In the published version of this article [1], an overlap discrepancy was identified in some of the slides in Fig. (7). This error was unintentional and occurred during the manuscript preparation stage by the authors. This correction does not affect the study’s quantitative analyses, results, or conclusions. The authors apologize for this error and any inconvenience it may have caused. The original article can be found online at: https://www.eurekaselect.com/article/146623 The authors apologizes for this oversight and any inconvenience caused to the readers.
INTRODUCTION:Overexpression of Epidermal Growth Factor Receptor (EGFR) plays a critical role in the progression and high mortality of Non-Small Cell Lung Cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) demonstrate promising efficacy as first-line therapy, acquired resistance remains a major clinical challenge. Increasing evidence suggests that microRNAs (miRNAs) regulate EGFR signaling pathways and may influence therapeutic response and the development of resistance. METHODS:This study aimed to identify EGFR-targeting microRNAs (miRNAs) and evaluate their binding stability using in silico approaches. Experimentally validated EGFR-targeting miRNAs were retrieved from miRTarBase and subsequently screened using miRDB and TargetScan based on their expression in lung adenocarcinoma cell lines. The secondary structures of miRNA-EGFR duplexes and three-dimensional structures of the miRNA-EGFR complexes were generated using RNAfold and RNAComposer, respectively. Binding affinity was evaluated using HNADOCK molecular docking. Further validation included survival and co-expression analyses using OncomiR and starBase, RNA-Binding Protein (RBP) interaction analysis using POSTAR3, and pathway enrichment analysis using DIANA-miRPath. RESULTS:Three miRNAs-miR-7-5p, miR-133b, and miR-302b-3p were identified as potential regulators of EGFR. Molecular docking analysis demonstrated strong binding affinities, with docking scores of -339.30, -476.76, and -491.18 kcal/mol, respectively. Survival analysis revealed no significant association between the expression of these miRNAs and patient prognosis. In contrast, co-expression analysis demonstrated a significant correlation between miR-133b and EGFR expression. Several upregulated RNA- Binding Proteins (RBPs) that interact with EGFR were identified, suggesting enhanced post-transcriptional regulation that may contribute to the development of EGFR-TKI resistance. Pathway enrichment analysis further identified hsa-miR-7-5p as being significantly associated with EGFR-mediated PI3K-Akt signaling and the NSCLC pathway. DISCUSSION:These findings highlight candidate miRNAs as potential regulators of EGFR signaling and possible biomarkers influencing targeted therapy response. CONCLUSION:Further experimental and clinical validation is required to confirm their therapeutic relevance in EGFR-TKI-resistant lung cancer.
Introduction: Spindle cell soft tissue tumors (STTs) comprise a heterogeneous group of mesenchymal neoplasms characterized by considerable morphological overlap, making accurate diagnosis challenging. Histopathological examination supported by immunohistochemistry (IHC) remains the current diagnostic standard; however, emerging evidence suggests that microRNAs (miRNAs) may provide complementary diagnostic and prognostic biomarkers for these tumors. This study evaluated the clinicopathological spectrum of spindle cell soft tissue tumors and highlights the potential relevance of miRNA-based molecular profiling in improving diagnostic precision. Materials and Methods: A prospective observational study was conducted on 55 surgically resected spindle cell soft tissue tumors received at King George's Medical University, Lucknow. Clinical, radiological, and histopathological findings were systematically evaluated. Tumors were classified according to the WHO classification and graded using the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system where applicable. Morphology-directed immunohistochemistry employing SMA, S-100, desmin, CD34, myogenin, Bcl-2, EMA, β-catenin, CD99, and CD68 was performed to establish lineage differentiation and confirm histopathological diagnoses. Published evidence regarding miRNA dysregulation in major spindle cell tumor subtypes was integrated to provide molecular context for the observed pathological findings. Results: Among the 55 tumors, 50.9% were malignant, 29.1% intermediate, and 20.0% benign, with a mean patient age of 32.5 years. Malignant tumors occurred predominantly in patients older than 40 years and most frequently involved the lower extremities. Synovial sarcoma and rhabdomyosarcoma represented the predominant malignant spindle cell tumors, whereas schwannoma and neurofibroma were the most common benign lesions. Most malignant tumors were deep-seated, measured ≥5 cm, and were classified as FNCLCC grade 3. Immunohistochemistry was indispensable for confirming lineage differentiation in morphologi-cally overlapping lesions. Furthermore, current evidence indicates that subtype-specific miRNA signatures may complement conventional pathology by improving diagnostic accuracy, prognostic assessment, and future therapeutic stratification. Conclusion: Accurate diagnosis of spindle cell soft tissue tumors requires an integrated clinicopathological approach combining histomorphology and immunohistochemistry. The clinicopathological patterns identified in this study provide a valuable framework for future investigations evaluating miRNA expression as diagnostic and prognostic biomarkers in spindle cell soft tissue tumors. Incorporating validated miRNA signatures into routine pathological evaluation may further refine tumor classification and advance precision oncology.
