Preeclampsia is a complex, progressive multisystem hypertensive disorder during pregnancy that significantly contributes to increased maternal and perinatal morbidity and mortality. Two screening algorithms are in clinical use for detecting preeclampsia: first-trimester screening, which has been developed and validated for predicting early-onset preeclampsia but is less effective for late-onset disease; and the sFlt-1:PlGF biomarker ratio (soluble tyrosine kinase and placental growth factor) used in suspected cases of preeclampsia. This ratio has a high negative predictive value, allowing for the reliable exclusion of the disease. Both of these screening tests have not met expectations. This review attempts to summarize the current knowledge on the pathogenesis and prediction of preeclampsia and to draw attention to novel biomarkers with a focus on microRNAs and galectins. Although these molecules belong to two distinct biological classes, they functionally converge in regulating placental and immune pathways. Ample evidence supports their involvement in the molecular mechanisms underlying preeclampsia. Based on current knowledge, galectin-13, C19MC members, and miRNA-210 are associated with the trophoblast/placenta and conditions of placental ischemia or hypoxia. Their levels differ significantly in pregnant women at risk of preeclampsia as early as the late first and early second trimester, making them potential markers for predicting preeclampsia.

Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.

Kawasaki disease (KD) is an acute vasculitis primarily affecting children, with a potential risk of developing coronary artery aneurysms (CAAs) and cardiovascular complications. The emergence of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has provided insights into Kawasaki disease pathogenesis and opened new avenues for diagnosis and therapeutic intervention. Furthermore, polymorphism analysis of ncRNA genes offers significant insights into genetic predisposition to Kawasaki disease, facilitating tailored treatment approaches and risk assessment to improve patient outcomes. Exosomal ncRNAs, which are ncRNAs encapsulated within extracellular vesicles, have garnered significant attention as potential biomarkers for Kawasaki disease and CAA due to their stability and accessibility in biological fluids. This review comprehensively discusses the biogenesis, components, and potential of exosomal and non-exosomal ncRNAs in Kawasaki disease diagnosis and prognosis prediction. It also highlights the roles of non-exosomal ncRNAs, such as miRNAs, lncRNAs, and circRNAs, in Kawasaki disease pathogenesis and their implications as therapeutic targets. Additionally, the review explores the current diagnostic and therapeutic approaches for Kawasaki disease and emphasizes the need for further research to validate these ncRNA-based biomarkers in diverse populations and clinical settings.

Pathogenic degeneration of cartilage and the generation of fibrotic cartilage are crucial characteristics linked to the progression of osteoarthritis (OA). The current research aims to explore the potential function of the miR-137/BMP7 pathway in regulating the fibrogenic transition of chondrocytes associated with OA, as well as assess the therapeutic potential of andrographolide.

Samples of cartilage from the knees of patients with OA and individuals without OA were gathered to investigate the expression patterns of miR-137, BMP7, and markers associated with fibrosis. A cell model using primary chondrocytes stimulated with interleukin (IL)-1β was developed to study the involvement of the miR-137/BMP7 axis during the fibrogenic transition of these cells. Additionally, we utilized an animal model of OA in order to assess the beneficial effects of the anti-inflammatory natural compound andrographolide on the fibrogenesis induced by OA in vivo.

Elevated levels of fibrogenic and inflammatory factors were linked to decreased miR-137 expression in OA samples. In IL-1β-treated chondrocytes, there was an upregulation of fibrogenic markers alongside a reduction in miR-137 levels. The overexpression of miR-137 inhibited fibrogenesis through the negative regulation of BMP7. Additionally, treatment with andrographolide was effective in attenuating the fibrogenic phenotype in chondrocytes and mitigating OA pathogenesis via modulating the miR-137/BMP7 pathway.

miR-137 downregulation and BMP7 overexpression might contribute to the fibrogenic features in OA-related chondrocytes. Andrographolide attenuates fibrogenic phenotype in chondrocytes and alleviates the severity of OA by modulating the miR-137/BMP7 axis.

A decline in cellular quality control mechanisms is one of the processes of brain aging. Autophagy and proteostasis are two regulatory mechanisms that maintain cellular component turnover to preserve cellular homeostasis, optimal function, and neuronal health by eliminating damaged and aggregated proteins and preventing neurodegenerative disorders (NDDs). Impaired autophagy and proteostasis are significant hallmarks of aging and many age-related NDDs. MicroRNAs are noncoding RNA molecules that have recently been shown to be essential for regulating several biological processes, such as autophagy, proteostasis, cellular differentiation, and development by targeting mRNA's 3'untranslated region (3'UTR). During brain aging, miRNAs have been shown to dysregulate proteostasis and autophagy, resulting in abnormal cellular activity and protein aggregation, a characteristic of age-related NDDs. This review highlights the complex interactions of miRNAs in the orchestration of proteostasis and autophagy. This dysregulation impairs autophagic flux and proteostasis and accelerates age-related disorders, neuroinflammation, and neurodegeneration. Understanding the complex interactions among miRNAs, autophagy, and proteostasis in the aging brain is essential for novel therapeutics development for age-related NDDs.

As living standards elevate, cancers are appearing in growing numbers among younger individuals globally and these risks escalate with advancing years. One of the reasons is that instability in the cancer genome reduces the effectiveness of conventional drug treatments and chemotherapy, compared with more targeted therapies. Previous research has discovered non-coding RNAs' crucial role in shaping genetic networks involved in cancer cell growth and invasion through their influence on messenger RNA production or protein binding. Additionally, the interaction between non-coding RNAs and oxidative stress, a crucial process in cancer advancement, cannot be overlooked. Essentially, oxidative stress results from the negative effects of radicals within the body and ties directly to cancer gene expression and signaling. Therefore, this review focuses on the mechanism between non-coding RNAs and oxidative stress in cancer progression, which is conducive to finding new cancer treatment strategies.

