Search Results (10,461)

Background/Objectives: IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis leading to renal failure. MicroRNAs have been shown to play an important role in the pathogenesis and clinical course of IgA nephropathy; therefore, they offer the possibility of noninvasive diagnosis of this disease and have some value in predicting disease prognosis. This study aimed to evaluate the plasma levels of miR-148a-3p, miR-425-3p, and miR-20a-5p in patients with IgA nephropathy and their correlation with selected clinical parameters. Methods: This study included 44 patients with IgA nephropathy and 46 control subjects. Results: The results of our study indicated that in patients with IgA nephropathy, the increased plasma levels of miR-148a-3p and miR-425-3p correlated negatively with eGFR values. According to the Haas classification, plasma levels of miR-20a-5p were statistically significantly increased in patients with histopathological changes classified as Stages 3, 4, and 5 compared with patients with histopathological changes classified as Stages 1 and 2. Conclusions: The results of our study suggest the possible involvement of miR-148a-3p, miR-425-3p, and miR-20a-5p in the pathogenesis of IgA nephropathy. Full article

Background: Our research team analyzed the microRNA (miRNA)-197-3p involved in cardioprotection, and we demonstrated that the overexpression of miRNA-197-3p could be linked to a higher risk of cardiac damage. Recent research indicated that miRNA-197-3p inhibits the effector proteins of the anaesthetic preconditioning mechanism of halogenated drugs. In this scenario, we proposed to determine the role of miRNA-197-3p in cardiac injury and its effects on myocardial conditioning under halogenated exposure. Hypothesis: Patients having myocardial revascularization surgery have increased heart damage due to postoperative miRNA-197-3p upregulation. Methods: Human cardiac myocytes (HCMs) were used in an in vitro hypoxia/reperfusion (H/R) model. The miRNA-197-3p-MIMIC was transfected into the HCMs. Three H/R-induced HCM groups were performed: negative MIMIC-control transfected, MIMIC transfected, and non-transfected. Each H/R cell group was exposed to Propofol (P), Sevoflurane (S), or non-exposed. Healthy cell cultures were the control group. ELISA assays were used to assess the Akt1 and p53 cell secretion capacity, and the Next Generation Sequencing assay was used to measure the differential expression of miRNA targets. Results: The secretion capacity of H/R-induced HCMs transfected with the MIMIC was higher under sevoflurane exposure regarding Akt-1 cytokine (I/R + S: 0.80 ± 0.06 ng/mL; I/R + P: 0.45 ± 0.28 ng/mL; p > 0.05), and lower regarding p53 cytokine (I/R + S: 38.62 ± 6.93 ng/mL; I/R + P: 43.34 ± 15.20 ng/mL; p > 0.05) compared to propofol. In addition, a significant gene overexpression of five miRNAs, in the sevoflurane group, was linked to cardioprotection: miRNA-29-3p, 24-3p, 21-3p, 532, and miRNA-335-5p. Conclusions: miRNA-197-3p inhibits the cardioprotection induced by halogenated exposure and can be considered a biomarker of cardiac damage. Additional research is required to validate our findings in other clinical settings. Full article

MicroRNAs (miRNAs) are small regulatory RNAs that are expressed in a tissue-specific manner during the development of plants and animals. The genes of miRNAs have been found to produce the following two products: (i) primary transcripts of these genes (pri-miRNA) are processed to give rise to mature miRNA, and (ii) in some cases, the pri-miRNA molecules can be translated to form small peptides, named as miPEPs. Gene silencing by artificial microRNAs (amiRNAs) is one of the potential crucial methods for the regulation of desired genes to improve horticultural plants. Likewise, external application of chemically synthesized miPEPs may help plants to resist biotic/abiotic stresses and grow faster. These potent and reliable derivatives of miRNA genes can be applied for improving useful traits in crop plants. This review summarizes the progress in research on the artificial gene derivatives involved in regulating plant development, virus and pest diseases, and abiotic stress resistance pathways. We also briefly discuss the molecular mechanisms of relevant target genes for future research on breeding in plants. In general, this review may be useful to researchers who are implementing amiRNA and miPEP for accelerating breeding programs and developmental studies in crop plants. Full article

