Search Results (8,474)

Spinal cord injury (SCI) results in a cascade of primary and secondary damage, with apoptosis being a prominent cause of neuronal cell death. The X-linked inhibitor of apoptosis (XIAP) plays a critical role in inhibiting apoptosis, but its expression is reduced following SCI, contributing to increased neuronal vulnerability. This study investigates the regulatory role of miR-199a-5p on XIAP expression in the context of SCI. Using bioinformatic tools, luciferase reporter assays, and in vitro and in vivo models of SCI, we identified miR-199a-5p as a post-transcriptional regulator of XIAP. Overexpression of miR-199a-5p significantly reduced XIAP protein levels, although no changes were observed at the mRNA level, suggesting translational repression. In vivo, miR-199a-5p expression was upregulated at 3 and 7 days post-injury, while XIAP expression inversely decreased in both neurons and oligodendrocytes, being particularly significant in the latter at 7 dpi. These findings suggest that miR-199a-5p contributes to the downregulation of XIAP and may exacerbate neuronal apoptosis after SCI. Targeting miR-199a-5p could offer a potential therapeutic strategy to modulate XIAP levels and reduce apoptotic cell death in SCI. Full article

High-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment options and a poor prognosis. Epigenetic factors, such as microRNAs (miRNAs) and DNA methylation, play pivotal roles in cancer progression, yet their specific contributions to HGSOC remain insufficiently understood. In this study, we performed comprehensive high-throughput analyses to identify dysregulated miRNAs in HGSOC and investigate their epigenetic regulation. Analysis of tissue samples from advanced-stage HGSOC patients revealed 20 differentially expressed miRNAs, 11 of which were corroborated via RT-qPCR in patient samples and cancer cell lines. Among these, miR-145-3p was consistently downregulated post-neoadjuvant therapy and was able to distinguish tumoural from control tissues. Further investigation confirmed that DNA methylation controls MIR145 expression. Functional assays showed that overexpression of miR-145-3p significantly reduced cell migration and induced G0/G1 cell cycle arrest by modulating the cyclin D1-CDK4/6 pathway. These findings suggest that miR-145-3p downregulation enhances cell proliferation and motility in HGSOC, implicating its restoration as a potential therapeutic target focused on G1/S phase regulation in the treatment of HGSOC. Full article

N-methyl-n’-nitroso-n’-nitroso guanidine (MNNG) can induce esophageal squamous cell carcinoma (ESCC), and microRNAs are associated with the development of ESCC and may serve as potential tumor prognostic markers. Thus, the aim of this study was to evaluate the potential function of miR-101-3p in MNNG-induced ESCC. An investigation of risk factors in patients with ESCC was carried out and the concentration of nine nitrosamines in urine samples was detected by the SPE-GC-MS technique. Then, we performed cancer tissue gene sequencing analysis, and RT-qPCR verified the expression level of miR-101-3p. Subsequently, the relationship between miR-101-3p potential target genes and the ESCC patients’ prognosis was predicted. Finally, we investigated the function of miR-101-3p in MNNG-induced ESCC pathogenesis and the regulatory mechanism of the signaling pathway by in vivo and in vitro experiments. The results revealed that high dietary nitrosamine levels are high-risk factors for ESCC. MiR-101-3p is down-regulated in ESCC tissues and cells, and its potential target genes are enriched in cell migration and cancer-related pathways. MiR-101-3p target genes include AXIN1, CK1, and GSK3, which are involved in the regulation of the Wnt signaling pathway. MiR-101-3p overexpression promotes apoptosis and inhibits the proliferation and migration of Eca109 cells. The Wnt pathway is activated after subchronic exposure to MNNG, and the Wnt pathway is inhibited by the overexpression of miR-101-3p in Eca109 cells. Down-regulated miR-101-3p may exert tumor suppressive effects by regulating the Wnt pathway and may be a useful biomarker for predicting ESCC progression. Full article

Despite advances in treatment, prostate cancer remains a leading cause of cancer-related deaths among men, highlighting the urgent need for innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulatory molecules in cancer biology. In this research, we investigated the tumor-suppressive role of miR-5100 in PCa and its underlying molecular mechanism. By using RT-qPCR, we observed lower miR-5100 expression in PCa cell lines than in benign prostate cells. Functional assays demonstrated that miR-5100 overexpression significantly suppressed PCa cell proliferation, migration, and invasion. By using RNA-sequencing, we identified 446 down-regulated and 806 upregulated candidate miR-5100 target genes overrepresenting cell cycle terms. Mechanistically, E2F7 was confirmed as a direct target of miR-5100 using the reporter gene assay and RIP assay. By conducting flow cytometry analysis, cell cycle progression was blocked at the S phase. E2F7 overexpression partially mitigated the suppressive impact of miR-5100 in PCa cells. In conclusion, miR-5100 is a tumor suppressor in PCa by blocking cell cycle and targeting E2F7. Full article

