An enzyme-free and label-free multiplex detection of miRNAs by entropy-driven circuit coupled with capillary electrophoresis.

MicroRNAs (miRNAs) are currently recognized as important biomarkers for the early diagnosis and prognostic treatment of cancer. Herein, we developed a simple and label-free method for the multiplex detection of miRNAs, based on entropy-driven circuit (EDC) amplification and non-gel sieving capillary electrophoresis-LED induced fluorescence detection (NGCE-LEDIF) platform. In this system, three different lengths of fuel chains were designed to catalyze three EDC, targeting miRNA-21, miRNA-155, and miRNA-10b, respectively. In the presence of target miRNA, the EDC cycle amplification reaction was triggered, generating numerous stable double-strands products (F-DNA/L-DNA). Since the three miRNAs correspond to three different lengths of F-DNA/L-DNA, they can be easily isolated and detected by NGCE. This strategy has good sensitivity, with detection limits of 68 amol, 292.2 amol, and 394 amol for miRNA-21, miRNA-155, and miRNA-10b, respectively. Additionally, this method has good specificity and can effectively distinguish single-base mismatches of miRNA. The recoveries of the three miRNAs in deproteinized healthy human serum ranged from 91.28 % to 108.4 %, with a relative standard deviation (RSD) of less than 7.9 %. This method was further applied to detect cellular miRNAs in human breast cancer (MCF-7) cell extracts, revealing an up-regulation of miRNA-21, miRNA-155, and miRNA-10b in MCF-7 cells. The successful spiked recovery in human serum and RNA extraction from MCF-7 cells underscores the practicality of this method. Therefore, this strategy has broad application prospects in biomedical research.

miRNA-based electrochemical biosensors for ovarian cancer.

Ovarian cancer, a prevalent and deadly cancer among women, presents a significant challenge for early detection due to its heterogeneous nature. MicroRNAs, short non-coding regulatory RNA fragments, play a role in various cellular processes. Aberrant expression of these microRNAs has been observed in the carcinogenesis-related processes of many cancer types. Numerous studies highlight the critical role of microRNAs in the initiation and progression of ovarian cancer. Given their clinical importance and predictive value, there has been considerable interest in developing simple, prompt, and sensitive miRNA biosensor strategies. Among these, electrochemical sensors have demonstrated advantageous characteristics such as simplicity, sensitivity, low cost, and scalability. These microRNA-based electrochemical biosensors are valuable tools for early detection and point-of-care applications. This article discusses the potential role of microRNAs in ovarian cancer and recent advances in the development of electrochemical biosensors for miRNA detection in ovarian cancer samples.

Recent advances in the development and clinical application of miRNAs in infectious diseases.

In the search for new biomarkers and therapeutic targets for infectious diseases, several molecules have been investigated. Small RNAs, known as microRNAs (miRs), are important regulators of gene expression, and have emerged as promising candidates for these purposes. MiRs are a class of small, endogenous non-coding RNAs that play critical roles in several human diseases, including host-pathogen interaction mechanisms. Recently, miRs signatures have been reported in different infectious diseases, opening new perspectives for molecular diagnosis and therapy. MiR profiles can discriminate between healthy individuals and patients, as well as distinguish different disease stages. Furthermore, the possibility of assessing miRs in biological fluids, such as serum and whole blood, renders these molecules feasible for the development of new non-invasive diagnostic and prognostic tools. In this manuscript, we will comprehensively describe miRs as biomarkers and therapeutic targets in infectious diseases and explore how they can contribute to the advance of existing and new tools. Additionally, we will discuss different miR analysis platforms to understand the obstacles and advances of this molecular approach and propose their potential clinical applications and contributions to public health.

Lymph node metastasis determined miRNAs in esophageal squamous cell carcinoma.