INTRODUCTION:Multiple Sclerosis (MS) involves immune dysfunction and demyelination in the central nervous system. Blood biomarkers can distinguish MS patients and identify early disease. The long non-coding RNA GAS5 regulates cell growth and immune activity. This study examines GAS5 expression in PBMCs of Relapsing-Remitting MS (RRMS) patients and its associated miRNAs in exosomes. MATERIALS AND METHODS:In this study, we constructed the GAS5-miRNAs-mRNAs regulatory network using data from multiple bioinformatics databases. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from Relapsing-Remitting Multiple Sclerosis (RRMS) patients and healthy controls for expression analysis of GAS5 and related miRNAs using qRT-PCR. Additionally, Human Microglial Cells (HMC3) were subjected to oxidative stress, and GAS5/miRNA expression was evaluated in cells and exosomes to explore redox-related regulatory mechanisms. RESULTS:Our findings demonstrated significantly higher GAS5 expression levels in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) compared with healthy controls (P = 0.0121). Receiver Operating Characteristic (ROC) analysis further indicated that GAS5 possesses a moderate ability to discriminate RRMS patients from controls, yielding an Area Under the Curve (AUC) of 0.6498. The in silico analysis revealed that hsa-miR-651-5p emerged as a central component in the regulatory network of GAS5, with its target genes primarily implicated in transcription and apoptosis regulation. Additionally, RUNX1, YY1, GSK3B, FMR1, and KLF2 were identified as entities linked to GAS5. In this regard, our findings indicate a significant association between redox imbalance and the dysregulation of GAS5 and miR-651-5p expression in the HMC3 cell line and its derived exosomes. DISCUSSION:These findings suggest a potential association between redox imbalance and dysregulation of the GAS5/miR-651-5p axis in RRMS. The preferential packaging of miR-651-5p into exosomes under oxidative stress conditions suggests the engagement of redox-responsive regulatory pathways and raises the possibility that exosomal miR-651-5p and GAS5 participate in a coordinated regulatory network contributing to cellular adaptation in RRMS. CONCLUSION:GAS5 can serve as a mitochondria-associated regulatory lncRNA for RRMS, and redox imbalance appears to influence its regulation, highlighting its role in the cellular stress response.
