Search Results (8,590)

Circular RNAs (circRNAs) have been reported to be closely associated with tumor progression in multiple malignancies. However, the specific mechanism by which circPRKCA influences tumor progression has not been fully elucidated. CircPRKCA is highly expressed in non-small cell lung cancer (NSCLC) tissues and cells. Knockdown of circPRKCA inhibits the malignant behaviors of NSCLC cells. RNA sequencing results revealed that FRMD6 and SNAI2 mRNAs are positively correlated with circPRKCA. Subsequently, we proved that circPRKCA acts as a molecular sponge for miR-200b-3p. Additionally, miR-200b-3p binds to the 3′ untranslated regions (3′UTRs) of FRMD6 and SNAI2 mRNAs to promote their degradation. Overexpression of circPRKCA thereby suppresses this degradation process and coun-teracts the tumor-suppressive effects induced by miR-200b-3p. CircPRKCA functions as the sponge of miR-200b-3p, suppressing the SNAI2/FRMD6 mRNA degradation driven by miR-200b-3p and accelerating NSCLC progression. Full article

This study aimed to investigate the molecular mechanisms underlying dopaminergic injury induced by gestational and lactational atrazine (ATR) exposure in rat offspring, with a particular focus on non-coding RNA-mediated regulation. Pregnant rats were exposed to ATR during gestation and lactation. Offspring underwent behavioral testing at postnatal day 21 (PND21) and were sacrificed for midbrain tissue collection at PND28. Behavioral alterations, histopathological changes in the substantia nigra, and dopaminergic marker expression were assessed to evaluate ATR-induced neurotoxicity. Whole-transcriptome sequencing was then performed to identify differentially expressed mRNAs, miRNAs, and lncRNAs, followed by co-expression, protein–protein interaction, and competing endogenous RNA (ceRNA) network analyses. Key targets were validated by qRT-PCR. Candidate molecules identified from transcriptomic and ceRNA analyses were further examined in an ATR-induced neurotoxicity model established in RA-differentiated SK-N-SH cells. Dual-luciferase reporter, Ago2-RNA immunoprecipitation, and biotin-labeled RNA pull-down assays were used to examine putative binding relationships and molecular interactions. In addition, lentivirus-mediated Elavl4 overexpression was performed to further evaluate the role of this candidate regulator in ATR-induced Nurr1 downregulation. Gestational and lactational ATR exposure induced significant behavioral abnormalities in rat offspring. These changes were accompanied by histopathological alterations in the substantia nigra, including reduced TH immunoreactivity, as well as abnormal expression of dopaminergic markers, characterized by decreased TH and Nurr1 levels and increased α-syn expression. Together, these findings indicate the presence of dopaminergic injury. Whole-transcriptome analysis further revealed widespread dysregulation of mRNAs, miRNAs, and lncRNAs in ATR-exposed offspring. Subsequent integrative analysis suggested a potential ceRNA regulatory relationship among Elavl4, miR-301a-5p, and Nurr1, which was further supported by qRT-PCR. Dual-luciferase reporter, RIP, and RNA pull-down assays supported direct interactions between miR-301a-5p and both Elavl4 and Nurr1, as well as their association with the Ago2-containing silencing complex. Moreover, Elavl4 overexpression partially reversed ATR-induced Nurr1 downregulation in vitro. Gestational and lactational ATR exposure induced behavioral abnormalities and dopaminergic injury in rat offspring. Whole-transcriptome analysis combined with experimental validation suggests a potential association between the Elavl4/miR-301a-5p/Nurr1 ceRNA axis and ATR-induced dopaminergic injury, providing insight into the post-transcriptional mechanisms underlying developmental neurotoxicity. Full article