Pancreatic cancer is recognized as one of the most lethal types of cancer globally, characterized by a high mortality rate and a bleak prognosis, which greatly contributes to cancer-related deaths. Forecasts suggest that by 2030, pancreatic cancer will exceed other cancer types in prevalence. The disease presents considerable difficulties owing to the lack of prominent symptoms in its early stages, restricted options for early detection, rapid progression, and unfavorable outcomes. Presently, traditional methods for diagnosing pancreatic cancer primarily rely on imaging techniques. However, these methods often entail significant costs, require considerable time, and necessitate specialized skills for both operating the equipment and interpreting the resulting images. To overcome these obstacles, the use of biosensors has been proposed as a potentially valuable tool for the early detection of pancreatic cancer. MicroRNAs (miRs), a type of small non-coding RNA molecules, have emerged as highly sensitive molecular diagnostic tools that have the potential to function as precise indicators for a range of diseases, including cancer. Biosensors have been suggested as a potential solution for tackling these challenges, offering a promising approach for the early detection of pancreatic cancer. Small non-coding RNA molecules known as MicroRNAs (miRs) have become recognized as extremely sensitive molecular diagnostic tools and can act as precise biomarkers for different diseases, such as cancer. Moreover, this manuscript presents a thorough summary of the latest innovations in nano-biosensors that have been specifically developed for the identification of non-coding RNAs related to pancreatic cancer.

Despite significant advances in cardiology over the past few decades, cardiovascular diseases (CVDs) remain the leading cause of global mortality and morbidity. This underscores the need for novel therapeutic interventions that go beyond symptom management to address the underlying causal mechanisms of CVDs. RNA-based therapeutics represent a new class of drugs capable of regulating specific genetic and molecular pathways, positioning them as strong candidates for targeting the root causes of a wide range of diseases. Moreover, owing to the vast diversity in RNA form and function, these molecules can be utilized to induce changes at different levels of gene expression regulation, making them suitable for a broad array of medical applications, even within a single disease context. Several RNA-based therapies are currently being investigated for their potential to address various CVD pathologies. These include treatments aimed at promoting cardiac revascularization and regeneration, preventing cardiomyocyte apoptosis, reducing harmful circulating cholesterols and fats, lowering blood pressure, reversing cardiac fibrosis and remodeling, and correcting the genetic basis of inherited CVDs. In this review, we discuss the current landscape of RNA therapeutics for CVDs, with an emphasis on their classifications, modes of action, advancements in delivery strategies and considerations for their implementation, as well as CVD targets with proven therapeutic potential.

Mesenchymal stem cell (MSC) therapy has emerged as a promising approach for addressing various eye-related conditions. Yet, its clinical application faces challenges due to issues such as limited biocompatibility and difficulties in effectively delivering treatment to specific ocular tissues. Recent studies have shifted attention towards MSC-derived exosomes, which share similar regenerative, reparative, and immunomodulatory capabilities with their origin cells. This review delves into the latest research on the use of MSC-derived exosomes for treating anterior segment diseases of the eye. It explores the exosomes' composition, biological functions, and the methods used for their isolation, as well as their roles in disease progression, diagnosis, and therapy. The review critically assesses the therapeutic advantages and mechanisms of action of MSC-derived exosomes in treating conditions like dry eye disease, Sjogren's syndrome, keratoconus, corneal lesions, and corneal allograft rejection. Additionally, it discusses the obstacles and future prospects of employing MSC-derived exosomes as innovative therapies for anterior segment eye diseases. This comprehensive overview underscores the significant potential of MSC-derived exosomes in transforming the treatment paradigm for anterior segment eye disorders, while also highlighting the necessity for further research to enhance their clinical application.

Several microRNAs (miRNAs) have been identified as potential biomarkers widely dispersed in animals since 1993, and they have become a significant molecular biology research area. Because of their ability to activate extracellular molecules, stabilise bodily tissues, control cell-to-cell signals, and be easily extracted, miRNAs are outstandingly nominated as biomarkers. However, there is growing interest in targeting miRNAs to monitor physiological reproductive performance, including reproductive system development, embryo development, fertilisation, endocrinology, and animal welfare in stressful conditions. Moreover, miRNAs play significant roles in gene expression regulation; single miRNAs may have overlapping roles, and on a broader scale, multiple mRNAs govern a single function. Also, miRNAs serve as an intermediary messenger between the environment and reproductive performance, making them a vital component of miRNAs as performance biomarkers under environmental conditions like heat stress. This makes describing a unique miRNA's consequences and functions exceptionally challenging, which may confound many researchers. Also, enhancing our comprehension of miRNAs in response to testicular heat stress could potentially aid in preventing and treating spermatogenesis disorders. Therefore, the present review highlights miRNA's regulatory mechanisms on reproductive performance under heat stress to employ these findings in improving reproduction physiology research.

MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers. Notably, miR-145-5p plays a vital role in the pathophysiology underlying HIV and chronic obstructive pulmonary diseases associated with cigarette smoke. This miRNA is abundant in biofluids and shows potential as a biomarker for the diagnosis and prognosis of several infectious diseases, such as hepatitis B, tuberculosis, and influenza. Additionally, numerous studies have indicated that other non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate miR-145-5p. Given the significance of miR-145-5p, a comprehensive overview focusing on its roles in health and disease is essential. This review discusses the dual role of miR-145-5p as a protagonist and antagonist in important human diseases, with particular emphasis on disorders of the respiratory, digestive, nervous, reproductive, endocrine, and urinary systems.

Purpose: Chronic venous leg ulcers (CVLUs) comprise the majority of lower-extremity wounds, yet their pathophysiology is not fully understood. While research has shown that microRNAs are an important component of wound inflammation, few have explored the role of microRNAs (miRNAs) in the healing of CVLUs. This scoping review examines miRNAs in CVLUs and the association with wound healing. Methods: In December 2023, we searched MEDLINE/PubMed, Embase, Scopus, and CINAHL for studies published in 2013-2023 examining miRNAs in CVLU healing. Results: Six studies met inclusion criteria. MicroRNAs were extracted from various specimens including serum, skin biopsy samples, and adipose tissue-derived mesenchymal cells from individuals with CVLUs. Overexpression of miR-221, miR-222, miR-92a, and miR-301a-3p hindered angiogenesis, while overexpression of miR-296, miR-126, miR-378, and miR-210 facilitated angiogenesis. Overexpression of miR-34a/c, miR-301a-3p, miR-450-5p, miR-424-5p, miR-516-5p, and miR-7704 increased local inflammatory responses and inhibited keratinocytes proliferation, impairing healing, while overexpression of miR-19a/b and miR-20 downregulated keratinocytes' inflammatory response, promoting healing. Downregulation of miR-205, miR-96-5p, and miR-218-5p enhanced cellular proliferation and promoted wound healing. Downregulation of miR-17-92 was linked with impaired healing. Discussion: MicroRNAs play a role in regulating angiogenesis, inflammatory responses, and cell migration in chronic-wound healing. However, studies of miRNAs in CVLUs are limited and lack a standardized approach to measurement and quantification. Further research is warranted to elucidate the mechanisms underlying microRNA involvement in CVLU healing to better understand the pathophysiology and for the future development of targeted therapies.