INTRODUCTION:Gliomas, particularly Glioblastoma Multiforme (GBM), remain highly lethal despite surgery, radiotherapy, and chemotherapy, largely due to their infiltrative biology, marked molecular heterogeneity, and the restrictive Blood-Brain Barrier. RNA interference (RNAi)-based therapeutics, including Small Interfering RNA (siRNA) and emerging microRNA (miRNA)-modulating strategies, enable targeted silencing of oncogenic drivers. However, their clinical application is constrained by rapid systemic clearance, nuclease-mediated degradation, off-target effects, and inefficient brain delivery. OBJECTIVE:This review evaluates recent advances in RNA-based precision gene silencing for glioma, with particular focus on siRNA therapeutics, emerging miRNA strategies, nanocarrier-enabled delivery systems, and theranostic integration for imaging-guided therapy. METHOD:A comprehensive literature search (1998-2026) of PubMed, Scopus, and Google Scholar was performed to identify preclinical and early clinical studies addressing glioma pathobiology, RNA interference mechanisms, siRNA targets, nanocarrier platforms, and imaging-guided theranostic systems, with emphasis on orthotopic models, registered clinical trials, and mechanistically well-characterized datasets. RESULTS:Non-viral nanocarriers (lipid nanoparticles, bio-reducible polymers, dendrimer-gold, exosomes) enable siRNA protection, BBB penetration, and knockdown of EGFR, STAT3, BCL-2, VEGF, and GLUT-3 in orthotopic glioma models. Emerging miRNA-based strategies, including anti-miR-21 and miR-100 modulation, showed potential for reversing chemoresistance. Combination therapies with temozolomide/doxorubicin produced greater efficacy than single-agent approaches. Theranostic imaging platforms (PET/MRI/SPECT) enabled real-time monitoring of biodistribution and treatment responses. CONCLUSION:RNA-based theranostic strategies show promising potential for glioma therapy. However, further optimization of delivery systems, improved safety profiles, and successful clinical translation remain necessary.
Colorectal cancer (CRC) ranks among the most frequent and lethal cancers globally, with early detection remaining a significant challenge because of asymptomatic early stages and limitations of current screening methods. This underscores the pressing need for new, non-invasive biomarkers for early CRC detection to enhance patient outcomes. Advancements in the molecular biology of cancer have highlighted the importance of non-coding RNAs (ncRNAs) in the genesis and progression of CRC. Exosomal non-coding RNAs (ncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) have shown promise in this regard. These molecules, carried by small extracellular vesicles known as exosomes, are key players in cell communication and have been associated with the regulation of essential cancer pathways, including cell proliferation, metastasis, and drug resistance. This review discusses the potential of exosomal ncRNAs as innovative biomarkers and therapeutic targets in CRC. This study covers their role in cancer biology, the challenges in their application, and future directions for leveraging these ncRNAs to advance CRC diagnosis and treatment. Exploring exosomal ncRNAs opens new avenues for enhancing CRC management through early detection and targeted therapy, potentially transforming oncology patient care.
INTRODUCTION/OBJECTIVE:MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that modulate cancer-related processes, including cell growth, proliferation, differentiation, and invasion. While numerous oncogenic (oncomiRs) and tumor suppressor (TS) miRNAs have been characterized, structural features distinguishing these groups are not fully understood. This study investigates whether guanine (G) enrichment in precursor miRNA (pre-miRNA) terminal loop (TL) regions across the human miRNome is associated with tumor-suppressive activity in lung cancer. METHODS:We analyzed 955 human pre-miRNA TL region sequences to quantify G residue enrichment. G-rich TL miRNAs were identified using a G-enrichment score, with G-free TL miRNAs as controls. Functional annotations were compiled from 831 published studies. Publicly available transcriptomic and proteomic datasets were analyzed to assess miRNA expression and target regulation in lung adenocarcinoma (LUAD). RESULTS:G-rich TL miRNAs (n=42) exhibited higher TS-to-oncomiR ratios than G-free control miRNAs. The enrichment of TS miRNAs among G-rich TL miRNAs was significantly stronger in lung cancer compared to the pan-cancer background (Breslow-Day test, p = 0.027). miR-139, a TS miRNA with a G-rich TL region, was consistently downregulated in LUAD at all stages, accompanied by increased expression of its validated oncogenic target, CCNB1. DISCUSSION:The association between G-rich TL regions and TS function suggests that TL G content may affect miRNA processing efficiency, stability, and functional activity in lung cancer. The inverse expression patterns of miR-139 and CCNB1 in LUAD are consistent with a potential functional contribution of this structural feature to disease progression. CONCLUSION:G-rich TL architecture is associated with TS miRNA function, particularly in lung cancer. miR-139, a TS miRNA characterized by a G-rich TL region, exemplifies this relationship by targeting the oncogene CCNB1. These findings underscore the potential relevance of TL sequence composition in miRNA-mediated tumor suppression and support its consideration in future research strategies aimed at restoring vulnerable TS miRNAs.
