Search Results (4,190)

Helper component-proteinase (HC-Pro), encoded by tobacco vein banding mosaic virus (TVBMV), can cause various viral symptoms and even abortion. HC-Pro counteracts host-mediated inhibition by interfering with the accumulation of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, it is unclear whether the abortion phenotype of transgenic plants expressing HC-Pro is related to the abnormal expression of TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING cell factors (TCPs), which are involved in regulating fertility. In this study, the molecular mechanisms through which HC-Pro causes various sterile phenotypes in plants were investigated. Reverse transcription–quantitative polymerase chain reaction (RT–qPCR) and Northern blotting revealed that in HC-Pro transgenic plants, the expression levels of TCP4 and TCP24 significantly increased. The increased expression of TCP4 further upregulated LIPOXYGENASE2 (LOX2), a gene encoding a key enzyme in the synthesis of jasmonic acid (JA) precursors. Further studies confirmed that the aberrant expression of TCP3, TCP4 and TCP24 blocks the elongation of petals and anthers and that the aberrant expression of TCP4 and TCP24 blocks the release of pollen. This study demonstrated that HC-Pro affects the expression levels of the miR319-targeted genes TCP2, TCP3, TCP4, TCP10 and TCP24, thereby affecting the normal development of floral organs and resulting in plant abortion. Both tobacco and Arabidopsis thaliana were used as model systems in this study on virus-mediated fertility, which provides important information for understanding how viral pathogenicity affects the regulation of fertility in crops. Full article

Background: Early diagnosis of lung cancer requires lung nodule biopsies, which can lead to severe complications. This study aimed to identify optimized panels of exosomal microRNAs (miRNAs) for non-invasive diagnosis of early-stage non-small cell lung cancer (NSCLC). Materials and Methods: This study comprised four phases: discovery, validation, optimization, and confirmation. In the discovery phase, next-generation sequencing profiled 2656 exosomal miRNAs in serum samples (n = 76) from patients with benign lung nodules and stage-specific NSCLC. The validation phase used qPCR to analyze selected miRNAs in serum samples (n = 75). The optimization phase employed a self-devised diagnostic platform, the “up-down ratio (UDR),” to identify miRNA panels. The confirmation phase involved miRNA–target gene interaction and enrichment analyses. Results: The discovery phase identified 15 candidate miRNAs, of which six were validated by qPCR: miR-1976, miR-150-5p, miR-301b-3p, miR-369-3p, miR-497-5p, and miR-610. UDR platform identified a panel of four miRNAs optimized for early detection of NSCLC with ROC over 0.93. Bioinformatics analysis revealed 20 target genes, with VEGFA, BCL2, and PTEN showing strong interactions with the miRNAs, particularly with miR-150-5p, miR-205-5p, miR-1976, miR-301b-3p, and miR-497-5p. Conclusions: This four-phase study suggests that exosomal miRNA panels have potential diagnostic value for early-stage lung cancer. The UDR platform enabled the selection of a four-miRNA panel (miR-150-5p, miR-301b-3p, miR-369-3p, and miR-497-5p), with bioinformatics analyses providing supportive evidence. Full article

Background/Objectives: Aseptic loosening (AL) is among the most common causes of late failure following total hip arthroplasty (THA), often necessitating complex revision surgery. Current diagnostic tools, mainly based on clinical and radiological findings, are primarily able to identify advanced changes of periprosthetic osteolysis (PPOL). Therefore, early detection of AL remains a challenge. Circulating microRNAs (miRNAs) have emerged as promising, minimally invasive biomarkers in musculoskeletal disorders. This study investigates the expression of inflammation-related miRNAs let-7i-5p, let-7e-5p, miR-15a-5p, miR-30a-3p and miR-130a-3p in patients with confirmed AL after THA to evaluate their potential role in AL. Methods: AL patients undergoing revision were compared with asymptomatic post-THA individuals and controls with degenerative osteoarthritis. Preoperative, peripheral blood samples were collected; total RNA was extracted; and quantitative real-time PCR (qRT-PCR) was performed to quantify miRNA expression. The relative expression of miRNAs was calculated using the 2–ΔΔCt method after proper normalization of Ct values. Statistical analysis assessed differences between groups. Results: The under investigation miRNAs exhibited distinct expression patterns. Several targets demonstrated significant downregulation in AL patients, suggesting a potential link to inflammatory and osteolytic pathways like Toll-like receptor 4 (TLR4)–Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, NLRP3 inflammasome activation and macrophage polarization. Conclusions: The observed alterations in circulating miRNAs support their capability as biomarkers for early detection of AL following THA. Larger cohorts could facilitate translation into routine clinical diagnostics. Full article

MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from forty (40) EC patients and twenty (20) healthy controls using qPCR panels. POLE exonuclease domain mutations (P286R, V411L) were genotyped, and subgroup analyses were conducted between POLE-mutated (n = 7) and POLE-wild-type (n = 33) tumors. Bioinformatic analyses included validated miRNA–mRNA interactions, target enrichment, and Gene Ontology (GO) pathway mapping. Comparison of EC versus healthy endometrium revealed 50 significantly dysregulated (∣log₂ (FoldReg)∣ > 1 and BH FDR < 0.05) miRNAs, including up-regulation of the oncogenic hsa-miR-181a-5p, hsa-miR-23a-3p, hsa-miR-200c-3p, and down-regulation of tumor-suppressive let-7 family members. Target enrichment implicated canonical oncogenic regulators such as MYC, TP53, and VEGFA. POLE-mutated tumor analysis demonstrated a miRNA signature, with 19 miRNAs significantly down-regulated, including let-7f-5p and hsa-miR-200b-3p. Findings for the EC versus healthy endometrium comparison were validated against TCGA-UCEC sequencing data which confirmed concordant dysregulation of key miRNAs across platforms. Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC. Full article

Background: Preeclampsia is a complex hypertensive disorder of pregnancy associated with significant maternal and foetal morbidity and mortality. Its pathogenesis involves placental hypoxia, oxidative stress, and impaired trophoblast invasion. Recent evidence highlights the role of microRNAs, particularly microRNA-210 (miR-210), in the molecular disruptions underlying preeclampsia. Aim: This study aims to explore the pathogenic, diagnostic, and therapeutic significance of miR-210 in preeclampsia, with emphasis on its molecular mechanisms, biomarker potential, and prospects as a therapeutic target. Methods: A systematic narrative review was conducted following PRISMA guidelines. A total of 498,184 articles were identified through eight scientific databases, and, after duplicate removal and eligibility screening, 111 peer-reviewed studies published between 2015 and 2025 were included in the final analysis. The selected literature focused on miR-210’s expression in placental tissue and maternal circulation, its molecular targets, and its clinical relevance. Results: miR-210 is consistently upregulated in preeclamptic placentas and maternal plasma. It contributes to shallow trophoblast invasion, impaired angiogenesis, mitochondrial dysfunction, and the activation of a hypoxia-induced HIF-1α feedback loop. These mechanisms are central to the disease’s pathophysiology. Clinically, miR-210 demonstrates high stability in circulation and early detectability, making it a promising diagnostic and prognostic biomarker. Experimental models have also demonstrated the therapeutic potential of miR-210 inhibition using antisense oligonucleotides or HIF-1α modulators. Conclusions: miR-210 is both a marker and mediator of preeclampsia. Its integration into diagnostic protocols and therapeutic strategies, alongside clinical validation and standardisation, may enhance early detection and personalised care in high-risk pregnancies. Full article

Nowadays, nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disorder worldwide. From the clinical point of view, it evolves from steatosis to nonalcoholic steatohepatitis, which can lead to cirrhosis and finally to hepatocellular carcinoma. The mechanisms involved in its progression to more pathological stages and NAFLD pathogenesis are not completely understood. The research concerning NAFLD has become urgent and important because the age of NAFLD diagnosis is progressively decreasing, and its relationship with cancer risk is already well known. Because NAFLD ultimately leads to disability and imposes a major socioeconomic burden, timely diagnosis and effective treatment of NAFLD is particularly important. In the development of NAFLD, noncoding RNAs (ncRNAs) represented by microRNAs, long noncoding RNAs, circular RNAs, and piRNAs are epigenetic factors that play important regulatory roles. In the current review, we present updated information regarding the role of miRNAs, lncRNAs, circRNAs, and piRNAs, aiming to develop a good understanding of their regulatory functions in hepatic metabolism and concerning their potential use as biomarkers for early NAFLD/NASH diagnosis and as therapeutic targets. Full article