Patients with acute myocardial infarction (AMI) can be identified by myocardial enzymes in peripheral blood, but no protein markers have been found in urinary exosomes derived from AMI patients.

In the present study, a comprehensive proteomics analysis of urinary exosomes derived from patients with AMI was performed. Firstly, we employed the outstanding separation method known as EXODUS to isolate urinary exosomes from AMI patients and healthy controls. Then, we characterized urinary exosomes by nanoparticle tracking analysis (NTA), western blotting and transmission electron microscopy (TEM). After that, we identified the protein components of exosomes through label-free proteomics and conducted bioinformatics analysis.

High-quality exosomes were obtained through separation using EXODUS, which could be demonstrated by NTA, Western blotting and TEM. NTA analysis showed that partilce amount in AMI patients was significantly higher than healthy controls. The equal-volume Western blotting experiment indicated that the expression level of classic exosomal markers Alix, heat shock protein90 (HSP90), CD63 and TSG101 (Tumor susceptibility gene101) in AMI patents was obviously stronger than healthy subjects. We first described the protein profiles of urinary exosomes in AMI patients through proteomics. In this study, We have identified 3194 proteins, among which a total of 30 differential proteins were detected between the urinary exosomes of AMI patients and healthy controls. We investigated F2 and OLR1 among identified exosomal proteins significantly elevated in AMI group, whereas F3 and APCS dysregulated in AMI development.

F2, F3, OLR1 and APCS are able to distinguish individuals between the AMI group and the healthy controls, and the protein panel represent a novel prospective non-invasive biomarkers for the diagnostic process of acute myocardial infarction.

Asthma is the most common chronic pulmonary disease in children. MicroRNAs (miRNAs) play a regulatory role in the occurrence and development of asthma. We aimed to explore the differential expression of miRNAs in the peripheral blood of children with asthma and identify a miRNA that can alleviate asthma inflammation.

We used high-throughput sequencing to analyze differences in peripheral blood miRNA between children with acute asthma and healthy children, followed by target gene prediction and functional enrichment analysis. We inhibited miR-142-3p's expression in asthmatic mice to observe asthma symptoms. Inflammatory changes in lung tissue were assessed using hematoxylin and eosin staining and ELISA. Subsequently, the target gene of miR-142-3p was identified through a dual-luciferase reporter assay, and PTEN and AKT expression levels in mice lung tissue were determined using qPCR and western blot.

Fifty one differentially expressed miRNAs were identified. Inhibition of miR-142-3p expression in asthmatic mice reversed the downregulation of PTEN and activation of AKT in lung tissue, while also significantly alleviating symptoms and pulmonary inflammation in the asthmatic mice.

miRNAs were differentially expressed in the peripheral blood of children with asthma. miR-142-3p regulates airway inflammation via the PTEN/AKT pathway.

Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype with limited biomarkers and therapeutic options. Thus, the present study aimed to evaluate the biomarker and therapeutic potential of Phosphatase and Tensin Homologue (PTEN)-regulating microRNAs (miRNAs) in 2D and 3D ccRCC models. Extracellular vesicles (EVs) from four renal cell lines were characterized, and selected miRNAs (hsa-miR-200c-3p, hsa-miR-25-3p, and hsa-miR-301a-3p) were quantified in cells and EVs. PTEN mRNA levels were measured intracellularly. 786-O cells were transfected with miRNA inhibitors in both models and effects on miRNA and PTEN expression were assessed alongside phenotypic alterations. The expression of target miRNAs increased with ccRCC cell aggressiveness, both intracellularly and in EVs, while PTEN mRNA expression decreased. Combined inhibition of these miRNAs significantly increased PTEN expression, reducing tumor cell proliferation and migration in 2D models and decreasing spheroid size and metabolic capacity in 3D models. These miRNAs show potential as biomarkers for monitoring disease aggressiveness and as therapeutic targets in ccRCC, potentially leading to more effective and personalized treatment approaches for ccRCC patients.

Endothelial cell senescence contributes to vascular remodeling in hypertension, a condition that lacks specific clinical treatments. While plant-derived nanovesicles have shown anti-inflammatory properties that reduce endothelial inflammation, their role in endothelial cell senescence is less understood. Here, we isolated and purified nanovesicles from Semen Sinapis albae (SDNVs), a traditional Chinese medicine with antihypertensive properties, and evaluated their therapeutic effects on vascular remodeling in spontaneously hypertensive rats (SHRs) compared to nifedipine, a standard antihypertensive drug. SDNVs were as effective as nifedipine in reducing blood pressure and exceeded nifedipine in mitigating vascular wall thickening, collagen fiber disarray, and in decreasing senescence markers in aortic tissues. In vitro, SDNVs inhibited angiotensin II-induced senescence in human umbilical vein endothelial cells (HUVECs). miRNA and mRNA sequencing revealed that SDNVs downregulate CD38 expression through miR393a delivery, mediating their anti-senescence effects. Our results suggest that SDNVs significantly alleviate hypertension-associated vascular remodeling by targeting CD38 via miR393a, thus reducing endothelial cell senescence. Compared to conventional drugs like nifedipine, SDNVs offer a potentially more effective approach to vascular remodeling. These insights may guide the development of novel therapeutics for hypertension-induced vascular remodeling.

The occurrence of diabetic cardiomyopathy (DCM) can be independent of several risk factors such as hypertension and myocardial ischemia, which can lead to heart failure, thus seriously threatening human health and life. Sustained hyperglycemic stimulation can induce cardiomyocyte apoptosis, which is recognized as the pathological basis of DCM. It has been demonstrated that dysregulation induced by apoptosis is closely associated to progression of DCM, but mechanisms behind it requires further clarification. Currently, increasing evidence has shown that non-coding RNA (ncRNA), especially microRNA, long-chain non-coding RNA (lncRNA), and circular RNA (circRNA), play a regulative role in apoptosis, thus affecting the progression of DCM. Notably, some ncRNAs have also exhibit potential significance as biomarkers and/or therapeutic targets for patients with DCM. In this review, recent findings regarding the potential mechanisms of ncRNA in regulating apoptosis and their role in the progression of DCM were systematically summarized in this research. The conclusion reveals that ncRNA abnormalities exert a crucial role in pathological changes of DCM, which offers potential therapeutic targets for the prevention of DCM.