Background: Lung cancer ranks among the most common and deadly malignant tumors worldwide. Drug resistance is a critical factor hindering the effect of chemotherapy for lung cancer. Exosomes, as intercellular signaling molecule carriers, play an important role in carcinogenesis, metastasis and drug resistance. Our study was aimed at exploring the impact of exosomes derived from docetaxel (DTX)-resistant lung cancer cells on regulating biological behaviors of DTX-sensitive cells, further investigating the molecular mechanisms regarding exosome-mediated intercellular communication. Methods: We extracted and identified the exosomes derived from A549, A549/DTX, H1299 and H1299/DTX cells, and then analyzed the expression of exosomal miR-373-3p between DTX-sensitive and DTX-resistant cells. Cell proliferation and apoptosis experiments were verified using a CCK-8 assay, a colony formation assay, a TUNEL assay and flow cytometry. The molecular interaction between miR-373-3p and PDCD4 was evaluated using a dual-luciferase reporter assay. The function of miR-373-3p was further assessed using an in vivo mouse xenograft model. Results: We found that the exosomal miR-373-3p level from DTX-resistant A549/DTX or H1299/DTX cells significantly exceeded that from DTX-sensitive A549 or H1299 cells. In addition, both exosomes derived from DTX-resistant lung cancer cells and miR-373-3p mimics could promote the proliferation of DTX-sensitive cells and inhibit their apoptosis. Moreover, we identified PDCD4 as a key target gene of miR-373-3p, which could induce the malignant behaviors of DTX-sensitive cells by reducing PDCD4 expression. Conclusions: Our results demonstrated that DTX-resistant lung cancer cells could transfer miR-373-3p to DTX-sensitive cells through exosomes, where miR-373-3p could exert its carcinogenic effect via targeting PDCD4. Full article

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are critical regulators of tumor progression; however, the biological role and molecular mechanisms of miR-589-3p in LUAD remain unclear. In this study, the expression levels of miR-589-3p and WWC2 were analyzed using The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) datasets via the UALCAN platform. Flow cytometric apoptosis analysis and functional assays including CCK-8, colony formation, AO/EB staining, and Transwell invasion assays were performed in LUAD cell lines. The interaction between miR-589-3p and WWC2 was validated using dual-luciferase reporter assays, Western blotting, and rescue experiments. miR-589-3p expression was significantly elevated in LUAD tissues compared with normal lung tissues (p < 0.05) and was positively associated with an advanced tumor stage and lymph node metastasis (p < 0.05). Inhibition of miR-589-3p significantly suppressed proliferation and colony formation (p < 0.05), reduced invasive capacity (p < 0.05), and markedly increased apoptosis (p < 0.01) in LUAD cells. Dual-luciferase reporter assays confirmed WWC2 as a direct target of miR-589-3p, with miR-589-3p mimics significantly reducing WWC2 wild-type reporter activity (p < 0.05). WWC2 expression was significantly downregulated in LUAD tissues (p < 0.05), and WWC2 knockdown reversed the anti-proliferative, pro-apoptotic, and anti-invasive effects induced by miR-589-3p inhibition (p < 0.01). These findings demonstrate that miR-589-3p promotes lung adenocarcinoma progression by directly suppressing WWC2. The miR-589-3p/WWC2 axis represents a novel molecular mechanism contributing to LUAD malignancy and may provide a foundation for future mechanistic and translational studies. Full article

2,3′,4,4′,5-Pentachlorobiphenyl (PCB118) is a persistent environmental pollutant associated with adverse female reproductive outcomes; however, its effects on uterine function and epigenetic regulation remain incompletely understood. This study investigated whether PCB118 disrupts uterine decidualization and angiogenesis through miRNA-mediated regulatory pathways. Human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs) were exposed to an environmentally relevant, non-cytotoxic concentration of PCB118. Decidualization and angiogenesis were evaluated in vitro, and underlying mechanisms were investigated using molecular and miRNA-based approaches. In vivo validation of miR-542-3p expression was performed in pregnant mice following PCB118 exposure. PCB118 exposure was associated with reduced expression of decidualization markers, including prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1), as well as impaired angiogenic capacity in HUVECs. PCB118 treatment was accompanied by increased miR-542-3p expression, which was associated with decreased integrin-linked kinase (ILK) levels and changes in transforming growth factor beta 1 (TGF-β1) and total Smad2 protein abundance. ILK overexpression partially restored decidualization and angiogenesis-related phenotypes, supporting a functional involvement of ILK in these processes. Consistently, elevated miR-542-3p expression was observed in murine endometrial tissues following PCB118 exposure, suggesting physiological relevance in vivo. PCB118 exposure is associated with impaired decidualization and angiogenesis, potentially involving dysregulation of the miR-542-3p/ILK signaling axis, suggesting a potential role for epigenetic modulation in PCB118-associated reproductive dysfunction. Full article