Granulosa cell ferroptosis is a critical factor in follicular atresia and premature ovarian insufficiency (POI). As a regulated form of programmed cell death, ferroptosis is gaining significant attention in reproductive medicine research. MicroRNAs (miRNAs) play a crucial role in regulating key aspects of ferroptosis, including the glutathione-GPX4 pathway, glutamate/cystine transport, and iron and lipid metabolism. The present study demonstrates that miR-26a positively modulates ferroptosis by targeting SLC7A11, a member of the solute carrier family. We found that oocytes and granulosa cells are susceptible to the ferroptosis inducer erastin, and employed RNA sequencing to delineate the miRNA expression profiles during erastin-induced damage and ferroptosis. Notably, miR-26a expression was significantly upregulated in erastin-treated oocytes. Importantly, overexpression of miR-26a promoted ferroptosis in granulosa cells, while its knockdown inhibited this process. Ectopic miR-26a expression suppressed SLC7A11, thereby increasing ferroptosis. Our findings indicate that miR-26a influences ferroptosis by inhibiting glutathione synthesis, reducing cellular antioxidant capacity, and suggesting a potential strategy to enhance reproductive potential. Full article

Background/Objectives: Recently, epigenetic mechanisms have been recognized as crucial in atopic dermatitis development. The emphasis of this research was on expanding existing knowledge about the epigenetic aspects of atopic dermatitis, as well as identifying new molecules that could serve as disease biomarkers. Methods: The research was conducted as a cross-sectional study examining two groups: the group with atopic dermatitis (50 patients) and the control group (50 healthy adults). The serum levels of total immunoglobulin E (IgE) and eosinophil count (Eos%) were performed in routine laboratory analyses, and the detection of microRNAs from peripheral blood was performed using RT-PCR. Results: Analysis of selected miRNA expressions in patients with atopic dermatitis and controls revealed that only the expression and the relative expression of miRNA-146a were statistically significantly higher in patients with atopic dermatitis than in the control group (p = 0.042 and p = 0.021, respectively). There was a weak positive correlation between miRNA-146a expression and the eosinophilia/IgE level (r = 0.22 and r = 0.25, respectively). MiRNA-21, miRNA-29b, miRNA-143 and miRNA-223 were significantly upregulated in patients with higher SCORAD (p < 0.001, p < 0.001, p < 0.001 and p = 0.015, respectively). ROC curve analysis revealed the specificity of miRNA-146a as 82% and the sensitivity as 62%. The area under the ROC curve (AUC) was 0.7, indicating its diagnostic potential. Conclusions: Our findings imply that miRNA-146a might serve as a biomarker of atopic dermatitis, suggesting its relevance in the development of the disease, while miRNA-21, miRNA-29b, miRNA-143 and miRNA-223 may have an impact on disease progression. Our findings provide a preliminary basis that should precede validation through larger, multicentric studies and use in diagnostics, targeted personalized treatments and monitoring of treatment efficacy in atopic dermatitis. Full article

Drought stress severely limits peanut productivity, highlighting the urgent need to understand the molecular mechanisms that underlie drought adaptation. While microRNAs (miRNAs) are known to play essential roles in plant stress responses, their functional contributions in polyploid crops like peanut remain insufficiently explored. This study provides the first integrated transcriptomic analysis of drought-responsive miRNAs in tetraploid peanut (Arachis hypogaea). We performed high-throughput sRNA sequencing on a drought-tolerant cultivar Fenhua 8 under PEG6000-simulated drought stress, identifying 10 conserved drought-responsive miRNAs. Among these, ahy-miR398 and ahy-miR408 were significantly downregulated under drought conditions. Degradome sequencing revealed that ahy-miR398 targets copper chaperones for superoxide dismutase (CCSs), potentially reducing SOD activation and amplifying oxidative stress. In contrast, ahy-miR408 targets laccase 12 (LAC12), P-type ATPase copper transporters (COPAs), and a blue copper protein-like (PCL) gene. These targets are involved in copper homeostasis and the regulation of reactive oxygen species (ROS), suggesting that ahy-miR408 plays a role in oxidative stress management. Functional validation in transgenic Arabidopsis lines overexpressing ahy-miR398 or ahy-miR408 showed significantly reduced drought tolerance, with impaired seed germination, shorter primary roots, and exacerbated growth suppression during water deprivation. Taken together, these findings highlight a novel miRNA-mediated regulatory network in peanut drought adaptation, centered on copper-associated oxidative stress management. This study provides new insights into miRNA-based regulation in polyploid crops and offers potential molecular targets for breeding climate-resilient peanut varieties, especially in arid regions where yield stability is crucial. Full article

