Search Results (6,399)

High temperatures are one of the most important abiotic stressors affecting the survival and growth of American shad (Alosa sapidissima). Building on previous omics sequencing studies of A. sapidissima liver and gills under high temperature stress, this study focused on investigating the regulatory role of miR-1236-3p and its target gene hsp90b1. The results indicate that the full-length cDNA of the hsp90b1 gene is 2023 bp and comprises a 5’ end of 58 bp, a 3’ end of 84 bp, and a coding region of 1881 bp, encoding 626 amino acids. Sequence alignment and phylogenetic tree analysis reveal that the hsp90b1 sequence is highly conserved across species. In situ hybridization showed that hsp90b1 is mainly localized in the cytoplasm. Software prediction identified a potential binding site between miR-1236-3p and hsp90b1. Through the construction of wild-type and mutant 3’UTR hsp90b1 dual luciferase reporter plasmids, the targeted relationship between the two was confirmed. In addition, the spatiotemporal expression levels of the hsp90b1 was found to be highest in the multicellular stage and liver tissue at a cultivation temperature of 27 °C; miR-1236-3P was highly expressed in the hatching stage and heart tissue at 30 °C. These findings provide a theoretical foundation for further investigating the regulatory role of non-coding RNA in A. sapidissima heat stress and offer data for subsequent molecular breeding studies. Full article

MicroRNA-22 (miR-22) is a negative regulator of mitochondrial biogenesis, as well as lipid and glucose metabolism, in metabolically active tissues. Silencing miR-22 holds promise as a potential treatment of obesity and metabolic syndrome, as it restores metabolic capacity—enhancing oxidative metabolism—and reduces ectopic fat accumulation in chronic obesity, a driver of impaired metabolic flexibility and muscle mass loss. Intramuscular adipose accumulation and defective mitochondrial function are features associated with obese-mediated muscle atrophy and hallmarks of neuromuscular disorders such as Duchenne muscular dystrophy. Therefore, miR-22 could represent a compelling molecular target to improve muscle health across various muscle-wasting conditions. This study describes a pharmacological strategy for the inhibition of miR-22 in skeletal muscle by employing a mixmer antisense oligonucleotide (ASO, anti-miR-22). Administration of the ASO in a mouse model of obesity positively modulated myogenesis while protecting dystrophic mice from muscle function decline, enhancing fatigue resistance, and limiting pathological fibrotic remodeling. Mechanistically, we show that anti-miR-22 treatment promotes derepression of genes involved in mitochondrial homeostasis, favoring oxidative fiber content regardless of the disease model, thus promoting a more resilient phenotype. Furthermore, we suggest that miR-22 inhibition increases autophagy by transcriptional activation of multiple negative regulators of mammalian target of rapamycin (mTOR) signaling to decrease immune infiltration and fibrosis. These findings position miR-22 as a promising therapeutic target for muscle atrophy and support its potential to restore muscle health. Full article

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF (OFO), OF + ago (OFO and miR-144 agomir), and OF + anta (OFO and miR-144 antagomir). Histological results showed that OFO significantly reduced myofiber density (from 758.00 ± 13.69 to 636.57 ± 13.44 N/mm²) and decreased the percentage of myofibers with diameters > 50 μm (from 53.45% to 38.52%). OFO intake significantly increased the content of malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), and 3-nitrotyrosine (3-NT), and significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in muscle. OFO treatment significantly up-regulated the expression of inflammatory factors (NF-κB, TNF-α, HO-1, and IL-6), significantly down-regulated NQO1. Moreover, OFO reduced muscle differentiation and maturation by down-regulating the expression of MyoG, MYHC1, and protein synthesis genes (AKT3, TOR, and S6K1), and up-regulating the expression of protein hydrolysis genes (FoxO3a, MuRF1, HSP70, Beclin-1, P62, and ATG8). Moreover, miR-144 agomir exacerbated OFO-induced muscle damage by suppressing Nrf2, whereas miR-144 antagomir mitigated these effects. Silencing miR-144 re-activates Nrf2, alleviating oxidative damage, enhancing protein deposition, and improving muscle quality. These findings suggest that targeting the miR-144/Nrf2 axis could counteract OFO-induced muscle deterioration. Full article