PURPOSE: There is no golden noninvasive and effective technique to diagnose lymph node metastasis (LNM) for esophageal squamous cell carcinoma (ESCC) patients. Here, a classifier was proposed consisting of miRNAs to screen ESCC patients with LNM from the ones without LNM. METHODS: miRNA expression and clinical data files of 93 ESCC samples were downloaded from TCGA as the discovery set and 119 ESCC samples with similar dataset GSE43732 as the validation set. Differentially expressed miRNAs (DE-miRNAs) were analyzed between patients with LNM and without LNM. LASSO regression was performed for selecting the DE-miRNA pair to consist the classifier. To validate the accuracy and reliability of the classifier, the SVM and AdaBoost algorithms were applied. The CCK-8 and wound healing assay were used to evaluate the role of the miRNA in ESCC cells. RESULT: There were 43 DE miRNAs between the LNM+ group and LNM- group. Among them, miR-224-5p, miR-99a-5p, miR-100-5p, miR-34c-5p, miR-503-5p, and miR-452-5p were identified by LASSO to establish the classifier. SVM and AdaBoost showed that the model could classify the ESCC patients with LNM from the ones without LNM precisely and reliably in 2 data sets. miR-224-5p in the classifier as the top contributor to discriminate the two groups of patients based on AdaBoost, promoted ESCC cell proliferation and migration in vitro. CONCLUSION: The classifier based on these 6 miRNAs could classify the ESCC patients with LNM from the ones without LNM successfully.

The Growth of A549 Cell Line is Inhibited by Pemetrexed Through Up-regulation of hsa-MiR-320a Expression.

Background: Lung cancer deaths are increasing worldwide and the most common form of lung cancer treatment is chemotherapy. Pemetrexed (PMX) has been shown to be effective as a second-line treatment for advanced patients. Drugs can alter the expression of MicroRNAs, and MicroRNAs also can either enhance or reduce the drug's effectiveness and this is a two-way relationship. Hsa-MiR-320a is known to play a crucial role in the lung cancer. This study aims to investigate the expression of hsa-MiR-320a in lung cancer cells after treatment with PMX. Materials and Methods: A549 cells were cultured and treated with varying concentrations of PMX. Various parameters were measured, including cell viability, reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) release, apoptosis assay, caspase 3 and 7 enzyme activity, and scratch assay. Additionally, gene expression profiles of hsa-MiR-320a, VDAC1, STAT3, BAX, and BCL2 were evaluated. Results: PMX reduced the viability and increased apoptosis. After 48 h, ROS production was 3.366-fold higher than in control cells and the LDH release rate was increased by 39%. PMX also up-regulated the expression of hsa-MiR-320a by about 12-fold change. Conclusion: Changes in the expression of MicroRNAs occur after chemotherapy, and these changes play a crucial role in regulating the growth of cancer cells. Identifying these MicroRNAs can be helpful in predicting the efficacy of the chemotherapy or introducing it as combination therapy. Our research has been shown that hsa-MiR-320a can serve as a biomarker of PMX efficacy and also has the potential to be used in combination therapy.

Upregulation of microRNAs correlates with downregulation of HERV-K expression in Parkinson's disease.

Human endogenous retroviruses (HERVs) involvement in neurological diseases has been extensively documented, although the etiology of HERV reactivation remains unclear. MicroRNAs represent one of the potential regulatory mechanisms of HERV reactivation. We identified fourteen microRNAs predicted to bind the HERV-K transcript, and subsequently analyzed for their gene expression levels alongside those of HERV-K. We documented an increased expression of four microRNAs in patients with Parkinson's disease compared to healthy controls, which correlated with a downregulation of HERV-K transcripts. We hypothesize that specific microRNAs may bind to HERV-K transcripts, leading to its downregulation.

The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors.

Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (p < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (n = 9), borderline (n = 12), or benign (n = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (p-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0-8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

Bioinformatic Analysis from a Descriptive Profile of miRNAs in Chronic Migraine.

Chronic migraines have been described chiefly only from a clinical perspective. However, searching for reliable molecular markers has allowed for the discovery of the expression of different genes mainly associated with inflammation, neuro-vascularization, and pain-related pathways. The interest in microRNAs (miRs) that can regulate the expression of these genes has gained significant relevance since multiple miRs could play a key role in regulating these events. In this study, miRs were searched in samples from patients with chronic migraine, and the inclusion criteria were carefully reviewed. Different bioinformatic tools, such as miRbase, targetscan, miRPath, tissue atlas, and miR2Disease, were used to analyze the samples. Our findings revealed that some of the miRs were expressed more (miR-197, miR-101, miR-92a, miR-375, and miR-146b) and less (miR-133a/b, miR-134, miR-195, and miR-340) than others. We concluded that, during chronic migraine, common pathways, such as inflammation, vascularization, neurodevelopment, nociceptive pain, and pharmacological resistance, were associated with this disease.