microRNAs (miRNAs) influence many biological processes at the post-transcriptional level. However, the molecular characterization of miRNAs in the Myzus persicae response to Brassica yellows virus (BrYV) stress remains unclear. In this study, we present the results of miRNA profiling in Myzus persicae under two different treatments: treatment one (raised on turnip plants), and treatment two (raised on Arabidopsis thaliana). A total of 72 known and 113 novel mature miRNAs were identified in both non-viruliferous and viruliferous aphids, under treatment one. In treatment two, 72 known and 112 novel mature miRNAs were identified in BrYV-free aphids; meanwhile, 71 known and 115 novel miRNAs were identified in BrYV-carrying aphids. Moreover, eight upregulated and four downregulated miRNAs were identified in viruliferous aphids under treatment two, whereas only two miRNAs were differentially expressed under treatment one. These results indicated the relative BrYV level could influence miRNA expression in aphids. KEGG enrichment analysis showed the predicted genes targeted by differentially expressed miRNAs were primarily involved in Peroxisome, neuroactive ligand–receptor interaction, and metabolism of xenobiotics by cytochrome P450 pathways. Taken together, these findings reveal the effect of BrYV on miRNAs in Myzus persicae and provide key clues for further studies on the molecular mechanisms of BrYV transmission via aphids. Full article

Background/Objectives: Studies in adults have demonstrated the essential role of microRNAs in developing hypertension and their effect on hypertension sequelae. In this preliminary study, we aimed to investigate the expression of five miRNA particles, miRNA-21, miRNA-27a, miRNA-27b, miRNA-133a, and miRNA-145, in school-aged children with primary hypertension and to examine their correlations with blood pressure and arterial and heart properties. Methods: In 22 hypertensive children (15.1 ± 1.9 years), we measured blood pressure parameters (office, central, and 24 h), the urinary albumin/creatinine ratio, and the pulse wave velocity (PWV) before and after one hour of aerobic exercise. The left ventricular mass index (LVMI) and common carotid artery intima–media thickness (cIMT) were also assessed. The relative miRNA expression was calculated using the 2^−ΔΔCt method with miRNA-16 as an endogenous control and the pre-exercise miRNA expression levels as the control (baseline). Results: We found a statistically significant decrease in both the office and 24 h ambulatory diastolic blood pressure after 1 h of exercise (82.2 ± 8.5 mm Hg versus 78.6 ± 8.8 mm Hg, p = 0.01 and 75.0 ± 8.3 mm Hg versus 73.0 ± 7.4 mm Hg, p = 0.02). The increase in miRNA-133a expression after exercise correlated positively with the LVMI. Furthermore, the rise in miRNA-145 expression after exercise correlated negatively with the systolic and diastolic office and 24 h blood pressure and with markers of arterial damage: 24 h PWV and cIMT. Conclusions: In conclusion, miRNA-133a may be a biomarker of left ventricular hypertrophy in children with elevated blood pressure. Additionally, changes in miRNA-145 expression induced by exercise might reduce the blood pressure after exercise and protect against arterial damage. Both miRNA-133a and miRNA-145 may be involved in epigenetic alterations in children affected by primary hypertension that may contribute to the exacerbation of HMOD. Full article

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism. The genetic defect in WD affects the ATP7B gene, which encodes the ATP7B transmembrane protein, which is essential for maintaining normal copper homeostasis in the body. It is primarily expressed in the liver and acts by incorporating copper into ceruloplasmin (Cp), the major copper transport protein in the blood. In conditions of excess copper, ATP7B transports it to bile for excretion. Mutations in ATP7B lead to impaired ATP7B function, resulting in copper accumulation in hepatocytes leading to their damage. The toxic “free”—unbound to Cp—copper released from hepatocytes then accumulates in various organs, contributing to their damage and clinical manifestations of WD, including hepatic, neurological, hematological, renal, musculoskeletal, ophthalmological, psychiatric, and other effects. While most clinical manifestations of WD correspond to identifiable organic or cellular damage, the pathophysiology underlying its psychiatric manifestations remains less clearly understood. A search for relevant articles was conducted in PubMed/Medline, Science Direct, Scopus, Willy Online Library, and Google Scholar, combining free text and MeSH terms using a wide range of synonyms and related terms, including “Wilson’s disease”, “hepatolenticular degeneration”, “psychiatric manifestations”, “molecular mechanisms”, “pathomechanism”, and others, as well as their combinations. Psychiatric symptoms of WD include cognitive disorders, personality and behavioral disorders, mood disorders, psychosis, and other mental disorders. They are not strictly related to the location of brain damage, therefore, the question arises whether these symptoms are caused by WD or are simply a coincidence or a reaction to the diagnosis of a genetic disease. Hypotheses regarding the etiology of psychiatric symptoms of WD suggest a variety of molecular mechanisms, including copper-induced CNS toxicity, oxidative stress, mitochondrial dysfunction, mitophagy, cuproptosis, ferroptosis, dysregulation of neurotransmission, deficiencies of neurotrophic factors, or immune dysregulation. New studies on the expression of noncoding RNA in WD are beginning to shed light on potential molecular pathways involved in psychiatric symptomatology. However, current evidence is still insufficient to definitively establish the cause of psychiatric symptoms in WD. It is possible that the etiology of psychiatric symptoms varies among individuals, with multiple biological and psychological mechanisms contributing to them simultaneously. Future studies with larger samples and comprehensive analyses are necessary to elucidate the mechanisms underlying the psychiatric manifestations of WD and to optimize diagnostics and therapeutic approaches. Full article

