The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.

Myeloid ecotropic virus insertion site 1 (MEIS1) is a transcription factor involved in a myriad of functions such as hematopoiesis, cardiac regeneration, cell cycle progression, and limb and organ development. Its functional versatility extends beyond developmental biology, as aberrant MEIS1 expression has been implicated in various pathological contexts like carcinogenesis, cardiomyopathies, and neurodegenerative disorders. Recent advances in the field have uncovered novel layers of MEIS1 regulation, focusing on post-transcriptional and translational mechanisms, which collectively fine-tune its activity, stability, and subcellular localization. These include chromatin remodeling, epigenetic modifications in the enhancer and promoter regions, and protein modifications like phosphorylation and ubiquitination. The sophisticated regulation of MEIS1 including its interplay with non-coding RNAs (ncRNAs), either being an upstream or downstream of ncRNAs, equally represents an important regulatory mechanism orchestrating MEIS1 expression and function. This review explores the multifaceted roles of MEIS1, emphasizing its dynamic regulatory networks and their implications in physiological and pathological conditions. It also provides forward-thinking guidance on the utilization of MEIS1 in targeted therapies across various clinical settings, highlighting its potential as a key regulatory factor in disease modulation and therapeutic innovation.

MicroRNA (miRNA) clusters, defined as genomically co-localized miRNAs regulated by a shared promoter and processed from polycistronic transcripts, exhibit synergistic regulatory roles in developmental processes. Among these, the evolutionarily conserved miR-125/let-7 cluster has been identified as a key regulator of neural stem cell (NSC) dynamics. In this study, we used Dicer conditional knockout (cKO) mice to confirm the essential role of miRNAs in mouse neocortical layer formation. The miR-125/let-7 cluster is co-expressed in mice and shows significant enrichment in upper-layer (UL) neurons. Using in utero electroporation (IUE), we found that miR-125b or let-7b overexpression partially rescues cortical phenotypes in Dicer-deficient mice, restoring proper UL organization but failing to rescue laminar fate defects in deep-layer cortical neurons. Our findings demonstrate that the miR-125b/let-7b exhibits a specialized function in regulating UL neuronal fate specification in mice and promotes the differentiation of NSC. Notably, miR-125b and let-7b exhibit both overlapping and distinct regulatory functions. Collectively, these results underscore the cooperative mechanisms by which miRNA clusters orchestrate cortical development.

Tumors are associated with the highest mortality rates worldwide. For more than a decade, research has focused on the genetic involvement of proteins in cancer; however, a complete class of molecular non‑coding (nc)RNAs have been discovered in recent years, and these are considered to be associated with cancer. Notably, ncRNAs are highly conserved and multifunctional. These interact with multiple signaling pathways, influencing cell cycle progression and various physiological processes. Therefore, the present review aimed to investigate ncRNA, microRNA, transfer RNA‑derived small RNA, PIWI‑interacting RNA and long non‑coding RNA to further understand the associated generation processes, functional mechanisms and therapeutic roles in tumors. The present review demonstrated the critical role of ncRNAs in tumors, and may provide a novel theoretical basis for the role of ncRNAs as biomarkers or therapeutic tools in the treatment of cancer.

Extracellular vesicles are secreted by virtually every cell and allow the transfer of bioactive molecules including proteins, nucleic acids, and lipids to other cell types across the body. This study of the role of extracellular vesicles and their cargo in postoperative cognitive dysfunction after hip or knee replacement surgery reports differential protein and microRNA expression in patients with postoperative cognitive decline versus improvement. This small study in a select surgical population highlights the potential for extracellular vesicles and their contents to play a signalling role in postoperative neurocognitive disorders.

MicroRNAs (miRNAs) are evolutionarily conserved small regulatory elements that are ubiquitous in cells and are found to be abnormally expressed during the onset and progression of several human diseases. miRNAs are increasingly recognized as potential diagnostic and therapeutic targets that could be inhibited by small molecules (SMs). The knowledge of SM-miRNA associations (SMAs) is sparse, mainly because of the dynamic and less predictable 3D structures of miRNAs that restrict the high-throughput screening of SMs. Toward augmenting the costly and laborious experiments determining the SM-miRNA interactions, machine learning (ML) has emerged as a cost-effective and efficient platform. In this article, various aspects associated with the ML-guided predictions of SMAs are thoroughly reviewed. Firstly, a detailed account of the SMA data resources useful for algorithms training is provided, followed by an elaboration of various feature extraction methods and similarity measures utilized on SMs and miRNAs. Subsequent to a summary of the ML algorithms basics and a brief description of the performance measures, an exhaustive census of all the 32 ML-based SMA prediction methods developed so far is outlined. Distinctive features of these methods have been described by classifying them into six broad categories, namely, classical ML, deep learning, matrix factorization, network propagation, graph learning, and ensemble learning methods. Trend analyses are performed to investigate the patterns in ML algorithms usage and performance achievement in SMA prediction. Outlining key principles behind the up-to-date methodologies and comparing their accomplishments, this review offers valuable insights into critical areas for future research in ML-based SMA prediction.