Background/Objectives: MicroRNAs (miRNAs) are key regulators of gene expression and have been implicated in multiple aspects of cancer progression. However, the role of miR-214-3p in breast cancer remains controversial. In this study, we investigated the functional role of miR-214-3p and explored its potential regulatory target in breast cancer, particularly in triple-negative breast cancer (TNBC). Methods: miR-214-3p expression was evaluated in breast cancer cell lines. Luciferase reporter assays were performed to assess functional targeting of the FRK 3′-UTR. Functional assays, including proliferation, migration, and invasion assays, were conducted following miR-214-3p overexpression or FRK silencing. Results: miR-214-3p was markedly upregulated in TNBC cells (MDA-MB-231), while Fyn-related kinase (FRK), a potential tumor suppressor, showed an inverse expression trend. Luciferase reporter assays demonstrated that miR-214-3p functionally targets the 3′-UTR of FRK. Functional analyses revealed that overexpression of miR-214-3p significantly increased cell proliferation, migration, and invasion. Notably, silencing of FRK recapitulated these effects, supporting its role as a functional mediator of miR-214-3p. Conclusions: This study identifies a miR-214–FRK regulatory axis in breast cancer and suggests its contribution to aggressive tumor behavior. Targeting miR-214-3p or modulating FRK activity may represent a potential therapeutic strategy. Full article

Background: Recurrence poses a major challenge in epithelial ovarian cancer (EOC), often occurring despite optimal first-line therapy. Dormant cancer cells are believed to play a key role, yet the mechanisms driving their reactivation remain unclear. This study examined whether exosomes released by normal peritoneal mesothelial cells (PMCs) and fibroblasts (PFBs) undergoing iatrogenic senescence after carboplatin and paclitaxel exposure contribute to EOC recurrence. Methods and Results: Senescent PMCs and PFBs secreted markedly more exosomes, identified by CD9, CD63, and CD81, compared with young cells. Exosomes from both cell types more effectively reactivated dormant EOC cells (pEOCs, A2780, OVCAR-3, SKOV-3) than non-exosomal medium constituents. Importantly, senescent PMC-derived exosomes most strongly reactivated pEOCs and SKOV-3, whereas those from senescent PFBs exerted greater effects on pEOCs, OVCAR-3, and SKOV-3. Kinetic studies of exosome internalization revealed that this process was generally more efficient in the presence of exosomes derived from senescent cells compared with those from young donor cells. Compositional analysis revealed distinct profiles between young and senescent exosomes compared in two variants: young PMCs/senescent PMCs and young PFBs/senescent PFBS. Senescent PMC exosomes displayed reduced miR-210-3p, miR-409-3p, and miR-421, alongside elevated MMP1, MMP3, and VEGF, while senescent PFB exosomes showed increased amphiregulin and osteopontin but lower MMP1, MMP3, TIMP1, bFGF, VEGF, and HGF. Functionally, senescent PMC exosomes enhanced pEOC migration, invasion, and spheroid formation, and induced the expression of CCL11 and ABCB1. Senescent PFB exosomes promoted migration and upregulated CCL11, TGF-β1, BIRC5, and CHEK1. Conclusions: These findings suggest that therapy-induced senescence in peritoneal cells may contribute to EOC recurrence by reactivating dormant tumor cells through exosomal signaling. Full article

Background: Foster adolescents face elevated socioemotional risk, yet the joint and differential contributions of family adversity, attachment insecurity, and relational trauma to distinct adjustment domains remain poorly understood. The present study aimed to examine their joint, incremental, and differential contribution to emotional regulation difficulties and social competence. Methods: Forty-six adolescents (12–17 years; 63% female) in residential care in Uruguay completed self-report measures of family problems, attachment dimensions (anxiety, avoidance, socioemotional functioning), and relational trauma (SENA, CAA-R, CaMir-R). Hierarchical multiple regression examined their sequential prediction of emotional regulation difficulties and social competence. Results: Emotional regulation difficulties were explained by family problems, avoidant attachment, and relational trauma, whereas social competence was explained by anxious attachment and socioemotional attachment functioning. Final models explained 49% and 47% of variance, respectively. Discussion: This differential predictive pattern aligns with theoretical distinctions between deactivating and hyperactivating attachment strategies. Relational trauma’s specific contribution to regulatory, but not social, functioning supports neurobiologically grounded models of complex trauma. Conclusions: Findings suggest that emotional regulation difficulties were more closely associated with family problems, avoidant attachment, and relational trauma, whereas social competence was more strongly linked to anxious attachment and socioemotional attachment functioning. These results support differentiated, attachment-informed, and trauma-sensitive approaches in residential care settings. Full article