Background/Objectives: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both in vitro and in vivo. Methods: A periodontitis model was induced in Sprague Dawley rats by ligating the mandibular first molars. Sixty rats were divided into four groups: control (C), periodontitis (PD), periodontitis + CLH gel once daily (G1), and periodontitis + CLH gel thrice daily (G3). Clinical, micro-computed tomography (micro-CT), biological, and histological evaluations were performed, focusing on osteoclastogenesis, osteogenesis, and inflammatory cytokine production. The effect of CLH gel on inflammatory responses in RAW264.7 cells was also assessed through co-culture assays under Porphyromonas gingivalis (P. gingivalis) infection, with RNA-sequencing, qPCR, and Western blot analyses to explore underlying mechanisms. Results: CLH gel significantly reduced gingival and systemic inflammation and mitigated bone loss by enhancing the bone volume to tissue volume ratio and trabecular thickness via the RANKL/OPG axis in rats. The G3 group showed marked reductions in osteoclasts and increases in osterix-positive cells compared to other groups. In vitro, CLH gel reduced the inflammatory phenotype of macrophages in the periodontitis microenvironment by modulating Type II interferon (IFN-γ) networks. Conclusions: CLH gel reduced inflammation and bone loss in rat periodontitis, promoting osteogenesis and inhibiting osteoclastogenesis. It also suppressed macrophage inflammation via Type II interferon networks under P. gingivalis stimulation. These findings suggest that CLH gel has potential as an adjunctive therapy for periodontitis. Full article

Osteoarthritis (OA) is a chronic progressive degenerative joint disease that affects a significant portion of the equine population and humans worldwide. Current treatment options for equine OA are limited and incompletely curative. Horses provide an excellent large-animal model for studying human OA. Recent advances in the field of regenerative medicine have led to the exploration of extracellular vesicles (EVs)—cargoes of microRNA, proteins, lipids, and nucleic acids—to evaluate their diagnostic value in terms of disease progression and severity, as well as a potential cell-free therapeutic approach for equine OA. EVs transmit molecular signals that influence various biological processes, including the inflammatory response, apoptosis, proliferation, and cell communication. In the present review, we summarize recent advances in the isolation and identification of EVs, the use of their biologically active components as biomarkers, and the distribution of the gap junction protein connexin 43. Moreover, we highlight the role of mesenchymal stem cell-derived EVs as a potential therapeutic tool for equine musculoskeletal disorders. This review aims to provide a comprehensive overview of the current understanding of the pathogenesis, diagnosis, and treatment strategies for OA. In particular, the roles of EVs as biomarkers in synovial fluid, chondrocytes, and plasma for the early detection of equine OA are discussed. Full article

Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50–5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68–4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83–1.58) or metachronous (Median 1.83, IQR 1.29–3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19–3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = −0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions. Full article

Human milk (HM) is a complex biofluid rich in nutrients and bioactive compounds essential for infant health. Recent advances in omics technologies—such as proteomics, metabolomics, and transcriptomics—have shed light on the influence of HM on bone development and health. This review discusses the impact of various HM components, including proteins, lipids, carbohydrates, and hormones, on bone metabolism and skeletal growth. Proteins like casein and whey promote calcium absorption and osteoblast differentiation, supporting bone mineralization. Long-chain polyunsaturated fatty acids like docosahexaenoic acid (DHA) contribute to bone health by modulating inflammatory pathways and regulating osteoclast activity. Additionally, human milk oligosaccharides (HMOs) act as prebiotics, improving gut health and calcium bioavailability while influencing bone mineralization. Hormones present in HM, such as insulin-like growth factor 1 (IGF-1), leptin, and adiponectin, have been linked to infant growth, body composition, and bone density. Research has shown that higher IGF-1 levels in breast milk are associated with increased weight gain, while leptin and adiponectin influence fat mass and bone metabolism. Emerging studies have also highlighted the role of microRNAs (miRNAs) in regulating key processes like adipogenesis and bone homeostasis. Furthermore, microbiome-focused techniques reveal HM’s role in establishing a balanced infant gut microbiota, indirectly influencing bone development by enhancing nutrient absorption. Although current findings are promising, comprehensive longitudinal studies integrating omics approaches are needed to fully understand the intricate relationships among maternal diet, HM composition, and infant bone health. Bridging these gaps could offer novel dietary strategies to optimize skeletal health during infancy, advancing early-life nutrition science. Full article