Gene therapy has a pivotal role in treating new diseases. In addition to the recent mRNA-based COVID-19 vaccines produced by Pfizer-BioNTech and Moderna against severe acute respiratory syndrome corona virus 2, several new gene therapies have recently been approved as effective treatments for fatal genetic disorders such as Duchenne's muscular dystrophy, familial transthyretin amyloidosis, hemophilia A, hemophilia B, spinal muscle atrophy, early cerebral autoleukodystrophy, and β-thalassemia. This review provides novel insights into RNA therapeutics focusing on endogenous RNA species, RNA structure and function, and chemical modifications that improve the stability and distribution of RNAs. Furthermore, it includes updated knowledge on clinically approved gene therapies rendering a comprehensive understanding of the biochemical basis and clinical application of gene therapies. SIGNIFICANCE STATEMENT: There have recently been significant advances in clinical translation of RNA therapeutics. This review discusses the diverse types of RNA species, RNA structure and function, backbone and chemical modifications to RNAs, and every RNA therapeutic approved for clinical use at the time of writing.

Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC.

To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53].

The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86).

We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.

Since the inception of Molecular Therapy in 2000, the field of gene therapy has made remarkable progress, evolving from no approved clinical products to 23 clinical gene therapy products today. In this review, we aim to capture the transformative changes in the field by surveying the literature over this period, with a particular focus on advancements in gene delivery vector technology, disease and tissue targeting, and the revolutionary molecular tools that have become central to the field. We also discuss the current challenges facing gene therapy and the need for greater collaboration to ensure its accessibility worldwide.

Nephrotic syndrome is a complex renal condition characterized by abnormal protein permeability into the urine space, leading to edema and renal failure. Recent research suggests that deregulation of microRNAs contributes to the pathogenesis of this disease. MicroRNAs are small, non-coding RNA molecules that regulate gene expression by binding to complementary messenger RNA sequences. In this study, we employed bioinformatics techniques to analyze microRNA expression in urine samples from nephrotic syndrome patients and healthy control participants. Our results revealed a significant disruption of microRNA expression profiles in patients with nephrotic syndrome, indicating that these microRNAs may play a crucial role in the disease. This study highlights the potential of urinary microRNAs as biomarkers for nephrotic syndrome and warrants further investigation into their functional significance in the disease pathogenesis.

Organ transplantation is the only effective treatment for patients with end-stage organ failure. Although modern immunosuppressive protocols are very effective and improve quality of life, there is still a need for improvements to eliminate their side effects and to induce transplantation tolerance to allografts. The microRNAs (miRNAs) emerged as promising candidates for regulations of several immune functions. The most advanced research of miRNAs documented that several miRNAs form very complex regulatory networks involved in fine and precise mechanisms of multiple pathophysiological process in cells. This review describes the origin of miRNAs and their action mechanisms by which they regulate several immune and cell biology processes, highlighting the fast progress of miRNA research involved in transplant rejection, recent clinical trials, and describing prospects and possible limitations.

RNA therapeutics came to global attention when mRNA-based vaccines provided an answer to the SARS-CoV-2 pandemic. The immense significance of this development notwithstanding, it is important to note that almost a decade prior to the pandemic, RNA drugs had made important inroads toward the amelioration of disease. The first class of RNA therapies to be introduced into clinical use were the antisense oligomers and siRNA drugs which generally induce a therapeutic effect by acting to brake or to modulate mRNA expression. RNA therapeutics is quickly becoming the fourth pillar of pharmacotherapy, and will have broad applications, including for the treatment of cardiovascular disease.

The United States (US) Food and Drug Administration (FDA) has approved several antisense oligomers (ASOs) and siRNA-based drugs to treat disorders associated with cardiovascular disease. In addition, multiple RNA-based drugs are in clinical trials to assess their safety and efficacy in patients with cardiovascular disorders, such as Zodasiran, a siRNA therapy that targets angiopoietin-like protein 3 (ANGPTL3) to reduce LDL cholesterol.

Because of limitless sequence choice; speed of design; and relative ease of synthesis, RNA drugs will be rapidly developed, will have broad applications, and will be generated at lower cost than other drug types. This review aims to highlight RNA therapies for cardiovascular diseases that are approved, and those that are under clinical evaluation.

Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement. However, a thin endometrial layer (≤ 7 mm) may have a significant effect on microenvironment tolerance, which is further related to successful embryo implantation or conception, either naturally or after assisted reproductive technology. Moreover, this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells (EECs), which results in altered signaling biomolecule secretion, including exosome content. In the context of endometrium regeneration, mesenchymal stromal cells (MSCs) and umbilical cord (UC)-derived stem cells have been applied in clinical trials with promising results. It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs. Specifically, microRNAs in exosomes secreted by the hypoxic damaged EECs, such as miR-214-5p and miR-21-5p, play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Taking into consideration the above information, UC-MSCs may be considered as a modern intervention for endometrial regeneration.

