Search Results (8,880)

Background: Miscarriage is defined as the spontaneous loss of a pregnancy before fetal viability and includes all pregnancy losses occurring from conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive miscarriages. Emerging evidence suggests that both miR-99a and miR-143 may serve as promising biomarkers for recurrent pregnancy loss. Methods: A total of 42 women of reproductive age (18–45 years) were enrolled in this study. The control group consisted of 13 women with no history of recurrent miscarriage, whereas the study group included 29 women diagnosed with spontaneous miscarriages/recurrent implantation failure. Results: Both miR-99a and miR-143 showed significantly lower relative expression in women with recurrent miscarriage/recurrent implantation failure compared with the control group. Conclusions: Despite the relatively small sample size, statistically significant differences in the expression of miR-99a and miR-143 were observed between the case and control groups, with lower relative expression of both miRNAs in the case group. These findings suggest that both microRNAs may be associated with molecular pathways involved in reproductive failure. Furthermore, investigating the expression patterns of miR-99a and miR-143 may contribute to a better understanding of the molecular mechanisms underlying recurrent miscarriage/recurrent implantation failure. Such insights may facilitate the development of genetic risk profiles for women with unexplained pregnancy loss and implantation failure, as well as support the identification of potential therapeutic targets. Further studies are required to determine their potential value as molecular markers and to clarify their functional relevance in reproductive failure. Full article

Purpose of Review: Obesity is a growing global health challenge, with severe obesity projected to affect up to 25% of individuals with obesity by 2030. Bariatric surgery remains the most effective treatment, yet the molecular mechanisms underlying its metabolic benefits are not fully understood. This review summarizes current evidence on the role of microRNAs in bariatric/metabolic surgery and evaluates their potential as biomarkers and therapeutic targets. Recent Findings: Bariatric surgery induces significant alterations in circulating and tissue-specific miRNA profiles, particularly those involved in glucose metabolism, inflammation, and adipose tissue remodeling. Among the most frequently reported candidates, miR-122, miR-221, miR-27a, miR-126, miR-144, miR-222, miR-223, miR-375, miR-92a, and miR-155 have been associated with weight loss, improved insulin sensitivity, and diabetes remission. Emerging data suggest that these miRNAs may act not only as biomarkers of metabolic recovery but also as regulators of insulin signaling, inflammatory pathways, and adipocyte function. Summary: Current evidence supports a role for miRNAs in the metabolic adaptations observed after bariatric surgery. Although further validation is required, miRNAs show promise as minimally invasive biomarkers for predicting and monitoring treatment response and may provide insight into the molecular mechanisms underlying obesity remission and improvement of obesity-related comorbidities. Full article

Adipose tissue development significantly influences meat quality and economic traits in beef cattle. In this study, we identified a novel circular RNA derived from two exons (exons 3 and exons 9) of the NID2 gene, designated as circNID2, which exhibits high structural stability and marked upregulation during bovine adipocyte differentiation. Functional assays demonstrated that circNID2 suppresses the proliferation and apoptosis of bovine preadipocytes while robustly promoting adipogenic differentiation and lipid accumulation. Although containing several putative open reading frames, circNID2 lacks protein-coding potential. Mechanistically, circNID2 functions as a competing endogenous RNA by sponging miR-339a, thereby relieving the post-transcriptional repression of its downstream target, Neuronatin (NNAT). Functional rescue experiments further validated that circNID2 partially neutralizes the regulatory effects of miR-339a on preadipocyte proliferation, apoptosis, and differentiation. Collectively, these findings demonstrate that circNID2 regulates bovine preadipocyte function through the newly established circNID2/miR-339a/NNAT axis. This study provides novel insights into the post-transcriptional mechanisms governing mammalian adipogenesis and highlights circNID2 as a potential molecular target for improving fat deposition traits in cattle. Full article