Cystic fibrosis (CF) is an inherited genetic disease caused by dysregulation of the cystic fibrosis transmembrane regulator (CFTR) gene, a chronic hyperinflammatory state and frequently occurring severe bacterial infections of the lungs. Novel protocols for treating CF inflammation are highly needed. Among the most interesting fields of pre-clinical investigation, the use of natural products, including those used in ethnopharmacology, appears to be promising. Examples of natural ethnopharmacological products that should be further investigated as potential anti-inflammatory agents for CF include inhibitors of the Toll-like receptor 4 (TLR4)/Nuclear Factor κB (TLR4/NFκB) pathway, such as parthenolide, curcumin and garlic-related constituents. In addition, “miRNA therapeutics” protocols have been reported as able to dampen the expression of pro-inflammatory genes. These two fields of investigation deserve, in the near future, further experimental efforts. Notably, these two approaches can be combined in order to develop novel strategies to improve the inhibitory activity on the expression of key pro-inflammatory genes activated in cystic fibrosis, including those induced by Pseudomonas aeruginosa infection. Full article

Gene therapy and RNA (ribonucleic acid)-based therapeutic strategies have emerged as promising alternatives to conventional diabetes treatments, significantly expanding the therapeutic landscape using viral and non-viral vectors, and RNA modalities such as mRNA (messenger ribonucleic acid), siRNA (small interfering ribonucleic acid) and miRNA (micro ribonucleic acid). Recent advancements in these fields have led to notable preclinical successes and ongoing clinical trials, yet they are accompanied by debates over safety, efficacy and ethical considerations that underscore the complexity of clinical translation. This review offers a comprehensive analysis of the underlying mechanisms by which these treatments target diabetes, critically evaluating the fundamental concepts and mechanistic insights that form their basis, while highlighting current research gaps, such as the challenges in long-term stability and efficient delivery of RNA-based therapies, and potential adverse effects associated with gene therapy techniques. By synthesizing diverse perspectives and controversies, the review outlines future directions and interdisciplinary approaches aimed at overcoming existing hurdles, ultimately setting the stage for innovative, personalized diabetes management and addressing the broader clinical and regulatory implications of these emerging therapeutic strategies. Full article

Bats are natural reservoirs for diverse viruses, yet they rarely develop disease, suggesting unique antiviral adaptations. In this study, we performed a comprehensive genome-wide analysis in the common vampire bat (Desmodus rotundus), integrating comparative genomics, functional annotation, microRNA (miRNA) discovery, target prediction, and network-based analyses. Comparative genomic analysis revealed that Phyllostomus discolor exhibits the highest protein homology (97.4%) with D. rotundus. Alignment of interferon regulatory factors (IRFs) indicated strong conservation of IRF1, IRF5, and IRF8, while IRF4 and IRF7 showed divergence, reflecting bat-specific modulation of interferon signaling. Functional annotation of previously uncharacterized proteins identified immune-related elements, including toll-like receptor 4, syncytin-1, and endogenous retroviral sequences, highlighting the integration of viral components into host immunity. We further identified 19 novel miRNAs in D. rotundus, with high-confidence target genes such as SOD2, TRIM28, and FGFR1 involved in antiviral defense, apoptosis regulation, and oxidative stress response. Functional enrichment analyses revealed processes associated with wound healing, apoptosis suppression, infection response, and longevity. Network entropy analysis highlighted central regulatory hubs, including MYC, BCL2, and KIF1B, influencing cell cycle, survival, and immune balance. Collectively, these results demonstrate that D. rotundus employs an integrated regulatory network combining conserved immune factors, lineage-specific gene divergence, and miRNA-mediated fine-tuning to achieve viral tolerance without pathology. This study expands our understanding of bat antiviral biology and provides candidate molecular targets for future functional and translational research. Full article

Leishmania major is a unicellular protozoan that causes cutaneous leishmaniasis in mammals and is mainly transmitted by the sand fly Phlebotomus papatasi. However, the contribution of microRNAs (miRNAs) and protein-coding genes to its pathogenic mechanisms remains largely unexplored. In this study, we systematically analyzed miRNAs and protein-coding genes in L. major, its insect vector, and mammalian hosts. Comparative genomic analysis revealed 2963 conserved proteins shared among the three groups, highlighting a core set of proteins across protozoa, vectors, and hosts. Among mammals, human proteins exhibited the highest homology with L. major, while P. papatasi displayed the lowest proportion of homologs. Functional annotation of 94 hypothetical proteins identified 27 infection-related proteins, including 24 protein kinases and three tyrosine phosphatases, which may represent novel therapeutic targets. In addition, an EST-based approach identified 29 novel miRNAs in L. major. Phylogenetic analysis indicated that these miRNAs diverged into two distinct evolutionary branches, and homology analysis revealed that seven miRNAs were absent in all mammalian species. For example, miR-10117-3p was detected only in nematode Heligosmoides polygyrus. Furthermore, miRNA-gene interaction network analysis highlighted four key genes potentially involved in L. major infection. Collectively, our findings expand current knowledge of protozoan virulence by identifying novel miRNAs and infection-related proteins and provide promising candidates for future drug development against leishmaniasis. Full article