Asthma is a chronic respiratory disease affecting over 262 million people worldwide, with obesity-associated asthma emerging as a distinct endotype of increasing prevalence characterized by metabolic inflammation and airway remodeling. Unlike allergic asthma, this phenotype is driven by chronic low-grade inflammation, originating from hypertrophic and hypoxic adipose tissue. This dysregulated state leads to the activation of pro-inflammatory pathways and the secretion of cytokines, contributing to airway dysfunction and remodeling. Recent evidence highlights non-coding RNAs (ncRNAs) as key regulators of these processes. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) influence inflammation and remodeling by modulating immune cell polarization, cytokine secretion, extracellular matrix composition, and airway smooth muscle cell (ASMC) proliferation. Notably, H19, MEG3, GAS5, miR-26a-1-3p, and miR-376a-3p have been implicated in both asthma and obesity, suggesting their role in linking metabolic dysfunction with airway pathology. Moreover, ncRNAs regulate Treg/Th17 balance, fibroblast activation, and autophagy-related pathways, further influencing airway remodeling. Our in silico analysis highlighted the IGF1R signaling pathway as a key enriched mechanism, linking selected ncRNAs with metabolic dysregulation and inflammation in obesity-related asthma. This paper reviews how ncRNAs regulate inflammation and airway remodeling in obesity-associated asthma, emphasizing their potential molecular links between metabolic dysfunction and airway pathology. Full article

Background: Cardiometabolic syndromes, including diabetes, obesity, and metabolic syndrome, significantly contribute to cardiovascular fibrosis, a major driver of heart failure. Non-coding RNAs (ncRNAs)—notably microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—have emerged as critical epigenetic regulators of fibrotic remodeling. Recent studies indicate that widely used metabolic modulators can influence ncRNA expression, potentially impacting on cardiovascular fibrosis. This review synthesizes evidence on the interplay between metabolic therapies and ncRNA regulation, with emphasis on therapeutic and biomarker potential of miRNAs. Methods: A literature search was manually curated and conducted on PubMed for studies published mainly in the last decade and evaluating the effects of metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, glucagon-like peptide 1 (GLP-1) receptor agonists, and fatty acid oxidation inhibitors on ncRNA expression in the context of cardiovascular fibrosis. Data from in vitro, in vivo, and clinical studies were extracted and categorized by drug class, ncRNA target, and functional outcomes. Results: Several metabolic modulators specifically downregulate pro-fibrotic (miR-21, miR-92, H19, and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)) and upregulate anti-fibrotic ncRNAs (miR-29, miR-133a, miR-711, miR-133a, miR-30a and miR-200 family). This results in global attenuation of the transforming growth factor- beta (TGF-β) signaling, which limits extracellular matrix (ECM) accumulation thus improving myocardial compliance. Across drug classes, changes in ncRNA profiles paralleled improvements in fibrosis-related endpoints. Conclusions: Metabolic modulators exert anti-fibrotic effects partly through ncRNA regulation, offering novel therapeutic strategies and potential biomarkers for cardiovascular fibrosis in cardiometabolic disease. Targeting metabolic–ncRNA crosstalk may enable more precise and synergistic interventions for preventing or reversing pathological remodeling. Full article

The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown adipocytes via a comparative analysis using typical mouse brown adipose tissue sections. We found that swine brown adipocytes were distributed in an island-like pattern, with three typical characteristics: (1) numerous mitochondria and small lipid droplets, (2) a cellular volume smaller than that of white adipocytes, and (3) expression of specific marker genes (EBF2 and ATP2B4). The expression levels of the thermogenesis-related genes UCP2/3 were not significantly increased. Thus, we conducted ceRNA network analysis, revealing that high expression of the key microRNA miR-10383 increased the thermogenic efficiency of UCP3 in the cold exposure group. In addition, the epigenetic memory of UCP3 was disrupted. Chromatin accessibility and Whole-Transcriptome Sequencing of Groin Adiposesibility results revealed peaks in the promoter regions of the UCP2/3 genes. In our discussion of the study’s limitations, we explain how to repeat the experiment to significantly increase the UCP2/3 protein content. This study fills a research gap regarding brown fat in pigs and can provide a reference for future studies on fat metabolism. Full article

Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA–mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration. Full article