INTRODUCTION:Cervical lymph node metastasis is a well-established determinant of reduced overall survival in patients with Oral Squamous Cell Carcinoma (OSCC). MicroRNA-21 (miR-21), a key oncogenic regulator, has been implicated in tumor progression and metastasis. Given the reported association between miR-21 expression and lymph node involvement, this study aimed to evaluate the relationship between miR-21 expression, lymph node metastasis, and overall survival in OSCC patients. METHODOLOGY:This observational follow-up study included 60 patients with OSCC who had undergone surgical treatment. Expression levels of miR-21 were quantified in both salivary and tumor tissue samples, and histopathologically confirmed lymph node metastasis was recorded as a predictor variable. Patients were followed up through in-person clinical examinations or telephonic communication. Overall survival, measured in months post-surgery, was the primary outcome. Potential confounders, including age, sex, histological grade, and TNM stage, were considered. Kaplan-Meier survival analysis and Hazard Ratio (HR) estimation were performed to evaluate associations. RESULTS:Kaplan-Meier analysis demonstrated a significant reduction in overall survival among patients with positive lymph node metastasis (P ≤ 0.005). Although differences in survival by miR-21 expression were not statistically significant, elevated miR-21 levels were associated with an increased risk of mortality. Hazard ratios ranged from 1.3 to 1.6 for tumor tissue and 1.19 to 1.63 for salivary samples, indicating a higher risk of adverse outcomes in patients with expression levels above the defined cutoff. DISCUSSION:Elevated miR-21 expression was associated with reduced overall survival, although statistical significance was not achieved in survival curve analysis. However, hazard ratio estimates suggest a clinically meaningful increase in mortality risk. The relationship between miR-21 expression and survival appears to be influenced by the presence of cervical lymph node metastasis. CONCLUSION:High miR-21 expression is associated with an increased risk of mortality in OSCC patients, particularly in the presence of lymph node metastasis. These findings support the potential role of miR-21 as a prognostic biomarker in OSCC.
INTRODUCTION:Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Identifying reliable biomarkers for early diagnosis and understanding the underlying molecular mechanisms are critical for improving patient outcomes. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers due to their stability in blood and involvement in various pathophysiological processes. This pilot case-control study aims to perform small RNA sequencing using next-generation sequencing in the plasma of Indian CAD patients to identify differentially expressed miRNAs and evaluate their potential as biomarkers. METHODS:Plasma samples were collected from 30 angiographically verified CAD patients and 30 age-and gender-matched controls with normal coronary arteries. Small RNA libraries were prepared and sequenced using Illumina's NextSeq 2000. Differentially expressed miRNAs were identified using the DESeq2 package, followed by target gene prediction using the miRDB, TargetScan, and miRTarBase databases. Functional enrichment analysis was performed using DAVID. RESULTS:Twelve significantly dysregulated circulating miRNAs were identified in CAD patients. miR-6806-3p, miR-3614-5p, miR-548e-3p, miR-147b-3p, and let-7d-3p demonstrated novel associations with CAD, whereas miR-125a-3p, miR-495-3p, and miR-143-3p were highlighted for their significant roles in regulating key molecular pathways implicated in CAD pathogenesis. DISCUSSION:This study represents the first comprehensive NGS-based analysis of small RNAs in the plasma of Indian CAD patients. The twelve identified circulating miRNAs highlight their intricate roles in CAD pathogenesis by targeting key target genes involved in critical biological pathways. CONCLUSION:The identified miRNAs highlight their potential as diagnostic biomarkers; however, validation in larger and more diverse cohorts is required to confirm their clinical utility.