Understanding the molecular mechanisms underlying anxiety and ethanol-related behaviors is crucial for developing effective therapeutic interventions. This study identifies a novel role for microRNA miR-181a and its target, Sirtuin 1 (SIRT-1), in the hippocampus as contributors to anxiety-like behavior and voluntary ethanol intake. Using male and female C57BL/6 mice, we explored the causal relationship between hippocampal miR-181a expression and these behaviors. Lentivirus vectors were delivered into the hippocampus for focal miR-181a overexpression in mice. Then behaviors were observed by elevated plus maze (EPM) and open field (OF) tests. Results showed that the viral approach employed to overexpress miR-181a, in the hippocampus, resulted in increased anxiety-like behavior in the EPM and OF tests. Additionally, miR-181a overexpression exacerbated voluntary ethanol intake and preference in the two-bottle choice paradigm without affecting saccharin or quinine consumption. Mechanistically, miR-181a gain-of-function reduced SIRT-1 expression in the hippocampus. These findings demonstrate that miR-181a upregulation in the hippocampus promotes anxiety and ethanol-related behaviors, likely through SIRT-1 repression. This work highlights miR-181a as a key molecular mediator in the epigenetic regulation of mood disorders and ethanol consumption.

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.

MicroRNAs (miRNAs) hold significant promise as circulating cancer biomarkers and unlike many other molecular markers, they can provide valuable insights that extend beyond tumour biology. The expression of circulating miRNAs may parallel the cellular composition and dynamic activity within the tumour microenvironment and reveal systemic immune responses. The functional complexity of miRNAs-where a single miRNA can regulate multiple messenger RNAs (mRNAs) to fine tune fundamental processes, and a single mRNA can be targeted by multiple miRNAs-underscores their broad significance and impact. However, this complexity poses significant challenges for translating miRNA research into clinical practice. In melanoma, specific miRNA signatures have shown notable diagnostic, prognostic and predictive value, with lineage-specific and immune-related miRNAs frequently identified as valuable markers. In this review, we explore the role of circulating miRNAs as potential biomarkers in melanoma, and highlight the current status and advances required to translate miRNA research into therapeutic opportunities.

MicroRNAs (miRNAs) are a class of non-coding RNA sequences that regulate gene expression post-transcriptionally. The miR-99 family, which is highly evolutionarily conserved, comprises three homologs: miR-99a, miR-99b, and miR-100. Its members are under-expressed in most cancerous tissues, suggesting their cancer-repressing properties in multiple cancers; however, in some contexts, they also promote malignant lesion progression. MiR-99 family members target numerous genes involved in various tumor-related processes such as tumorigenesis, proliferation, cell-cycle regulation, apoptosis, invasion, and metastasis. We review the recent research on this family, summarize its implications in cancer, and explore its potential as a biomarker and cancer therapeutic target. This review contributes to the clinical translation of the miR-99 family members.

Circulating microRNAs (miRNAs) are emerging markers for cardiovascular prevention and control. miRNAs associated to vascular damage are candidates to play a causal role in the microvascular dysfunction of heart failure (HF). The aim was to evaluate the observational and causal (Mendelian randomization) association of miRNAs related with vascular alterations (miR-126-3p, miR-1260b and miR-374a-5p) with HF incidence in a sample from the general population.

Plasma miRNAs levels were measured in 985 Hortega Study participants using real time quantitative polymerase chain reaction (RT-qPCR). Single nucleotide polymorphisms (SNPs) were genotyped with the TOPMED imputable Illumina GSA array. We identified genetic instrumental variables for miR-126-3p (33 SNPs), miR-1260b (22 SNPs) and miR-374a-5p (35 SNPs) and run several Mendelian randomization approaches.

The hazard ratio (95 % confidence interval) of HF by a 10-fold increase in miR-126-3p, miR-1260b and miR-374a-5p was 1.53 (1.09, 2.14), 1.38 (1.03, 1.86), and1.30 (1.09, 1.57), respectively. The corresponding rate differences were 9.7 (-0.1, 19.5), 12.0 (0.4, 23.6) and 9.1 (1.2, 17.1) per 10000 person-years. In flexible dose-response analysis, increased miRNAs levels were associated with higher HF risk, both in the relative and additive scale. In Mendelian randomization analysis, consistently suggestive positive causal associations were found with HF for increased miR-126-3p and miR-1260b levels, but not for miR-374a-5p.

In observational analysis, miR-126-3p, miR-1260b and miR-374a-5p levels were positively associated with HF incidence. Mendelian randomization analysis supported a causal role for miR-126-3p and miR-1260b, thus suggesting a potential use as prognostic and therapeutic targets for HF prevention and control.

Ovarian cancer (OV) remains the deadliest gynecological malignancy, with non-coding RNA-mediated transcriptomic deregulation significantly influencing its prognosis and heterogeneous progression. In this study, we prioritized miRNA-mediated gene expression profiles by identifying key negative correlations between miRNA-mRNA pairs. We developed a machine learning-based non-coding index (NCI), incorporating a four-gene signature (GAS1, GFPT2, ZFHX4, and KCNA1) to predict patient prognosis and therapeutic response. Validation across multiple datasets revealed that OV patients with higher NCI scores had significantly poorer survival outcomes and resistance to immunotherapy. Additionally, we established a four-class subtyping taxonomy through unsupervised clustering, validated in four independent datasets. The S1 and S3 subtypes were characterized by high NCI scores, abundant stromal and immune infiltration, with the S3 subtype exhibiting the worst survival. Conversely, the S2 subtype showed downregulation of immune response genes, while the S4 subtype displayed epithelial differentiation and favourable prognosis. Integrative analyses of bulk and single-cell transcriptomic data revealed that the S3 subtype had a significantly higher fibroblast proportion compared to other subtypes, whereas the S1 subtype was marked by high T cell content. Through ridge regression-based drug sensitivity analyses, we prioritized candidate therapeutics for each subtype. Notably, the S3 subtype demonstrated sensitivity to dasatinib but resistance to methotrexate. Finally, we developed a user-friendly Shiny-based website to facilitate the application of our prognostic and subtype classification models (https://jli-bioinfo.shinyapps.io/NCI_online/). This study establishes a critical prognostic marker and proposes a novel molecular classification framework grounded in miRNA-regulated gene expression profiles, advancing our understanding of the non-coding mechanisms driving OV heterogeneity.