The bidirectional relationship between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) represents a critical intersection in metabolic medicine. Therefore, the present review examines the most recent data regarding molecular mechanisms linking OSA and T2DM, analyzing key biomarkers including hypoxia-inducible factors (HIF 1α), inflammatory mediators, adipokines, microRNAs, hormones, and neuropeptides that serve as both diagnostic indicators and potential therapeutic targets. Key molecular findings from the scientific literature report elevated HIF-1α promoting insulin resistance, decreased SIRT1 levels, dysregulated microRNA-181a and microRNA-199a, increased inflammatory cytokines (TNF-α, IL-6, CRP), and altered adipokine profiles with reduced adiponectin and elevated leptin and resistin. Current clinical evidence reveals significant therapeutic potential for modern antidiabetic medications in the management of OSA. GLP-1 receptor agonists, particularly tirzepatide, received FDA approval as the first medication for moderate-to-severe OSA in obese adults, showing a 55–63% AHI reduction. SGLT2 inhibitors also demonstrate promising results through weight loss and cardiovascular protection mechanisms. This integrated approach represents the evolution toward comprehensive OSA management beyond traditional mechanical ventilation strategies. Future research should focus on developing personalized treatment algorithms based on individual molecular biomarker profiles, investigating combination therapies, and exploring novel targets, including chronotherapy agents. Full article

Background/Objectives: Oocyte maturation is a process involving both nuclear and cytoplasmic development regulated by epigenetic changes in gene expression. Cyclin-B3 (CCNB3) and cyclin-A2 (CCNA2) genes are thought to be involved in oocyte maturation; however, the expression profiles and key function in Metaphase-I (MI) and Metaphase-II (MII) phases have yet to be fully elucidated. Small non-coding RNA sequences are involved in epigenetic regulation of specific transcriptional targets, whereas microRNAs (miRNAs) participate in the post-transcriptional and translational repression of target genes. This study examined the expression levels of CCNB3, CCNA2, and their associated miRNAs (miR-17, miR-106b, miR-190a, miR-1275) in cumulus oophorous complex (COC) cells derived from MI and MII oocytes of NOR and DOR IVF cases, with particular emphasis on elucidating their functions during the transition from MI to MII stage. Methods: Follicular fluid containing cumulus–oocyte complex (COC) cells obtained from oocytes of 120 cases in each group NOR MI (n = 30), NOR MII (n = 30), DOR MI (n = 30), and DOR MII (n = 30) who were admitted to the Istanbul Bahçeci Health Group Assisted Reproductive Treatment Center. Following total RNA isolation from COC cells, the gene and protein expression levels of CCNB3 and CCNA2, along with the expression of miR-17, miR-106b, miR-190a, and miR-1275, were assessed using (qPCR-based assay) and immunohistochemistry (IHC). To investigate the functional roles of COC cell populations, morphological analysis was performed using H&E staining. Additionally, metadata of the cases, including age, number of oocytes, fertilization, and embryonic development rates, were evaluated. Results: The expressions of miR-17 and miR-1275 were significantly elevated in both NOR MI and DOR MI groups compared to their respective NOR MII and DOR MII groups (p < 0.05). Additionally, miR-106b levels were higher in the NOR MII group relative to NOR MI (p < 0.05), while an increase was also observed in DOR MI compared to DOR MII (p < 0.05). No difference was observed in miR-190a expression between the NOR and DOR (p > 0.05). Based on the results of H and E staining, the NOR MI, NOR MII, DOR MI, and DOR MII groups exhibited distinct variations in cellular morphology, nuclear characteristics, cytoplasmic volume, and cell density. Conclusions: CCNB3 is predicted to be a potential candidate for determining MI between the NOR and DOR cases. On the other hand, only for the NOR MII cases could CCNA2 provide evidence of oocyte maturation. Moreover, we determined the relationship between related genes and miRNAs which target CCNA2 and CCNB3. Genetic and protein expression analysis across diverse molecular pathways and miRNAs yielded comprehensive preliminary data regarding the developmental stages of oocytes at the MI and MII phases, and their fertilization potential following maturation shows potential and warrants prospective validation with clinical performance evaluation. Full article