Background: Immunodeficiencies are a heterogeneous group of disorders classified etiologically as primary (congenital) or secondary (acquired). Primary immunodeficiencies (PIDs), such as common variable immunodeficiency (CVID), result from genetic mutations that impair the development and function of lymphocytes. Secondary immunodeficiencies (SIDs) arise as a consequence of chronic diseases, lymphoid malignancies, or immunosuppressive therapies. Aim of the study: The purpose of this study was to assess the serum expression profile of selected microRNAs (miRNAs) in patients with CVID and in those with chronic lymphocytic leukemia (CLL) and coexisting SID, compared to healthy individuals. Methods: Digital PCR (dPCR) was applied to quantify the serum expression levels of selected miRNAs in patients with CVID, patients with CLL and SID, and in healthy controls. Results: dPCR revealed significantly reduced levels of miR-16, miR-30c, miR-181a, miR-29a, miR-150, and miR-326 in the CVID group, potentially reflecting impaired regulatory mechanisms of the immune system. In contrast, elevated levels of miR-21, miR-125b, and miR-155 were observed in the CLL group with SID, suggesting their role in tumorigenesis and secondary immunosuppression. Correlations between miRNA levels and the expression of immune checkpoints (PD-1, CTLA-4, CD200) indicated the involvement of a complex regulatory network encompassing both humoral and cellular immune mechanisms. Conclusions: The results provide preliminary evidence that selected miRNAs could reflect disease-specific immune dysregulation patterns and may hold potential as diagnostic and prognostic biomarkers in both PIDs and SIDs. Full article

This study explores the use of mid-infrared (MIR) free-electron laser (FEL) irradiation as a tool for tailoring the surface properties of electrochemically synthesized TiO₂—graphene quantum dots (QDs). The QDs, prepared in colloidal form via a cost-effective electrochemical method in a KCl—citric acid medium, were exposed to MIR wavelengths (5.76, 8.02, and 9.10 µm) at the Kyoto University FEL facility. Post-irradiation measurements revealed a pronounced inversion of zeta potential by 40–50 mV and approximately 10% reduction in hydrodynamic size, indicating double-layer contraction and ionic redistribution at the QD—solvent interface. Photoluminescence spectra showed enhanced emission for GQDs and TiO₂/GQD composites, while Tauc analysis revealed modest bandgap blue shifts (0.04–0.08 eV), both consistent with trap-state passivation and sharper band edges. TEM confirmed intact crystalline structures, verifying that FEL-induced modifications were confined to surface chemistry rather than bulk lattice damage. Taken together, these results demonstrate that MIR FEL irradiation provides a resonance-driven, non-contact method to reorganize ions, suppress defect states, and improve the optoelectronic quality of QDs. This approach offers a scalable post-synthetic pathway for enhancing electron transport layers in perovskite solar cells and highlights the broader potential of photonic infrastructure for advanced nanomaterial processing and interface engineering in optoelectronic and energy applications. Full article

MicroRNA (miRNA), as a key post-transcriptional regulatory factor, plays a crucial role in embryonic development. The coordination of endoderm cell convergence and cardiac precursor cell (CPC) migration is critical for cardiac tube fusion. Defects in endoderm can impair the normal migration of CPCs towards the midline, leading to cardia bifida. Although the role of the microRNA-183 family (miR-183, miR-96 and miR-182) in cardiovascular diseases has been reported, the mechanism by which they regulate early heart development remains unclear. In this study, we used zebrafish as a model to elucidate the roles of the microRNA-183 family in early heart development. miRNA mimics were injected into Tg (cmlc2: eGFP) and Tg (sox17: eGFP) transgenic embryos to overexpress the miR-183 family. The results showed that, at 36 hpf, single or co-injection of miR-183/96/182 mimics caused defects in endoderm convergence, with a hole in the endoderm, and a significant down-regulation of the endoderm marker gene sox32. Additionally, embryos with single or co-injection of miR-183/96/182 mimics exhibited cardia bifida and tail blisters, with significantly down-regulated expression levels of genes related to heart development, including cmlc2, vmhc, amhc, nppa, gata4, gata5, nkx2.5, bmp2b, and bmp4. The phenotype caused by overexpression of the miR-183 family is highly consistent with loss of the sphingosine 1-phosphate receptor S1Pr2. Bioinformatics analysis result found that miR-183 can bind to 3′-UTR of the s1pr2 to regulate its expression; overexpression of miR-183 led to a significant decrease in the expression of the s1pr2 gene. Dual luciferase assay results suggest that s1pr2 is a bona fide target of miR-183. In summary, the miR-183 family regulates endoderm convergence and cardiac precursor cell migration via the S1Pr2 signaling pathway. This study reveals that the miR-183 family is a key regulatory factor in endoderm convergence and cardiac precursor cell migration during the early zebrafish development, elucidating the molecular mechanisms underlying early cardiac precursor cell and endoderm cell movement. Full article