Hemorrhagic neurovascular diseases, with high mortality and poor outcomes, urge novel biomarker discovery and therapeutic targets. Micro-ribonucleic acids (miRNAs) are potent post-transcriptional regulators of gene expression. They have been studied in association with disease states and implicated in mechanistic gene interactions in various pathologies. Their presence and stability in circulating fluids also suggest a role as biomarkers. This review summarizes the current state of knowledge about miRNAs in the context of cerebral cavernous malformations (CCMs), a disease involving cerebrovascular dysmorphism and hemorrhage, with known genetic underpinnings. We also review common and distinct miRNAs of CCM compared to other diseases with brain vascular dysmorphism and hemorrhage. A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, queried all peer-reviewed articles published in English as of January 2025 and reported miRNAs associated with four hemorrhagic neurovascular diseases: CCM, arteriovenous malformations, moyamoya disease, and intracerebral hemorrhage. The PubMed systematic search retrieved 154 articles that met the inclusion criteria, reporting a total of 267 unique miRNAs identified in the literature on these four hemorrhagic neurovascular diseases. Of these 267 miRNAs, 164 were identified in preclinical studies, while 159 were identified in human subjects. Seventeen miRNAs were common to CCM and other hemorrhagic diseases. Common and unique disease-associated miRNAs in this systematic review motivate novel mechanistic hypotheses and have potential applications in diagnostic, predictive, prognostic, and therapeutic contexts of use. Much of current research can be considered hypothesis-generating, reflecting association rather than causation. Future areas of mechanistic investigation are proposed alongside approaches to analytic and clinical validations of contexts of use for biomarkers.

Sepsis is a highly dangerous and complex condition that can result in death. It is characterized by a strong reaction to an infection, causing dysfunction in multiple bodily systems and a high risk of mortality. The transformation of macrophages is a vital stage in the procedure as they possess the capability to interchange between two separate types: M1, which promotes inflammation, and M2, which inhibits inflammation. The choice greatly affects the immune response of the host. This analysis underscores the rapidly expanding roles of exosomes and microRNAs (miRNAs) in regulating the trajectory of macrophage polarization during episodes of sepsis. Exosomes, extremely small extracellular vesicles, facilitate cellular communication by transferring biologically active compounds, including miRNAs, proteins, and lipids. We investigate the impact of changes in exosome production and composition caused by sepsis on macrophage polarization and function. Unique microRNAs present in exosomes play a significant role in controlling crucial signaling pathways that govern the phenotype of macrophages. Through thorough examination of recent progress in this area, we clarify the ways in which miRNAs derived from exosomes can either aggravate or alleviate the inflammatory reactions that occur during sepsis. This revelation not only deepens our comprehension of the underlying mechanisms of sepsis, but it also reveals potential new biomarkers and targets for treatment. This assessment aims to amalgamate diverse research investigations and propose potential avenues for future investigations on the influence that exosomes and miRNAs have on macrophage polarization and the body's response to sepsis. These entities are essential for controlling the host's reaction to sepsis and hold important functions in this mechanism.

The 2024 Nobel Prize honored groundbreaking microRNA (miRNA) discoveries that unveiled the critical functions of miRNAs in fundamental biology and human health. Despite promising therapeutic potential, there are no Food and Drug Administration (FDA)-approved miRNA-based cancer therapies. This commentary discusses the progress and challenges of miRNA-based cancer therapeutics and their potential impact on future clinical oncology.

Clearance of circulating plasma LDL (low-density lipoprotein) cholesterol by the liver requires hepatic LDLR (low-density lipoprotein receptor). Complete absence of functional LDLR manifests in severe hypercholesterolemia and premature atherosclerotic cardiovascular disease. Since the discovery of the LDLR 50 years ago by Brown and Goldstein, all approved lipid-lowering medications have been aimed at increasing the abundance and availability of LDLR on the surface of hepatocytes to promote the removal of LDL particles from the circulation. As such a critical regulator of circulating and cellular cholesterol, it is not surprising that LDLR activity is tightly regulated. Despite over half a century's worth of study, there are still many facets of LDLR biology that remain unexplored. This review will focus on pathways that regulate the LDLR and emerging concepts of LDLR biology.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common forms of dementia globally. AD is characterized by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau in the brain, leading to progressive memory loss and cognitive decline, significantly impairing daily life. In contrast, FTD is marked by selective degeneration of the frontal and/or temporal lobes, typically resulting in profound changes in personality and social behavior, speech disorders, and psychiatric symptoms. Numerous studies have found microRNAs (miRNAs)-small, non-coding RNA molecules that regulate gene expression post-transcriptionally-to be dysregulated in AD and FTD. As a result, miRNAs have emerged as promising novel biomarkers for these diseases. This review examines the current understanding of miRNAs in AD and FTD, emphasizing their potential as accessible, noninvasive biomarkers for diagnosing these prevalent neurodegenerative disorders.

Bovine viral diarrhoea (BVD), a condition triggered by bovine viral diarrhoea virus (BVDV), is recognized globally as a prevalent pathogen among ruminants and markedly affects the economics of animal husbandry. MicroRNAs, a class of small noncoding RNAs, play pivotal roles in regulating a myriad of biological processes.The ATG7-LC3 pathway, a canonical autophagy mechanism, is integral in defending against pathogenic invasion and maintaining cellular homeostasis.