Exosomes, a subtype of extracellular vehicles (EVs), play a pivotal role in cellular communication and have gained considerable attention in dermatological research. Formed through the inward budding of the endosomal membrane, exosomes facilitate the transfer of proteins, lipids, and nucleic acids, including microRNAs (miRNAs), thereby influencing the behavior and function of recipient cells. These vesicles are secreted by various cell types, including keratinocytes, and are crucial for maintaining skin homeostasis, regulating immune responses, and promoting wound healing. Exosomes have demonstrated therapeutic potential in addressing dermatological conditions such as hair disorders, skin cancers and photoaging through enhanced regeneration and reduced oxidative stress. However, they are also implicated in disease progression, with pathogens utilizing exosome release to evade host immune responses. Recent studies highlight the diverse origins and functions of exosomes, suggesting their promise as innovative therapeutic agents in dermatology. As research continues to elucidate their multifaceted roles, exosomes represent a frontier in understanding intercellular communication and developing novel treatments for skin-related diseases, underscoring their potential impact on both health and clinical applications. This review synthesizes the existing literature on exosome biology and isolation with a focus on their implications in dermatological contexts. Full article

Spinal cord injury (SCI) involves complex pathological processes that often result in significant and long-term neurological deficits. Increasingly, research has identified microRNA-21 (miR-21) as a pivotal regulator in SCI, with studies focusing on its roles in inflammation, apoptosis, and tissue repair. This review synthesizes current findings on miR-21’s involvement in post-injury molecular events, emphasizing its interactions with regulatory targets such as Phosphatase and Tensin Homolog (PTEN) and Programmed Cell Death Protein 4 (PDCD4), as well as its broader effects on inflammatory and apoptotic signaling pathways. Evidence from both in vitro and in vivo studies suggests that modulating miR-21 influences lesion size, cellular dynamics, and functional recovery, highlighting its potential as a therapeutic target for SCI. Nonetheless, the clinical translation of miR-21-based therapies poses significant challenges, including the need to optimize dosages, delivery mechanisms, and long-term safety profiles. Further research is crucial to fully delineate miR-21’s therapeutic potential and determine its feasibility for integration into SCI treatment protocols. This review aims to provide a comprehensive overview of miR-21’s roles in SCI pathology, offering insights into the molecular mechanisms underlying recovery and the emerging potential of miR-21 in SCI management to enhance outcomes and quality of life for affected patients. Full article

Different types of microRNA participate in the post-transcriptional regulation of target genes. The content of several hypoxia-dependent miRNAs in plant cells, including miR775, increases in the conditions of oxygen deficiency. Electrophoretic studies of total RNA samples from the leaves of flooded seedlings of maize (Zea mays L.) revealed the presence of two interfering complexes with miR775 at 12 h of hypoxic incubation. A nucleotide sequence analysis of a sample containing the interfering complex of miR775 with mRNA from maize leaves showed a high degree of homology with the ICL/PEPM_KPHMT lyase family domain. It corresponded to a fragment of fructose-1,6-bisphosphate aldolase mRNA. By real-time PCR, we established the dynamics of the content of transcripts of aldolase isoenzyme genes under hypoxia in maize leaves. A decrease in the transcriptional activity of the aldolase 1 gene (Aldo1) correlated with a high content of miR775 in maize leaf cells. The fraction of extracellular vesicles sedimented at 100,000× g, was enriched with miR775. The accumulation of aldolase 2 (Aldo2) mRNA transcripts under hypoxic conditions indicates its participation in maintaining glycolysis when Aldo1 expression is inhibited. We conclude that an increase in the total content of free miR775 and its participation in the suppression of the Aldo1 gene represents an important mechanism in developing the adaptive reaction of cellular metabolism in response to hypoxia. Full article

Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between HIV-1 infection and changes of the intrinsic cellular miRNA milieu. This interrelationship may direct potential alterations of the host cells’ environment beneficial for the virus or its suppression of replication. Whether this tightly balanced and controlled battle can be exploited therapeutically remains to be further addressed. In this context, the fluoroquinolone antibiotic Enoxacin has been demonstrated as a potent modulator of miRNA processing. Here, we test the hypothesis that this applies also to selected HIV-1-related miRNAs. Methods: We studied the effect of Enoxacin on HIV-1 replication coupled with miRNA qRT-PCR analysis of HIV-1-related miRNAs in CEM-SS and MT-4 T-cells. The effects of miRNA mimic transfections combined with Enoxacin treatment on HIV-1 replication were assessed. Finally, we employed an in vitro DICER1 cleavage assay to study the effects of Enoxacin on a pro-HIV-1 miRNA hsa-miR-132 processing. Results: We established that Enoxacin, but not the structurally similar compound nalidixic acid, exhibits strong anti-HIV-1 effects in the T-cell line CEM-SS, but not MT-4. We provide experimental data that this effect of Enoxacin is partly attributed to the specific downregulation of mature hsa-miR-132-3p, but not other tested pro- or anti-HIV-1 miRNAs, which is likely due to affecting DICER1 processing. Conclusions: Our findings show an anti-retroviral activity of Enoxacin at least in part by downregulation of hsa-miR-132-3p, which may be relevant for future antiviral therapeutic applications by modulation of the RNA interference pathway. Full article

The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms. A key target in this process is the cystine/glutamate transporter (xCT), which is essential for redox balance and ferroptosis resistance. Additionally, p53-induced miR-34c-5p suppresses cancer cell proliferation and drug resistance by modulating Myc, an oncogene further influenced by non-coding RNAs like circular RNA NOTCH1 (CricNOTCH1) and long non-coding RNA MALAT1. However, the exact role of these molecules in ferroptosis remains unclear. To address this, we introduce the first dynamic Boolean model that delineates the influence of these ncRNAs and p53 on ferroptosis, apoptosis, and senescence within the DDR context. Validated through gain- and loss-of-function perturbations, our model closely aligns with experimental observations in cancers such as oral squamous cell carcinoma, nasopharyngeal carcinoma, and osteosarcoma. The model identifies crucial positive feedback loops (CricNOTCH1/miR-34c/Myc, MALAT1/miR-34c/Myc, and Myc/xCT) and highlights the therapeutic potential of using p53 proteoforms and ncRNAs to combat drug resistance and induce cancer cell death. Full article

The immune-modulatory effects of mesenchymal stromal cells (MSCs) are widely used to treat inflammatory disorders, with indoleamine 2,4-dioxygenase-1 (IDO-1) playing a pivotal role in suppressing stimulated T-cell proliferation. Taking that three-dimensional (3D) cultures enhance MSCs’ anti-inflammatory properties compared with two-dimensional (2D) cultures, the differentially expressed miRNAs were examined. Thus, we identified hsa-miR-4662a-5p (miR-4662a) as a key inducer of IDO-1 via its suppression of bridging integrator-1 (BIN-1), a negative regulator of the IDO-1 gene. The IDO-1-inducing potential of miR-4662a was conserved across primary MSCs from various donors and sources but exhibited variability. Notably, iPSC-derived MSCs (iMSCs) demonstrated superior IDO-1 induction and immune-modulatory efficacy compared with their donor-matched primary MSCs. Accordingly, iMSCs expressing miR-4662a (4662a/iMSC) exhibited stronger suppressive effects on T-cell proliferation and more potent suppressive effects on graft-versus-host disease (GVHD), improving survival rates and reducing tissue damage in the liver and gut. Our results point to the therapeutic potential of standardized, off-the-shelf 4662a/iMSC as a robust immune-modulating cell therapy for GVHD. Full article