Background/Objectives: MicroRNAs (miRNAs) regulate gene expression and are proposed as biomarkers in colorectal cancer (CRC). This study evaluated miR-185-5p, miR-141-5p, and miR-21-5p expression in CRC tissues; their association with tumor location, histopathology, and clinical outcomes; and the suitability of miR-16-5p and miR-151a-3p as housekeeping controls. Previous reports suggest tumor-suppressive roles for miR-185 and miR-141 and an oncogenic function for miR-21, though findings remain inconsistent. Methods: Paired tumor and adjacent normal tissues from 70 CRC patients were analyzed. RNA was extracted from FFPE samples, and miRNA expression quantified by RT-qPCR. Relative expression values were normalized to miR-151a-3p. Tumor–normal differences, localization effects, and associations with clinicopathological and outcome variables were assessed using repeated-measures ANOVA and non-parametric tests. Results: miR-185-5p and miR-141-5p were significantly reduced in tumors compared with normal mucosa while miR-21-5p was upregulated. miR-16-5p showed higher expression in normal tissue, indicating its instability and unsuitability as a housekeeping control. A modest but significant localization effect was observed for miR-185, while other miRNAs were minimally influenced by location. Baseline asymmetry between non-tumor samples, observed for miR-185-5p, further indicated sidedness effects. None of the miRNAs were associated with stage, histological type, grade, invasion, immune infiltration, progression, or five-year survival. Conclusions: miR-185-5p, miR-141-5p, and miR-21-5p show robust tumor–normal differences, supporting their diagnostic potential, while miR-16-5p is unsuitable as a housekeeper. Modest but significant localization effect was observed for miR-185 in right-sided tumors. None showed prognostic value in stage I–III CRC. Larger, location-stratified studies are warranted. Full article

Studies have shown that the iron concentration in the peritoneal fluid of women is associated with the severity of endometriosis. Therefore, investigation of iron metabolism-related genes (IM-RGs) in endometriosis holds significant implications for both prevention and therapeutic strategies in affected patients. Differentially expressed IM-RGs (DEIM-RGs) were identified by intersecting IM-RGs with differentially expressed genes derived from GSE86534. Mendelian randomization analysis was employed to determine DEIM-RGs causally associated with endometriosis, with subsequent verification through sensitivity analyses and the Steiger test. Biomarkers associated with IM-RGs in endometriosis were validated using expression data from GSE86534 and GSE105764. Functional annotation, regulatory network construction, and immunological profiling were conducted for these biomarkers. Single-cell RNA sequencing (scRNA-seq) (GSE213216) was utilized to identify distinctively expressed cellular subsets between endometriosis and controls. Experimental validation of biomarker expression was performed via reverse transcription–quantitative polymerase chain reaction (RT-qPCR). BMP6 and SLC48A1, biomarkers indicative of cellular BMP response, were influenced by a medicus variant mutation that inactivated PINK1 in complex I, concurrently enriched by both biomarkers. The lncRNA NEAT1 regulated BMP6 through hsa-mir-22-3p and hsa-mir-124-3p, while SLC48A1 was modulated by hsa-mir-423-5p, hsa-mir-19a-3p, and hsa-mir-19b-3p. Immune profiling revealed a negative correlation between BMP6 and monocytes, whereas SLC48A1 displayed a positive correlation with activated natural killer cells. scRNA-seq analysis identified macrophages and stromal stem cells as pivotal cellular components in endometriosis, exhibiting altered self-communication networks. RT-qPCR confirmed elevated expression of BMP6 and SLC48A1 in endometriosis samples relative to controls. Both BMP6 and SLC48A1 were consistently overexpressed in endometriosis, reinforcing their potential as biomarkers. Moreover, macrophages and stromal stem cells were delineated as key contributors. These findings provide novel insights into therapeutic and preventive approaches for patients with endometriosis. Full article