In this study, we observed significant downregulation of bta-miR-221 in cells infected with BVDV. We further established that overexpression of bta-miR-221 markedly attenuated BVDV replication in Madin‒Darby bovine kidney (MDBK) cells. Through bioinformatics prediction analysis, we identified ATG7, an autophagy-related gene, as a direct downstream target of bta-miR-221. However, the intricate relationships among bta-miR-221, the ATG7-LC3 pathway, and BVDV infection remained unclear. Our study revealed that ATG7 expression was significantly elevated in BVDV-infected cells, whereas bta-miR-221 mimics repressed both endogenous and exogenous ATG7 expression. Following BVDV infection, we noted a decrease in LC3I expression, its conversion to LC3II, a significant increase in ATG7 expression, and a notable decrease in SQSTM1/p62 expression. By employing laser confocal microscopy and immunoprecipitation assays, we elucidated the regulation of the ATG7-LC3 pathway by bta-miR-221 in MDBK cells. Our findings recealed that BVDV infection enhanced the ATG7-LC3 interaction, inducing autophagy through the suppression of bta-miR-221 in MDBK cells. Consequently, bta-miR-221 emerged as a potent inhibitor of BVDV, impacting its proliferation and replication within the host.

This research sheds light on novel aspects of virus-host interactions and lays a foundation for the development of antiviral therapeutics.

MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha-DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute. We also highlight newly identified cis-acting elements and their impact on miRNA maturation, informed by advanced high-throughput and structural studies, and discuss recently discovered mechanisms of clustered miRNA processing, target recognition and target-directed miRNA decay (TDMD). Lastly, we explore multiple regulatory layers of miRNA biogenesis, mediated by RNA-protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications.

Throughout their life cycle, plants are inevitably confronted with various challenges imposed by adverse environmental conditions, including both biotic and abiotic stresses. To adapt to these environmental fluctuations, plants have evolved a highly efficient regulatory mechanism, in which microRNAs (miRNAs) play pivotal roles. miRNAs are a class of 20-24 nucleotide non-coding RNAs generated from MIR genes, which regulate gene expression at the post-transcriptional level through mRNA degradation or translational repression. Over the past decades, accumulating evidence has demonstrated that miRNAs serve as master regulators in plant responses to biotic stresses, such as those caused by bacteria, fungi, oomycetes, viruses, nematodes, and insects. In this review, we summarize recent advances in miRNA biogenesis and highlight the regulatory roles of plant miRNAs in biotic stress tolerance. Additionally, we discuss future directions of miRNA research.

Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of "non-coding RNA", "HIF-1α", and "colorectal cancer", along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research.

Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.

Cancer is a rising issue worldwide, and numerous studies have focused on understanding the underlying reasons for its occurrence and finding proper ways to defeat it. By applying technological advances, researchers are continuously uncovering and updating treatments in cancer therapy. Their vast functions in the regulation of cell growth and proliferation and their significant role in the progression of diseases, including cancer. This review provides a comprehensive analysis of ncRNAs in breast cancer, focusing on long non-coding RNAs such as HOTAIR, MALAT1, and NEAT1, as well as microRNAs such as miR-21, miR-221/222, and miR-155. These ncRNAs are pivotal in regulating cell proliferation, metastasis, drug resistance, and apoptosis. Additionally, we discuss experimental approaches that are useful for studying them and highlight the advantages and challenges of each method. We then explain the results of these clinical trials and offer insights for future studies by discussing major existing gaps. On the basis of an extensive number of studies, this review provides valuable insights into the potential of ncRNAs in cancer therapy. Key findings show that even though the functions of ncRNAs are vast and undeniable in cancer, there are still complications associated with their therapeutic use. Moreover, there is an absence of sufficient experiments regarding their application in mouse models, which is an area to work on. By emphasizing the crucial role of ncRNAs, this review underscores the need for innovative approaches and further studies to explore their potential in cancer therapy.

The enteric nervous system (ENS), an elaborate network of neurons and glia woven through the gastrointestinal tract, is integral for digestive physiology and broader human health. Commensurate with its importance, ENS dysfunction is linked to a range of debilitating gastrointestinal disorders. MicroRNAs (miRNAs), with their pleiotropic roles in post-transcriptional gene regulation, serve as key developmental effectors within the ENS. Herein, we review the regulatory dynamics of miRNAs in ENS ontogeny, showcasing specific miRNAs implicated in both congenital and acquired enteric neuropathies, such as Hirschsprung's disease (HSCR), achalasia, intestinal neuronal dysplasia (IND), chronic intestinal pseudo-obstruction (CIPO), and slow transit constipation (STC). By delineating miRNA-mediated mechanisms in these diseases, we underscore their importance for ENS homeostasis and highlight their potential as therapeutic targets.