Tomato is a widely grown horticultural crop, and its growth process is often affected by high temperatures. Caseinolytic Protease B (ClpB), a homologous protein to heat shock protein 101 (HSP101), plays a vital role in plant heat adaptation and development. In this study, we identified six SlClpB genes in tomatoes, distributed across four chromosomes. Collinearity analysis revealed that the gene pairs SlClpB-2 and SlClpB-3A, as well as SlClpB-3C and SlClpB-12, resulted from segmental duplication events. Phylogenetic and motif analyses showed that ClpB proteins possess highly conserved domains across different species. We used RNA-seq data to analyze the expression patterns of the ClpB family. Among them, SlClpB-3A and SlClpB-12 exhibited increased expression in multiple tissues under heat stress. Specifically, SlClpB-2, SlClpB-3A, and SlClpB-3C were highly expressed in the fruit orange stage and in flower buds under heat treatment, while in seedlings, SlClpB-2 and SlClpB-3A exhibited heat-induced expression. Real-time quantitative fluorescent PCR (qRT-PCR) results showed that the expression of SlClpB-2 and SlClpB-3A was significantly increased under heat stress in the leaves and buds of Ailsa Craig, Micro-Tom, and M82. Overall, our findings provide valuable insights into the regulatory mechanisms of SlClpB genes in response to heat stress. Full article

Benzene, toluene, and xylene (BTX) co-exist in human environments, yet their individual and combined effects on genetic damage at low exposure levels are not fully understood. Additionally, single nucleotide polymorphisms in microRNAs (mirSNPs) might be involved in cancer etiology by affecting the related early health damage. To investigate the influence of BTX exposure, mirSNPs, and their interactions on genetic damage, we conducted a cross-sectional study in 1083 Chinese petrochemical workers, quantifying the BTX cumulative exposure levels and multiple genetic damage biomarkers. Additionally, we genotyped multiple common mirSNPs. Benzene and a BTX mixture were positive associated with the olive tail moment (OTM) and tail DNA% (p < 0.05). Higher levels of toluene and xylene enhanced the association of benzene with genetic damage levels. Genotypes and/or mutant allele counts of miR-4482-related rs11191980, miR-4433-related rs136547, miR-27a-related rs2594716, miR-3130-related rs725980, and miR-3928-related rs878718 might significantly influence genetic damage levels. Stronger effect estimates of benzene/BTX exposure were found in carriers of miR-196a-2-related rs11614913 heterozygotes and of wild homozygotes of miR-1269b-related rs12451747, miR-612-related rs12803915, and miR-4804-related rs266437. Our findings provide further support of the involvement of BTX co-exposure, mirSNPs, and their gene–environment interactions in determining the severity of DNA strand break in a complex manner. Full article

The differentiation/maturation trajectories of different blood cell types stemming from a CD34⁺ common ancestor takes place in different biologically relevant multidimensional spaces. Here, we generated microRNA and cytokine profiles from highly purified populations of hematopoietic progenitors/precursors derived from cord blood hematopoietic stem/progenitor cells. MicroRNA and cytokine landscapes were then analyzed to find their mutual relationships under the hypothesis that the highly variable miRNome corresponds to the ‘force field’ driving the goal of a stable phenotype (here corresponding to the cytokine abundance pattern) typical of each cell kind. The high dimensionality and lack of linearity of the hematopoietic process pushed us to adopt a distance–geometry approach to compare different trajectories, while a complex network analysis was instrumental in revealing the fine structure of microRNA–cytokine relations. Importantly, the approach enabled us to identify a limited number of factors (represented either by microRNAs or cytokines) corresponding to crucial nodes responsible for connecting distinct interaction modules. Subtle changes in ‘master nodes’, keeping the connections between different regulatory networks, may therefore be crucial in influencing hematopoietic differentiation. These findings highlight the extremely interconnected network structures underlying hematopoiesis regulation and identify key factors in the microRNA/cytokine landscape that may be potentially crucial for influencing network stability. Full article

Background/Objectives: Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. Methods: This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. Results: MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others—miR17-5p, miR-193-3p, miR-372, and miR-542-3p—secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting—as do miR-29c and miR-519d-3p—important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. Conclusions: This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications. Full article