Understanding the Dosage-Dependent Role of Dicer1 in Thyroid Tumorigenesis.

Tumors originating from thyroid follicular cells are the most common endocrine tumors, with rising incidence. Despite a generally good prognosis, up to 20% of patients experience recurrence and persistence, highlighting the need to identify the underlying molecular mechanisms. Dicer1 has been found to be altered in papillary thyroid cancer (PTC). Studies suggest that Dicer1 functions as a haploinsufficient tumor suppressor gene: partial loss promotes tumorigenesis, while complete loss prevents it. To investigate the effects of partial or total Dicer1 loss in PTC in vitro, we generated stable Dicer1 (+/-) cell lines from TPC1 using CRISPR-Cas9, though no Dicer1 (-/-) lines could be produced. Therefore, siRNA against Dicer1 was transfected into Dicer1 (+/-) cell lines to further decrease its expression. Transcriptomic analysis revealed changes in proliferation and cell locomotion. BrdU staining indicated a slow-down of the cell cycle, with fewer cells in S phase and more in G0-G1-phase. Additionally, transwell assays showed decreased invasion and migration after Dicer1 knockdown by siRNA. Moreover, Dicer1 overexpression led to decreased proliferation, invasion, and increased apoptosis. Our findings deepen the understanding of Dicer1's role in thyroid cancer, demonstrating that both complete elimination and overexpression of Dicer1 inhibit thyroid oncogenesis, highlighting Dicer1 as a promising target for novel therapeutic strategies.

Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors.

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.

From virus to cancer: Epstein-Barr virus miRNA connection in Burkitt's lymphoma.

In Burkitt's lymphoma (BL), Epstein-Barr virus-encoded microRNAs (EBV miRNAs) are emerging as crucial regulatory agents that impact cellular and viral gene regulation. This review investigates the multifaceted functions of EBV miRNAs in the pathogenesis of Burkitt lymphoma. EBV miRNAs regulate several cellular processes that are essential for BL development, such as apoptosis, immune evasion, and cellular proliferation. These small, non-coding RNAs target both viral and host mRNAs, finely adjusting the cellular environment to favor oncogenesis. Prominent miRNAs, such as BART (BamHI-A rightward transcript) and BHRF1 (BamHI fragment H rightward open reading frame 1), are emphasized for their roles in tumor growth and immune regulation. For example, BART miRNAs prevent apoptosis by suppressing pro-apoptotic proteins, whereas BHRF1 miRNAs promote viral latency and immunological evasion. Understanding the intricate connections among EBV miRNAs and their targets illuminates BL pathogenesis and suggests novel treatment approaches. Targeting EBV miRNAs or their specific pathways offers a feasible option for developing innovative therapies that aim to disrupt the carcinogenic processes initiated by these viral components. future studies should focus on precisely mapping miRNA‒target networks and developing miRNA-based diagnostic and therapeutic tools. This comprehensive article highlights the importance of EBV miRNAs in Burkitt lymphoma, indicating their potential as biomarkers and targets for innovative treatment strategies.

Nexus of NFκB/VEGF/MMP9 signaling in diabetic retinopathy-linked dementia: Management by phenolic acid-enabled nanotherapeutics.