MicroRNAs (miRNAs) are critical regulators of the skeleton. In the growth plate, these small non-coding RNAs modulate gene networks that drive key stages of chondrogenesis, including proliferation, differentiation, extracellular matrix synthesis and hypertrophy. These processes are orchestrated through the interaction of pivotal pathways including parathyroid hormone-related protein (PTHrP), Indian hedgehog (IHH), and bone morphogenetic protein (BMP) signaling. This review highlights the miRNA-mRNA target networks essential for chondrocyte differentiation. Many miRNAs are differentially expressed in resting, proliferating and hypertrophic cartilage zones. Moreover, differential enrichment of specific miRNAs in matrix vesicles is also observed, providing means for chondrocytes to influence the function and differentiation of their neighbors by via matrix vesicle protein and RNA cargo. Notably, miR-1 and miR-140 emerge as critical modulators of chondrocyte proliferation and hypertrophy by regulating multiple signaling pathways, many of them downstream from their mutual target Hdac4. Demonstration that a human gain-of-function mutation in miR-140 causes skeletal dysplasia underscores the clinical relevance of understanding miRNA-mediated regulation. Further, miRNAs such as miR-26b have emerged as markers for skeletal disorders such as idiopathic short stature, showcasing the translational relevance of miRNAs in skeletal health. This review also highlights some miRNA-based therapeutic strategies, including innovative delivery systems that could target chondrocytes via cartilage affinity peptides, and potential applications related to treatment of physeal bony bridge formation in growing children. By synthesizing current research, this review offers a nuanced understanding of miRNA functions in growth plate biology and their broader implications for skeletal health. It underscores the translational potential of miRNA-based therapies in addressing skeletal disorders and aims to inspire further investigations in this rapidly evolving field.

MicroRNAs (miRNAs) are ~22-nucleotide small non-coding RNAs that play critical roles in gene regulation. The discovery of miRNAs in Caenorhabditis elegans in 1993 by the research groups of Victor Ambros and Gary Ruvkun opened a new era in RNA research. Typically, miRNAs act as negative regulators of gene expression by binding to complementary sequences within the 3' untranslated regions of their target mRNAs. This interaction results in translational repression and/or target destabilization. The expression levels and activities of miRNAs are fine-tuned by multiple factors, including the miRNA biogenesis pathway, variability in target recognition, super-enhancers, post-transcriptional modifications, and target-directed miRNA degradation. Together, these factors form complex mechanisms that govern gene regulation and underlie several pathological conditions, including Argonaute syndrome, genetic diseases driven by super-enhancer-associated miRNAs, and miRNA-deadenylation-associated bone marrow failure syndromes. In addition, as miRNA genes have evolved rapidly in vertebrates, miRNA regulation in the brain is characterized by several unique features. In this review, we summarize recent insights into the role of miRNAs in human diseases, focusing on miRNA biogenesis; regulatory mechanisms, such as super-enhancers; and the impact of post-transcriptional modifications. By exploring these mechanisms, we highlight the intricate and multifaceted roles of miRNAs in health and disease.

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate target gene expression in many eukaryotes. MiRNAs are essential for post-transcriptional regulation, influencing various biological functions, including oocyte growth and maturation, fertilization, early embryo development, and implantation. In recent decades, numerous studies have identified a substantial number of miRNAs associated with mammalian oocyte maturation and early embryo development, utilizing methods such as small RNA sequencing and modulating miRNA expression through overexpression or inhibition. In this review, we introduce the biosynthesis of miRNAs and their regulatory roles in germ cells, summarizing the expression patterns and post-transcriptional regulation of miRNAs during bovine oocyte maturation and early embryo development, as well as their potential application in bovine assisted reproductive technology (ART).

MicroRNAs (miRNAs) add a new dimension to HD forecast, diagnosis, and therapy based on the potential applications. The miRNA-related research in the heart disease (HD) field has received close attention in the past two decades. However, there is a lack of studies that comprehensively and objectively analyze the current situation of miRNA application in the HD field using the bibliometrics method.

To comprehensively analyze the global scientific outputs of miRNAs in HD research from 2004 to 2023.

All the articles and reviews of miRNA-related research in the HD field were retrieved using the Web of Science core collection (WOSCC) title search, and bibliometric analysis was performed in Microsoft Excel 2019, CiteSpace, VOSviewer, and Bibliometrics (R-Tool of R-Studio).

3,874 publications were included in the bibliometric analysis. Collaborative network analysis indicates that China with the maximum number of publications (2,063) and the USA with the highest total citations (59,331) are influential countries in this field. Peking Union Medical College is the most prolific university with the maximum publications (134), and the University of California System is the most authoritative institution regarding betweenness centrality (0.27). PLOS ONE tops the journal list of publications, closely followed by the International Journal of Molecular Sciences and Scientific Reports with more than 100 articles. Considering the number of publications, citations, and total link strength overall, Olson. Eric N, Van Rooij Eva, Thum Thomas, Yang Baofeng, Wang Kun; and Lu Yanjie are authoritative authors in this field. The expression changes and regulatory mechanisms of specific miRNAs in various heart biological and pathophysiological processes have been the continuous research hotspots. "exosomes", "extracellular vesicles", "autophagy", and "management" have been novel hot research topics since 2018, which focused on the diagnosis and treatment of HD. The current research development trend is how to translate the achievement of miRNA-related diagnosis and therapeutic drugs for HD into the clinic.

Our study revealed the intellectual structure of miRNA in HD research, which may help scholars understand this field comprehensively and find partners.