Reproductive disorders, including preeclampsia (PE), endometriosis, premature ovarian failure (POF), and polycystic ovary syndrome (PCOS), present substantial challenges to women's reproductive health. Exosomes (EXOs) are cell-derived vesicles containing molecules that influence target cells' gene expression and cellular behavior. Among their cargo, microRNAs (miRNAs)-short, non-coding RNAs typically 19-25 nucleotides in length-play a crucial role in post-transcriptional gene regulation and have been extensively studied for their therapeutic potential. miRNAs are considered therapeutic targets because they regulate key cellular pathways such as proliferation, apoptosis, angiogenesis, and tissue repair. This review examines the role of exosomal miRNAs from sources such as mesenchymal stem cells (MSCs), plasma, and amniotic fluid in female reproductive disorders, including PE, POF, PCOS, and endometriosis. We discuss their biological origins, mechanisms of miRNA sorting and packaging, and their therapeutic applications in modulating disease progression. By categorizing miRNAs according to their beneficial or detrimental effects in specific conditions, we aim to simplify the understanding of their roles in female infertility.

(1) Background: The follicular fluid (FF) comprises a large portion of ovarian follicles, and serves as both a communication and growth medium for oocytes, and thus should be representative of the metabolomic status of the follicle. This review aims to explore FF biomarkers as well as their effects on fertilization, oocyte, and embryo development, and later on implantation and maintenance of pregnancy. (2) Methods: This review was registered in the PROSPERO database with the ID: CRD42025633101. We parsed PubMed, Scopus, and Google Scholar for research on the effects of different FF biomarkers on IVF/ICSI outcomes in normo-ovulatory women. Included studies were assessed for risk of bias using the NOS scale. Data were extracted and tabulated by two independent researchers. (3) Results: 22 included articles, with a sample size range of 31 to 414 and a median of 60 participants, contained 61 biomarkers, including proteins, growth factors, steroid and polypeptide hormones, inflammation and oxidative stress markers, amino acids, vitamins, lipids of different types, and miRNAs. Most of the biomarkers studied had significant effects on IVF/ICSI outcomes, and seem to have roles in various cellular pathways responsible for oocyte and embryo growth, implantation, placental formation, and maintenance of pregnancy. The FF metabolome also seems to be interconnected, with its various components influencing the levels and activities of each other through feedback loops. (4) Conclusions: FF biomarkers can be utilized for diagnostic and therapeutic purposes in IVF; however, further studies are required for choosing the most promising ones due to heterogeneity of results. Widespread adoption of LC-MS and miRNA microarrays can help quantify a representative FF metabolome, and we see great potential for in vitro supplementation (IVS) of some FF biomarkers in improving IVF/ICSI outcomes.

In recent years, the cardioprotective effects of the volatile anesthetic sevoflurane (SEV) have been confirmed, yet its underlying molecular mechanisms remain incompletely elucidated. Notably, lncRNA LINC00265 has been identified as dysregulated in damaged cardiomyocytes, potentially contributing to disease progression. However, limited research has focused on the interplay between SEV and lncRNA LINC00265. The main objective of this study was to explore the mechanism and role of lncRNA LINC00265 in mediating the cardioprotective effects of SEV against myocardial injury. An in vitro hypoxia/reoxygenation (H/R) model was created in AC16 cells following pretreatment with varying concentrations of SEV. RT-qPCR was used to evaluate the levels of lncRNA LINC00265, miR-370-3p, IL-6, and TNF-α. The concentrations of CK-MB and cTnI were determined using ELISA. Cell viability was evaluated using CCK-8, and apoptosis was quantified by flow cytometry. Additionally, the relationship between lncRNA LINC00265 and miR-370-3p was confirmed using a dual-luciferase reporter assay. Prolonged hypoxia gradually rose in lncRNA LINC00265 levels, which was reversed by SEV pretreatment. SEV pretreatment mitigated H/R-induced decreases in cell viability, increases in apoptosis, and excessive production of IL-6, TNF-α, CK-MB, and cTnI. However, the protective effects of SEV were counteracted by lncRNA LINC00265 overexpression. A negative regulatory relationship between lncRNA LINC00265 and miR-370-3p was discovered. miR-370-3p overexpression mitigated diminished protective effects of SEV by elevated lncRNA LINC00265 in myocardial injury. lncRNA LINC00265 could diminish the protective effects of SEV against myocardial injury by functioning as a sponge for miR-370-3p.

The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy.

Colorectal cancer (CRC) is the third most diagnosed cancer and a leading cause of cancer-related mortality in Morocco, often detected at late stages. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for CRC detection, with miR-21, miR-29a, and miR-92a showing significant diagnostic potential. This study aimed to evaluate the expression levels of these miRNAs in a Moroccan population and their efficacy as diagnostic biomarkers.

A prospective study was conducted using blood samples from 50 CRC patients and 50 healthy controls. Circulating miRNA expression levels were quantified through reverse transcription quantitative PCR (RT-qPCR), with normalization to miR-1228-3p. Statistical analyses, including the Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve analysis, sensitivity (Sen), and specificity (Spe) evaluations, were performed to assess the diagnostic accuracy of individual miRNAs and their combined performance as panels.

The expression levels of miR-21, miR-29a, and miR-92a were significantly elevated in CRC patients compared to healthy controls (all p < 0.001). ROC analysis demonstrated that miR-92a exhibited the highest individual diagnostic performance (AUC: 0.938), followed by miR-21 (AUC: 0.907) and miR-29a (AUC: 0.898). Sensitivity and specificity were 88% and 90%, 92% and 56%, and 76% and 94%, respectively. Combinatorial analysis revealed that the miR-29a and miR-92a panel achieved the highest diagnostic accuracy (AUC: 0.976), surpassing individual miRNAs and other combinations, highlighting its potential as a robust, non-invasive biomarker panel for CRC.

This study highlights the potential of the miR-29a and miR-92a combination, which achieved excellent diagnostic efficiency (AUC: 0.976). These findings underscore miRNA utility in enhancing early detection and reducing CRC-related mortality in Morocco.