Sorghum seeds accumulate substantial amounts of condensed tannins (CTs), which are also referred to as proanthocyanidins (PAs), contributing to their characteristic astringent taste. Flavan-3-ol polymers, known as PAs, are sequestered within plant vacuoles and become catalytically activated via laccase enzymes. However, the biological roles and regulatory pathways of laccases in sorghum are still largely unclear. Here, integrated transcriptomic and metabolomic profiling of developing sorghum seeds identified 7942 differentially expressed genes between low- and high-CT lines, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealing flavonoid biosynthesis as a key pathway; weighted gene co-expression network analysis (WGCNA) further pinpointed SbLAC14 as a hub gene within the module most strongly correlated with CT content. We then examined its regulation by microRNA397 (SbmiR397-5p). Dual-luciferase assays confirmed the binding of SbmiR397-5p to SbLAC14 in co-transformed tobacco leaves. Overexpressing SbLAC14 in transgenic Arabidopsis significantly increased CT accumulation while decreasing catechin and epicatechin levels. Furthermore, transgenic plants overexpressing miR397 (OEmiR397-5p) exhibited reduced CT content, accompanied by a lightening of seed color. Conversely, transgenic lines overexpressing a miR397-insensitive laccase transcript exhibited a reversed phenotypic outcome. Our findings indicate that SbmiR397-5p negatively regulates the expression of SbLAC14 in relation to CT biosynthesis, identifying it as a potential target for manipulating CT metabolism in sorghum. Those results provide a genetic entry point for metabolic engineering and breeding efforts aimed at modulating grain phenolic profiles. Full article

Estrogen receptor (ER)-positive breast cancer (BrCa) accounts for two-thirds of all BrCa cases worldwide. Therefore, ER-targeted endocrine therapy is the standard treatment for this disease. There has been a recent trend towards developing combination therapies using molecularly targeted drugs to improve outcomes. This study aimed to identify therapeutic targets demonstrating efficacy when combined with fulvestrant (a selective ER downregulator/degrader). We generated microRNA (miRNA) signatures from fulvestrant-treated MCF-7 cells by RNA sequencing. From the signature, we evaluated miR-374b-5p because its expression was elevated by fulvestrant treatment in MCF-7 cells. Also, in expression analysis by subtype of BrCa patients, miR-374b-5p expression was suppressed only in luminal BrCa. Ectopic expression assays revealed that miR-374b-5p attenuated the malignant phenotypes of MCF-7 cells. We searched for genes regulated by miR-374b-5p and discovered that 11 (NEK2, NUF2, HMMR, DEPDC1B, FOXM1, ELOVL6, KIF20A, NCAPH, CENPK, FAM83D, and KIAA0101) are closely involved in BrCa molecular pathogenesis. Among these target genes, we focused on forkhead box M1 (FOXM1), a transcription factor regulating cell cycle progression and division. Notably, combination therapy with fulvestrant and a FOXM1 inhibitor significantly suppressed MCF-7 cell proliferation. From the miRNA signature established in this study, we identified antitumor miR-374b-5p and its target genes and used these findings to explore candidate drugs with potential efficacy when combined with fulvestrant. Full article

Background and Objectives: Circulating microRNAs (miRNAs) are emerging as accessible biomarkers for multiple sclerosis (MS). In experimental models, miR-221 and miR-222 have been linked to immune and Th17-related pathways, while interleukin-23 (IL-23) is a cytokine driving autoimmune inflammation. This observational study evaluated the expression of circulating miR-221/222 and serum IL-23 concentrations in treatment-naive adult patients with MS. Materials and Methods: This prospective, cross-sectional case–control study included 43 untreated adult patients with MS (36 with relapsing–remitting MS and 7 with primary progressive MS) and 37 healthy controls. Demographic features, Expanded Disability Status Scale (EDSS) scores, magnetic resonance imaging involvement, initial symptoms, serum IL-23 concentration, and miR-221/222 expression were recorded. Total RNA, including small RNAs, was isolated; complementary DNA was synthesized by reverse transcription from RNA templates; and reverse transcription–quantitative real-time PCR (RT-qPCR) was performed using RNU6-2 as the endogenous small RNA reference. Individual ΔΔCt values were specified as the primary inferential scale, while 2^−ΔΔCt fold-change was retained only for descriptive reporting. Results: The relative expression (2^−ΔΔCt) of miR-221 and miR-222 was higher in patients than in controls. Within the patient group, miR-221 and miR-222 relative expression did not differ by age, sex, EDSS, time since MS diagnosis, MRI involvement area, or initial symptoms. No statistically significant difference in IL-23 levels was observed between the patient and control groups. Conclusions: The presence of unaltered IL-23 levels alongside significantly elevated miR-221 and miR-222 expressions in treatment-naive MS patients during the remission phase suggests their potential utility as biomarkers for immune regulation. Given the cross-sectional design of this study, no causal or regulatory relationship between miR-221/222 and IL-23 can be inferred. Full article