INTRODUCTION:In different kinds of tumors, miR-195-3p showed converse roles. How-ever, the role of miR-195-3p in lung adenocarcinoma (LUAD) remains unclear. To explore the prognostic role and potential underlying mechanisms of miR-195-3p in LUAD. METHODS:In this study, we analyzed the correlation between the miR-195-3p expression level and clinicopathological features in LUAD based on the TCGA Database. The prognostic role of miR-195-3p was explored, and we then constructed a nomogram. The expression levels of miR-195-3p in LUAD tumor tissues and adjacent normal lung tissues were further determined by qRT-PCR in clinical samples. Finally, we explored the mechanisms by which miR-195-3p affects patient prognosis. RESULTS:The results showed that miR-195-3p was expressed at decreased levels in LUAD tumor tissue. Furthermore, elevated miR-195-3p expression was associated with a better prognosis and served as an independent prognostic factor in LUAD. CD34 immunohistochemical staining showed that miR-195-3p expression was negatively correlated with microvessel density (MVD). Overexpression of miR-195-3p inhibited the migration and tube formation ability of HUVEC (Human Umbilical Vein Endothelial Cells). DISCUSSION:Our findings demonstrate that miR-195-3p expression is significantly downregulated in LUAD tumor tissues compared to normal lung tissues, corroborating its tumor-suppressive role. The experiment suggests that this miRNA may exert its prognostic influence by modulating angiogenesis. However, this study still has several limitations that need to be addressed in future work. CONCLUSION:These findings indicate that miR-195-3p is a useful prognostic biomarker in LUAD, as well as a potential therapeutic target.
OBJECTIVE:Recurrent spontaneous abortion (RSA) represents a significant reproductive health challenge. The intricate balance of immune regulation at the maternal-fetal interface is crucial for maintaining pregnancy, involving complex interactions among multiple molecular pathways. In this way, TLR2 and the BAX have emerged as key players in immune modulation during pregnancy. This study examines the expression profiles of BAX and TLR2 in both maternal blood and fetal tissues across various trimesters, aiming to elucidate their potential role in RSA pathogenesis. MATERIALS AND METHODS:Blood and fetal tissue samples were collected from 120 participants (60 RSA cases and 60 controls) in the first and second trimesters. The gene expression of all specimens was measured using real-time PCR analysis. Correspondingly, Western blot analysis was used to evaluate the protein expression of all samples. RESULTS:The p-values of BAX (0.0168) and TLR2 (0.0014) are much smaller than 0.05, indicating that the difference in these genes' expression between the two trimesters is statistically significant. BAX expression is substantially different between the first and second trimesters (p-value = 0.0168). There is a significant difference in TLR2 expression between the first and second trimesters (p-value = 0.0014). The p-values for both comparisons are extremely small (p<0.05), indicating that the difference in BAX and TLR2 expression between normal and RSA patients is highly significant. Notably, both BAX and TLR2 are significantly upregulated in RSA patients compared to normal blood, with statistically significant differences in expression. BAX shows a substantial decrease in expression between the first and second trimesters, indicating a downregulation of apoptotic processes as the pregnancy advances. Meanwhile, the protein expression of these genes had remarkable upregulation except for a decrease in the tissues of the embryos of the first trimester. CONCLUSION:The expression of BAX is highly upregulated in RSA patients compared to normal blood. The slight reduction in expression in the second trimester suggests that BAX, which is involved in apoptosis, may play a more prominent role in the early stages of pregnancy complications such as RSA. Its continued elevated expression in the second trimester indicates its sustained involvement in the pathophysiology of RSA.
