-3p were differentially expressed in the frontonasal process during embryonic days 10.5 to 13.5 (E10.5–E13.5) in mice. Overexpression of these miRNAs led to a suppression of cell proliferation in cultured mouse embryonic frontonasal mesenchymal (MEFM) cells as well as in O9-1 cells, a cranial neural crest cell line. Through advanced bioinformatic analyses and miRNA-gene regulation assays, we identified that miR-28a-5p regulated a total of 25 genes, miR-302a-3p regulated 23 genes, miR-302b-3p regulated 22 genes, and miR-302d-3p regulated 20 genes. Notably, the expression of miR-302a/b/d-3p—unlike miR-28a-5p—was significantly upregulated by excessive exposure to all-trans retinoic acid (atRA) that induces craniofacial malformations. Inhibition of these miRNAs restored the reduced cell proliferation caused by atRA by normalizing the expression of target genes associated with frontonasal anomalies. Therefore, our findings suggest that miR-302a/b/d-3p plays a crucial role in the development of frontonasal malformations. Full article

Asthma places a significant burden at individual and societal levels, but there remains no gold-standard objective test for asthma diagnosis or asthma severity risk prediction. MicroRNAs (miRNAs) are short non-coding RNA sequences that are attracting interest as biological signatures of health and disease status. We sought to construct serum miRNA panels that could serve as potential biomarkers to aid in the diagnosis of asthma and predict asthma severity. Thirty-five asthma-related miRNAs were screened in the serum of three patient groups (never-asthma, mild-asthma, and severe-asthma; n = 50/group) drawn from two well-characterised cohorts. miRCURY LNA technology was used, followed by GeneGlobe analysis. The associations of miRNA expression with clinical outcomes of interest and diagnostic value of the proposed miRNA panels were assessed. We identified an asthma diagnosis panel comprising upregulated miR-223-3p, miR-191-5p, and miR-197-3p (area under curve (AUC) = 0.813, sensitivity 76% and specificity 72%). Compared with mild-asthma individuals, we also identified an asthma severity risk panel comprising upregulated miR-223-3p plus downregulated miR-30a-5p, miR-660-5p, and miR-125b-5p (AUC = 0.759, sensitivity 78%, specificity 64%). Individual miRNAs showed associations with worse clinical asthma severity and impaired quality of life. miRNA panels with high sensitivity and specificity offer potential as biomarkers for asthma diagnosis and asthma severity. Full article

Noise-induced hearing loss (NIHL) is a significant occupational health issue, characterized by permanent damage to the cochlea due to prolonged exposure to high-intensity noise. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive indicators of inner ear pathology and potential modulators of cellular stress responses. Nevertheless, their specific roles in NIHL remain inadequately characterized. This study evaluated miRNA expression in the peripheral blood of individuals with bilateral NIHL (n = 12) and matched healthy controls (n = 6) using GeneChip^® miRNA 4.0 arrays. The Transcriptome Analysis Console software was used for differential expression analysis, and bioinformatic predictions of gene targets and pathway enrichment were performed using TargetScan (version 8.0) and the Enrichr tool. Among the 72 differentially expressed miRNAs (FDR < 0.05), hsa-miR-486-2, hsa-miR-664b-3p, hsa-miR-4485, hsa-miR-501, and hsa-miR-663b were notably upregulated, while hsa-miR-6723, hsa-miR-194-2, hsa-miR-668-5p, hsa-miR-4722-3p, and hsa-miR-4716 showed significant downregulation. Enrichment analyses indicated involvement in apoptosis regulation, mitochondrial stability, and cell cycle control. Principal component analysis (PCA) and clustering methods revealed clear molecular distinctions between the patient and control groups. The observed alterations in c-miRNA profiles highlight their relevance to NIHL-related cellular stress and degeneration. These findings support their utility as candidate biomarkers for diagnosis and prognosis, warranting further validation in functional and longitudinal studies. Full article

Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. Full article