Search Results (2,226)

Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ² test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ² test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article

This study aims to identify molecular markers with prognostic value for biochemical pregnancy in follicular fluid (FF) samples from women with endometriosis after assisted reproductive technology (ART) intervention. Levels of growth differentiation factor-9 (GDF-9), bone morphogenetic protein-15 (BMP-15), and anti-Mullerian hormone (AMH) proteins were semi-quantified by Western blotting and microRNAs 20a_1, 145_1, 320a_1, 125-b-5p, 212-3p, and 199_a by qPCR in FF samples from women submitted to ART with a previous diagnosis of endometriosis (n = 20) or male factor infertility (controls) (n = 44). An increase in GDF-9 and BMP-15 and a decrease in AMH mature protein were observed, as well as an increase in miR20a_1 (p = 0.04), miR145_1 (p = 0.003), and miR320a_1 (p = 0.006) in FF samples collected from women with endometriosis compared with controls. A reduction was observed in miR125b-5p (p = 0.004) and 212-3p (p = 0.02) in endometriosis. Receiver operating characteristic (ROC) curve analysis indicated that miR125b-5p, miR212-3p, and miR-145_1 are potential predictors of endometriosis, and miR145_1 and miR320a_1 of biochemical pregnancy in controls. Although limited by a small sample size, the current study demonstrated alterations in AMH, BMP-15, GDF-9, and specific miRNA levels in FF samples harvested from women with endometriosis, emphasizing their potential roles in endometriosis-related infertility. These microRNAs, dysregulated in women with endometriosis, unveil their biomarker properties and their predictive value for ART success. Full article

RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential. Full article

We experimentally investigate the structural, magnetic, transport, and electronic properties of two d⁵ iridate double perovskite materials La₂BIrO₆ (B = Mg, Zn). Notably, despite similar crystallographic structure, the two compounds show distinctly different magnetic behaviors. The M = Mg compound shows an antiferromagnetic-like linear field-dependent isothermal magnetization below its transition temperature, whereas the M = Zn counterpart displays a clear hysteresis loop followed by a noticeable coercive field, indicative of ferromagnetic components arising from a non-collinear Ir spin arrangement. The local structure studies authenticate perceptible M/Ir antisite disorder in both systems, which complicates the magnetic exchange interaction scenario by introducing Ir-O-Ir superexchange pathways in addition to the nominal Ir-O-B-O-Ir super-superexchange interactions expected for an ideally ordered structure. While spin–orbit coupling (SOC) plays a crucial role in establishing insulating behavior for both these compounds, the rotational and tilting distortions of the IrO₆ (and MO₆) octahedral units further lift the ideal cubic symmetry. Finally, by measuring the Ir-L₃ edge resonant inelastic X-ray scattering (RIXS) spectra for both the compounds, giving evidence of spin–orbit-derived low-energy inter-J-state (intra t_2g) transitions (below ~1 eV), the charge transfer (O 2p → Ir 5d), and the crystal field (Ir t_2g → e_g) excitations, we put forward a qualitative argument for the interplay among effective SOC, non-cubic crystal field, and intersite hopping in these two compounds. Full article

Breast cancer (BC) is one of the most common malignancies among women worldwide. Despite advances in early detection and treatment, prognosis remains highly variable. Molecular biomarkers, such as microRNAs (miRNAs), have emerged as promising tools to refine prognostic assessment. Among them, miR-21 is consistently overexpressed in solid tumors and implicated in key oncogenic pathways. This systematic review and meta-analysis aimed to clarify the prognostic significance of miR-21 in BC and explore its molecular mechanisms through bioinformatic analyses. A systematic search of PubMed, Scopus, and Web of Science up to April 2025 identified 18 eligible observational studies. Pooled analyses showed that high miR-21 expression was significantly associated with poorer overall survival (OS) (HR = 2.37, 95% CI: 1.42–3.98) and recurrence-related outcomes (DFS/RFS) (HR = 2.10, 95% CI: 1.32–3.34). Subgroup analyses confirmed robust associations across different cut-off definitions and revealed particularly strong effects in triple-negative BC (HR = 5.69) and mixed subtypes (HR = 2.55), but no significant association in HER2-positive BC. Bioinformatic analysis identified target genes such as PTEN, BCL2, STAT3, and MYC, involved in apoptosis regulation, proliferation, NF-κB signaling, and immune modulation. These findings provide consistent evidence that miR-21 is a promising minimally invasive prognostic biomarker in BC, particularly in aggressive subtypes, and support its integration into future multimodal prognostic models. Full article