N6-methyladenosine (m6A) methylation is the most prevalent RNA modification that is regulated by three regulatory factors: "writers", "erasers" and "readers". m6A modification regulates RNA stability and other mechanisms, including translation, cleavage, and degradation. Current research has demonstrated that m6A methylation is involved in the regulation of occurrence and development of cancers by controlling the expression of cancer-related genes. This review summarizes the role of m6A modification on messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) in cervical cancer (CC). We highlight the dual role of m6A regulatory factors, which act as oncogenes or tumor suppressors depending on the cellular context and downstream targets. Additionally, we examine how ncRNAs reciprocally regulate m6A modification in two ways: by guiding the deposition or removal of m6A modifications on RNA targets, and by modulating the expression of m6A regulatory factors. These interactions further contribute to tumor progression. Furthermore, the therapeutic potential of targeting m6A modification has been emphasized in CC. Moreover, recent advances in small-molecule inhibitors targeting m6A regulators and RNA-based therapies which may offer new treatment strategies have been summarized. Finally, we discuss the current challenges in m6A modification research and provide suggestions for future research directions. This review aims to deepen the understanding of m6A modification in CC and contribute to the development of targeted and personalized treatment strategies.

Lung cancer is the leading cause of cancer-related deaths worldwide, primarily due to late-stage detection, which limits treatment options. Early detection and screening can increase survival rates, but traditional medical imaging methods are costly and inconvenient. Point-of-care biosensors present a promising alternative, being user-friendly, less labor-intensive, and minimally invasive. With high sensitivity and selectivity, these biosensors detect lung cancer-associated biomarkers, including protein and nucleic acid, in biological fluids such as serum, urine, and saliva. Integrating artificial intelligence (AI) with biosensors has further improved their performance. AI algorithms can analyze complex data, differentiate lung cancer patients from healthy individuals, and even predict the risk of cancer metastasis. Despite these advancements, a comprehensive review of AI-coupled biosensors for lung cancer screening and detection has not yet been conducted. The clinical translation of these biosensors is challenged by a lack of standardization in biomarker selection, the number of biomarkers tested, and the determination of clinical cut-off values. This review focuses on recent advances in biosensors for lung cancer screening and detection, the challenges in their clinical application, and the role of AI in improving biosensor performance. Additionally, it explores future perspectives on the evolution of AI-assisted biosensors into comprehensive health monitoring systems, aiming to bridge the gap between technological innovation and practical clinical use.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fatal disease that lacks of not only effective treatments, but also presents delays in its diagnosis, since reliable clinical biomarkers are unavailable. In recent years, advancements in high-throughput sequencing strategies have led to the identification of novel ALS biomarkers, facilitating earlier diagnosis and assessment of treatment efficacy. Since immortalized lymphocytes obtained from peripheral blood are a suitable model to study pathological features of ALS, we employed these samples with the aim of characterize the dysregulated miRNAs in ALS patients. Next-generation sequencing (NGS) was utilized in order to analyze the expression profiles of miRNAs in immortalized lymphocytes from healthy controls, sporadic ALS (sALS), and familial ALS with mutations in superoxide dismutase 1 (SOD1-ALS). The screening analysis of the NGS data identified a set of dysregulated miRNAs, of which nine candidates were selected for qRT-PCR validation, identifying for the first time the possible importance of hsa-miR-6821-5p as a potential ALS biomarker. Furthermore, the up-regulated miRNAs identified are predicted to have direct or indirect interactions with genes closely related to ALS, such as SIGMAR1, HNRNPA1 and TARDBP. Additionally, by Metascape enrichment analysis, we found the VEGFA/VEGFR2 signaling pathway, previously implicated in neuroprotective effects in ALS, as a candidate pathway for further analyses.

Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of patients with colon cancer (CC). Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development.

N6-methyladenosine (m6A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m6A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m6A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m6A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m6A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m6A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m6A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m6A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m6A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m6A modification in other types of cancers.

Parkinson's disease (PD) is the second most common neurodegenerative condition after Alzheimer's. Abnormal accumulation of alpha-synuclein (α-syn) aggregates disrupts the balance of dopaminergic (DA-ergic) synapse components, interfering with dopamine transmission and leading to synaptic dysfunction and neuronal loss in PD. However exact molecular mechanism underlying DA-ergic neuronal cell loss in the SNpc in not known. MicroRNAs (miRNAs) are observed in various compartments of neural elements including cell bodies, nerve terminals, mitochondria, synaptic vesicles and synaptosomes. However, miRNAs expression and cellular distribution are unknown in the soma and synapse compartment in PD and healthy state. To address this void of information, we isolated synaptosomes and cytosolic fractions (soma) from post-mortem brains of PD-affected individuals and unaffected controls (UC) and processed for miRNA sequencing analysis. A group of miRNAs were significantly altered ( p < 0.05) with high fold changes (variance +/- > 2-fold) in their expressions in different comparisons: 1. UC synaptosome vs UC cytosol, 2. PD synaptosome vs PD cytosol, 3. PD synaptosome vs UC synaptosome, 4. PD cytosol vs UC cytosol. Our study unveiled some potential miRNAs in PD and their alteration and unique distribution in the soma and synapses of SNpc in PD and controls. Further, gene ontology enrichment analysis showed the involvement of deregulated miRNAs in several molecular function and cellular components: synapse assembly formation, cell junction organization, cell projections, mitochondria, Calcium ion binding and protein binding activities.

Insect metamorphosis is a complex developmental process regulated by microRNAs (miRNAs) and hormonal signaling pathways. Key genes driving insect ontogenic changes are precisely modulated by miRNAs, which interact with 20-hydroxyecdysone (20E) and juvenile hormone (JH) to coordinate developmental transitions. Over the past decade, significant progress has been made in understanding miRNA biogenesis, their regulatory roles in gene expression, and their involvement in critical biological processes, including metamorphosis and chitin metabolism. miRNAs are now recognized as essential regulators of chitin metabolism and hormonal signaling, ensuring precise control of insect development. Disrupting the expression of participating genes in hormone signaling pathways through miRNAs leads to aberrant metamorphosis and consequent lethal outcomes, highlighting their potential as targets for pest control. This review summarizes current advances in miRNA-mediated regulation of insect metamorphosis and chitin metabolism, with a focus on their interactions with 20E and JH signaling pathways. By integrating recent findings, we provide insights into the molecular mechanisms underlying miRNA function in developmental transitions and their potential applications in insect pest management strategies. © 2025 Society of Chemical Industry.