AIMS: The purpose of this review is to highlight the therapeutic effectiveness of phenolic acids in slowing the progression of diabetic retinopathy (DR)-linked dementia by addressing the nuclear factor kappa B (NFκB)/matrix metalloproteinase-9 (MMP9)/vascular endothelial growth factor (VEGF) interconnected pathway. MATERIALS AND METHODS: We searched 80 papers published in the last 20 years using terms like DR, dementia, phenolic acids, NFkB/VEFG/MMP9 signaling, and microRNAs (miRs) in databases including Pub-Med, WOS, and Google Scholar. By encasing phenolic acid in nanoparticles and then controlling its release into the targeted tissues, nanotherapeutics can increase their effectiveness. Results were summarized, and compared, and research gaps were identified throughout the data collection and interpretation. KEY FINDINGS: Amyloid beta (Aß) deposition in neuronal cells and drusen sites of the eye leads to the activation of NFkB/VEGF/MMP9 signaling and microRNAs (miR146a and miR155), which in turn energizes the accumulation of pro-inflammatory and pro-angiogenic microenvironments in the brain and retina leading to DR-linked dementia. This study demonstrates the potential of phenolic acid-enabled nanotherapeutics as a functional food or supplement for preventing and treating DR-linked dementia, and oxidative stress-related diseases. SIGNIFICANCE: The retina has mechanisms to clear metabolic waste including Aß, but the activation of NFkB/ MMP9/ VEGF signaling leads to fatal pathological consequences. Understanding the role of miR146a and miR155 provides potential therapeutic avenues for managing the complex pathology shared between DR and dementia. In particular, phenolic acid nanotherapeutics offer a dual benefit in retinal regeneration and dementia management.

Human mesenchymal stroma/stem-like cell-derived taxol-loaded EVs/exosomes transfer anti-tumor microRNA signatures and express enhanced SDF-1-mediated tumor tropism.

BACKGROUND: The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds. METHODS: EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA. RESULTS: EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%. CONCLUSIONS: These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products.

Improving Stroke Outcome Prediction Using Molecular and Machine Learning Approaches in Large Vessel Occlusion.

Introduction: Predicting stroke outcomes in acute ischemic stroke (AIS) can be challenging, especially for patients with large vessel occlusion (LVO). Available tools such as infarct volume and the National Institute of Health Stroke Scale (NIHSS) have shown limited accuracy in predicting outcomes for this specific patient population. The present study aimed to confirm whether sudden metabolic changes due to blood-brain barrier (BBB) disruption during LVO reflect differences in circulating metabolites and RNA between small and large core strokes. The second objective was to evaluate whether integrating molecular markers with existing neurological and imaging tools can enhance outcome predictions in LVO strokes. Methods: The infarction volume in patients was measured using magnetic resonance diffusion-weighted images, and the 90-day stroke outcome was defined by a modified Rankin Scale (mRS). Differential expression patterns of miRNAs were identified by RNA sequencing of serum-driven exosomes. Nuclear magnetic resonance (NMR) spectroscopy was used to identify metabolites associated with AIS with small and large infarctions. Results: We identified 41 miRNAs and 11 metabolites to be significantly associated with infarct volume in a multivariate regression analysis after adjusting for the confounders. Eight miRNAs and ketone bodies correlated significantly with infarct volume, NIHSS (severity), and mRS (outcome). Through integrative analysis of clinical, radiological, and omics data using machine learning, our study identified 11 top features for predicting stroke outcomes with an accuracy of 0.81 and AUC of 0.91. Conclusions: Our study provides a future framework for advancing stroke therapeutics by incorporating molecular markers into the existing neurological and imaging tools to improve predictive efficacy and enhance patient outcomes.

MiR-192 and miR-731 synergically inhibit RGNNV infection by targeting ULK1-mediated autophagy in sea perch (Lateolabrax japonicus).

MicroRNAs (miRNAs) are crucial regulators of gene expression and are closely linked to viral infections. Nervous necrosis virus (NNV) poses a significant threat to global fish aquaculture. This study investigates the roles of miR-192 and miR-731 in controlling NNV infection and associated autophagy in sea perch (Lateolabrax japonicus). Our findings reveal that both miRNAs are upregulated in infected brain tissues and cells of sea perch, leading to reduced NNV replication. miR-192 and miR-731 synergistically reduce NNV replication by downregulating the RNA-dependent RNA polymerase and capsid protein genes, and disrupting autophagy by altering LC3 distribution and autophagy-related protein expressions. Additionally, L. japonicus unc-51 like autophagy activating kinase 1 protein (LjULK1) was identified as the target of miR-192 and miR-731. LjULK1 is integrally associated to the ULK-VAPs-Atg13 autophagic signaling, enhancing NNV-induced autophagy, and facilitating viral infection. Modulating LjULK1 expression counteracts the inhibitory effects of miR-192 and miR-731 on NNV, suggesting these miRNAs act as negative regulators of NNV infection by targeting LjULK1-mediated autophagy. Our findings reveal a novel miRNAs-regulated antiviral mechanism against NNV, offering insights into potential strategy to prevent NNV infection in fish.