Contrary to a common misconception that the fertilizing spermatozoon acts solely as a vehicle for paternal genome delivery to the zygote, this chapter aims to illustrate how the male gamete makes other essential contributions , including the sperm borne-oocyte activation factors, centrosome components, and components of the sperm proteome and transcriptome that help to lay the foundation for pregnancy establishment and maintenance to term, and the newborn and adult health. Our inquiry starts immediately after sperm plasma membrane fusion with its oocyte counterpart, the oolemma. Parallel to and following sperm incorporation in the egg cytoplasm, some of the sperm structures (perinuclear theca) are dissolved and spent to induce development, others (nucleus, centriole) are transformed into zygotic structures enabling it, and yet others (mitochondrial and fibrous sheath, axonemal microtubules and outer dense fibers) are recycled as to not stand in its way. Noteworthy advances in this research include the identification of several sperm-borne oocyte activating factor candidates, the role of autophagy in the post-fertilization sperm mitochondrion degradation, new insight into zygotic centrosome origins and function, and the contributions of sperm-delivered RNA cargos to early embryo development. In concluding remarks, the unresolved issues, and clinical and biotechnological implications of sperm-vectored paternal inheritance are discussed.

Epigenetics influence and are influenced by the impact of social and environmental challenges on biological outcomes. Therefore, pinpointing epigenetic factors associated with social adversity and traumatic stress enables understanding of the mechanisms underlying vulnerability and resilience. We hypothesized that micro-RNAs (miRNAs) expression may be associated with post-traumatic stress disorder symptom severity (i.e., PTSS) following exposure to social adversity. To test this hypothesis, we leveraged blood-derived RNA samples (n=632) and social adversity data from 483 unique participants in the Detroit Neighborhood Health Study, a community-based, prospective cohort of predominantly African Americans. Results identified 86 miRNAs that are associated with social adversities (financial difficulties, perceived discrimination, cumulative trauma) and PTSS. These miRNAs are primarily involved in the immune response, brain and neural function, as well as cell cycle and differentiation, and 22(25%) have previously been associated with conditions related to PTSD, including traumatic brain injury and stress response. Our findings offer a fresh perspective on understanding the epigenetic role of miRNA in the interaction between social adversity and traumatic stress.

The miR-183/96/182 cluster (miR-183C) is required for normal functions of sensory neurons (SN) and various immune cells, including myeloid cells (MC). This research aims to reveal the roles of miR-183C of SN in the interplay of corneal sensory nerves (CSN) and MC during Pseudomonas aeruginosa (PA) keratitis.

Double-tracing mice with SN-specific (SNS) conditional knockout of miR-183C (CKO) and age- and sex-matched wild type (WT) controls were used. Their CSN are labeled with Red Fluorescent Protein (RFP); MC with Enhanced Green (EG)FP. The left corneas were scarified and infected with ATCC19660 PA. Corneal flatmounts were prepared at 3, 6, and 12 hours post-infection (hpi) and 1, 3, and 5 days (d)pi for confocal microscopy. Myeloperoxidase (MPO) assay and plate count were performed at 1 dpi.

In WT mice, CSN began to degenerate as early as 3 hpi, starting from the fine terminal CSN in the epithelial/subepithelial layers, most prominently in the central region. By 1 dpi, CSN in the epithelium/subepithelial layer were nearly completely destroyed, while stromal nerves persisted. From 3 dpi, CSN were obliterated in both layers. In CKO vs WT mice, CNS followed a slightly slower pace of degeneration. CSN density was decreased at 3 and 6 hpi. However, at 3 dpi, residual large-diameter stromal CSN were better preserved.MC were decreased in the central cornea at 3 and 6 hpi, but increased in the periphery. Both changes were more prominent in CKO vs WT mice. At 12 hpi, densely packed MC formed a ring-shaped band circling a "dark" zone nearly devoid of MC, colocalizing with CSN most degenerated zone in the central cornea. In CKO vs WT, the ring center was larger with fewer MC. At 1 dpi, the entire cornea was filled with MC; however, MC density was lower in CKO mice. An MPO assay showed decreased neutrophils in PA-infected cornea of CKO mice. This led to a decreased severity of PA keratitis at 3 dpi.

This double-tracing model reveals the interplay between CSN and MC during PA keratitis with greater clarity, providing new insights into PA keratitis. CSN-imposed modulation on innate immunity is most impressive within 24 hours after infection. Functionally, the miR-183C in CSN modulates CSN density and the dynamics of MC fluxes- a neuroimmune interaction in display.

Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

We have thoroughly searched the literature and found three studies that investigated the roles of miR-223 in platelet function by utilizing miR-223 global knockout mice, and three studies that explored the association between miR-223 and residual platelet reactivity by measuring miR-223 levels in platelets of patients treated with clopidogrel for cardiac artery disease. We assessed platelet function in response to different agonists and evaluated P2y12 levels in male and female miR-223-deficient platelets.

Integrin activation and α granule secretion were similar between WT and KO platelets in response to all agonists in platelets from both female and male mice, although both genotypes showed elevated thrombin response in females compared to males.

In all studies, including ours, taken together, miR-233 appears to play a modest role in platelet function and development of HTPR.