BACKGROUND:About 80-90% of all oral cancers worldwide are Oral Squamous Cell Carcinomas (OSCCs), making them the most common type of oral malignancy. Due to its propensity for lymph node metastasis, lack of accurate prognostic indicators, and delayed diagnosis, OSCC remains linked to high morbidity and mortality despite advancements in surgical and therapeutic approaches. A mucin-type transmembrane glycoprotein, Podoplanin (PDPN), is well known as a lymphatic endothelial marker and plays roles in metastasis, Epithelial-Mesenchymal Transition (EMT), and tumor progression and growth. The goal of the current study was to determine whether podoplanin's immunohistochemistry expression in OSCC and its association with other clinicopathological parameters could serve as a biomarker for the course and outcome of the disease. METHODS:This observational study was conducted over one year in the Department of Pathology in collaboration with the Department of Surgical Oncology, King George's Medical University, Lucknow. A total of 110 histopathologically confirmed, treatment-naïve cases of OSCC were included. Detailed clinical and demographic data were collected. Tumour specimens were processed and evaluated as per the College of American Pathologists (CAP) guidelines. Immunohistochemistry was performed using anti-podoplanin (D2-40 clone) monoclonal antibody. The expression of podoplanin was assessed semi-quantitatively using the German Immunoreactive Score (IRS), which combines staining intensity and percentage of positive tumour cells. RESULTS:The age of patients ranged from 23 to 75 years, with a mean of 45.3 years; the predominant age group was 31-40 years (35.5%). Males constituted 83.6% of the study population, and 89.1% had a history of tobacco, smoking, or alcohol use. The most commonly affected sites were the buccal mucosa (33.6%) and anterior tongue (30.9%). Most tumours were larger than 2.5 cm (58.2%) and exhibited a depth of invasion exceeding 10 mm (54.5%). Advanced pathological stage (Stage III-IV) was observed in 79.1% of cases, and 64.5% had nodal metastasis. Welldifferentiated tumours were most common (48.2%). Podoplanin expression ranged from weak (IRS 0-6) in 35.5% to strong (IRS >6) in 64.5%. Strong podoplanin expression correlated positively with larger tumour size, moderate to well-differentiated tumours, and nodal metastasis (N1-N3), although no significant association was found with early vs. late pathological stage. Interestingly, T4-stage and poorly differentiated tumours showed a tendency toward weak expression. DISCUSSION:The study confirms that strong podoplanin expression correlates with parameters indicative of tumour aggressiveness, including size, differentiation, and nodal involvement. These findings align with several prior studies, though the lack of significant association with pathological stage or overall survival underscores the complexity of podoplanin's role in tumour biology. The expression pattern-predominantly peripheral and membranous-suggests podoplanin may be involved in tumour invasion fronts and early carcinogenic events. CONCLUSION:The study findings suggest that podoplanin overexpression is significantly associated with tumour size, differentiation, and lymph node metastasis in OSCC, indicating its potential utility as a prognostic biomarker. Although the survival analysis did not demonstrate a statistically significant correlation with podoplanin expression, the trend toward higher mortality in patients with strong expression warrants further exploration. This study adds to the growing body of evidence supporting podoplanin's role in tumour progression and highlights its promise as a diagnostic and prognostic adjunct in oral cancer. Multicentric studies with larger cohorts and long-term follow-up are recommended to validate these observations.
For more than over two decades, mRNA vaccines have been successfully administered and continues to be a promising platform for preventive and therapeutic uses. A key advantage of mRNA-based therapies over DNA-based approaches is that the mRNA molecule only needs to reach the cytoplasm for translation, bypassing the need for nuclear entry. Unlike pre-designed peptide vaccines, which may be restricted to specific MHC haplotypes, mRNA vaccines encode full-length antigens, allowing the host's cells to process and present a diverse array of epitopes suitable for a wide range of MHC haplotypes within a population. The binding of mRNA molecules to pattern recognition receptors enables them to be designed as self- adjuvants, a feature absent in peptide and protein-based vaccines. Since mRNA can encode and produce any protein, it enables the development of preventive and curative vaccinations to combat a range of illnesses, such as infections and cancer, as well as protein replacement therapies. The recent SARS-CoV-2 pandemic underscored the critical need for rapid vaccine platforms, a challenge effectively met by mRNA technology. Companies and research centers have created a variety of SARS-CoV-2 vaccines. These include older types of vaccines, such as those using viruses and proteins, as well as more advanced vaccines that utilize DNA and mRNA technology. This review outlines the recent advancements and advantages of mRNA vaccine technology, including how to design, synthesize, and deliver them to the target cells, as well as the immune system's response to these vaccines.