(1) Background: MicroRNA-129 (miR-129) participates in tumor progression and chemoresistance in various cancer types. In this study, the role of miR-129-3p, the main mature form of miR-129, in tumor progression and chemoradiotherapy resistance in head and neck cancer was evaluated. (2) Methods: RT-PCR, western blotting, cell proliferation assays, cell apoptosis assays, and cell invasion and migration assays were used. (3) Results: In this study, the miR-129-3p overexpression suppressed the proliferation, invasion, and migration of SNU1041, SCC15, and SCC25 human HNSCC cell lines. Additionally, it induced apoptosis and enhanced radiation-/cisplatin-induced apoptosis of SNU1041, SCC15, and SCC25 cells. Therefore, miR-129-3p could suppress tumor progression and enhance chemoradiosensitivity in human HNSCC. Furthermore, miR-129-3p was downregulated in fresh tumor tissues from patients with HNSCC compared with that in the adjacent normal mucosa. In a nude mouse xenograft model with SNU15 cells, the miR-129-3p overexpression significantly decreased tumor growth, as measured by tumor weight and volume. (4) Conclusions: Our study provides evidence that miR-129-3p suppresses tumor progression and chemoradioresistance in HNSCC. This finding may serve as a basis for developing miR-129-3p-based therapeutic strategies. Full article

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune, multisystemic fibrotic disorder. The immune-mediated, inflammatory, and fibrosing intersections of IgG4-RD and systemic sclerosis raised a question about platelets’ role in IgG4-RD. Materials and Methods: By borrowing transcriptomic data from Nakajima et al. (GEO repository, GSE66465) we sought a platelet contribution to the pathogenesis of IgG4-RD. GEO2R and BRB-ArrayTools were used for class comparisons, and WebGestalt for functional enrichment analysis. During the selection of differentially expressed genes (DEGs), the translationally active but significantly low amount of platelet mRNA was specifically considered. The platelet-specific gene signature derived was used for cluster analysis of patient and control groups. Results: When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected. Among these, a molecular signature of 22 platelet-specific genes harbored genes important for leukocyte–platelet aggregate formation (i.e., CLEC1B, GP1BA, ITGA2B, ITGB3, SELP, and TREML1) and extracellular matrix synthesis (i.e., CLU, PF4, PPBP, SPARC, and THBS1). Functional enrichment analysis documented significantly enriched terms related to platelets, including but not limited to “platelet reactivity”, “platelet degranulation”, “platelet aggregation”, and “platelet activation”. During clustering, the 22 gene signatures successfully discriminated IgG4-RD and the control and the IgG4-RD before and after treatment groups. Conclusions: Patients with IgG4-RD apparently display an activated platelet phenotype with a potential contribution to disease immunopathogenesis. If the platelets’ role is validated through further carefully designed research, the therapeutic potentials of selected conventional and/or novel antiplatelet agents remain to be evaluated in patients with IgG4-RD. Transcriptomics and/or proteomics research with platelets should take into account the relatively low amounts of platelet mRNA, miRNA, and protein. Secondary analysis of omics data sets has great potential to reveal new and valuable information. Full article

Extrachromosomal circular DNAs (eccDNAs) has been found to be widespread and functional in various organisms. However, comparative analyses of pre- and post-infection of virus are rarely known. Herein, we investigated the changes in expression patterns of eccDNA following infection with Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) and explore the role of eccDNA in viral infection. Circle-seq was used to analyze eccDNAs in the midgut of BmCPV-infected and BmCPV-uninfected silkworms. A total of 5508 eccDNAs were identified, with sizes varying from 72 bp to 17 kb. Most of eccDNAs are between 100 to 1000 bp in size. EccDNA abundance in BmCPV-infected silkworms was significantly higher than in BmCPV-uninfected silkworms. GO and KEGG analysis of genes carried by eccDNAs reveals that most are involved in microtubule motor activity, phosphatidic acid binding, cAMP signaling pathway, and pancreatic secretion signaling pathways. Several eccDNAs contain sequences of the transcription factor SOX6, sem-2, sp8b, or Foxa2. Association analysis of eccDNA-mRNA/miRNA/circRNA revealed that some highly expressed genes are transcribed from relevant sequences of eccDNA and the transcription of protein coding genes influenced the frequency of eccDNA. BmCPV infection resulted in changes in the expression levels of six miRNAs, but no known miRNAs with altered expression levels due to changes in eccDNA abundance were identified. Moreover, it was found that 1287 and 924 sequences representing back-spliced junctions of circRNAs were shared by the junctions of eccDNAs in the BmCPV-infected and uninfected silkworms, respectively, and some eccDNAs loci were shared by circRNAs on Chromosomes 2, 7, 11, 14, and 24, suggesting some eccDNAs may exert its function by being transcribed into circRNAs. These findings suggest that BmCPV infection alter the expression pattern of eccDNAs, leading to changes in RNA transcription levels, which may play roles in regulating BmCPV replication. In the future, further experiments are needed to verify the association between eccDNA-mRNA/miRNA/circRNA and its function in BmCPV infection. Full article