Heart failure (HF) remains a major cause of mortality despite the advances in pharmacological treatment. Anticoagulation therapies, including Clopidogrel, Aspirin, Warfarin, and novel oral anticoagulants (NOACs) such as Apixaban, Rivaroxaban, Edoxaban, and Dabigatran, are frequently administered to HF patients to prevent thromboembolism and adverse, life-threatening outcomes (e.g., stroke and myocardial infarction). In these settings, drug resistance and variability in responsivity to therapeutic approaches are challenging issues. Recent studies suggest that non-coding RNAs, particularly microRNAs (miRs) may play a modulatory role in HF therapy context, affecting drug efficacy. Specific miRs have been associated with resistance to Clopidogrel (e.g., miR-223 and miR-26a), Aspirin (e.g., miR-19b-1-5p and miR-92a) and Warfarin (e.g., miR-133 and miR-137). Moreover, Digoxin, a cardiac glycoside acting also over bleeding risk, upregulates miR-132, which is involved in HF-associated cardiac alteration and hypertrophy. Evidence linking miR expression to NOAC pharmacodynamics, cardiac remodeling and regulation of the coagulation is growing. These findings highlight the need of deeply harnessing the potential of miRs as predictive biomarkers or therapeutic targets in HF. Improving the knowledge on the relationship between miR and anticoagulant drugs in HF patients will contribute to personalization of the anticoagulant therapies, aimed at enhancing patient responsivity and minimizing adverse effects, ultimately improving patient life quality. Full article

Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO₂) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO₂ (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO₂) was recorded when PaCO₂ was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO₂, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO₂ and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO₂, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO₂ and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article

Chronic inflammation driven by Cyclooxygenase-2 (COX-2) overexpression plays a key role in lung cancer (LC) progression, making it a critical therapeutic target. This study explores thymoquinone (TQ), a potent bioactive phytochemical derived from Nigella sativa, known for its anti-inflammatory and anti-cancer effects, focusing on its ability to suppress lipopolysaccharide (LPS)-induced COX-2 expression via microRNA hsa-miR-199a-3p modulation in LC cells. Using A549 and SHP-77 LC cells, we tested the effect of TQ under LPS stimulation and miRNA inhibition. Advanced techniques like TaqMan qPCR, luciferase reporter gene constructs, and anti-miRNA transfection confirmed that miR-199a-3p directly silences COX-2. Western blot and ELISA assays revealed that TQ dramatically reduces COX-2 protein and PGE2 levels by boosting miRNA-199a-3p. Importantly, TQ also blocked MAPK (p38, JNK, ERK) and NF-κB activation, even when miR-199a-3p was suppressed, proving its multi-targeted action beyond miRNA regulation. These findings reveal a novel anti-inflammatory mechanism, where TQ curbs COX-2-driven inflammation by enhancing miR-199a-3p, simultaneously shutting down pro-cancer MAPK/NF-κB signaling pathways. Given the strong link between chronic inflammation and LC aggressiveness, this study positions TQ as a promising therapeutic candidate, especially for inflammation-mediated lung cancer progression. Its dual ability to modulate miRNA and key signaling cascades makes it a compelling option for future LC treatment strategies. Full article