Acute myocardial infarction (AMI) causes high mortality, with cardiomyocyte apoptosis playing a critical role. Although circular RNAs modulate cardiac disorders, related mechanisms remain unclear. Here, we identify circRERE as a previously unrecognized pro-apoptotic regulator under ischemic stress. circRERE is markedly upregulated in ischemic myocardium and promotes apoptosis by sponging miR-27a-3p to elevate Caspase9. Using epigallocatechin gallate-primed exosomes (EGCG-primed exosomes, Exo^EGCG) as a tool to modulate circRERE, we found that Exo^EGCG significantly reduced circRERE levels, restored miR-27a-3p activity, and suppressed Caspase9. Gain- and loss-of-function tests confirmed that circRERE mediates Exo^EGCG-derived protection. Collectively, circRERE represents a novel and actionable target for AMI, with Exo^EGCG serving as an effective delivery platform. Full article

This study presents a comparative evaluation of multiple-approach optical spectroscopic sensor—Laser-Induced Breakdown Spectroscopy (LIBS), Mid-Infrared Spectroscopic sensing (MIRS), and Hyperspectral Imaging (HSI)-based sensors operating in the Visible–Near-Infrared (VNIR) and Short-Wave Infrared (SWIR) ranges—for the quantitative detection of calcium carbonate (CaCO₃) in pelletized CaCO₃-CaO mixtures. The objective was to assess and compare the sensing performance of these optical sensor platforms for carbonate quantification. Each spectroscopic sensor dataset was processed using chemometric calibration methods, including Partial Least Squares Regression (PLSR), to ensure robust and reproducible quantitative predictions. Although the samples consisted of binary CaCO₃-CaO mixtures, the sensing task focused exclusively on CaCO₃ content. Results indicate that LIBS, MIRS, and HSI-SWIR-based sensing approaches achieved comparable quantitative performance, with LIBS providing the highest prediction accuracy. In contrast, the HSI-VNIR sensor configuration demonstrated lower predictive capability relative to the other optical sensing modalities. These findings highlight the potential and limitations of different optical sensor technologies for carbonate detection in heterogeneous mineral systems. Full article

Our previous work demonstrated that bovine milk-derived extracellular vesicles (mEVs) could alleviate the inflammatory response of mice colitis, along with hundreds of differentially expressed (DE) mRNAs. This study further analyzed the profiles of non-coding RNAs (ncRNAs) and explored the correlation with DE mRNAs by constructing ceRNA networks. Six-week-old male C57BL/6 mice were fed either a control diet or a diet added with mEVs for 30 days. Then the mice were given dextran sulphate sodium in drinking water for 7 days to induce colitis. A total of 40 miRNAs, 541 lncRNAs and 643 circRNAs exhibited changes in mEVs pretreatment group. Among these DE miRNAs, mEVs pretreatment significantly increased the expressions of miR-122, miR-147, miR-210, miR-1224, miR-148a, and miR-212, which might participate in the inflammatory response of the colitis models. The expression of Tug1 increased after mEVs pretreatment, while Snhg5 and H19 decreased, which might be involved in intestinal barrier restoration. Functional analysis of the DE ncRNAs suggested mEVs might exert protective effects not only through modulation of inflammatory responses but also by enhancing intestinal stem cell function and epithelial regeneration, which were mainly regulated by Wnt and Hippo signaling pathways according to the ceRNA networks. Full article

Vascular dementia (VaD) is a leading cause of cognitive decline and arises from heterogeneous cerebrovascular pathologies, most commonly cerebral small vessel disease and chronic cerebral hypoperfusion. Microglia, the brain’s resident immune cells, exert a dual, stage-dependent influence during VaD progression, initially supporting neuroprotection through debris clearance and tissue repair, but later contributing to chronic neuroinflammation, synaptic loss, and white matter injury. Emerging evidence suggests that multiple molecular pathways, including purinergic receptors, Toll-like receptors and inflammasome cascades, complement-mediated synaptic pruning, and homeostatic and metabolic regulators, such as TREM2 (triggering receptor expressed on myeloid cells 2) and CSF1R (colony-stimulating factor 1 receptor), govern microglial functional transitions. Furthermore, post-transcriptional regulation by microRNAs (e.g., miR-30 family, miR-124, miR-146a, and miR-155) modulates these phenotypes, offering potential biomarkers and therapeutic targets. Understanding these interconnected molecular and epigenetic networks provides a framework for reprogramming microglia from pro-inflammatory to reparative states, thereby providing a mechanistic basis for precision interventions to preserve neurovascular integrity and mitigate cognitive impairment in VaD. Full article