Circular RNAs (circRNAs) make up approximately 10% of the human transcriptome. CircRNAs belong to the broad group of non-coding RNAs and characteristically are formed by backsplicing into a stable circular loop. Their main role is to regulate transcription through the inhibition of miRNAs' expression, termed miRNA sponging. CircRNAs promote tumorigenesis/lymphomagenesis by competitively binding to miRNAs at miRNA binding sites. In diffuse large B-cell lymphoma (DLBCL), several circRNAs have been identified and their expression is related to both progression and response to therapy. DLBCL is the most prevalent and aggressive subtype of B-cell lymphomas and accounts for about 25% to 30% of all non-Hodgkin lymphomas. DLBCL displays great heterogeneity concerning histopathology, biology, and genetics. Patients who have relapsed or have refractory disease after first-line therapy have a very poor prognosis, demonstrating an important unmet need for new treatment options. As more circRNAs are identified in the future, we will better understand their biological roles and potential use in treating cancer, including DLBCL. For example, circAmotl1 promotes nuclear translocation of MYC and upregulation of translational targets of MYC, thus enhancing lymphomagenesis. Another example is circAPC, which is significantly downregulated in DLBCL and correlates with disease aggressiveness and poor prognosis. CircAPC increases expression of the host gene adenomatous polyposis coli (APC), and in doing so inactivates the canonical Wnt/β-catenin signaling and restrains DLBCL growth. MiRNAs belong to the non-coding regulatory molecules that significantly contribute to lymphomagenesis through their target mRNAs. In DLBCL, among the highly expressed miRNAs, are miR-155-5p and miR-21-5p, which regulate NF-ĸB and PI3K/AKT signaling pathways. The aim of this review is to describe the function and mechanism of regulation of circRNAs on miRNAs' expression in DLBCL. This will help us to better understand the regulatory network of circRNA/miRNA/mRNA, and to propose novel therapeutic targets to treat DLBCL.

BACKGROUND B: acterial leaf streak (BLS) is a bacterial disease that severely affects rice leaves, leading to significant yield reductions. microRNAs (miRNAs) are short non-coding RNAs extensively involved in the growth, development, and stress responses of plants and animals. However, miRNAs that regulate the response of rice to bacterial leaf streak are still relatively scarce. RESULTS: The indica rice variety Dular exhibits resistance to BLS, whereas the variety 9311 is highly susceptible to the disease. By conducting miRNA sequencing and transcriptome sequencing on both Dular and 9311 before and after BLS inoculation, we identified 19 miRNAs that were significantly downregulated at both 12 and 24 h post-inoculation in Dular, and 9 miRNAs that were significantly upregulated at the same time points in 9311. Additionally, through degradome sequencing, we identified 23 miRNA- mRNA regulatory modules that likely play crucial roles in rice resistance to BLS, and 4 miRNA- mRNA regulatory modules that may be important in rice susceptibility to the disease. DISCUSSION: Current studies on rice disease resistance miRNAs primarily focus on those involved in resistance to rice blast and bacterial blight, with the miRNA-target mRNA regulatory mechanisms for BLS remaining unclear. This study has identified miRNA-mRNA modules that may play significant roles in rice responses to BLS, contributing to the understanding of the miRNA regulatory network involved in rice defense against BLS infection.

Innate immunity is the first line of defence against pathogenic microorganisms and is nearly universal among eukaryotes. The innate immune system is composed of various organs, cells and immune molecules. MicroRNAs (miRs) are a class of small non‑coding RNAs (~22 nucleotides) that are widely involved in post‑transcriptional regulation of proteins within the innate immune system through the recognition of seed sequences. The present review summarizes the role of the miR‑29 family in innate immunity, with a focus on its specific functions in the differentiation of T cells, B cells, natural killer cells and macrophages, as well as the mechanisms by which the miR‑29 family participates in innate immune signalling. Additionally, this review discusses how the miR‑29 family helps the host combat infections by hepatitis B and C viruses, human immunodeficiency virus and influenza A virus through the regulation of specific signalling molecules. This comprehensive analysis of existing studies emphasizes the importance of the miR‑29 family in maintaining immune balance and defence against pathogens.

The E2F family of transcription factors is conserved in higher eukaryotes and plays pivotal roles in controlling gene expression during the cell cycle. Most canonical E2Fs associate with members of the Dimerisation Partner (DP) family to activate or repress target genes. However, atypical repressors, such as E2F7 and E2F8, lack DP interaction domains and their functions are less understood. We report here that EFL-3, the E2F7 homologue of Caenorhabditis elegans, regulates epidermal stem cell differentiation. We show that phenotypic defects in efl-3 mutants depend on the Nemo-like kinase LIT-1. EFL-3 represses lit-1 expression through direct binding to a lit-1 intronic element. Increased LIT-1 expression in efl-3 mutants reduces POP-1/TCF nuclear distribution, and consequently alters Wnt pathway activation. Our findings provide a mechanistic link between an atypical E2F family member and NLK during C. elegans asymmetric cell division, which may be conserved in other animals.

To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE).

Adult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures. Tail vein plasma collected 48 h after TBI for miRNA analysis was available from 209 vEEG monitored animals (45 sham, 164 TBI [32 with epilepsy]). Based on small RNA sequencing and previous data, the seven most promising brain enriched miRNAs (miR-183-5p, miR-323-3p, miR-434-3p, miR-9a-3p, miR-124-3p, miR-132-3p, and miR-212-3p) were validated by droplet digital polymerase chain reaction (ddPCR).