Background/Objectives: The relationship between gut microbiota (GM) and microRNAs (miRs) related to lipid metabolism in individuals with metabolic syndrome (MetS) remains unclear. This pilot study examined the relationship between Bacteroidetes and Firmicutes abundance at the phylum level and the plasma levels of miR-122 and miR-370, both of which are associated with lipid metabolism, in Korean individuals with MetS and in healthy controls. We also evaluated the potential of these miRs as biomarkers for MetS. Methods: This study enrolled 7 individuals with MetS and 8 controls. The abundance of GM was analyzed by 16S rRNA amplicon sequencing. To evaluate the relationship between the dominant phyla in the 2 groups, the log ratio of Firmicutes to Bacteroidetes (F/B) was calculated using a centered log-ratio (CLR) transformation. The abundance of the 2 plasma miRs was also quantified by real-time quantitative PCR (RT-qPCR). Pearson’s and Spearman’s correlation analyses were then performed to evaluate the relationship between Bacteroidetes and Firmicutes abundance, the clinical parameters, and plasma levels of the 2 miRs. Additionally, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to evaluate the potential of the 2 miRs as MetS biomarkers. Results: The 2 most abundant phyla were Bacteroidetes and Firmicutes. Bacteroidetes made up an average of 24.7% in the MetS group and 69.7% in the control group. Meanwhile, the average abundance of Firmicutes was 69.8% in the MetS group and 26.5% in the control group. The log F/B ratios in the MetS and control groups were 0.7 ± 0.5 and −0.4 ± 0.1 (p < 0.001), respectively. FDR analysis revealed significant correlations between Bacteroidetes abundance and BMI, DBP, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05), as well as between Firmicutes abundance and BMI, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05). Plasma levels of the 2 miRs differed significantly between the MetS and control groups: miR-122 (1.43 vs. 0.73; p = 0.0065) and miR-370 (1.39 vs. 0.83; p = 0.0089). The AUC values for miR-122 and miR-370 were 0.946 (p < 0.001) and 0.964 (p < 0.001), respectively. Pearson’s and Spearman’s correlation analyses revealed significant negative correlations between Bacteroidetes abundance and levels of miR-122 (p = 0.0048 and p = 0.0045, respectively) and miR-370 (p = 0.0003 and p < 0.0001, respectively), as well as significant positive correlations between Firmicutes abundance and levels of miR-122 (p = 0.0038 and p = 0.0027, respectively) and miR-370 (p = 0.0004 and p < 0.0001, respectively). However, as our exploratory findings were based on a small sample size, the high correlation results may partly reflect the separation between the MetS and control groups. Conclusions: Our exploratory findings suggest that the GM abundances of individuals with MetS may be significantly associated with plasma levels of miR-122 and miR-370, which are related to lipid metabolism. These miRs may therefore serve as potential MetS biomarkers. Full article

Intracranial aneurysms (IAs) are potentially devastating cerebrovascular lesions, and predicting rupture risk remains a major clinical challenge. Conventional radiological and clinical scores offer only partial risk stratification, highlighting the need for complementary approaches. Liquid biopsy represents a promising non-invasive strategy to identify circulating biomarkers that reflect aneurysm biology and instability. We conducted a systematic review according to PRISMA 2020 guidelines, screening PubMed, Scopus, and Web of Science up to August 2025. Forty-eight eligible studies, encompassing 3515 IA patients, evaluated circulating RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in serum, plasma, blood, or cerebrospinal fluid. Multiple candidates emerged as consistently dysregulated: upregulation of miR-21, miR-126, and miR-200a-3p, and downregulation of miR-143 and let-7b-5p were recurrently observed across independent cohorts. LncRNAs, such as MALAT1 and MIAT, and circRNAs, including circ_0000690 and circ_0021001, demonstrated diagnostic and prognostic potential, with some correlating with rupture status and clinical severity indices. Despite encouraging findings, heterogeneity in study design, sample handling, and analytic methods limits reproducibility. Large-scale, multicenter validation studies are essential to translate these biomarkers into clinical practice. Full article

Background/Objectives: To investigate microRNA (miRNA) expression profiles in the anterior lens capsules of patients with glucocorticoid-induced cataracts (GIC) and to identify miRNAs potentially associated with glucocorticoid (GC) exposure and posterior subcapsular cataract (PSC) formation. Methods: A total of 33 participants were divided into four groups based on their GC usage history and cataract type: GIC (n = 10), age-related PSC (n = 6), GC-treated age-related cataract (ARC) (n = 7), and normal control (n = 10). Anterior lens capsule samples were obtained during cataract surgery and total RNA was extracted for quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of 12 selected miRNAs were quantified using a customized miScript miRNA PCR array. Results: Among the twelve miRNAs analyzed, seven (let-7a-5p, let-7d-5p, miR-15a-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p) were significantly differentially expressed among the groups (p < 0.05). In the GIC group, let-7a-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p were significantly upregulated, whereas let-7d-5p, miR-15a-5p and miR-16-5p were significantly downregulated compared to that in the normal control group. No significant differences in miRNA expression were observed between the GIC and age-related PSC groups or between the GIC and GC-treated ARC groups. Conclusions: This study demonstrates distinct miRNA expression patterns in the anterior lens capsules of patients with GIC. Altered expression of specific miRNAs may be linked to the pathogenesis of GC-induced PSC formation. These findings provide a molecular basis for further investigation into the regulatory roles of miRNAs in GC-associated cataracts. Full article