BACKGROUND:Musculoskeletal pain is highly prevalent among runners and often im-pairs performance and quality of life. Exercise-based interventions, such as kinesiology-guided programs, are increasingly used to promote recovery and prevent recurrence; however, individual responses vary widely. Circulating miRNA may serve as molecular biomarkers to elucidate un-derlying mechanisms and predict therapeutic outcomes. This study aimed to assess changes in circulating miRNAs in runners following a kinesiology-based intervention and to explore their potential involvement in pain-related biological processes. METHODS:Seventeen long-distance runners with musculoskeletal pain underwent a six-week ki-nesiology-based intervention. Pain intensity and physical activity were assessed pre- and post-intervention. Plasma levels of four inflammation- and muscle-related miRNAs (hsa-let-7a-5p, hsa-miR-133b, hsa-miR-146a-5p, and hsa-miR-155-5p) were quantified using qRT-PCR. Bioin-formatic analyses were conducted to explore molecular networks involving the most responsive miRNAs. RESULTS:Among the four analyzed miRNAs, three showed a downregulation after the interven-tion, with a statistically significant reduction in hsa-let-7a-5p (p = 0.035) and a near-significant decrease in hsa-miR-133b (p = 0.068). No significant associations were found between miRNA changes and pain remission in regression analysis. However, integrative network and pathway analyses revealed the involvement of hsa-let-7a-5p and hsa-miR-133b in molecular pathways re-lated to inflammation, tissue remodeling, and neuroimmune signaling. DISCUSSION:The observed modulation of hsa-let-7a-5p and hsa-miR-133b suggests that these miRNAs may be sensitive to physiological changes induced by kinesiological intervention, po-tentially reflecting systemic adaptations rather than directly mediating pain remission. The lack of correlation with pain reduction may be due to the small sample size or the multifactorial nature of pain modulation. Nonetheless, the bioinformatic evidence highlights plausible biological mechanisms that merit further investigation. CONCLUSIONS:These findings suggest that hsa-let-7a-5p and hsa-miR-133b may reflect biological adaptations to functional recovery, even if they are not predictive of clinical outcomes. Further research is needed to validate their role in musculoskeletal rehabilitation and to assess their po-tential utility in guiding personalized exercise-based strategies.
INTRODUCTION:Alzheimer's disease (AD) is a late-onset neurodegenerative disease that affects older people. Deregulations of miRNAs play essential roles in AD pathogenesis; as a re-sult, they might be potential biomarkers for AD development, diagnosis, and treatment. This case-control study aimed to assess the expression of miR-214, miR-204, miR-15a, miR-25, and inves-tigate their correlations with the expression of IL-33, plasma level of Malondialdehyde (MDA), and Mini-Mental State Examination (MMSE) score of the AD patients. METHODS:Blood samples were obtained from 125 participants, including 75 AD patients and 50 healthy controls. Plasma MDA level was assessed using the ZellBio ELISA kit. Total RNA was extracted from blood lymphocytes using RiboExTM (GeneAll), and expression levels of miRNAs and IL-33 were evaluated by qRT-PCR. RESULTS:Results showed that miR-15a and miR-25, and IL-33 were downregulated in the pa-tients' group, but miR-214 and miR-204 were upregulated. Besides, the plasma level of MDA was significantly higher in the AD patients. A statistically significant negative correlation was observed between miR-15a and IL-33 expression. The MDA level showed a negative correlation with MMSE and a positive correlation with IL-33. Correlations between the miRNAs and MDA or MMSE scores were all non-significant. However, ROC curve analysis revealed that expres-sions of the studied miRNAs, IL-33, and the plasma level of MDA effectively differentiate AD patients from healthy controls. DISCUSSION:Results showed that expression levels of miR-214, miR-204, miR-25, miR-15a, and IL-33 and MDA plasma levels are deregulated in AD patients, highlighting their potential relation with AD pathogenesis. CONCLUSION:Expression levels of the studied miRNAs and IL33, and plasma level of MDA might be considered as potential biomarkers for AD development and diagnosis.