Post-myocardial infarction (MI) remodeling is accompanied by metabolic stress, but the myocardial genes associated with copper handling are poorly defined. We sought to prioritize a tissue-derived candidate rather than establish a copper-dependent mechanism. Regional MI transcriptomes and an in-house left anterior descending coronary artery ligation mouse RNA-sequencing cohort were integrated with protein quantitative trait locus-based Mendelian randomization (MR). Follow-up comprised local and external tissue validation, cardiac single-cell RNA sequencing, Genotype-Tissue Expression co-expression, computational perturbation, and CRIP2 knockdown or overexpression in H9c2 cells exposed to hypoxia/reoxygenation (H/R). CRIP2 showed a nominal protective-direction MR association (odds ratio 0.831, 95% confidence interval 0.735–0.939; p = 0.0031), but did not pass the Bonferroni threshold. Crip2 was lower in the local MI model (p = 0.0168; n = 5 per group) and in an independent dataset. A prespecified lipoylated-tricarboxylic-acid module was negatively enriched after MI (normalized enrichment score −1.63; false discovery rate 0.012), whereas the broader copper-homeostasis set was not significant. Single-cell data localized Crip2 mainly to cardiomyocytes, but were not adequately replicated for condition-level inference. Under H/R, Atp7a was the only copper-handling transcript whose knockdown-by-oxygen interaction remained significant after adjustment (q = 0.0405). CRIP2 overexpression was associated with higher Cell Counting Kit-8 metabolic activity during H/R (interaction p = 0.00551), whereas the knockdown interaction was not significant. Copper abundance, mitochondrial function, and cuproptosis markers were not measured. The data prioritize CRIP2 for mechanistic study, but do not show that it regulates copper flux or post-MI remodeling. Full article

Background: Childhood obesity is a growing health concern and added sugar intake has been associated with increased obesity risk. Emerging evidence suggests that miR-143-5p and miR-223-3p are involved in metabolic regulation. Therefore, this study evaluated their plasma expression according to added sugar intake and their association with cardiometabolic risk parameters. Methods: This cross-sectional study included 91 children aged 6–12 years, comprising 44 with normal weight and 47 with overweight/obesity. Anthropometric measurements, clinical characteristics, and dietary added sugar intake were assessed. Plasma expression of miR-143-5p and miR-223-3p was quantified by RT-qPCR. Results: Compared with low added sugar intake, high added sugar intake was associated with lower plasma miR-143-5p expression and higher miR-223-3p expression. Both miR-143-5p and miR-223-3p expression levels were higher in children with overweight/obesity and insulin resistance than in their respective counterparts. In adjusted analyses, neither miRNA was associated with cardiometabolic risk parameters. However, added sugar intake was positively associated with miR-223-3p expression (β = 0.188, 95% CI: 0.022, 0.354) and glucose levels (β = 1.944, 95% CI: 0.133, 3.755). Conclusions: These findings suggest that higher added sugar intake is associated with altered circulating miRNA expression and higher fasting glucose concentrations in school-aged children. Full article