Comparison of miRNA Profiles of Primary Tumors and Metastatic Tumors of Salivary Gland Tumors and Their Role in Prognosis: A Systematic Review.

Background: MicroRNAs (miRNAs) are implicated in several biological processes, such as control of tissue homeostasis, cell signaling, differentiation, proliferation, neoplastic transformation, and activation/inhibition of apoptotic mechanisms. In this systematic review, we evaluated the changes in the expression pattern of miRNAs in salivary gland tumors (SGTs). Methods: A comprehensive search was conducted in PubMed, and Scopus with no language and date restrictions in Feb 2023. All the studies on SGTs that evaluated miRNA profiling were included. Relevant data regarding the overexpression and down-regulation of the miRNAs were extracted. The quality of the included studies was evaluated with Newcastle-Ottawa checklist. The altered expression of miRNAs was evaluated between SGTs and normal cases, benign and malignant tumors, and primary and high-grade tumors. Results: Thirteen studies were included in this systematic review. There were considerable differences between malignant and benign tumors regarding the miRNAs expression level. In the five studies, the miRNA profile of the primary tumors was compared with metastatic tumors to reveal the involvement of the miRNA in the prognosis of the salivary tumors. The miRNAs expression changes were correlated with tumor size, stage, recurrence, and occurrence of solid components. Perineural invasion and lymph node metastasis were also reported in ACCLM cell line and recurrence of adenoid cystic carcinoma (ACC) tissues. Conclusion: The miRNA profiling confirms their prognostic value in salivary gland tumors. Significant alternations of the miRNAs expression are useful for distinguishing different types of salivary tumors and malignant tumors from benign types. The miRNA expression changes also affect the prognosis of salivary tumors.

The Application of microRNAs in Papillary Thyroid Cancer: A Bibliometric and Visualized Analysis.

Objective: Thyroid cancer is the most common malignant endocrine tumor, with papillary thyroid carcinoma (PTC) being the most prevalent type, accounting for 85% of thyroid cancer cases. Here, we conducted a bibliometric analysis of the literature in the field of microRNAs in PTC research to demonstrate current trends and research hotspots, and present a visual map of past and emerging trends. Methods: We searched the Web of Scientific Core Collection (WoSCC) database for publications from 1999 to 2023 centered on this field. Next, we employed visualization tools such as VOSviewer, CiteSpace, and Microsoft Excel 2019 to present co-occurrence and co-citation analyses, trends, hotspots, and visual representations of contributions from authors, institutions, journals, and countries/regions. Results: The bibliometric analysis encompassed the period from 1999 to 2023, with 994 papers from 54 countries/regions. The country with the most publications and highest total citations was the People's Republic of China, but the United States held the highest average citation rate. Among the top ten productive institutions, the Ohio State University (Ohio State Univ) was the most prominent contributor to this field. The JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (J Clin Endocrinol Metab) ranked first in terms of citation counts and average citations among the top ten productive journals. In terms of keywords, "circular RNAs", "promotes", and "progression" have become prominent research areas. Conclusion: This study elucidates current trends, hotspots, and emerging frontiers in miRNA research within PTC, and provides new insights and guidance for future identification of new PTC biomarkers and clinical trials.

miR-374 family is a key regulator of chronic primary pain onset.