In the gut, microRNAs (miRNAs) produced by intestinal epithelial cells are secreted into the lumen and can shape the composition and function of the gut microbiome. Crosstalk between gut microbes and the host plays a key role in irritable bowel syndrome (IBS) and inflammatory bowel diseases, yet little is known about how the miRNA-gut microbiome axis contributes to the pathogenesis of these conditions. Here, we investigate the ability of miR-21, a miRNA that we found decreased in fecal samples from IBS patients, to associate with and regulate gut microbiome function. When incubated with the human fecal microbiota, miR-21 revealed a rapid internalization or binding to microbial cells, which varied in extent across different donor samples. Fluorescence-activated cell sorting and sequencing of microbial cells incubated with fluorescently labeled miR-21 identified organisms belonging to the genera Bacteroides, Limosilactobacillus, Ruminococcus, or Coprococcus, which predominantly interacted with miR-21. Surprisingly, these and other genera also interacted with a miRNA scramble control, suggesting that physical interaction and/or uptake of these miRNAs by gut microbiota is not sequence-dependent. Nevertheless, transcriptomic analysis of the gut commensal Bacteroides thetaiotaomicron revealed a miRNA sequence-specific effect on bacterial transcript levels. Supplementation of miR-21, but not of small RNA controls, resulted in significantly altered levels of many cellular transcripts and increased transcription of a biosynthetic operon for indole and L-tryptophan, metabolites known to regulate host inflammation and colonic motility. Our study identifies a novel putative miR-21-dependent pathway of regulation of intestinal function through the gut microbiome with implications for gastrointestinal conditions.

The mammalian gut represents one of the largest and most dynamic host-microbe interfaces. Host-derived microRNAs (miRNAs), released from the gut epithelium into the lumen, have emerged as important contributors to host-microbe crosstalk. Levels of several miRNAs are altered in the stool of patients with irritable bowel syndrome or inflammatory bowel disease. Understanding how miRNAs interact with and shape gut microbiota function is crucial as it may enable the development of new targeted treatments for intestinal diseases. This study provides evidence that the miRNA miR-21 can rapidly associate with diverse microbial cells form the gut and increase levels of transcripts involved in tryptophan synthesis in a ubiquitous gut microbe. Tryptophan catabolites regulate key functions, such as gut immune response or permeability. Therefore, this mechanism represents an unexpected host-microbe interaction and suggests that host-derived miR-21 may help regulate gut function via the gut microbiota.

Extracellular vesicles (EVs) are nanovesicles that facilitate intercellular communication by carrying essential biomolecules under physiological and pathological conditions including microRNAs (miRNAs). They are found in various body fluids, such as blood, urine, and saliva, and their levels fluctuate with disease progression, making them valuable diagnostic tools. However, isolating EVs is challenging due to their small size and biological complexity. Here, we summarize the principles behind the most common EV isolation methods including ultracentrifugation, precipitation, immunoaffinity, sorting, ultrafiltration, size exclusion chromatography, and microfluidics while highlighting protocol strengths and weaknesses. We also review the main strategies to identify and quantify circulating miRNAs with a particular focus on EV-encapsulated miRNAs. Since these miRNAs hold special clinical interest derived from their superior stability and therapeutic potential, the information provided here should provide valuable guidance for future research initiatives in the promising field of disease diagnostic and treatment based on EV-encapsulated miRNAs.

Nucleic acid therapeutics have become increasingly recognized in recent years for their capability to target both coding and non-coding sequences. Several types of nucleic acid modalities, including siRNA, mRNA, aptamer, along with antisense oligo, have been approved by regulatory bodies for therapeutic use. The field of nucleic acid therapeutics has been brought to the forefront by the rapid development of vaccines against COVID-19, followed by a number of approvals for clinical use including much anticipated CRISPR-Cas9. However, obstacles such as the difficulty of achieving efficient and targeted delivery to diseased sites remain. This review provides an overview of nucleic acid therapeutics and highlights substantial advancements, including critical engineering, conjugation, and delivery strategies, that are paving the way for their growing role in modern medicine.

Although microRNAs (miRNAs) binding to messenger RNAs (mRNAs) generally results in mRNA degradation and reduced protein expression, their interaction with the internal ribosome entry sites (IRES) of certain RNA viruses enhances viral amplification and expression. In this study, we utilized the natural hepatitis C cirus (HCV) 5' UTR region, which contains miR-122 binding sites, as the IRES of circular RNA (circRNAs) constructs. These circRNAs allowed inducible expression of downstream genes with high specificity in response to both exogenous and endogenous miR-122. Substituting the miR-122 binding sites with those for other miRNAs also resulted in the translational activation of circRNAs by their respective miRNAs in transfected cells. Furthermore, mouse models administered intravenously with lipid nanoparticle-formulated circRNAs containing miRNA binding sites (circRNA-LNP) exhibited higher expression in targeted tissues compared to those with mutated binding sites. Our research introduces a novel strategy for tissue-specific regulation of circRNA expression, potentially broadening the therapeutic applications of circRNAs and paving the way for more precise and effective treatments in gene therapy.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a hepatic form of metabolic syndrome, often co-occurs with type 2 diabetes (T2D) and now affects approximately 30% of the global population. MASLD encompasses conditions from simple steatosis to metabolic dysfunction-associated steatohepatitis, with oxidative stress (OS) driving progression through inflammation. This study analyzes the expression levels of circulating miRNAs and redox status markers in MASLD patients with and without T2D, exploring their potential as disease biomarkers. The expressions of miR-21, miR-34a, and miR-122 were analyzed in the platelet-poor plasma of 147 participants, divided into three groups: MASLD + T2D (48), MASLD (50), and a control group (49). Total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and superoxide anion radical (O2•-) were measured in serum and plasma. Logistic regression showed that miR-21, miR-34a, TOS, TAS, O2•-, and IMA were positive predictors of MASLD, while miR-21 and TAS were negative predictors of T2D in MASLD. Although miR-122 did not show a significant association with either condition, in combination with miR-34a and other markers such as lipid status and liver enzymes, a new significant predictor of MASLD was identified. Circulating miRNAs in combination with redox status markers, lipid status and liver enzymes show potential as MASLD biomarkers.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with complex pathophysiological mechanisms such as oxidative stress, inflammation, apoptosis, and endothelial dysfunction driving disease progression. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as key regulators of gene expression involved in these processes, positioning them as potential biomarkers and therapeutic targets in CVD management. Simultaneously, flavonoids, naturally occurring polyphenolic compounds found in various plant-based foods, have gained attention for their cardioprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Recent studies suggest a novel intersection between flavonoids and miRNAs, where flavonoids may modulate the expression of specific miRNAs implicated in CVD pathogenesis. This review explores the potential of flavonoids as miRNA modulators, focusing on their ability to regulate miRNAs associated with cardiac fibrosis, hypertrophy, and vascular inflammation. By bridging the therapeutic potential of flavonoids with miRNA targeting, this review highlights innovative pathways for advancing CVD treatment strategies. Additionally, preclinical and clinical evidence supporting these interactions is discussed, alongside the challenges and opportunities in developing flavonoid-based miRNA therapies. Unlocking this synergy could pave the way for more effective, personalized approaches to CVD management, addressing unmet needs in contemporary cardiovascular care.