Introduction: Cystinuria is an inherited disorder characterized by impaired proximal tubular reabsorption of cystine, resulting in recurrent cystine stone formation. Mutations in the SLC3A1 and SLC7A9 genes are the main genetic causes of the disease, while variants in PBX1 have also been associated with cystinuria in specific populations. Despite advances in understanding its molecular basis, cystinuria remains clinically heterogeneous, making disease progression and prognosis difficult to predict. This study aimed to investigate circulating microRNAs (miRNAs) as potential molecular biomarkers, characterize their expression profile in patients with cystinuria, and evaluate their association with clinical indicators of disease severity. Methods: The study group included 16 patients with a clinically established diagnosis of cystinuria, while the control group consisted of 11 healthy individuals without a history of nephrolithiasis. Candidate miRNAs were selected based on their predicted regulatory interactions with genes implicated in cystinuria pathogenesis. Eight microRNAs (miR-29a-3p, miR-29b-3p, miR-29c-3p, miR-1207-3p, miR-10a-3p, miR-3658, miR-141-3p, and miR-200a-3p) were analyzed by quantitative real-time PCR (qPCR). Results: Among the eight miRNAs evaluated, miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Higher expression levels of miR-10a, miR-141, and miR-200a were significantly associated with a greater number of previous surgical procedures (p < 0.05). Additionally, increased miR-10a expression was associated with impaired renal function, defined as serum creatinine levels above 1.2 mg/dL. Conclusions: miR-10a, miR-141, miR-200a, and miR-3658 were significantly downregulated in patients with cystinuria compared with healthy controls. Within the cystinuria cohort, higher expression of miR-10a was associated with impaired renal function, whereas increased expression of miR-10a, miR-141, and miR-200a correlated with a greater number of surgical interventions, suggesting a potential relationship with disease severity. Further studies in larger, genetically characterized cohorts are warranted to clarify the biological role and clinical utility of these miRNAs as biomarkers of cystinuria. Full article

Behçet’s disease (BD) is a chronic, multisystem vasculitis characterized by dysregulated immune responses and prominent Th1/Th17 polarization; however, the upstream epigenetic regulatory mechanisms driving this inflammatory imbalance remain incompletely understood. Here, we investigated the coordinated expression and diagnostic relevance of key long non-coding RNAs (lncRNAs; NEAT1 and MEG3) and microRNAs (miR-124 and miR-146a), and their association with IL-17/IL-6-mediated inflammation in BD. In a case–control study, serum levels of the selected non-coding RNAs were quantified by quantitative real-time PCR, while cytokine concentrations were measured using ELISA, complemented by bioinformatic interaction analysis and integrated statistical and machine learning approaches. Patients with BD exhibited marked downregulation of NEAT1, MEG3, miR-124, and miR-146a (p < 0.0001), accompanied by significantly elevated IL-17 and IL-6 levels. Individually, biomarkers demonstrated strong discriminatory capacity (AUC 0.83–0.92), while combined panels further improved classification performance. Multivariate modeling identified these non-coding RNAs as independent predictors of BD, and machine learning analysis identified miR-146a and IL-17 as the most influential contributors to disease classification. Notably, selected biomarkers showed associations with specific clinical manifestations, supporting their potential clinical relevance. Bioinformatic analyses identified putative interactions between NEAT1 and miR-124/miR-146a, while MEG3 demonstrated independent diagnostic value without evidence of direct interaction with the investigated miRNAs. Collectively, these findings provide a hypothesis-generating framework for future mechanistic investigations and support the potential diagnostic value of the investigated biomarker panel, although validation in larger multicenter cohorts and disease-control populations is warranted. Full article

Walnut (Juglans regia L.) is a monoecious species with far more male than female flowers, yet the molecular mechanisms regulating sex differentiation remain largely unexplored. In this study, we investigated the effects of exogenous brassinolide (BR) on the female-to-male flower bud ratio and its regulatory mechanisms. We identified 23 April to 13 May as the critical physiological differentiation period for the ‘Xin xin 2’ variety. Exogenous application of 0.05 mg/L BR during this period significantly increased the female-to-male flower bud ratio across three consecutive years (2023–2025). Hormone metabolomics revealed that BR treatment induced sex-specific changes in ethylene and auxin contents. Transcriptomic analysis showed that BR differentially regulated MADS-MIKC genes in female and male buds. Integrated miRNA-mRNA analysis identified sex-specific regulatory modules targeting MADS-MIKC genes, including four in female buds and two in male buds. RT-qPCR and dual-luciferase assays confirmed that jre-miR156g directly targets the 3’-untranslated region of JrSPL5, with reciprocal expression patterns. Collectively, our findings demonstrate that exogenous BR increases the female-to-male flower bud ratio in walnut through multi-layered regulation involving hormone signaling, sex-specific expression of MADS-MIKC genes, and miRNA-mRNA regulatory cascades. This study provides a theoretical basis for breeding high-yielding walnut varieties by manipulating sex expression. Full article