Background/Objectives: Retinal ischemia–reperfusion (I/R) injury is a common mechanism in glaucoma, diabetic retinopathy, and retinal vein occlusion, leading to progressive loss of retinal ganglion cells (RGCs). This study investigates the regulatory role of miR-21-5p and its interaction with Signal Transducer and Activator of Transcription 3 (STAT3) in retinal I/R injury. Methods: An acute intraocular hypertension (AIH) rat model was used to induce retinal I/R. The interaction between miR-21-5p and STAT3 was examined by dual-luciferase reporter assays. miR-21-5p and STAT3 expression were quantified by qRT-PCR and Western blotting. Retinal morphology, microglial polarization, and RGC survival were assessed by H&E staining and immunofluorescence. In vitro, microglia and RGCs were subjected to oxygen–glucose deprivation/reperfusion (OGD/R), and microglial-conditioned media (MCM) were applied to RGCs. Results: (1) miR-21-5p ameliorated AIH-induced retinal damage in vivo. (2) Overexpression of miR-21-5p inhibits M1 polarization of RM cultured in vitro. (3) MCM from miR-21-5p-overexpressing microglia attenuated OGD/R-induced RGC death. (4) miR-21-5p downregulates STAT3 expression to inhibit RM M1 polarization. (5) miR-21-5p down-regulation of STAT3 levels inhibits M1 polarization and reduces apoptosis of RGCs in retinal microglia of AIH rats. Conclusions: miR-21-5p alleviates retinal I/R injury by restraining microglial M1 polarization through direct repression of STAT3, thereby promoting RGC survival. These findings identify the miR-21-5p/STAT3 axis as a potential therapeutic target for ischemic retinal diseases. Full article

Background: Intracranial aneurysm (IA) rupture is a life-threatening cerebrovascular event with a mortality rate of up to 40%, affecting approximately 500,000 people globally each year. Although environmental pollutants such as 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) have been implicated in the pathogenesis of IA, the causal relationship and underlying mechanisms remain unclear. This study aims to systematically explore the potential causal role of PBDE-47 in the development of IA by integrating multi-omics approaches. Methods: We utilized the UK Biobank Drug Proteomics Project (UKB-PPP) genome-wide association study (GWAS) data, including 2940 plasma proteins and 1400 metabolites, along with IA genetic data from 456,348 individuals, to perform a two-sample Mendelian randomization (MR) analysis. Instrumental variables were selected based on genome-wide significance (p < 5 × 10⁻⁸) or suggestive thresholds (p < 5 × 10⁻⁵). Analytical methods included inverse variance weighting (IVW), MR-Egger, weighted median, MR-PRESSO, and Steiger filtering for sensitivity analysis. Molecular docking and 100-nanosecond molecular dynamics simulations were used to evaluate interactions between PBDE-47 and proteins. Mediation analysis assessed the roles of plasma metabolites and miRNAs, and SMR-HEIDI tests were used to verify causal relationships. Results: MR analysis identified 93 plasma proteins potentially causally associated with IA, including 53 protective factors and 40 risk factors. By integrating PBDE-47 targets, IA-related genes, and metabolite-related genes, we identified 15 hub genes. Molecular docking revealed potential binding between PBDE-47 and F2R (binding energy: −5.516 kcal/mol), and SMR-HEIDI testing supported F2R as a potential causal risk factor for IA. Molecular dynamics simulations indicated the stability of the complex structure. Mediation analysis suggested that F2R may influence IA risk through eight plasma metabolites, and miR-130b-3p may indirectly promote IA development by upregulating F2R. Conclusions: Our findings suggest that exposure to PBDE-47 may have a potential causal relationship with IA risk, potentially mediated through the “PBDE–47–F2R–metabolite–miRNA” regulatory axis. These results provide preliminary evidence for early diagnostic biomarkers and targeted interventions for IA. The multi-omics analytical framework established in this study offers new insights into environmental determinants of neurovascular diseases, although further validation is needed to address potential limitations. Full article

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