Introduction: Chronic primary pain conditions (CPPCs) are linked to catecholamine activation of peripheral adrenergic receptors. Yet, catecholamine-dependent epigenetic mechanisms, such as microRNA (miRNA) regulation of mRNA transcripts, remain largely unknown. Objectives: We sought to identify RNA species correlated with case status in 3 pain cohorts, to validate RNAs found to be dysregulated in a mouse model of CPPC onset, and to directly test the role of adrenergic receptors in miRNA regulation. Furthermore, we tested antinociceptive effects of miR-374 overexpression. Methods: We used RNA-seq and quantitative reverse transcription polymerase chain reaction to measure RNA expression in 3 pain cohorts. Next, we validated identified RNAs with quantitative reverse transcription polymerase chain reaction in a mouse model of CPPC onset, measuring expression in plasma, peripheral (adipose, muscle, dorsal root ganglia [DRG]), and central (spinal cord) tissues. Then, we stimulated adrenergic receptors in primary adipocyte and DRG cultures to directly test regulation of microRNAs by adrenergic signaling. Furthermore, we used in vitro calcium imaging to measure the antinociceptive effects of miR-374 overexpression. Results: We found that one miRNA family, miR-374, was downregulated in the plasma of individuals with temporomandibular disorder, fibromyalgia syndrome, or widespread pain following a motor vehicle collision. miR-374 was also downregulated in plasma, white adipose tissue, and spinal cord from mice with multisite mechanical sensitivity. miR-374 downregulation in plasma and spinal cord was female specific. Norepinephrine stimulation of primary adipocytes, but not DRG, led to decreased miR-374 expression. Furthermore, we identified tissue-specific and sex-specific changes in the expression of predicted miR-374 mRNA targets, including known (HIF1A, NUMB, TGFBR2) and new (ATXN7, CRK-II) pain targets. Finally, we demonstrated that miR-374 overexpression in DRG neurons reduced capsaicin-induced nociceptor activity. Conclusions: Downregulation of miR-374 occurs between adrenergic receptor activation and mechanical hypersensitivity, and its adipocyte source implicates adipose signaling in nociception. Further study of miR-374 may inform therapeutic strategies for the millions worldwide who experience CPPCs.

Decoding the intricacies: a comprehensive analysis of microRNAs in the pathogenesis, diagnosis, prognosis and therapeutic strategies for COVID-19.

The pandemic of coronavirus disease-19 (COVID-19), provoked by the appearance of a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), required a worldwide healthcare emergency. This has elicited an immediate need for accelerated research into its mechanisms of disease, criteria for diagnosis, methods for forecasting outcomes, and treatment approaches. microRNAs (miRNAs), are diminutive RNA molecules, that are non-coding and participate in gene expression regulation post-transcriptionally, having an important participation in regulating immune processes. miRNAs have granted substantial interest in their impact on viral replication, cell proliferation, and modulation of how the host's immune system responds. This narrative review delves into host miRNAs' multifaceted roles within the COVID-19 context, highlighting their involvement in disease progression, diagnostics, and prognostics aspects, given their stability in biological fluids and varied expression profiles when responding to an infection. Additionally, we discuss complicated interactions between SARS-CoV-2 and host cellular machinery facilitated by host miRNAs revealing how dysregulation of host miRNA expression profiles advances viral replication, immune evasion, and inflammatory responses. Furthermore, it investigates the potential of host miRNAs as therapeutic agents, whether synthetic or naturally occurring, which could be harnessed to either mitigate harmful inflammation or enhance antiviral responses. However, searching more deeply is needed to clarify how host's miRNAs are involved in pathogenesis of COVID-19, its diagnosis processes, prognostic assessments, and treatment approaches for patients.

Host combats porcine reproductive and respiratory syndrome virus infection at non-coding RNAs level.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global swine industry. The emergence of new, highly virulent strains has precipitated recurrent outbreaks worldwide, underscoring the ongoing battle between host and virus. Thus, there is an imperative to formulate a more comprehensive and effective disease control strategy. Studies have shown that host non-coding RNA (ncRNA) is an important regulator of host - virus interactions in PRRSV infection. Hence, a thorough comprehension of the roles played by ncRNAs in PRRSV infection can augment our understanding of the pathogenic mechanisms underlying PRRSV infection. This review focuses on elucidating contemporary insights into the roles of host microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in PRRSV infection, providing both theoretical foundations and fresh perspectives for ongoing research into the mechanisms driving PRRSV infection and its pathogenesis.