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal. Full article

The rising global prevalence of inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, is paralleled by an increased risk of colitis-associated colorectal cancer. Persistent intestinal inflammation promotes genetic instability and epigenetic reprogramming within epithelial and immune cells, driving the multistep transition from inflammation to neoplasia. This review integrates human and preclinical model evidence with literature mining and bioinformatic analyses of genetic, epigenetic, and ncRNA data to dissect molecular mechanisms driving colitis-associated colorectal cancer from chronic inflammation. We highlight how pro-inflammatory cytokines (e.g., TNF-α, IL-6), oxidative stress, and microbial dysbiosis converge on key transcriptional regulators such as NF-κB and STAT3, inducing DNA methylation and histone modifications (e.g., H3K27me3); altering chromatin dynamics, gene expression, and non-coding RNA networks (e.g., miR-21, MALAT1, CRNDE); ultimately reshaping pathways involved in proliferation, apoptosis, and immune evasion. This review updates new potential associations of entities with these diseases, in their networks of interaction, summarizing major aspects of genetic and chromatin-level regulatory mechanisms in inflammatory bowel disease and colorectal cancer, and emphasizing how these interactions drive the inflammatory-to-neoplastic transition. By underscoring the reversibility of epigenetic changes, we explore their translational potential in early detection, surveillance, and precision epigenetic therapy. Understanding the interplay between genetic mutations and chromatin remodeling provides a roadmap for improving diagnostics and personalized treatments in inflammatory bowel disease-associated colorectal carcinogenesis. Full article

Obesity is a major global health issue associated with an increased risk of early-onset metabolic disorders and chronic inflammation. Identifying the epigenetic mechanisms that contribute to obesity-related metabolic and inflammatory dysregulation is crucial for developing effective prevention and treatment strategies. This pilot study aimed to investigate the effects of obesity on the expression of microRNAs (miRNAs) related to metabolic disorders in human peripheral blood mononuclear cells from metabolically healthy obese subjects and non-obese controls. Differentially expressed miRNAs in TaqMan human miRNA arrays were quantified using quantitative PCR. To validate the robustness and generalizability of our findings, we performed cross-validation using the publicly available GSE155096 dataset. The expression of miR-145-5p was significantly increased (4.913-fold change) in obese individuals compared to the non-obese control group. Two miRNAs, miR-27b-3p and miR-17-5p, were downregulated 2.207- and 1.448-fold, respectively, approaching significance. A positive correlation was established between miR-145-5p and free triiodothyronine, eosinophils, and vitamin D. A cross-validation analysis confirmed the direction of change for these key miRNAs. The data suggest that miR-145-5p, miR-27b-3p, and miR-17-5p could be implicated in the progression of obesity in causing metabolic abnormalities, clarifying how molecular factors cause the metabolic deregulation associated with obesity. Full article

Background/Objectives: Critical limb ischemia (CLI) is a severe manifestation of peripheral arterial disease with limited treatment options. Mesenchymal stromal cell (MSC) therapy has shown promise, but variability in efficacy suggests that paracrine mechanisms, particularly extracellular vesicle (EV)-associated microRNAs (miRNAs), may play a central role. Methods: We analyzed angiogenesis-related miRNAs in bone marrow-derived MSCs (BM-MSCs) and their EVs. Five angiomiRs (miR-9, miR-105, miR-126, miR-135b, miR-210) were examined; only miR-126, miR-135b, and miR-210 were consistently detected in EVs. Expression variability was assessed across donor age and individuals. Functional evaluation was performed using co-culture of BM-MSCs with human umbilical vein endothelial cells (HUVECs) and by transfecting synthetic miRNAs into HUVECs. Tube formation assays quantified angiogenesis, and angiogenesis-related protein expression (VEGF, FGF, Endoglin, uPA) was analyzed. Biological replicates (multiple donors) and technical replicates (duplicate assays) were clearly defined to ensure reproducibility. Results: Co-culture of BM-MSCs and HUVECs significantly enhanced angiogenesis in a dose-dependent manner. EVs selectively packaged angiogenic miRNAs, with expression levels varying according to donor age and inter-individual variability. Transfection of miR-126, miR-135b, and miR-210 individually enhanced tube formation, while the miR-126 + miR-135b combination and triple transfection elicited the strongest effects. Protein analysis confirmed upregulation of VEGF, FGF, and Endoglin. Notably, miR-210 did not further enhance angiogenesis beyond miR-126 + miR-135b but may exert context-dependent effects. Conclusions: This study demonstrates that BM-MSC-derived EV miRNAs promote angiogenesis via combinatorial mechanisms, providing mechanistic support for ongoing CLI therapy. Our findings highlight the translational potential of EV-based nucleic acid therapeutics for ischemic disease. Full article