Introduction In animal taxa and jellyfish, the same genome encodes for the different phenotypes that characterize life stages that follow each other during ontogeny. This situation underscores the existence of profound regulation of genomic information at the epigenetic level. MicroRNAs are fundamental epigenetic regulators. The aim of this study is to evaluate the role of microRNA regulation during jellyfish metamorphosis and to explore the existence of evolutionarily conserved microRNAs. Methods Specimens belonging to the 4-metamorphosis stages of A. aurita (polyps, ephyra, young, and adult jellyfish) were bred and collected. The expression of 2,549 miRNAs for each stage was tested using microarray technology. The comparison of microRNA expression for each phase was performed using line plot analysis and Principal Component Analysis of variance (PCA), while the identification of microRNA clusters was performed via volcano plot analysis. Results A remarkable number of A. aurita miRNAs specifically hybridize with a human miRNA library. Each metamorphosis stage is characterized by a different level of expression of miRNAs: 1) Polyp vs. Ephyra stage: 128 upregulated, 2 downregulated; 2) Ephyra vs. Young stage: 2 upregulated, 135 downregulated; 3) Young vs. Adult stage: 69 upregulated, 6 downregulated. Specific functions inferred from known activities of corresponding miRNAs in higher animals (PubMed database) appear to be coherent with the correlated experimental model. Discussion Present results reveal that microRNAs with human homologs undergo specific expression changes throughout Aurelia aurita metamorphosis. This observation reinforces the hypothesis of a shared evolutionary origin of certain miRNA families between Cnidaria and Bilateria. The dynamic and stage-specific regulation pattern observed suggests that miRNAs play a key role in orchestrating the complex transitions involved in jellyfish development. These findings point to a broader conservation of epigenetic mechanisms, such as miRNA-mediated gene silencing, which may have emerged early in metazoan evolution and contributed to the regulation of cell differentiation and phenotype modulation. Conclusion The present study highlights the importance of Aurelia aurita as a model for investigating miRNA-driven epigenetic regulation in non-bilaterian animals. The identification of human-homologous miRNAs provides novel insights into the evolutionary stability of the epigenetic machinery and suggests conserved regulatory functions across distant taxa. Although limited by the use of a human-based microarray platform, the data presented here lay a solid foundation for future studies employing sequencing and functional assays to further explore the role of miRNAs in cnidarian development and evolution.
Difficulties in wound healing pose a considerable clinical problem and are a significant source of morbidity in the general population. Systemic disorders such as diabetes and venous insufficiency often result in chronic wounds and an impaired healing process. The healthcare cost of treating chronic wounds in the U.S. already exceeds 20 billion dollars per year and is expected to rise with an aging population and increasing incidence of diabetes. Recently, research and review articles have been used to understand the normal healing process and identify the reasons why certain wounds fail to heal, which should enable the development of more effective thera-peutic interventions. Animal models have provided valuable information; however, the healing process differs between humans and animals, and data obtained from in vitro studies can be chal-lenging to extrapolate to a clinical context. In conclusion, this study aims to summarize the current understanding of inflammation, epithelialization, and tissue repair processes, mainly through the use of data from in vitro and in vivo studies. Inflammation, re-epithelialization, granulation tissue development, and collagen remodeling are the fundamental steps in the healing process. As a result, any deviation from the normal sequence and time course of events may result in abnormal healing. Wound healing occurs to repair damaged, devitalized, or missing cells and tissues. In human beings, the result is the reestablishment of structural and functional integrity. This is a vital process that all living organisms undergo at some stage in their lives.
MicroRNAs (miRNAs) are molecules that regulate gene expression by targeting the 3′ untranslated region (UTR) of mRNAs. They are essential in numerous biological processes like growth, metabolism, and muscle development. miRNA research has become crucial in livestock breeding, offering solutions for improving animal health and productivity. This review focuses on miRNAs' roles in equine performance, reproduction, and disease, highlighting key findings and future applications in these areas. It discusses the use of circulating miRNAs (ci-miRNA) as biomarkers for athletic performance, particularly in endurance sports, by monitoring responses to exercise-induced stress and recovery. It also examines miRNAs involved in reproductive health, such as those influencing endometritis, oocyte maturation, and embryo development. In terms of disease, miRNAs are highlighted as potential biomarkers for osteoarthritis and sarcoids, offering insights into early diagnosis and treatment. Overall, the review emphasizes the promise of miR-NAs in improving equine care through personalized diagnostics and therapeutic approaches.