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers of liver fibrosis and hematological parameters in the course of non-alcoholic fatty liver disease (NAFLD). Methods: Two hundred and seven persons were included in the survey: 97 with NAFLD and 110 healthy controls. Serological concentrations of miR-126-3p, miR-197-3p, and miR-1-3p were measured in all participants. Direct indices of liver fibrosis [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin] together with indirect markers (AAR, APRI, FIB-4 and GPR) were also evaluated. The assessment of hematological parameters concerned: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red blood cell distribution width (RDW), MPV to platelet (PLT) ratio (MPR), RDW to PLT ratio (RPR), neutrophil to lymphocyte (LYM) ratio (NLR), PLT to LYM ratio (PLR) and RDW to LYM ratio (RLR). Additionally, the NAFLD fibrosis score and BARD score were applied. Results: The concentration of miR-126-3p and miR-1-3p was higher, and miR-197-3p was lower in the NAFLD group (p < 0.0001). miR-197-3p correlated notably with hematological indices: negatively with PDW (p < 0.05) and positively with PLR (p < 0.05). Conclusions: Significant correlations between miRNA molecules and hematological markers in the course of NAFLD indicate inflammation as a potential background and create new possibilities for a diagnostic approach. Full article

Prostate cancer, a leading cause of cancer-related mortality among men, often presents challenges in accurate diagnosis and effective monitoring. This systematic review explores the potential of exosomal biomolecules as noninvasive biomarkers for the diagnosis, prognosis, and treatment response of prostate cancer. A thorough systematic literature search through online public databases (Medline via PubMed, Scopus, and Web of science) using structured search terms and screening using predefined eligibility criteria resulted in 137 studies that we analyzed in this systematic review. We evaluated the findings from these clinical studies, revealing that the load of exosomes in the blood and urine of prostate cancer patients, which includes microRNAs (miRNAs), proteins, and lipids, demonstrates disease-specific changes. It also shows that some exosomal markers can differentiate between malignant and benign hyperplasia of the prostate, predict disease aggressiveness, and monitor treatment efficacy. Notably, miRNA emerged as the most frequently studied biomolecule, demonstrating superior diagnostic potential compared to traditional methods like prostate-specific antigen (PSA) testing. The analysis also highlights the pressing need for a standardised analytic approach through multi-centre studies to validate the full potential of exosomal biomarkers for the diagnosis and monitoring of prostate cancer. Full article

Potassium, an essential inorganic cation, is crucial for the growth of oil crops like Brassica napus L. Given the scarcity of potassium in soil, enhancing rapeseed’s potassium utilization efficiency is of significant importance. This study identified 376 potassium utilization genes in the genome of B. napus ZS11 through homologous retrieval, encompassing 7 functional and 12 regulatory gene families. These genes are unevenly distributed across 19 chromosomes, and the proteins encoded by these genes are mainly localized in the cell membrane, vacuoles, and nucleus. Microsynteny analysis highlighted the role of small-scale replication events and allopolyploidization in the expansion of potassium utilization genes, identifying 77 distinct types of cis-acting elements within their promoter regions. The regulatory mechanisms of potassium utilization genes were provided by analyses of transcription factors, miRNA, and protein interaction networks. Under low potassium stress, the potassium utilization genes, particularly those belonging to the KUP and CBL families, demonstrate pronounced co-expression. RNA-seq and RT-qPCR analysis identified the BnaZSHAK5.2 gene, which is a high-affinity potassium ion transporter, playing a crucial role in the stress response to potassium deficiency in B. napus, as its expression is strongly induced by low potassium stress. A functional complementation study demonstrates that the BnaZSHAK5.2 gene could rescue the primary root growth of the Athak5 mutant under low potassium conditions, confirming its role in response to low potassium stress by sustaining root development. Full article