MicroRNAs (miRNAs) are conserved post-transcriptional regulators that play essential roles in cellular development and differentiation. Although miRNAs involved in oligodendrocyte lineage cell (OLLC) differentiation have been extensively studied in rodent models, their functions in human oligodendrocyte (OL) development remain poorly understood. To address this, we used a human embryonic stem cell (hESC) reporter system and an optimized differentiation protocol to generate and isolate well-characterized OLLCs at defined developmental stages. Next-generation sequencing-based miRNA profiling identified stage-specific miRNAs associated with OL lineage specification and maturation. In addition to canonical OL-associated miRNAs, we identified several previously uncharacterized oligodendrocyte progenitor cell (OPC)/oligodendrocyte (OL)-enriched miRNAs, including miR-3943, miR-4286, miR-1296-5p, miR-488-3p, miR-675-5p, and miR-128-3p, as potential novel regulators and molecular markers for human OLLC development. Computational target analysis further identified candidate regulatory genes, including ZNF488, DLX1, CSNK2B, and KCNJ1, and predicted their association with AKT, SMAD2/3, estrogen-receptor, and insulin-signaling pathways. Together, these findings provide a comprehensive stage-specific miRNA resource for human OL lineage development and provide insight into potential miRNA-mediated regulatory networks governing human OL development. Full article

Testicular germ cell tumors (TGCTs) are highly curable malignancies, yet their clinical management still relies heavily on conventional serum tumor markers, including alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase, which have limited sensitivity and specificity in several clinically relevant settings. Circulating microRNAs, particularly miR-371a-3p, have emerged as promising liquid biopsy biomarkers with potential applications across the TGCT disease continuum. This narrative review summarizes the current evidence on the biological basis, diagnostic performance, clinical utility, and limitations of circulating microRNAs in TGCTs. MiR-371a-3p demonstrates high diagnostic accuracy for viable non-teratomatous TGCTs and consistently outperforms classical serum tumor markers in primary diagnosis. Its rapid decline after effective treatment and its association with tumor burden support potential roles in chemotherapy monitoring, early relapse detection during surveillance, and the assessment of selected post-chemotherapy residual masses. However, its inability to detect teratoma remains a major biological limitation, particularly in non-seminomatous residual disease and surveillance settings. Additional barriers to implementation include assay heterogeneity, the lack of universally accepted cutoffs, the variable use of serum versus plasma, and the absence of broad regulatory approval. Emerging translational data suggest that miR-371a-3p may also contribute to tumor–microenvironment communication and cisplatin resistance, although these findings remain preclinical. Overall, miR-371a-3p represents one of the most promising biomarkers in TGCT management, but its routine clinical integration will require standardized analytical protocols and prospective validation in marker-guided decision pathways. Full article

Hypoxia-driven regulatory mechanisms play a critical role in tumor progression and therapeutic resistance in hepatocellular carcinoma (HCC), yet hypoxia-responsive microRNAs (HRMs) remain incompletely characterized. This study aimed to identify HRMs in canine HCC to evaluate their diagnostic potential and translational relevance to human disease. Next-generation sequencing of two canine HCC cell lines under normoxic and hypoxic conditions identified 332 and 321 differentially expressed miRNAs, respectively. Integrating these with tumor tissue data revealed 11 HRMs, featuring consistent upregulation of cfa-miR-210 and cfa-miR-34a, which was validated via RT-qPCR in hypoxic cells and clinical tissues. Both miRNAs were significantly elevated in plasma-derived extracellular vesicles (EVs), highlighting their value as promising circulating biomarkers (AUC 1.00 for miR-210; 0.98 for miR-34a). Target gene and pathway analyses identified shared regulatory nodes, including TGIF2 and SPRED1; and enrichment of MAPK, Ras, PI3K-Akt, and Rap1 signaling, broadly linked to hypoxia adaptation, cellular metabolism, and stress-response signaling. Cross-species comparison with human HCC datasets showed that, while miR-210 associates with poor prognosis in human HCC, miR-34a exhibits tumor-suppressive features. These findings define complementary HRM programs in canine HCC, reflecting conserved adaptive and stress-limiting regulatory mechanisms with potential diagnostic and translational relevance to human HCC. Full article

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article