All seven plasma miRNAs differentiated between TBI and sham-operated rats. None of the seven miRNAs differentiated TBI rats that did and did not develop epilepsy (p > .05), or rats with ≥3 vs <3 seizures in a month (p > .05). However, miR-212-3p differentiated rats that developed epilepsy with seizure clusters (i.e., ≥3 seizures within 24 h) from those without seizure clusters (.34 ± .14 vs .60 ± .34, adj. p < .05) with an area under the curve (AUC) of .81 (95% confidence interval [CI] .65-.97, p < .01, 64% sensitivity, 95% specificity). Lack of elevation in miR-212-3p also differentiated rats that developed epilepsy with seizure clusters from all other TBI rats (n = 146, .34 ± .14 vs .55 ± .31, p < .01) with an AUC of .74 (95% CI .61-.87, p < .01, 82% sensitivity, 62% specificity). Glmnet analysis identified a combination of miR-212-3p and miR-132-3p as an optimal set to differentiate TBI rats with vs without seizure clusters (cross-validated AUC .75, 95% CI .47-.92, p < .05).

miR-212-3p alone or in combination with miR-132-3p shows promise as a translational prognostic biomarker for the development of severe PTE with seizure clusters.

MicroRNAs (miRNAs) play a crucial role in regulating immune responses and have been implicated in the pathogenesis of various nasal diseases, including chronic rhinosinusitis (CRS), allergic rhinitis (AR), and sinonasal tumors. This review comprehensively explores the emerging role of miRNAs in inflammatory and oncological nasal diseases, highlighting their diagnostic, prognostic, and therapeutic potential.

A comprehensive review of the literature was conducted to summarize current findings on miRNA expression in nasal inflammatory conditions and tumors. Key studies evaluating miRNA-mediated regulatory mechanisms, potential biomarker applications, and therapeutic approaches were analyzed.

Altered miRNA expression profiles contribute to the pathogenesis of CRS, AR, and sinonasal tumors. Specific miRNAs, such as miR-125b and miR-155 are upregulated in CRS and AR, promoting inflammation and tissue remodeling. In sinonasal tumors, dysregulated miRNAs, including miR-126 and miR-34/miR-449 clusters, influence tumor progression and therapeutic response. Exosome-mediated miRNA delivery emerges as a promising avenue for precision medicine, offering novel strategies for miRNA-based diagnostics and therapies.

miRNAs are key regulators of nasal diseases, with potential applications in non-invasive diagnostics and targeted therapies. Further research into miRNA-based interventions may improve treatment outcomes and contribute to the development of personalized medicine approaches for nasal inflammatory disorders and malignancies.

MicroRNAs, a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally, are implicated in various pathological conditions including diabetes mellitus (DM). DM has been increasingly recognized as an inflammatory disease and monocytes play a key role in propagating inflammation under hyperglycemic conditions. We hypothesize that high glucose dysregulates microRNAs to promote monocyte inflammatory activity, which may contribute to the pathogenesis of DM. THP-1 monocytes were cultured in normal (5 mM) and high (25 mM) glucose conditions. RT-qPCR and Western blotting were performed to assay microRNAs and proteins, respectively. Monocytes were transfected with microRNA mimics using Lipofectamine RNAiMAX reagent. THP-1 monocyte growth was assessed using Calcein-AM dye and a Boyden chamber assay was applied to measure monocyte migration. The results showed that high glucose downregulated miR-139-5p associated with increased protein expression of CXCR4, an experimentally validated target of miR-139-5p. Correspondingly, treatment with high glucose resulted in a significant increase in THP-1 cell migration towards SDF-1, a cognate ligand for CXCR4. MiR-139-5p overexpression inhibited high glucose-induced CXCR4 expression, leading to reduced cell migration towards SDF-1. High glucose did not affect THP-1 monocyte growth. In conclusion, the miR-139-5p-CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration.

Background: In recent years, micro ribonucleic acids (miRNAs) have been recognized as key regulators in numerous biological processes, particularly in the development and progression of diseases. As a result, extensive research has focused on uncovering the critical involvement of miRNAs in disease mechanisms to better comprehend the underlying causes of human diseases. Despite these efforts, relying solely on biological experiments to identify miRNA-disease associations is both time-consuming and costly, making it an impractical approach for large-scale studies. Methods: In this paper, we propose a novel DeepWalk-based graph embedding method for predicting miRNA-disease association (DWMDA). Using DeepWalk, we extracted meaningful low-dimensional vectors from the miRNA and disease networks. Then, we applied a deep neural network to identify miRNA-disease associations using the low-dimensional vectors of miRNAs and diseases extracted via DeepWalk. Results: An ablation study was conducted to assess the proposed graph embedding modules. Furthermore, DWMDA demonstrates exceptional performance in two major cancer case studies (breast and lung), with results based on statistically robust measures, further emphasizing its reliability as a method for identifying associations between miRNAs and diseases. Conclusions: We expect that our model will not only facilitate the accurate prediction of disease-associated miRNAs but also serve as a generalizable framework for exploring interactions among various biological entities.