Following injury, many organs are capable of rapid regeneration of necrotic tissue to regain normal function. In contrast, the damaged heart typically replaces tissue with a collagen-rich scar, due to the limited regenerative capacity of its functional contractile cardiomyocytes (CMs). However, this regenerative capacity varies dramatically during development and between species. Furthermore, studies have shown that cardiac regeneration can be enhanced to return contractile function to the damaged heart following myocardial infarction (MI). In this review, we outline the proliferative capacity of CMs in utero, postnatally and in adulthood. We also describe the regenerative capacity of the heart following MI injury. Finally, we focus on the various therapeutic strategies that aim to augment cardiac regeneration in preclinical animal models. These include altering transcripts, microRNAs, extracellular matrix proteins and inducing metabolic rewiring. Together, these therapies aim to return function to the damaged heart and potentially improve the lives of the millions of heart failure patients currently suffering worldwide.

Neuroblastoma is a pediatric cancer that originates from neural crest cells and is the most common extracranial solid tumor in children under five years of age. While low-risk neuroblastoma often regresses spontaneously, high-risk neuroblastoma poses a significant clinical challenge. Recent advances in understanding neuroblastoma's molecular mechanisms have led to the development of targeted therapies that aim to selectively inhibit specific pathways involved in tumor growth and progression, improving patient outcomes while minimizing side effects. This review provides a comprehensive review of neuroblastoma biology and emerging therapeutic strategies. Key topics include (a) immunotherapies and immunotargets, (b) non-coding RNAs (long non-coding RNA, microRNA, and circular RNA), (c) molecular biomarkers and pathways, and (d) limitations and future directions.

Obesity-related cardiac dysfunction is a significant global health challenge. High-fat diets (HFDs) are well-established models of obesity. HFD has been reported to induce cardiac dysfunction and alter cardiac miRNA expression, DNA methylation and histone modifications. Nevertheless, it remains unclear whether cardiac miRNAs altered due to HFD target epigenetic regulator enzymes and function as epigenetic regulator miRNAs (epi-miRNAs), thereby contributing to HFD-induced epigenetic changes and cardiac dysfunction. To address this gap in our knowledge, this study aimed to identify putative cardiac epi-miRNAs and their potential epigenetic targets through an in silico analysis of a previously published miRNA dataset from Sprague Dawley rats subjected to HFD. Using two independent databases, miRDB and miRWalk, predicted miRNA-mRNA interactions were analyzed. A total of 71 miRNAs were identified in our present study as putative epi-miRNAs. A total of 34 epi-miRNAs were upregulated (e.g., miR-92b-3p, let-7c-5p, miR-132-3p), and 37 were downregulated (e.g., miR-21-3p, miR-29c-3p, miR-199a-3p) in response to HFD. Epi-miRNAs targeted 81 individual epigenetic regulators (e.g., Dnmt3a, Ezh2, Hdac4, Kdm3a) with 202 possible miRNA-target interactions. Most of the targeted epigenetic regulators were involved in histone modification. An epi-miRNA-target analysis indicated increased DNA methylation and histone acetylation and decreased histone methylation in the hearts of HFD-fed rats. These findings suggest the importance of epi-miRNA-induced epigenetic changes in HFD-related cardiac dysfunction.

This review comprehensively examines the diverse roles of noncoding RNAs (ncRNAs) in the pathogenesis and treatment of cardiovascular disease (CVD), focusing on microRNA (miRNA), long noncoding RNA (lncRNA), piwi-interacting RNA (piRNA), small-interfering RNA (siRNA), circular RNA (circRNA), and vesicle-associated RNAs. These ncRNAs are integral regulators of key cellular processes, including gene expression, inflammation, and fibrosis, and they hold great potential as both diagnostic biomarkers and therapeutic targets. The review highlights novel insights into how these RNA species, particularly miRNAs, lncRNAs, and piRNAs, contribute to various CVDs such as hypertension, atherosclerosis, and myocardial infarction. In addition, it explores the emerging role of extracellular vesicles (EVs) in intercellular communication and their therapeutic potential in cardiovascular health. The review underscores the need for continued research into ncRNAs and RNA-based therapies, with a focus on advancing delivery systems and expanding personalized medicine approaches to improve cardiovascular outcomes.

There is increasing evidence indicating that global temperatures are rising significantly, a phenomenon commonly referred to as 'global warming', which in turn is believed to be causing drastic changes to the global climate. Global warming (GW) directly impacts animal health, reproduction, production, and welfare, presenting several challenges to livestock enterprises. Thermal stress (TS) is one of the key consequences of GW, and all animal species, including livestock, have diverse physiological, epigenetic and genetic mechanisms to respond to TS. As a result, TS can significantly affect an animals' health, immune responsiveness, metabolic pathways etc. which can also influence the productivity, performance, and welfare of animals. Moreover, prolonged exposure to TS can lead to transgenerational and intergenerational changes that are mediated by epigenetic changes. For example, in several animal species, the effects of TS are encoded epigenetically during the animals' growth or productive stage, and these epigenetic changes can be transmitted intergenerationally. Such epigenetic changes can affect animal productivity by changing the phenotype so that it aligns with its ancestors' environment, irrespective of its immediate environment. Furthermore, epigenetic and genetic changes can also help protect cells from the adverse effects of TS by modulating the transcriptional status of heat-responsive genes in animals. This review focuses on the genetic and epigenetic modulation and regulation that occurs in TS conditions via HSPs, histone alterations and DNA methylation.