Minimally invasive surgery (MIS) has transformed modern surgical operations by reducing pain, trauma, scarring and recovery time for the patient. However, precision, stability and accuracy continue to limit surgical performance. Robots can exhibit better precision and stability than humans and have the potential to improve MIS results. This work presents the design and development of a patented 3R1T parallel robot for MIS. The mechanism incorporates a coaxial spherical parallel architecture enabling three rotational degrees of freedom, combined with a remotely actuated translational fourth degree of freedom, therefore reducing the weight of the moving structure, decreasing inertial forces and increasing the system accuracy. The kinematic design is analyzed to achieve the required workspace, motor torque requirements are calculated, and a control system with integrated inverse kinematics is developed. A prototype was manufactured, and preliminary experiments were conducted to evaluate the orientation repeatability of the robot. Results demonstrated a repeatability of ±22.86 μm, commensurate with typical MIS constraints. This suggests that the proposed robot offers potential improvements in precision and control for minimally invasive surgical procedures, over traditional manual methods. Full article

High-quality genomic DNA extraction remains a major bottleneck for fungal genomics, particularly for worldwide aerobic and non-photosynthetic mushroom species that rely on their rigid cell walls, interference between metabolites, polysaccharides, etc., and complex genomes. This study systematically compares five DNA extraction protocols involving four distinct sample preparation procedures (fresh (A), filtered (B), frozen (C) and cryogenic mycelium (D)) across mycelial cultures of eight Tunisian fungal strains representing Ascomycota and Basidiomycota to identify the optimal combination for genomic DNA extraction from mycelium. The eight phylogenetically diverse fungal species were analyzed using short-read (MiSeq and NextSeq550) and/or long-read (MinION Mk1C) sequencing technologies, giving a depth coverage between 3.7× and 83×. The generation and quality of the assemblies were assessed within the Galaxy platform, which revealed a gap percentage of 0–0.509%. Taxonomic characterization and phylogenetic inference were performed with SANGER technology using the Internal Transcribed Spacer (ITS) and D1/D2 region of the 26S rRNA gene, assigning the species to our eight different strains: Clitopilus baronii (BS6), Porostereum spadiceum (BS200), Trametes versicolor (BS22-9), Schizophyllum commune (BS23-13), Gloeophyllum abietinum (BS23-14), Irpex laceratus (BS100), Trichoderma asperellum (GC9) and Trichoderma harzianum (S3). The optimized DNeasy Plant Pro Kit protocol with cryogenic biomass treatment presents a safe and cost-effective method for fungal genome sequencing and taxonomic resolution. This integrated comparative evaluation of extraction for sequencing identifies an optimal Qiagen-based extraction strategy combined with cryogenic treatment for eight diverse Tunisian fungal species, guiding method selection based on specific cell wall characteristics rather than proposing a universal protocol limited by unequal replication and strain numbers. Full article

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited targeted treatment options. The urokinase plasminogen activator receptor (uPAR) contributes to tumor aggressiveness and may be regulated by microRNAs such as miR-221. This study aimed to evaluate the prognostic relevance of uPAR mRNA and miR-221 expression in TNBC. Methods: uPAR mRNA and miR-221 expression levels were quantified by real-time PCR in tumor tissues from 101 patients with TNBC. Associations with clinicopathological parameters and disease-free survival (DFS) were analyzed using univariate and multivariable Cox regression models. In silico analyses of publicly available datasets were performed for validation and, in addition, for further miR-221 target prediction. Results: In both univariate and multivariable analyses, high uPAR mRNA expression was associated with shorter DFS, whereas, in contrast, elevated miR-221 expression correlated with improved DFS. No inverse correlation between uPAR and miR-221 expression was observed, making a direct regulatory miR-221/uPAR axis in TNBC unlikely. Still, combined analysis revealed a pronounced additive prognostic effect, with high uPAR and low miR-221 expression identifying patients with the poorest DFS. These findings were supported by in silico analysis with publicly available patient data. Finally, other potential miR-221 targets were identified by applying in silico target prediction. Conclusions: uPAR and miR-221 represent independent prognostic markers in TNBC. Their combined expression provides additional prognostic value for disease-free survival and supports their potential relevance as biomarkers and therapeutic targets in TNBC. Full article